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Lorazepam reviews: Lorazepam User Reviews for Anxiety

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Lorazepam User Reviews for Anxiety

Also known as:
Ativan,
Lorazepam Intensol,
Ativan Injection

Lorazepam has an average rating of 8.0 out of 10 from a total of 565 ratings
for the treatment of Anxiety.
75% of users who reviewed this medication reported a positive effect, while 13% reported a negative effect.

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All conditionsAnxiety (614)Borderline Personality Disorder (3)Cervical Dystonia (7)Dysautonomia (1)ICU Agitation (2)Insomnia (110)Light Anesthesia (9)Nausea/Vomiting (32)Nausea/Vomiting, Chemotherapy Induced (3)Panic Disorder (98)Sedation (21)Status Epilepticus (10)

Lorazepam Rating Summary

8.0/10 average rating

565 ratings from 614 user reviews.

Compare all 141 medications used in the treatment of Anxiety.

10 44%
9 19%
8 12%
7 4%
6 3%
5 4%
4 1%
3 2%
2 2%
1 8%

Frequently asked questions

This information is NOT intended to endorse any particular medication. While these reviews might be helpful, they are not a substitute for the expertise, knowledge and judgement of healthcare practitioners.

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Lorazepam Article

[1]

Hui D, Benzodiazepines for agitation in patients with delirium: selecting the right patient, right time, and right indication. Current opinion in supportive and palliative care. 2018 Sep 19     [PubMed PMID: 30239384]

[3]

Berman E,Eyal S,Marom E, Trends in utilization of benzodiazepine and Z-drugs in Israel. Pharmacoepidemiology and drug safety. 2017 Dec     [PubMed PMID: 29027336]

[4]

Vinkers CH,Tijdink JK,Luykx JJ,Vis R, [Choosing the correct benzodiazepine: mechanism of action and pharmacokinetics]. Nederlands tijdschrift voor geneeskunde. 2012     [PubMed PMID: 22929751]

[5]

Yeary J,Garavaglia J,McKnight R,Smith M, Change in Management of Status Epilepticus With the Addition of Neurointensivist-Led Neurocritical Care Team at a Rural Academic Medical Center. Hospital pharmacy. 2018 Oct     [PubMed PMID: 30210147]

[6]

Vlastra W,Delewi R,Rohling WJ,Wagenaar TC,Hirsch A,Meesterman MG,Vis MM,Wykrzykowska JJ,Koch KT,de Winter RJ,Baan J Jr,Piek JJ,Sprangers MAG,Henriques JPS, Premedication to reduce anxiety in patients undergoing coronary angiography and percutaneous coronary intervention. Open heart. 2018     [PubMed PMID: 30275956]

[7]

Maurice-Szamburski A,Auquier P,Viarre-Oreal V,Cuvillon P,Carles M,Ripart J,Honore S,Triglia T,Loundou A,Leone M,Bruder N, Effect of sedative premedication on patient experience after general anesthesia: a randomized clinical trial. JAMA. 2015 Mar 3     [PubMed PMID: 25734733]

[8]

Heavner JJ,Akgün KM,Heavner MS,Eng CC,Drew M,Jackson P,Pritchard D IX,Honiden S, Implementation of an ICU-Specific Alcohol Withdrawal Syndrome Management Protocol Reduces the Need for Mechanical Ventilation. Pharmacotherapy. 2018 May 25     [PubMed PMID: 29800507]

[9]

Cevher Binici N,Topal Z,Demir Samurcu N,Cansız MA,Savcı U,Öztürk Y,Özyurt G,Tufan AE, Response of Catatonia to Amisulpride and Lorazepam in an Adolescent with Schizophenia. Journal of child and adolescent psychopharmacology. 2018 Mar     [PubMed PMID: 29406775]

[10]

Strand MC,Mørland J,Slørdal L,Riedel B,Innerdal C,Aamo T,Mathisrud G,Vindenes V, Conversion factors for assessment of driving impairment after exposure to multiple benzodiazepines/z-hypnotics or opioids. Forensic science international. 2017 Dec     [PubMed PMID: 29101905]

[11]

Naso AR, Optimizing patient safety by preventing combined use of intramuscular olanzapine and parenteral benzodiazepines. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2008 Jun 15     [PubMed PMID: 18541690]

[12]

Petrides AK,Melanson SEF,Kantartjis M,Le RD,Demetriou CA,Flood JG, Monitoring opioid and benzodiazepine use and abuse: Is oral fluid or urine the preferred specimen type? Clinica chimica acta; international journal of clinical chemistry. 2018 Jun     [PubMed PMID: 29499200]

[13]

Xiang J,Wu M,Lei J,Fu C,Gu J,Xu G, The fate and risk assessment of psychiatric pharmaceuticals from psychiatric hospital effluent. Ecotoxicology and environmental safety. 2018 Apr 15     [PubMed PMID: 29289864]

[14]

Arai T,Kogi K,Honda Y,Suzuki T,Kawai K,Okamoto M,Fujioka T,Murata N, Lorazepam as a Cause of Drug-Induced Liver Injury. Case reports in gastroenterology. 2018 May-Aug     [PubMed PMID: 30283291]

[15]

Wallace IR,Campbell EC,Trimble M, Use of a flumazenil infusion to treat chlordiazepoxide toxicity. Acute medicine. 2017     [PubMed PMID: 28424803]

[16]

Niedrig DF,Hoppe L,Mächler S,Russmann H,Russmann S, Benzodiazepine Use During Hospitalization: Automated Identification of Potential Medication Errors and Systematic Assessment of Preventable Adverse Events. PloS one. 2016     [PubMed PMID: 27711224]

[17]

Rubio González V,Redondo Martín S,Ruíz López Del Prado G,Muñoz Moreno MF,Velázquez Miranda A, [Hospital Emergencies Associated with the Consumption of Hypnotics and Sedatives, 2009-2013,Castilla y León, Spain]. Revista espanola de salud publica. 2016 Oct 24     [PubMed PMID: 27775683]

Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Ativan (lorazepam) and Xanax (alprazolam) are two prescription drugs indicated for the treatment of anxiety. Both drugs are available in brand or generic. They are classified in a group of medications called benzodiazepines, which work in the CNS (central nervous system). They work by increasing activity at receptors for a neurotransmitter called gamma-aminobutyric acid (GABA). By doing this, benzodiazepines produce a relaxing and calming effect and help promote sleep when taken at bedtime.

Ativan starts working within an hour, and the effects last for up to eight hours. Xanax starts working within an hour, and the effects last for about five hours (the extended-release version lasts up to about 11 hours). Both drugs have a half-life (the time it takes for the amount of drug to decrease by half) of about 12 hours. Both medications are therapeutically known as benzodiazepines; however, they do have some notable differences, as outlined below. Both drugs are controlled substances and classified as Schedule IV drugs.

What are the main differences between Ativan and Xanax?

Ativan and Xanax, both classified as benzodiazepines, are both available in brand name as well as generic. The generic of Ativan is lorazepam, and the generic of Xanax is alprazolam. Ativan is available in tablet form, injection, and oral concentrate. Xanax is available as both immediate-release and extended-release tablets, as well as an oral concentrate. Ativan is used in children 12 years and older; Xanax is used in adults. Both drugs are intended to be used for a short period of time, but often, patients continue long-term based on the doctor’s instruction, and with careful monitoring.

When either drug is being used, the dosage should be increased slowly, and when the drug is discontinued, it should be done by tapering slowly.

RELATED: Ativan details | Xanax details

Main differences between Ativan and Xanax
Drug class Benzodiazepine Benzodiazepine
Brand/generic status Brand and generic Brand and generic
What is the generic name? Lorazepam Alprazolam
What form(s) does the drug come in? Tablet
Oral concentrate
Injection
Immediate-release tablet
Extended-release tablet
Oral concentrate
What is the standard dosage? Usual range is 2 to 6 mg per day in divided doses (for example, 1 mg tablet taken 3 times daily) Usual range is 0. 25 mg to 0.5 mg taken 3 times daily; dosage varies
How long is the typical treatment? Short-term; some patients use longer under doctor supervision Short-term; some patients use longer under doctor supervision
Who typically uses the medication? Adults; children 12 and older Adults

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Conditions treated by Ativan and Xanax

Ativan and Xanax are both indicated in the management of anxiety disorders. Both drugs are indicated for the short-term relief of the symptoms of anxiety, and short-term relief of anxiety associated with depressive symptoms. Xanax is also indicated for the treatment of panic disorder, with or without agoraphobia. Both medications also have several off-label uses, outlined below.

Management of anxiety disorders Yes Yes
Short-term relief of the symptoms of anxiety Yes Yes
Short-term relief of anxiety associated with depressive symptoms Yes Yes
Treatment of panic disorder, with or without agoraphobia Off-label Yes
Rapid tranquilization of the agitated patient Off-label Off-label
Alcohol withdrawal delirium/alcohol withdrawal syndrome Off-label Off-label
Insomnia Off-label Off-label
Chemotherapy-associated anticipatory nausea and vomiting Off-label Off-label
Delirium Off-label Off-label
Depression No Off-label
Essential tremor Off-label Off-label
Ringing in the ears Off-label Off-label
Premenstrual syndrome Off-label Off-label

Is Ativan or Xanax more effective?

A placebo-controlled, double-blind study compared Ativan and Xanax in the treatment of patients with severe anxiety. Both drugs were found to be more effective than placebo, with Xanax being slightly more effective in later weeks of the study. However, another study of the two drugs for anxiety showed both drugs to be effective, with Ativan being slightly more effective.

Another study compared the two drugs in the treatment of panic disorder and found Ativan and Xanax to be equally effective.

The most effective medication for you should only be determined by your doctor, who will take into account your medical condition(s), history, and other medications you take.

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Coverage and cost comparison of Ativan vs. Xanax

Ativan is typically covered by insurance and Medicare Part D in its generic form of lorazepam. The brand-name Ativan may not be covered or have a high copay. A typical prescription of lorazepam would be for 30 tablets of 1 mg and cost about $24 out-of-pocket. Xanax is also typically covered by insurance and Medicare Part D in the generic form of alprazolam. The brand-name Xanax may not be covered or have a high copay. A typical prescription of alprazolam would be for 60 tablets of 0.5 mg and cost about $33 out-of-pocket. You can save money using a SingleCare coupon on generic Ativan or Xanax.

Try the SingleCare prescription discount card

Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage #30, 1 mg tablets of lorazepam #60, 0.5 mg tablets of alprazolam
Typical Medicare copay $0-$24 $0-$33
SingleCare cost $7-$17 $10-$20

Common side effects of Ativan vs. Xanax

Side effects of Ativan and Xanax tend to be greater at higher doses. The most common side effects of Ativan are sedation, dizziness, and weakness. Patients taking Xanax often experience sedation, dizziness, and weakness.

Other side effects that may occur with either drug include fatigue, lightheadedness, drowsiness, amnesia/memory impairment, confusion, disorientation, depression, euphoria, suicidal ideation/attempt, incoordination, lack of energy, dry mouth, tremor, convulsions/seizures, vertigo, visual disturbance (double or blurred vision), slurred speech, change in libido, impotence, decreased orgasm, headache, coma, respiratory depression, apnea/worsening of sleep apnea, worsening of obstructive pulmonary disease, and gastrointestinal (GI) symptoms including nausea, constipation, or diarrhea.

Other side effects may occur. Consult a healthcare professional for a complete list of side effects.

Side Effect Applicable? Frequency Applicable? Frequency
Sedation Yes 15.9% Yes 41-77%
Dizziness Yes 6. 9% Yes 1.8-30%
Weakness Yes 4.2% Yes 6-7%

Source: DailyMed (Ativan), DailyMed (Xanax)

Drug interactions of Ativan vs. Xanax

Benzodiazepines, such as Ativan and Xanax, should not be taken in combination with opioid painkillers, due to increased risk of sedation, respiratory depression, and overdose, possibly leading to death. If no other combination is possible, the patient should receive the drugs at the lowest possible dose and for the shortest duration, and be closely monitored. Benzodiazepines also should not be taken with other CNS depressants such as alcohol, antipsychotics, antidepressants, sedating antihistamines, and anticonvulsants.

An especially dangerous combination, nicknamed the “holy trinity,” is an opioid (usually a form of hydrocodone or Oxycontin) plus a benzodiazepine (usually Xanax) plus Soma (carisoprodol, a muscle relaxant). These drugs should never be prescribed together; the use of these three medications can result in very serious respiratory depression, overdose, or even death.

Other drug interactions may occur. Consult your healthcare provider for a full list of drug interactions.

Warnings of Ativan and Xanax

Ativan and Xanax have many similar warnings. Both drugs come with a boxed warning, which is the strongest warning required by the FDA. Benzodiazepines such as Ativan or Xanax should not be used in combination with opioid painkillers due to the risk of extreme sedation, severe respiratory depression, coma, or even death. If the combination cannot be avoided, the patient should take the lowest dose for the shortest period of time and be closely monitored. Patients should not drive or operate machinery until effects are known.

Other warnings for both drugs include:

  • Benzodiazepines may cause physical and psychological dependence—the risk is higher with higher doses, longer duration of use, or a history of drug or alcohol abuse. If you take a benzodiazepine, take the medication only as prescribed.
  • Benzodiazepines should be used for the short-term, and when discontinuing, the drug should be slowly tapered to avoid withdrawal symptoms. Withdrawal symptoms may include seizures, along with many other symptoms such as agitation, confusion, rapid heartbeat, vertigo, and other symptoms.
  • Patients with seizure disorders are at higher risk for withdrawal symptoms.
  • In patients with depression, there is a risk of suicide. Patients with depression should also be treated with an antidepressant and should be closely monitored.
  • Benzodiazepines should be used with caution in patients with impaired respiratory function (COPD, sleep apnea).
  • Use with caution and use lower doses in patients with severe hepatic insufficiency and/or encephalopathy.

Xanax has some additional warnings:

  • Patients with panic disorder often use higher doses of Xanax, so there may be a higher risk of dependence.
  • Early morning anxiety or anxiety symptoms between doses have occurred in patients with panic disorder. In these situations, it is recommended that the drug be given in smaller doses, more frequently, adding up to the same total daily dose.

Ativan or Xanax should not be used in pregnancy; both drugs are classified as pregnancy category D, meaning there is a risk to the fetus. If you are taking Ativan or Xanax and find out that you are pregnant, consult your doctor immediately.

Both drugs are on the Beers’ List (drugs that may be inappropriate in older adults). Older adults have increased sensitivity to benzodiazepines and there is an increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults when Ativan or Xanax is used.

Frequently asked questions about Ativan vs. Xanax

What is Ativan?

Ativan, also known by its generic name, lorazepam, is a benzodiazepine drug used to treat anxiety.

What is Xanax?

Xanax, also known by its generic name, alprazolam, is a benzodiazepine drug used to treat anxiety and panic disorder.

Are Ativan and Xanax the same?

Both drugs have many similarities, as well as some differences, as outlined above. Your healthcare provider can help you decide if Ativan or Xanax is right for you or a loved one.

Other drugs in the benzodiazepine category of medications that you may have heard of include Valium (diazepam), Dalmane (flurazepam), Restoril (temazepam), Klonopin (clonazepam), and Halcion (triazolam). All of these drugs are approved by the FDA.

Is Ativan or Xanax better?

Ativan and Xanax are both effective for anxiety and other psychological conditions and have similar side effects, warnings, and drug interactions. Consult your healthcare provider to see if one of these medications is appropriate for you and your condition.

Can I use Ativan or Xanax while pregnant?

Ativan or Xanax may cause fetal abnormalities and should not be used during pregnancy. If you are already taking Ativan and Xanax, and find out that you are pregnant, contact your healthcare provider for guidance.

Can I use Ativan or Xanax with alcohol?

No. The combination of Ativan or Xanax with alcohol is very dangerous and can lead to respiratory depression, extreme sedation, coma, or even death.

Is Ativan milder than Xanax?

It’s hard to categorize Ativan as milder or not; however, we do know that a dose of Xanax wears off faster than a dose of Ativan. Therefore, Xanax may be dosed more frequently than Ativan.

Which is better for anxiety, Xanax or Ativan?

Both medications are effective for anxiety. Ask your doctor if one of these drugs is right for you, taking into account your medical history and condition(s) and other medications you take.

What is the difference between Lorazepam and Xanax?

Both drugs, Ativan (lorazepam) and Xanax (alprazolam) are used to treat anxiety and a variety of other mental health conditions. They have many similarities, and some differences, too, outlined above.

Will Ativan stop a panic attack?

Ativan is used in the treatment of anxiety disorders and is also used off-label to treat panic disorders.

Is Ativan a narcotic?

Ativan is not a narcotic. It is classified as a benzodiazepine. It can be habit-forming and has the potential for abuse and dependence, so it is very important to take it as prescribed.

Ativan (Lorazepam) for Panic Disorder and Anxiety

Ativan (lorazepam) is a common medication used for the treatment of panic disorder and other anxiety conditions. It’s a type of benzodiazepine, a class of medications sometimes referred to as sedatives or tranquilizers due to their calming and relaxing effect on the body. Other common benzodiazepines include Xanax (alprazolam), Klonopin (clonazepam), and Valium (diazepam). 

While Ativan is most frequently used to treat anxiety disorders, it’s often prescribed to treat anxiety symptoms that accompany other psychiatric conditions as well as for other illnesses, despite not being approved for them by the Food and Drug Administration (aka an “off-label use”). For instance, some doctors prescribe Ativan for alcohol withdrawal, to prevent nausea and vomiting during chemotherapy, and for insomnia. 

Illustration by JR Bee, Verywell

How Ativan Treats Panic Disorder

Neurotransmitters in the brain, known as gamma-aminobutyric acid receptors (GABA), are partly responsible for regulating sleep and feelings of relaxation and anxiety. Ativan acts on these receptors to slow down the central nervous system (CNS). This reduces excess agitation and excitement in the brain, inducing a calming and relaxing effect.

By depressing the CNS, Ativan is also able to lessen the intensity of anxiety and panic attacks. Ativan works quickly, making it an effective solution to temporarily managing panic symptoms. The drug enters your system relatively rapidly and lasts a few hours.

Side Effects of Ativan

Some of the most common side effects of Ativan include:

  • Blurred vision
  • Constipation
  • Dizziness and lightheadedness
  • Drowsiness
  • Dry mouth
  • Headache
  • Heartburn
  • Lack of coordination or unsteadiness
  • Loss of interest in sex
  • Nausea

If these side effects continue or increase in severity, contact your doctor.

Some serious side effects are also possible if you take Ativan. These include mental and mood changes, hallucinations, thoughts of suicide, difficulty walking, and breathing issues. If you experience any of these symptoms, call your doctor right away.

Ativan and Addiction

Like all benzodiazepines, Ativan is classified as a controlled substance, which means its possession and use are regulated by the government. Ativan has the potential to be abused, leading to physical or psychological dependence. Typical withdrawal symptoms include sleep disturbances, irritability, increased nervousness, and muscle cramps.

Your doctor will likely discuss strategies to minimize the risk of addiction. Never attempt to stop your medication on your own. Should you decide to discontinue your prescription, your prescribing doctor will assist you in gradually decreasing your dosage.

Additional Precautions For Taking Ativan

Caution should be taken if you have a history of certain medical conditions. Before taking Ativan, consult your doctor if you’ve been diagnosed with these or any other medical condition:

  • Depression
  • Drug or alcohol addiction
  • Glaucoma
  • Liver disease
  • Lung disease
  • Sleep apnea

Ativan Drug Interactions

Ativan depresses the central nervous system (CNS). Alcohol and certain medications that have a similar effect on the CNS should be avoided. Make certain that your doctor is up to date on all of your current prescription and over-the-counter medications.

Drowsiness and Dizziness

Feeling tired and lightheaded are common side effects of Ativan. Until you are used to how this medication affects you, caution should be taken while driving or performing other tasks that require your full attention and concentration.

Pregnancy and Nursing

It is possible for Ativan to be passed to a child during pregnancy or while breastfeeding. Talk to your doctor about the risk of using Ativan while pregnant or nursing.

Older Adults Taking Ativan

The side effects of Ativan are often more noticeable in older adults. To limit these effects, your doctor may need to adjust your dosage. This information is intended to provide a general overview of the use of Ativan for panic disorder. Any questions or concerns you may have about your prescription should be addressed with your doctor or pharmacist.

Systematic review of catatonia treatment

1Department of Psychiatry, Reinier van Arkel, ‘s-Hertogenbosch, 2Department of Psychiatry, Vincent van Gogh Institute for Psychiatry, Venlo, 3Department of Psychiatry, GGzE, Eindhoven, the Netherlands

Objective: To investigate the evidence-based treatment of catatonia in adults. The secondary aim is to develop a treatment protocol.
Materials and methods: A systematic review of published treatment articles (case series, cohort or randomized controlled studies) which examined the effects of particular interventions for catatonia and/or catatonic symptoms in adult populations and used valid outcome measures was performed. The articles for this review were selected by searching the electronic databases of the Cochrane Library, MEDLINE, EMBASE and PSYCHINFO.
Results: Thirty-one articles met the inclusion criteria. Lorazepam and electroconvulsive therapy (ECT) proved to be the most investigated treatment interventions. The response percentages in Western studies varied between 66% and 100% for studies with lorazepam, while in Asian and Indian studies, they were 0% and 100%. For ECT, the response percentages are 59%–100%. There does not seem to be evidence for the use of antipsychotics in catatonic patients without any underlying psychotic disorder.
Conclusion: Lorazepam and ECT are effective treatments for which clinical evidence is found in the literature. It is not possible to develop a treatment protocol because the evidence for catatonia management on the basis of the articles reviewed is limited. Stringent treatment studies on catatonia are warranted.

Keywords: review, catatonia, therapeutics, electroconvulsive therapy, benzodiazepines, lorazepam, ECT

Introduction

Catatonia is a neuropsychiatric syndrome that was originally described by Karl Kahlbaum in 1874, and hence, Kraepelin considered catatonia as a subtype of dementia praecox.1,2 This conceptualization continued to exist for many years and, consequently, catatonia was classified as a subtype of schizophrenia up to and including Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R.48 Over time, this classification greatly affected recognition and treatment; however, from the late 70s, it became increasingly evident that catatonia is a condition that is associated with a variety of metabolic, neurologic, psychiatric and toxic conditions.3–5 DSM-IV, therefore, mentioned three entities of catatonia: as a subtype of schizophrenia, as a specification of affective disorders, and due to a medical condition.6 To emphasize the importance of recognizing catatonia, its classification in DSM-5 was altered.7 One of the new features of DSM-5 was the inclusion of catatonia under a separate heading in the chapter on Schizophrenia Spectrum and Other Psychotic Disorders.8 Catatonia appears in three forms in DSM-5: “catatonia associated with another mental disorder”, “catatonic disorder due to another medical condition” and “unspecified catatonia”.9

The pathophysiology and etiology of catatonia remains unclear. One of the hypotheses is that it may be explained by an alteration of the dopaminergic function.10,11 In addition, dysfunction of gamma-aminobutyric acid and glutamate systems may be implicated.12 Benzodiazepines and electroconvulsive therapy (ECT) are the most widely studied treatment methods. However, no uniform treatment method has yet been brought forward. To compare the differences in effects between medication, ECT and placebo, and to develop uniform advice, a Cochrane review was performed based on randomized controlled studies (RCTs). However, the conclusion was that none of the studies could be included in this review.13 A controlled study on the treatment of (chronic) catatonia in people with schizophrenia showed that benzodiazepines have no added value compared to placebo.14 Until now, no broadly accepted treatment guidelines have been described for catatonia. The purpose of this review of the literature is to establish the evidence-based treatment for catatonia in adults. The secondary aim is to develop a treatment protocol based on the available evidence.

Materials and methods

The study design was based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) method.15 We searched the databases of the Cochrane Library, MEDLINE, EMBASE and PSYCHINFO in July 2016 using catatonia (and related terms) AND treatment (and related terms) as keywords. We deliberately chose the general term treatment to obtain the broadest possible spectrum of treatment interventions. The main prerequisites were that the articles had been published in either English or Dutch language and that abstracts were available. Articles were selected for inclusion by two authors independent of each other on the basis of predefined inclusion criteria. Treatment manuscripts (irrespective of design) that investigated the effects of particular interventions on catatonia and/or catatonic symptoms in adult populations were included. Case series were included when at least three cases were described. A report was included if response to treatment was measured using a standardized rating instrument or scale. Consequently, all the included full-text articles were analyzed. The results of the included articles are presented in Tables 1–3.

Table 1 Characteristics of studies which investigated treatment of catatonia with benzodiazepines
Notes: aNumber of participants at final follow-up. bRosebush et al.33cLohr and Wisniewski (1987).49dModified McCall scale (1992).50
Abbreviations: BFCRS, Bush–Francis Catatonia Rating Scale; d, disorder; DSM, Diagnostic and Statistical Manual of Mental Disorders; ICD, International Classification of Diseases; IM, intramuscular; IV, intravenous; MRS, Modified Rogers Scale; PASS, positive symptoms subscale; PO, per os, oral administration; SAS, Simpson–Angus Scale; SCID, structured clinical interview for DSM disorders.

Table 2 Characteristics of studies which investigated treatment of catatonia with electroconvulsive therapy
Notes: aNumber of participants at final follow-up. bECT is superior over neuroleptics in catatonia. cRosebush et al.33
Abbreviations: BFCRS, Bush–Francis Catatonia Rating Scale; CGI-I, Clinical Global Impression for improvement; d, disorder; DSM, Diagnostic and Statistical Manual of Mental Disorders; ECT, electroconvulsive therapy; ICD, International Classification of Diseases; IV, intravenous; SCID, structured clinical interview for DSM disorders.

Table 3 Characteristics of studies which investigated treatment of catatonia with antipsychotics
Note: aNumber of participants at final follow-up.
Abbreviations: BFCRS, Bush–Francis Catatonia Rating Scale; CGI-I, Clinical Global Impression for improvement; DSM, Diagnostic and Statistical Manual of Mental Disorders; IV, intravenous; PANSS, Positive and Negative Syndrome Scale; SCID, structured clinical interview for DSM disorders.

Results

Identification

Our search strategy using Ovid database revealed 3,079 potentially relevant manuscripts in the Cochrane Library, MEDLINE, EMBASE and PSYCHINFO. Figure 1 describes the evaluation of these 3,079 publications.

Figure 1 Search and selection strategy. Flow diagram for included studies.

Systematic review results

In total, 31 articles met the inclusion criteria for systematic review. Most of these manuscripts were small scale and four investigations involved cohorts of over 50 people.16–19

Benzodiazepines

Treatment with benzodiazepines is the most extensively studied treatment method and is reported in 17 studies, of which the study characteristics are described in Table 1. Lorazepam is the most widely studied medication, which is administered in doses varying from 2 to 16 mg/day. Three studies investigated a lorazepam/diazepam protocol, with variable results.20–22 The manner of administration is mainly oral (PO). If PO administration is not possible because of the patient’s mental health state, parenteral methods (intramuscular [IM] or intravenous [IV]) are used. Four studies primarily opted for such a parenteral method.17,19,23,24 The reason for doing so was not mentioned. In most studies, lorazepam is administered PO as well IM and IV. Some studies chose diazepam, flunitrazepam or clonazepam as IM or IV therapy.25–27 Duration of therapy varies from the administration of just one dose to continued administration for as long as catatonic symptoms persist. Two studies27,28 explicitly describe that the effect of lorazepam wears off after 3–5 hours and that the symptoms subsequently return.

The average percentage, represented in terms of response and remission (Table 1), reported in Western studies varies between 66% and 100%.28,29 Asian studies report percentages between 0% and 100%.14,20 The percentages in India lie between 17% and 100% (full remission plus partial remission).16,19 The lowest percentages are reported in non-Western studies. If patients respond to benzodiazepines, the effect is usually visible within a few days.26,28,30 This effect can be evaluated by using the Bush–Francis Catatonia Rating Scale.26,31 Studies in which the patients displayed long-term symptomatology prior to treatment reported lower response and/or remission percentages.14,16,17,19,25 Overall, benzodiazepines seem to be well tolerated. It was observed that a high dose of lorazepam (16 mg/day) was tolerated without sedation.32 Five of the 17 studies actively reported no adverse effects.14,21,23,27,32 Only Rosebush et al reported one patient in whom marked agitation was seen after lorazepam treatment.33

Electroconvulsive therapy

Eleven studies described the effects of ECT as a treatment method for catatonia. The characteristics of these studies are described in Table 2. In six studies, ECT was administered as a secondary therapy when there was no or insufficient response to benzodiazepines.16,30,32,34–36 ECT was not only initiated after ineffective pharmacotherapy, but also as primary therapy, for example, in life-threatening situations.18,25,37–39 The reported bilateral ECT frequency was three times a week on average.25,30,35,36,38,39 In two studies, ECT was administered unilaterally, the hypothesis being that this would reduce the risk of cognitive side effects.34,38 Because of the small cohort involved in both studies, this hypothesis could not be confirmed. The total number of ECT sessions in the included studies varied from two to 13.

The percentages, represented in terms of response and remission (Table 2), ranged from 59% to 100%.16,37 Most articles were based on chart reviews and case studies and, consequently, lacked any form of randomization, control group, uniform treatment and crucial information on medication or co-medication. Of the 11 studies which investiged ECT, six studies actively reported about side effects. Cristancho et al34 describe that all patients tolerated ECT well without major adverse effects or cognitive impairment. However, in other studies, patients treated with ECT were observed to have cognitive/memory impairment or complained of headache during treatment.32,35,36 The risk of cognitive adverse effects may be related to higher ECT frequency and must be balanced against the risk of morbidity and mortality due to catatonia.37

Antipsychotics

Four studies (Table 3) examined the role of antipsychotics in treating catatonia. It should be noted that the examined cohorts largely consisted of patients with an underlying psychotic disorder. England et al concluded that clozapine has a beneficial effect on catatonic symptoms.32 On the other hand, classic antipsychotics may result in clinical deterioration and appear to be associated with the development of lethal catatonia or malignant neuroleptic syndrome. Hatta et al observed that patients responded better to an antipsychotic drug with low affinity for dopamine receptors (clozapine) than to an antipsychotic drug with high affinity (haloperidol).25 The main disadvantage of this study is that the effect cannot be attributed to any of the used antipsychotics due to the use of co-medication.

Treatment with olanzapine demonstrated mixed results.32 It was concluded that treatment with olanzapine decreased symptoms measured by the Positive and Negative Syndrome Scale score. However, another study did not include the use of an instrument for measuring catatonia, so no specific effect could be attributed to this treatment.40 Yoshimura et al observed that quetiapine was more significantly used around the time of recovery and discharge, compared to other antipsychotics.41 However, after 30 months, in most patients, this antipsychotic drug had been replaced with another due to lack of effect. Here too, the effect of co-medication is not entirely clear. Adverse effects such as worsening of catatonic symptoms, increasing confusion, agitation and restlessness in patients treated with typical antipsychotics have been mentioned.32 Others reported that tremor and rigidity occurred in most of the cases.25 Yoshimura et al observed that three patients on first-generation antipsychotics and risperidone developed a neuroleptic malignant syndrome.41

Other treatment methods

The use of carbamazepine in the acute phase of catatonia was examined in an open prospective study involving nine patients.23 Carbamazepine was administered when patients did not sufficiently respond to lorazepam. This study revealed that lorazepam initially produces good results, but its effect wears off after a few hours. Eventually, all patients were given carbamazepine, whereupon four patients recovered and one patient showed partial recovery. It should be noted that this study involved a small study group without adequate information about co-medication.

Packing therapy involves wrapping the catatonic patient in cold wet towels in order to reinforce, inter alia, sensory integration. The researchers concluded that it could be used as a co-intervention, but not as primary treatment.42

McDaniel et al described the effect of topiramate on catatonic symptoms in four cases unresponsive to benzodiazepines and antipsychotics.43 After treatment with topiramate, the patients showed recovery or improvement, but it is not clear whether this improvement was the result of the use of topiramate.

The effect of amineptine in patients with schizophrenia and chronic catatonia was examined in an RCT conducted by Ungvari. The author concluded that amineptine has no effect on catatonic symptomatology.44

Therapeutic efficiacy of the N-methyl-D-aspartate (NMDA) antagonist amantadine has been reported by Northoff et al45 and Freitas de Lucena et al.46 Northoff et al reported three cases with acute akinetic catatonia, in which IV infusion of 500 mg amantadine (if necessary, repeated after 24 hours) led to resolution of catatonic symptoms. Considerable reduction of scores in various motor scales was seen with most pronounced effects 4–6 hours after administration. Patients were not taking antipsychotic or any other psychotropic drugs. It should be mentioned that amantadine might exacerbate psychotic symptoms. Therefore, Northoff et al excluded cases of paranoid schizophrenia. Freitas de Lucena et al evaluated the use of amantadine for 4 weeks in five cases of acute catatonia in schizophrenia of schizoaffective disorder. Doses were increased up to 600 mg/day over a period of 4 weeks. Patients were medication free for at least 72 hours. Antipsychotic medication was reintroduced in the third week. In all five patients, amantadine led to considerable reduction in catatonic symptoms. The best response was observed between 10 and 21 days.

Discussion

There are currently no broadly accepted guidelines for the treatment of catatonia. The articles included in our review all have a level of evidence not exceeding 1b (individual RCT), of which most do not exceed 2b (individual cohort study).47 In addition, the diversity of methods and outcome measures used makes unambiguous interpretation of these studies impossible, and therefore, it was not feasible to develop an evidence-based treatment protocol. However, the investigated articles clearly show similarities in terms of design and results, which may prove useful in clinical practice and are a starting point for further research.

The response rate to benzodiazepines in Western studies lies between 66% and 100%.26–28,30,33 Non-Western studies reported the lowest response rates. A possible explanation for this is that these studies involved chronic, untreated catatonia.14,16,17 In addition, response seems to depend on dosage and frequency of administration. Studies which involved doses of 2–2.5 mg and more frequent administration (several times a day) showed higher response and remission.20–22,26,28–30 No evident side effects have been described for these dosages. The maximum daily dose used was 12–16 mg.16,32 As benzodiazepines can easily be administered in various settings, they are the therapy of first choice. Lorazepam is the most widely studied compound within this treatment framework. Some studies also examined the effect of diazepam,20–22 but there are no studies that explicitly measured the differences in effects between different types of benzodiazepines. The studies also varied in terms of manner of administration (PO, IM or IV). There are no indications that there is any preference based on efficacy in this respect. How long therapy should be continued was not really examined. There are, though, indications that prolonged treatment is required to obtain a lasting effect.23,27,28 When treatment with lorazepam proves beneficial, this effect is noticeable within several hours to a few days.19–22,24,27,28,30,33 No maximum term for treatment with lorazepam was mentioned, but if it does not entirely produce the desired effect within 4–5 days, it is recommended to consider ECT.16,30 ECT appeared to be a very effective treatment for patients who do not respond to benzodiazepines.16,18,25,30,32,34,36

In severe catatonia involving potentially life-threatening situations such as severe dehydration, autonomic dysregulation, thrombosis or decubitus, ECT may be a good alternative to pharmacotherapy. If treatment with lorazepam is nonetheless the preferred option, it is recommended to provide this therapy in this category of patients at a psychiatric department of a general hospital where the patient’s condition can be better monitored and appropriate measures can be taken (infusion, heparin). Chronic catatonic symptoms constitute another possible reason for opting for ECT in an earlier phase. Various studies described chronic catatonia as a significant patient characteristic of nonresponders to lorazepam.14,17,19 A possible explanation for this is that acute and chronic catatonia have different neurobiologic bases.14 There is no specific cut-off value between acute and chronic catatonia, but generally chronic catatonic symptoms are described as lasting for at least tens of days.17,19

ECT is a very effective therapy for catatonia, also when benzodiazepine (lorazepam) trials have failed.16,18,25,30,35,36 The response percentages vary between 59% and 100%.18,25,30,34,39 The reason why this therapy is a secondary treatment option (in most cases) is that ECT cannot be administered in all settings and because of the potential side effects.

The role of antipsychotics in treating catatonia is not entirely clear. They do seem to be an appropriate therapy when a psychotic disorder is considered to be the underlying cause of catatonia. In these cases, the results of the articles suggest to select an atypical instead of a typical antipsychotic to avoid the risk of deterioration of catatonic symptoms and induction of extrapyramidal movement disorders.

There is insuffient evidence to confirm the therapeutic effects of carbamazepine, topiramate and amineptine. Studies about NMDA antagonists do stress the importance of the potential involvement of glutamatergic dysfunction. However, double-blind control trials are needed to elaborate further on this hypothesis.

Conclusion

In summary, the results clearly showed that benzodiazepines and ECT are the only treatments for which there is clinical evidence. Identifying and treating the underlying disorder is essential in the treatment of catatonia. Moreover, the role of antipsychotics is not yet entirely clear. However, there does not seem to be evidence for the use of antipsychotics as therapy for catatonic patients without any underlying psychotic disorder. Typical antipsychotics can worsen the clinical picture. On the basis of the investigated articles, we were not able to develop a treatment protocol because the evidence for catatonia management is limited. Therefore, an urgent need is warranted for more stringent intervention studies in people with catatonia.

Acknowledgments

The authors thank Gertie van Bergen and Christien Geelen for their secretarial support and Sanne Rasing for her support in designing the review.

Disclosure

In the past, Frank MMA van der Heijden has received some personal fees from Lundbeck, Takeda, Servier and Janssen-Cilag (participation in advisory board and speaker fees). The authors report no other conflicts of interest in this work.


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Ativan: What You Need to Know About Anxiety Pills

On Thursday morning, news broke that Chris Cornell, the groundbreaking singer who helped shape grunge, died by suicide the night before in his Detroit hotel room. Cornell’s unexpected death shocked family, friends and fans, some of whom watched the 52-year-old vocalist and guitarist perform with Soundgarden hours before he passed. A local medical examiner ruled the cause of death as suicide by hanging.

Cornell’s wife, Vicky Cornell, released a statement on Friday morning remembering her late husband and father of three children, and also calling into question what may have led to his death. According to Vicky, Cornell may have taken more than his recommended dosage of Ativan, a medication used to ease symptoms of anxiety. During one of their last phone conversations, Cornell seemed “different” and was “slurring his words,” according to her statement. He had told her he “may have taken an extra Ativan or two,” which prompted her to call security to do a welfare check.

“What happened is inexplicable and I am hopeful that further medical reports will provide additional details,” Vicky said in the statement. “I know that he loved our children and he would not hurt them by intentionally taking his own life.”

It could take days to learn the results of Cornell’s full autopsy and toxicology reports, according to a spokesperson with the Wayne County Medical Examiner’s Office. So the role that Ativan played in his death by suicide is not yet known – a point Cornell’s family attorney, Kirk Pasich, acknowledges. Still, what exactly is Ativan’s connection to suicide? Could the drug contribute to a person’s death? We talked with medical experts find out more about the anti-anxiety medication. Here, what you need to know. 

What is Ativan?
Ativan is the brand name for lorazepam, a type of benzodiazepine medication used foremost to treat severe anxiety and panic disorders in the short term. Benzodiazepines – or “benzos,” as they’re commonly called – are a broad class of highly-addictive sedatives that “have some effective medicinal uses,” said Dr. Joseph Lee, medical director of the Hazelden Betty Ford Foundation Youth Continuum. (The experts interviewed by Rolling Stone spoke generally about Ativan, suicide and their alleged link. None of them have reported a connection to the Cornell family.) In addition to anxiety, Ativan and other benzodiazepines such as Xanax or Valium can be used to treat seizures and substance withdrawal symptoms, as well as help with sedation during medical procedures, Lee tells Rolling Stone.

Public health officials do not recommended the drug for people with addictive disease, depression, psychosis or lung or breathing problems.

How does Ativan affect your brain?
Benzodiazepines are depressants that slow down your nervous system to make you feel calm. They act on the brain’s gamma aminobutyric acid – or GABA – receptors, one of the most common neurotransmitters in the central nervous system. According to The Ochsner Journal, GABA receptors reduce the excitability of neurons, which creates a meditative effective on the brain.

Ativan is a short-acting anti-anxiety medication, often prescribed in low doses for a few weeks at a time. When used correctly, the medication can “work very nicely” for someone dealing with severe anxiety or panic attacks, says Dr. Stuart Gitlow, executive director of the Annenberg Physician Training Program in Addictive Disease and former president of the board of directors for the American Society of Addiction Medicine. For example, a person may take a low dose of Ativan if they’re experiencing panic attacks before boarding a plane. But when misused, Ativan could cause harmful side effects similar to alcohol, he says.

Prolonged use or abuse of Ativan will cause a person to “build up too much tolerance” to the point where the drug no longer works, Gitlow tells Rolling Stone. They would have to take higher and higher doses in order to “achieve the original effect” as the brain pushes back against “this outside artificial influence,” he says. “When the brain pushes back, what that essentially means is that after the drug wears off, you’re more anxious, more irritable, more distressed, more uncomfortable than you were to begin with.”

People who’ve taken an excessive amount of Ativan may exhibit unusual behaviors, shakiness, trouble speaking and slurred speech, among other symptoms, according to the U.S. National Library of Medicine. Those side effects are made worse when the medication is combined with another substance, such as alcohol or barbiturates.

What is the correlation between Ativan and suicide?
Research has shown that benzodiazepines, like alcohol, can cause anterograde amnesia if a person takes an excessive amount of the drug. Anterograde amnesia – or what’s otherwise known as “blackouts” – is the inability to create new memories, meaning that the brain doesn’t record events as they happen forward in time. In other words: You lose chunks of time.

Similar to alcoholic blackouts, people experiencing anterograde amnesia from consuming too many benzodiazepines can engage in disinhibited and dangerous behaviors. That can include driving while intoxicated, committing crimes and even attempting suicide, Lee says. “We’ve seen a lot of people who had no [prior] disruptive behaviors have really serious consequences from their benzodiazepine use,” he tells Rolling Stone. “So it can be a serious problem.” (Valeant Pharmaceuticals International, Inc., which manufactures Ativan, did not return Rolling Stone‘s request for comment.)

The experts who spoke with Rolling Stone noted that prolonged use or misuse of Ativan can exacerbate negative feelings in people with depression or a history of suicidal ideation (Cornell, a recovering addict, had been public about his issues with depression). Though rare, researchers have found a correlation between benzodiazepine misuse and increased suicide risk (a similar link has been with alcohol dependency). But it’s highly unlikely that Ativan would be the sole cause of a completed suicide, as suicide has no single cause, says Dr. Jeffrey Lieberman, chair of psychiatry at New York-Presbyterian/Columbia University Medical Center and former president of the American Psychiatric Association.

If someone were to die by suicide during an Ativan blackout, he continues, they may have been dealing with underlying mental health issues. “Ativan would be the least contributory factor,” Lieberman tells Rolling Stone.

Though not always, people who’ve attempted or died by suicide often exhibit signs beforehand, says Dr. Joel Dvoskin, a clinical psychologist and assistant professor in the University of Arizona’s Department of Psychiatry. They may tell you they have no reason to live or that they feel like a burden to others. They may seem depressed or angry. They may act reckless, abuse drugs, or say goodbye without reason.

Yet routinely, he adds, people take these signs as someone “being dramatic” or as a “cry for help.” “A suicide threat is a cry for help, but that doesn’t mean they’re not going to kill themselves,” Dvoskin tells Rolling Stone. “If somebody says something that implies suicide, take it seriously.”

What to do if you’re concerned about taking Ativan
Do not stop taking Ativan cold turkey. A sudden drop-off in daily use could have harmful consequences; not only could your anxiety worsen, you may also experience withdrawal symptoms such as hallucinations, convulsions, headaches, stomach pains and trouble sleeping, according to the U.S. National Library of Medicine.

“Like alcohol, withdrawal from these drugs like Ativan can be dangerous, potentially deadly,” Gitlow says. “So just stopping is not an option.”

Instead, Gitlow tells Rolling Stone, people who want to stop taking Ativan would need to decrease their dose slowly and under the care of their doctor. When a person tapers off Ativan, your body will have time to adjust to life without the drug, minimizing withdrawal symptoms. But, he notes, you will feel worse during the process until about a month or two after you’ve ended use. “There is unfortunately no way around that,” Gitlow said.

If you or someone you know is in crisis, call the National Suicide Prevention Lifeline at 1-800-273-8255. You do not have to go through this alone.

Chris Cornell’s wife Vicky issued a statement about her late husband. Watch here.

Which medications to avoid in people at risk of delirium: a systematic review | Age and Ageing

Abstract

Background: delirium is a common clinical problem and is associated with adverse health outcomes. Many medications have been associated with the development of delirium, but the strength of the associations is uncertain and it is unclear which medications should be avoided in people at risk of delirium.

Methods: we conducted a systematic review to identify prospective studies that investigated the association between medications and risk of delirium. A sensitivity analysis was performed to construct an evidence hierarchy for the risk of delirium with individual agents.

Results: a total of 18,767 studies were identified by the search strategy. Fourteen studies met the inclusion criteria. Delirium risk appears to be increased with opioids (odds ratio [OR] 2.5, 95% CI 1.2–5.2), benzodiazepines (3.0, 1.3–6.8), dihydropyridines (2.4, 1.0–5.8) and possibly antihistamines (1.8, 0.7–4.5). There appears to be no increased risk with neuroleptics (0.9, 0.6–1.3) or digoxin (0.5, 0.3–0.9). There is uncertainty regarding H2 antagonists, tricyclic antidepressants, antiparkinson medications, steroids, non-steroidal anti-inflammatory drugs and antimuscarinics.

Conclusion: for people at risk of delirium, avoid new prescriptions of benzodiazepines or consider reducing or stopping these medications where possible. Opioids should be prescribed with caution in people at risk of delirium, but this should be tempered by the observation that untreated severe pain can itself trigger delirium. Caution is also required when prescribing dihydropyridines and antihistamine h2 antagonists for people at risk of delirium and considered individual patient assessment is advocated.

Background

Delirium is a common clinical problem that is associated with increased morbidity, mortality, long-term care, length of inpatient stay and healthcare costs [1, 2]. Age >65, cognitive impairment, severe illness and hip fracture have been identified as risk factors for the development of delirium [3].

The pathophysiology of delirium is complex and incompletely understood, and multiple neurotransmitter pathways are implicated, particularly cholinergic and dopaminergic pathways [4]. Many medications can have deleterious effects on cholinergic and dopaminergic pathways [5, 6]. For example, antihistamine H1 medications, H2 antagonists, steroids and digoxin have increased in vitro anticholinergic activity [7], and neuroleptics, angiotensin converting enzyme inhibitors, dihydropyridines and antiparkinson medications have in vitro dopaminergic activity [5]. Direct effects of medications on opioid and gamma-aminobutyric acid (GABA) receptors may also be involved in the complex pathophysiology of delirium. A reduction in hepatic esterases, important enzymes in medication metabolism, has been observed in frail older people and in acute illness [8], and this may be a further important factor in the contribution of medications to delirium.

Multicomponent strategies can successfully reduce delirium incidence and usually incorporate a medication review [9]. However, it is unclear which medications should be targeted as high risk for delirium. We have conducted a systematic review of the literature to identify an evidence-based approach for this common clinical issue.

Methods

Types of study

We searched systematically for all randomised controlled trials (RCTs), prospective cohort studies and case–control studies that reported on medications and delirium in hospital patients or long-term care residents. Retrospective studies, reviews, case series and individual case reports were excluded. The diagnostic criteria for delirium are operationalised in the Diagnostic & Statistical Manual for Mental Disorders (DSM), volumes III, III-R and IV [10–12] and the International Classification of Diseases Volume 10 (ICD 10) [13]. The primary outcome measure for this review was delirium rate using the DSM or ICD criteria or a diagnostic tool validated against DSM III, III-R, IV or ICD 10.

Search strategy and study assessment

A search strategy for MEDLINE was developed, with appropriate amendments for EMBASE, PsychInfo, Allied & Complementary Medicine, with literature searching to October 2009. The full texts of all potentially relevant studies were obtained. The bibliographies of studies selected for inclusion were also reviewed for further potentially relevant articles. RCTs were assessed as described in the Cochrane Handbook for Systematic Reviews of Interventions [14]. Prospective cohort and case–control studies were assessed using the Newcastle–Ottawa checklist [15]. This allowed the studies to be quality graded into high, moderate and low, or potentially biased. As neuroleptic and benzodiazepine medications are used in the treatment of delirium symptoms, particular attention was directed to the reliability of study methods to examine the temporal relationship between prescription and the subsequent development of delirium. Studies that failed to address this important issue were downgraded. The quality assessment was to inform a sensitivity analysis whereby studies providing lower quality evidence were excluded from the final study summary table. Thus, a hierarchy of evidence was constructed with greatest emphasis given to the most reliable studies.

Data extraction and analysis

One review author extracted data using a bespoke database. Multivariate analyses were quality graded on the basis of an event-to-covariate ratio of >10 and the inclusion of three a priori risk factors for delirium (age, cognitive impairment or dementia and illness severity) in the analysis. As univariate data in the form of odds ratios (ORs)/risk ratios (RRs) do not control for potential confounding variables, these data were considered to provide a lower level of evidence to support an association between class of medication and delirium. Where no multivariate or univariate OR/RR was reported, the primary data were extracted and univariate RRs with confidence intervals (CI) for each medication class were calculated using RevMan 5 software.

Results

The review process is summarised in Figure 1 using the PRISMA guidelines [16].

Figure 1.

Figure 1.

Study characteristics

Fourteen studies [17–30] are included in the final analysis. A summary of study characteristics is presented in Table 1. Different populations were recruited: general medicine [17–19]; orthopaedic hip fracture/hip surgery [20, 21, 25, 28]; intensive care (ICU) [22, 26, 27]; a mixed medical and surgical patient group [29]; a mixed surgical population [24]; elective cardiac surgery [30]; and one study was based in long-term care [23]. Seven studies reported data for one single medication class [17, 19, 21–23, 25, 30] and seven studies reported multiple classes [18, 20, 24, 26–29]. Two studies [17, 21] excluded patients with severe dementia. One further study [23] excluded patients with Lewy body dementia, but included all patients with other dementias. Heterogeneity in study populations and methods precluded meta-analysis.

Table 1.

Study summary characteristics

Study
Study design
Year
Country
Healthcare setting
Sample size
Age (mean, SD)
Patients with cognitive impairment/dementia included/excluded
Delirium cases (n)
Diagnostic criteria
Study quality
Agostini et al. [17]  PC  2001  USA  General Medicine  426  80.3 (5.6)  Severe dementia excluded  21  CAM  Moderate 
Flacker et al. [18]  PC  1998  USA  General Medicine  67  86.2 (6.5)  Included  20  CAM  Potentially biased 
Foy et al. [19]  PC  1995  Australia  General Medicine  418  70.2 (6.8)  Excluded  21  DSM III  Moderate 
Gustafson et al. [20]  PC  1988  Sweden  Orthopaedics  111  79.3  Included  68  DSM III  Low 
Kalisvaart et al. [21]  RCT  2005  Netherlands  Orthopaedics  430  79.6  Severe dementia excluded  68  DSM IV  High 
Kim et al. [22]  RCT  1996  USA  ICU  111  65.9 (10.7)  Included  28  DSM III-R  Low 
Lackner et al. [23]  RCT  2008  USA  Long-term care  50  89.2 (1.0)  Included  CAM  Low 
Marcantonio et al. [24]  CC  1994  USA  Mixed surgical  1341  73 (8)  Included  91  CAM  Moderate 
Morrison et al. [25]  PC  2003  USA  Orthopaedics  541  Not given  Included  87  CAM  Moderate 
Pandharipande et al. [26]  PC  2006  USA  ICU  198  55.5 (17.0)  Included  Unclear  CAM-ICU  Moderate 
Pisani et al. [27]  PC  2009  USA  ICU  304  75  Included  239  CAM-ICU  Moderate 
Santos et al. [28]  PC  2005  Sweden  Orthopaedics  34  82.9 (6.3)  Included  19  CAM  Potentially biased 
Schor et al. [29]  PC  1992  USA  General Med/Surgery  325  80.5  Included  91  DSM III  Moderate 
van der Mast et al. [30]  PC  1999  Holland  Cardiac surgery  296  63  Included  40  DSM III-R  Low 
Study
Study design
Year
Country
Healthcare setting
Sample size
Age (mean, SD)
Patients with cognitive impairment/dementia included/excluded
Delirium cases (n)
Diagnostic criteria
Study quality
Agostini et al. [17]  PC  2001  USA  General Medicine  426  80.3 (5.6)  Severe dementia excluded  21  CAM  Moderate 
Flacker et al. [18]  PC  1998  USA  General Medicine  67  86.2 (6.5)  Included  20  CAM  Potentially biased 
Foy et al. [19]  PC  1995  Australia  General Medicine  418  70.2 (6.8)  Excluded  21  DSM III  Moderate 
Gustafson et al. [20]  PC  1988  Sweden  Orthopaedics  111  79.3  Included  68  DSM III  Low 
Kalisvaart et al. [21]  RCT  2005  Netherlands  Orthopaedics  430  79.6  Severe dementia excluded  68  DSM IV  High 
Kim et al. [22]  RCT  1996  USA  ICU  111  65.9 (10.7)  Included  28  DSM III-R  Low 
Lackner et al. [23]  RCT  2008  USA  Long-term care  50  89.2 (1.0)  Included  CAM  Low 
Marcantonio et al. [24]  CC  1994  USA  Mixed surgical  1341  73 (8)  Included  91  CAM  Moderate 
Morrison et al. [25]  PC  2003  USA  Orthopaedics  541  Not given  Included  87  CAM  Moderate 
Pandharipande et al. [26]  PC  2006  USA  ICU  198  55.5 (17.0)  Included  Unclear  CAM-ICU  Moderate 
Pisani et al. [27]  PC  2009  USA  ICU  304  75  Included  239  CAM-ICU  Moderate 
Santos et al. [28]  PC  2005  Sweden  Orthopaedics  34  82.9 (6.3)  Included  19  CAM  Potentially biased 
Schor et al. [29]  PC  1992  USA  General Med/Surgery  325  80.5  Included  91  DSM III  Moderate 
van der Mast et al. [30]  PC  1999  Holland  Cardiac surgery  296  63  Included  40  DSM III-R  Low 

Table 1.

Study summary characteristics

Study
Study design
Year
Country
Healthcare setting
Sample size
Age (mean, SD)
Patients with cognitive impairment/dementia included/excluded
Delirium cases (n)
Diagnostic criteria
Study quality
Agostini et al. [17]  PC  2001  USA  General Medicine  426  80.3 (5.6)  Severe dementia excluded  21  CAM  Moderate 
Flacker et al. [18]  PC  1998  USA  General Medicine  67  86.2 (6.5)  Included  20  CAM  Potentially biased 
Foy et al. [19]  PC  1995  Australia  General Medicine  418  70.2 (6.8)  Excluded  21  DSM III  Moderate 
Gustafson et al. [20]  PC  1988  Sweden  Orthopaedics  111  79.3  Included  68  DSM III  Low 
Kalisvaart et al. [21]  RCT  2005  Netherlands  Orthopaedics  430  79.6  Severe dementia excluded  68  DSM IV  High 
Kim et al. [22]  RCT  1996  USA  ICU  111  65.9 (10.7)  Included  28  DSM III-R  Low 
Lackner et al. [23]  RCT  2008  USA  Long-term care  50  89.2 (1.0)  Included  CAM  Low 
Marcantonio et al. [24]  CC  1994  USA  Mixed surgical  1341  73 (8)  Included  91  CAM  Moderate 
Morrison et al. [25]  PC  2003  USA  Orthopaedics  541  Not given  Included  87  CAM  Moderate 
Pandharipande et al. [26]  PC  2006  USA  ICU  198  55.5 (17.0)  Included  Unclear  CAM-ICU  Moderate 
Pisani et al. [27]  PC  2009  USA  ICU  304  75  Included  239  CAM-ICU  Moderate 
Santos et al. [28]  PC  2005  Sweden  Orthopaedics  34  82.9 (6.3)  Included  19  CAM  Potentially biased 
Schor et al. [29]  PC  1992  USA  General Med/Surgery  325  80.5  Included  91  DSM III  Moderate 
van der Mast et al. [30]  PC  1999  Holland  Cardiac surgery  296  63  Included  40  DSM III-R  Low 
Study
Study design
Year
Country
Healthcare setting
Sample size
Age (mean, SD)
Patients with cognitive impairment/dementia included/excluded
Delirium cases (n)
Diagnostic criteria
Study quality
Agostini et al. [17]  PC  2001  USA  General Medicine  426  80.3 (5.6)  Severe dementia excluded  21  CAM  Moderate 
Flacker et al. [18]  PC  1998  USA  General Medicine  67  86.2 (6.5)  Included  20  CAM  Potentially biased 
Foy et al. [19]  PC  1995  Australia  General Medicine  418  70.2 (6.8)  Excluded  21  DSM III  Moderate 
Gustafson et al. [20]  PC  1988  Sweden  Orthopaedics  111  79.3  Included  68  DSM III  Low 
Kalisvaart et al. [21]  RCT  2005  Netherlands  Orthopaedics  430  79.6  Severe dementia excluded  68  DSM IV  High 
Kim et al. [22]  RCT  1996  USA  ICU  111  65.9 (10.7)  Included  28  DSM III-R  Low 
Lackner et al. [23]  RCT  2008  USA  Long-term care  50  89.2 (1.0)  Included  CAM  Low 
Marcantonio et al. [24]  CC  1994  USA  Mixed surgical  1341  73 (8)  Included  91  CAM  Moderate 
Morrison et al. [25]  PC  2003  USA  Orthopaedics  541  Not given  Included  87  CAM  Moderate 
Pandharipande et al. [26]  PC  2006  USA  ICU  198  55.5 (17.0)  Included  Unclear  CAM-ICU  Moderate 
Pisani et al. [27]  PC  2009  USA  ICU  304  75  Included  239  CAM-ICU  Moderate 
Santos et al. [28]  PC  2005  Sweden  Orthopaedics  34  82.9 (6.3)  Included  19  CAM  Potentially biased 
Schor et al. [29]  PC  1992  USA  General Med/Surgery  325  80.5  Included  91  DSM III  Moderate 
van der Mast et al. [30]  PC  1999  Holland  Cardiac surgery  296  63  Included  40  DSM III-R  Low 

Three RCTs [21–23] presented estimates of effect size with confidence intervals or P values. Six prospective cohort studies [18, 25–27, 29, 30] presented the results of multivariate analyses. Three of the multivariate analyses were of moderate quality [25, 26, 29] and three low quality [18, 27, 30]. One nested case–control study [24] performed a matched analysis of control variables. Six prospective cohort studies [17–20, 28, 29] performed univariate analyses.

Medication classes

Results were found for neuroleptics [18, 20, 21, 29], opioid medications [18, 24–29], benzodiazepines [18–20, 24, 27–29], antihistamine H1 antagonists [17, 24], histamine H2 antagonists [22], dihydropyridines [30], antimuscarinincs [23], tricyclic antidepressants (TCAs) [20], antiparkinson medications [20], digoxin [29], steroids [29] and non-steroidal anti-inflammatory drugs (NSAIDs) [29].

A sensitivity analysis (Table 2) presents a hierarchy of evidence for the medication classes and individual agents within a class. The association of delirium with dose–response and duration of action of agents is also summarised (Table 3).

Table 2.

Evidence hierarchy table summarising the risk of delirium with different medication classes and different agents within a class of medications

Medication class
Study
Setting
Agent
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Neuroleptic  Kalisvaart et al. [21]  Orthopaedic (hip surgery)  Haloperidol  RCT  RR 0.9 (0.6–1.3)  High 
Schor  et al. [29]  Mixed medicine/surgery  All neuroleptics  Multivariate  OR 4.5 (1.8–10.5)  Moderate 
Opioid  Schor  et al. [29]  Mixed medicine/surgery  All opioids  Multivariate  OR 2.5 (1.2–5.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All opioids  Matched  OR 1.4 (0.5–4.3)  Moderate 
Pandharipande  et al. [26]  ICU  Fentanyl  Multivariate  OR 1.2 (1.0–1.5)  Moderate 
Pandharipande  et al. [26]  ICU  Morphine  Multivariate  OR 1.1 (0.9–1.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Meperidine (pethidine)  Matched  OR 2.7 (1.3–5.5)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Morphine  Matched  OR 1.2 (0.6–2.4)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Fentanyl  Matched  OR 1.5 (0.6–4.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Oxycodone  Matched  OR 0.7 (0.3–1.6)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Codeine  Matched  OR 1.1 (0.4–3.6)  Moderate 
Benzodiazepine  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Matched  OR 3.0 (1.3–6.8)  Moderate 
Pandharipande  et al. [26]  ICU  Lorazepam  Multivariate  OR 1.2 (1.1–1.4)  Moderate 
Pandharipande  et al. [26]  ICU  Midazolam  Multivariate  OR 1.7 (0.9–3.2)  Moderate 
Antihistamine (H1 Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  Matched  OR 1.8 (0.7–4.5)  Moderate 
Dihydropyridine  van der Mast  et al. [30]  Cardiac surgery  Nifedipine  Multivariate  OR 2.4 (1.0–5.8)  Low 
H2 Antagonist  Schor  et al. [29]  Mixed medicine/surgery  All H2 antagonists  Univariate  OR 1.4 (0.8–2.5)  Low 
Cardiac glycoside  Schor  et al. [29]  Mixed medicine/surgery  Digoxin  Univariate  OR 0.5 (0.3–0.9)  Low 
Steroid  Schor  et al. [29]  Mixed medicine/surgery  All steroids  Univariate  OR 0.5 (0.2–1.7)  Low 
NSAIDs  Schor  et al. [29]  Mixed medicine/surgery  All NSAIDs  Univariate  OR 0.4 (0.1–1.5)  Low 
Tricyclic antidepressant  Gustafson  et al. [20]  Orthopaedic (hip fracture)  All tricyclic antidepressants  Univariate  RR 1.7 (1.4–2.1)  Very low 
Antiparkinson  Gustafson  et al. [20]  Orthopaedic (hip fracture)  Antiparkinson  Univariate  RR 1.3 (0.9–1.7)  Very low 
Medication class
Study
Setting
Agent
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Neuroleptic  Kalisvaart et al. [21]  Orthopaedic (hip surgery)  Haloperidol  RCT  RR 0.9 (0.6–1.3)  High 
Schor  et al. [29]  Mixed medicine/surgery  All neuroleptics  Multivariate  OR 4.5 (1.8–10.5)  Moderate 
Opioid  Schor  et al. [29]  Mixed medicine/surgery  All opioids  Multivariate  OR 2.5 (1.2–5.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All opioids  Matched  OR 1.4 (0.5–4.3)  Moderate 
Pandharipande  et al. [26]  ICU  Fentanyl  Multivariate  OR 1.2 (1.0–1.5)  Moderate 
Pandharipande  et al. [26]  ICU  Morphine  Multivariate  OR 1.1 (0.9–1.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Meperidine (pethidine)  Matched  OR 2.7 (1.3–5.5)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Morphine  Matched  OR 1.2 (0.6–2.4)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Fentanyl  Matched  OR 1.5 (0.6–4.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Oxycodone  Matched  OR 0.7 (0.3–1.6)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Codeine  Matched  OR 1.1 (0.4–3.6)  Moderate 
Benzodiazepine  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Matched  OR 3.0 (1.3–6.8)  Moderate 
Pandharipande  et al. [26]  ICU  Lorazepam  Multivariate  OR 1.2 (1.1–1.4)  Moderate 
Pandharipande  et al. [26]  ICU  Midazolam  Multivariate  OR 1.7 (0.9–3.2)  Moderate 
Antihistamine (H1 Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  Matched  OR 1.8 (0.7–4.5)  Moderate 
Dihydropyridine  van der Mast  et al. [30]  Cardiac surgery  Nifedipine  Multivariate  OR 2.4 (1.0–5.8)  Low 
H2 Antagonist  Schor  et al. [29]  Mixed medicine/surgery  All H2 antagonists  Univariate  OR 1.4 (0.8–2.5)  Low 
Cardiac glycoside  Schor  et al. [29]  Mixed medicine/surgery  Digoxin  Univariate  OR 0.5 (0.3–0.9)  Low 
Steroid  Schor  et al. [29]  Mixed medicine/surgery  All steroids  Univariate  OR 0.5 (0.2–1.7)  Low 
NSAIDs  Schor  et al. [29]  Mixed medicine/surgery  All NSAIDs  Univariate  OR 0.4 (0.1–1.5)  Low 
Tricyclic antidepressant  Gustafson  et al. [20]  Orthopaedic (hip fracture)  All tricyclic antidepressants  Univariate  RR 1.7 (1.4–2.1)  Very low 
Antiparkinson  Gustafson  et al. [20]  Orthopaedic (hip fracture)  Antiparkinson  Univariate  RR 1.3 (0.9–1.7)  Very low 

Table 2.

Evidence hierarchy table summarising the risk of delirium with different medication classes and different agents within a class of medications

Medication class
Study
Setting
Agent
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Neuroleptic  Kalisvaart et al. [21]  Orthopaedic (hip surgery)  Haloperidol  RCT  RR 0.9 (0.6–1.3)  High 
Schor  et al. [29]  Mixed medicine/surgery  All neuroleptics  Multivariate  OR 4.5 (1.8–10.5)  Moderate 
Opioid  Schor  et al. [29]  Mixed medicine/surgery  All opioids  Multivariate  OR 2.5 (1.2–5.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All opioids  Matched  OR 1.4 (0.5–4.3)  Moderate 
Pandharipande  et al. [26]  ICU  Fentanyl  Multivariate  OR 1.2 (1.0–1.5)  Moderate 
Pandharipande  et al. [26]  ICU  Morphine  Multivariate  OR 1.1 (0.9–1.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Meperidine (pethidine)  Matched  OR 2.7 (1.3–5.5)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Morphine  Matched  OR 1.2 (0.6–2.4)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Fentanyl  Matched  OR 1.5 (0.6–4.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Oxycodone  Matched  OR 0.7 (0.3–1.6)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Codeine  Matched  OR 1.1 (0.4–3.6)  Moderate 
Benzodiazepine  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Matched  OR 3.0 (1.3–6.8)  Moderate 
Pandharipande  et al. [26]  ICU  Lorazepam  Multivariate  OR 1.2 (1.1–1.4)  Moderate 
Pandharipande  et al. [26]  ICU  Midazolam  Multivariate  OR 1.7 (0.9–3.2)  Moderate 
Antihistamine (H1 Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  Matched  OR 1.8 (0.7–4.5)  Moderate 
Dihydropyridine  van der Mast  et al. [30]  Cardiac surgery  Nifedipine  Multivariate  OR 2.4 (1.0–5.8)  Low 
H2 Antagonist  Schor  et al. [29]  Mixed medicine/surgery  All H2 antagonists  Univariate  OR 1.4 (0.8–2.5)  Low 
Cardiac glycoside  Schor  et al. [29]  Mixed medicine/surgery  Digoxin  Univariate  OR 0.5 (0.3–0.9)  Low 
Steroid  Schor  et al. [29]  Mixed medicine/surgery  All steroids  Univariate  OR 0.5 (0.2–1.7)  Low 
NSAIDs  Schor  et al. [29]  Mixed medicine/surgery  All NSAIDs  Univariate  OR 0.4 (0.1–1.5)  Low 
Tricyclic antidepressant  Gustafson  et al. [20]  Orthopaedic (hip fracture)  All tricyclic antidepressants  Univariate  RR 1.7 (1.4–2.1)  Very low 
Antiparkinson  Gustafson  et al. [20]  Orthopaedic (hip fracture)  Antiparkinson  Univariate  RR 1.3 (0.9–1.7)  Very low 
Medication class
Study
Setting
Agent
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Neuroleptic  Kalisvaart et al. [21]  Orthopaedic (hip surgery)  Haloperidol  RCT  RR 0.9 (0.6–1.3)  High 
Schor  et al. [29]  Mixed medicine/surgery  All neuroleptics  Multivariate  OR 4.5 (1.8–10.5)  Moderate 
Opioid  Schor  et al. [29]  Mixed medicine/surgery  All opioids  Multivariate  OR 2.5 (1.2–5.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All opioids  Matched  OR 1.4 (0.5–4.3)  Moderate 
Pandharipande  et al. [26]  ICU  Fentanyl  Multivariate  OR 1.2 (1.0–1.5)  Moderate 
Pandharipande  et al. [26]  ICU  Morphine  Multivariate  OR 1.1 (0.9–1.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Meperidine (pethidine)  Matched  OR 2.7 (1.3–5.5)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Morphine  Matched  OR 1.2 (0.6–2.4)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Fentanyl  Matched  OR 1.5 (0.6–4.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Oxycodone  Matched  OR 0.7 (0.3–1.6)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  Codeine  Matched  OR 1.1 (0.4–3.6)  Moderate 
Benzodiazepine  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Matched  OR 3.0 (1.3–6.8)  Moderate 
Pandharipande  et al. [26]  ICU  Lorazepam  Multivariate  OR 1.2 (1.1–1.4)  Moderate 
Pandharipande  et al. [26]  ICU  Midazolam  Multivariate  OR 1.7 (0.9–3.2)  Moderate 
Antihistamine (H1 Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  Matched  OR 1.8 (0.7–4.5)  Moderate 
Dihydropyridine  van der Mast  et al. [30]  Cardiac surgery  Nifedipine  Multivariate  OR 2.4 (1.0–5.8)  Low 
H2 Antagonist  Schor  et al. [29]  Mixed medicine/surgery  All H2 antagonists  Univariate  OR 1.4 (0.8–2.5)  Low 
Cardiac glycoside  Schor  et al. [29]  Mixed medicine/surgery  Digoxin  Univariate  OR 0.5 (0.3–0.9)  Low 
Steroid  Schor  et al. [29]  Mixed medicine/surgery  All steroids  Univariate  OR 0.5 (0.2–1.7)  Low 
NSAIDs  Schor  et al. [29]  Mixed medicine/surgery  All NSAIDs  Univariate  OR 0.4 (0.1–1.5)  Low 
Tricyclic antidepressant  Gustafson  et al. [20]  Orthopaedic (hip fracture)  All tricyclic antidepressants  Univariate  RR 1.7 (1.4–2.1)  Very low 
Antiparkinson  Gustafson  et al. [20]  Orthopaedic (hip fracture)  Antiparkinson  Univariate  RR 1.3 (0.9–1.7)  Very low 

Table 3.

Summary of results presenting risk of delirium for medications split by dose and duration of action

Medication class
Study
Setting
Agent
Dose
Study quality
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Opioids  Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent 10–30 mg  Moderate  Multivariate  RR 4.4 (0.3–68.6)  Moderate 
Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent <10 mg  Moderate  Multivariate  RR 25.2 (1.3–493.3)  Moderate 
Benzodiazepines  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  High dose (>5 mg diazepam or dose equivalent in 24 h)  Moderate  Matched  OR 3.3 (1.0–11.0)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Low dose (<5 mg diazepam or dose equivalent in 24 h  Moderate  Matched  OR 2.6 (0.8–9.1)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Long actinga  Moderate  Matched  OR 5.4 (1.0–29.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Short actingb  Moderate  Matched  OR 2.6 (1.1–8.5)  Moderate 
Antihistamine H1  Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  High dose (>25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.3–6.9)  Moderate 
Marcantonio  et al. [24]  MIxed surgical  Diphenhydramine  Low dose (<25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.5–4.1)  Moderate 
Medication class
Study
Setting
Agent
Dose
Study quality
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Opioids  Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent 10–30 mg  Moderate  Multivariate  RR 4.4 (0.3–68.6)  Moderate 
Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent <10 mg  Moderate  Multivariate  RR 25.2 (1.3–493.3)  Moderate 
Benzodiazepines  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  High dose (>5 mg diazepam or dose equivalent in 24 h)  Moderate  Matched  OR 3.3 (1.0–11.0)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Low dose (<5 mg diazepam or dose equivalent in 24 h  Moderate  Matched  OR 2.6 (0.8–9.1)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Long actinga  Moderate  Matched  OR 5.4 (1.0–29.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Short actingb  Moderate  Matched  OR 2.6 (1.1–8.5)  Moderate 
Antihistamine H1  Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  High dose (>25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.3–6.9)  Moderate 
Marcantonio  et al. [24]  MIxed surgical  Diphenhydramine  Low dose (<25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.5–4.1)  Moderate 

Table 3.

Summary of results presenting risk of delirium for medications split by dose and duration of action

Medication class
Study
Setting
Agent
Dose
Study quality
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Opioids  Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent 10–30 mg  Moderate  Multivariate  RR 4.4 (0.3–68.6)  Moderate 
Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent <10 mg  Moderate  Multivariate  RR 25.2 (1.3–493.3)  Moderate 
Benzodiazepines  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  High dose (>5 mg diazepam or dose equivalent in 24 h)  Moderate  Matched  OR 3.3 (1.0–11.0)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Low dose (<5 mg diazepam or dose equivalent in 24 h  Moderate  Matched  OR 2.6 (0.8–9.1)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Long actinga  Moderate  Matched  OR 5.4 (1.0–29.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Short actingb  Moderate  Matched  OR 2.6 (1.1–8.5)  Moderate 
Antihistamine H1  Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  High dose (>25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.3–6.9)  Moderate 
Marcantonio  et al. [24]  MIxed surgical  Diphenhydramine  Low dose (<25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.5–4.1)  Moderate 
Medication class
Study
Setting
Agent
Dose
Study quality
Type of analysis
Result OR/RR (95% CI)
Evidence quality
Opioids  Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent 10–30 mg  Moderate  Multivariate  RR 4.4 (0.3–68.6)  Moderate 
Morrison  et al. [25]  Orthopaedics (Hip fracture)  All opioids  Morphine dose equivalent <10 mg  Moderate  Multivariate  RR 25.2 (1.3–493.3)  Moderate 
Benzodiazepines  Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  High dose (>5 mg diazepam or dose equivalent in 24 h)  Moderate  Matched  OR 3.3 (1.0–11.0)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Low dose (<5 mg diazepam or dose equivalent in 24 h  Moderate  Matched  OR 2.6 (0.8–9.1)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Long actinga  Moderate  Matched  OR 5.4 (1.0–29.2)  Moderate 
Marcantonio  et al. [24]  Mixed surgical  All benzodiazepines  Short actingb  Moderate  Matched  OR 2.6 (1.1–8.5)  Moderate 
Antihistamine H1  Marcantonio  et al. [24]  Mixed surgical  Diphenhydramine  High dose (>25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.3–6.9)  Moderate 
Marcantonio  et al. [24]  MIxed surgical  Diphenhydramine  Low dose (<25 mg in 24 h)  Moderate  Matched  OR 1.5 (0.5–4.1)  Moderate 

Neuroleptic medications

All four studies [18, 20, 21, 29] described methods consistent with an attempt to identify a temporal relationship between neuroleptic administration and development of delirium. There is evidence from one high-quality RCT [21] to suggest that haloperidol does not appear to be associated with increased risk of delirium (RR 0.9, 95% CI 0.6–1.3). Evidence from one moderate quality multivariate analysis in one moderate quality prospective cohort study [29] suggests an association of increased risk of delirium with use of neuroleptic medications (OR 4.5, 95% CI 1.8–10.5). Two studies were of low quality [18, 20].

Opioid medications

There is evidence from two moderate quality multivariate analyses to support an association of increased delirium risk with opioid medications in medical and surgical patients (OR 2.5, 95% CI 1.2–5.2) [29]. There appears to be an inverse dose–response relationship in patients recovering from hip fracture with a substantially increased RR (25.2, 95% CI 1.3–493.3) for lower doses (morphine dose equivalent <10 mg) compared with a lower RR (4.4, 95% CI 0.3–68.6) for higher doses (morphine dose equivalent 10–30 mg) [25]. The wide confidence intervals suggest considerable uncertainty with this result.

Benzodiazepine medications

Six of the seven studies investigating benzodiazepines described methods consistent with an attempt to identify a temporal relationship between medication prescription and delirium [18–20, 24, 27, 29]. Two studies [19, 24] assessed a dose–response relationship for benzodiazepines. Two studies [24, 29] assessed delirium rates with short-acting versus long-acting benzodiazepine medications.

There is evidence from matched analysis data derived from one moderate quality nested case–control study [24] in a mixed surgical group of patients to suggest that benzodiazepine medications may be associated with increased risk of delirium (OR 3.0, 95% CI 1.3–6.8). Longer acting benzodiazepine medications may be associated with increased risk of delirium (OR 5.4, 95% CI 1.0–29.2) compared with short-acting benzodiazepines (OR 2.6, 95% CI 1.1–6.5). Higher dose of benzodiazepine medications during a 24-h period appears to be associated with increased risk of delirium (OR 3.3, 95% CI 1.0–11.0) compared with lower doses (OR 2.6, 95% CI 0.8–9.1). Wide confidence intervals imply significant uncertainty with these results.

Antihistamines (H

1 antagonists)

One moderate quality case–control study [24] and one low-quality prospective cohort study [17] reported the effects of antihistamine (H1) medications. Both studies reported data for diphenhydramine. Matched analysis data derived from the case–control study (OR 1.8, 95% CI 0.7–4.5) and multivariate data from the prospective cohort study (OR 2.1, 95% CI 0.9–5.2) suggest a trend towards increased risk of delirium with antihistamine medications.

Histamine (H

2) antagonists

One low-quality prospective double-blind RCT [22] compared the incidence of delirium in postoperative cardiac surgery patients treated with cimetidine versus ranitidine and found no significant difference (P < 0.05) in rates of delirium for patients prescribed either medication. One moderate quality prospective cohort study [29] reported univariate data that indicated a small, non-significant trend towards increased delirium risk with H2 antagonists (OR 1.4, 95% CI 0.8–2.5).

Medication classes with data from single studies

One low-quality prospective cohort study of cardiac surgery patients [30] reported multivariate data for nifedipine and suggested increased risk of delirium (OR 2.4, 95% CI 1.0–5.8). Univariate data from one moderate quality study [29] suggest that digoxin (OR 0.5, 95% CI 0.3–0.9) does not appear to be associated with significant risk of delirium. Univariate data from one low-quality prospective cohort study [20] suggests that tricyclic antidepressants (TCAs) may be associated with increased risk of delirium (RR 1.7, 95% CI 1.4–2.1). Univariate data from the same low-quality study suggest that there is no significant association between antiparkinson medications and delirium (RR 1.3, 95% CI 0.9–1.7) [20]. There is uncertainty regarding the association of steroids (OR 0.5, 95% CI 0.2–1.7) [29] and NSAIDs (OR 0.4, 95% CI 0.1–1.5) [29] with delirium. One low-quality RCT [23] compared oxybutinin with placebo and found no significant difference in delirium rates between the two study arms (P < 0.05). There was only one case of delirium recorded in this study and firm conclusions should not be drawn from this result.

Discussion

Medications are an important risk factor for delirium and may be the sole precipitant for 12–39% of cases of delirium [4]. It is therefore sensible to conduct a drug review for patients at risk of delirium. Ideally, such a review should be informed by an evidence base that identifies those agents at highest associated risk for delirium. However, our review has found that there is a paucity of data from higher quality prospective studies for a number of classes of medication. Of note is the general absence of a priori power calculations to inform sample size estimates with the potential for type II error due to small sample size. A possible weakness of our review methodology is that it relied on one person identifying the studies to be included from an extensive body of literature with the attendant risk of excluding some relevant studies. Only cautious inferences are therefore possible.

There is evidence from one high-quality RCT to suggest no increased incidence of delirium with the use of haloperidol in higher risk patients in an orthopaedic hip surgery setting. There are contrasting data from prospective cohort studies to suggest the presence of an association between the use of neuroleptics and increased risk of delirium. However, there are difficulties in using a cohort study design to reliably demonstrate a temporal relationship between neuroleptic use and delirium. Confounding can occur when the neuroleptic is initiated for possible delirium symptoms. The evidence from the high-quality RCT indicating no association between haloperidol and risk of delirium supports the possibility that the apparent association between neuroleptics and delirium in observational studies may indeed be confounded.

There is moderate quality evidence to suggest that opioids are associated with an approximately 2-fold increased risk of delirium in medical and surgical patients, and a smaller increased risk in ICU. Pethidine appears to have a higher risk of delirium compared with other members of the opioid class. This may be because pethidine can accumulate when renal function is impaired and is converted to a metabolite with anticholinergic properties [4]. Oxycodone appears to have a favourable profile when compared with other members of the opioid class of medications. There is moderate quality evidence to suggest that in situations where acute severe pain is likely (e.g. hip fracture patients), lower doses of opioids may paradoxically be associated with higher risk of delirium, although wide confidence intervals imply uncertainty with this finding. However, these results support the concept of acute severe pain as an important contributing factor for delirium and withholding opioid medications for fear of risk of delirium is clinically inappropriate, but the lowest dose consistent with pain control should be used.

There is moderate quality evidence to support an association between benzodiazepines and increased risk of delirium. The magnitude of the risk appears to be small to moderate in size. Higher doses of benzodiazepines and agents which have a longer duration of action appear to confer a further small increase in risk. There appears to be a weak association between lorazepam and, less so, midazolam, for delirium in ICU. The caveat of an apparent association being confounded by delirium symptoms pre-dating the administration of a benzodiazepine implies caution with these conclusions.

There is low-quality evidence to suggest a small to moderate risk for nifedipine and moderate quality evidence to suggest a trend towards an association for antihistamine H1 medications.

There is low-quality evidence to suggest no associated increased risk for digoxin. The evidence for H2 antagonists, TCAs, medications used to treat Parkinson’s disease, steroids, NSAIDs and oxybutynin is of low quality and the associated risks for delirium are uncertain.

Conclusions

For people at risk of delirium, avoid new prescriptions of benzodiazepines or consider reducing or stopping these medications where possible. Opioids should be prescribed with caution in people at risk of delirium, but this should be tempered by the observation that untreated severe pain can itself trigger delirium. Caution is also required when prescribing dihydropyridines and antihistamine h2 antagonists for people at risk of delirium and considered individual patient assessment is advocated.

There remains uncertainty regarding the risk of delirium associated with h3 antagonists, TCAs, antiparkinsonian medications, steroids, NSAIDs and oxybutinin. This uncertainty reflects an evidence absence due to a paucity of methodologically rigorous, adequately powered prospective studies. An association between these medications and delirium cannot therefore be excluded with confidence. In light of this uncertainty, a judgment that incorporates the risk of delirium in each individual patient should be taken when prescription of any of these medications is considered.

Delirium occurs when a susceptible patient is exposed to often multiple precipitating factors. This makes the study of single medication factors difficult. Large, well-designed, adequately powered prospective studies that investigate the risk of delirium with different classes of medication and include multivariate analyses that control for the important confounding variables of age, dementia and illness severity are required to address the uncertainties we have identified.

  • Delirium is a common clinical problem and is associated with adverse health outcomes.

  • Some medications can increase the risk of delirium, but it is unclear which ones should be avoided.

  • This systematic review provides an evidence hierarchy to help identify which medications to avoid in people at risk of delirium.

  • Opioids, benzodiazepines, dihydropyridines and antihistamines appear to be associated with increased risk of delirium.

  • There is uncertainty regarding the risk of delirium that is associated with a number of commonly prescribed medications.

Conflicts of interest

None declared.

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Features of management of elderly and senile patients / ConsultantPlus

In elderly and senile patients, delirium may be the first manifestation of the disease or develop as it progresses. Hospitalization, intensive care, and mechanical ventilation increase the risk of developing delirium. The development of delirium, especially the overactive form, can present additional difficulties in the treatment of patients.

Recommendations:

1.Regular delirium screening using recommended instruments in all elderly and senile patients hospitalized for COVID-19.

2. It is recommended to carry out the prevention of delirium in all elderly and senile patients hospitalized in connection with COVID-19, by correcting its triggers. Preventive measures include: regular orientation of the patient in his personality, in time and space, prevention of constipation, treatment of pain, treatment of bacterial pneumonia (it is highly likely to occur in patients with COVID-19), adequate oxygen therapy, prevention of urinary retention, and revision of concomitant therapy to minimize the prescription of drugs that increase the risk of delirium.

3. When behavioral disorders appear, it is necessary first of all to assess and correct the triggers for the development of delirium (see above). If these measures are ineffective and / or more rapid control of the situation is necessary to reduce the risk to the patient or others, an earlier than usual transition to pharmacological treatment may be required.

4. When prescribing fast acting tranquilizers, it is necessary to monitor the development of side effects, the state of vital signs (NPV, SpO2, blood pressure, heart rate), the level of hydration and consciousness, at least every hour until there is confidence in them. stability.It should be remembered that benzodiazepines depress respiration, and also do not exceed the maximum doses of haloperidol (2 mg / day, regardless of the route of administration), risperidone (1 mg / day in several doses), lorazepam (2 mg / day, regardless of the route of administration ).

In elderly and senile patients, COVID-19 increases the risk of developing malnutrition. An increase in this risk is associated both with clinical symptoms of the disease (decreased sense of smell and taste, decreased appetite, diarrhea, fever, weakness), and with social factors (self-isolation), which in some cases potentiate preexisting risks.Elderly patients with polymorbidity are more at risk of malnutrition and associated sarcopenia; it is in this group that the prognosis for COVID-19 is most unfavorable. Mechanical ventilation, especially prolonged ventilation, is a well-documented cause of malnutrition with loss of muscle mass and function, which, in turn, is further associated with reduced quality of life and loss of autonomy after hospital discharge. Adequate assessment of nutritional status, prevention and correction of malnutrition effectively reduce the risk of complications and improve clinical outcomes.

Recommended:

1. All elderly and senile patients hospitalized with COVID-19 should be screened for the risk of malnutrition using validated instruments.

2. Patients who are screened at risk of malnutrition or malnutrition should be corrected using oral enteral nutrition (PEP) products.

3. It is recommended to calculate the energy value of the diet of an elderly and senile patient, focusing on the level of 30 kcal per kg of body weight per day, the daily level of protein intake should be at least 1.0 – 1.2 g per kg of body weight per day ( in severe disease and diagnosed malnutrition – up to 2.0 g / kg of body weight per day).

4. It is recommended to prescribe PEP preparations, which provide the body with energy of at least 400 kcal / day and protein at least 30 g / day. In the absence of contraindications, PEP products containing dietary fiber are preferred to ensure optimal gastrointestinal function.

5. In cases where oral nutrition is not possible, it is recommended to start enteral tube feeding (EPF) without delay.

6. At discharge from the hospital, patients with malnutrition or at risk of developing it are recommended to use AEDs in order to optimize food intake and body weight, as well as to reduce the risk of decreased functionality.It is recommended to prescribe PEP for at least one month and evaluate the effectiveness and expected benefit of PEP once a month.


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Medication for depression and stress – treatment for depression without addiction, safe

In the modern world, with its stresses, frantic pace of life, instability, you rarely find a person who does not know what depression is. Often we complain of depression, although this word can hide a bad mood, and anxiety, and irritability, and grief, or other nervous disorders that have nothing to do with depression.

Depression Treatment

Noticing symptoms similar to depressive ones, many immediately run to the pharmacy for an antidepressant or some kind of sedative.

One cannot do without the advice of a specialist, but many ignore a visit to a doctor, preferring self-medication. Meanwhile, self-medication with psychotropic drugs can lead to the most serious consequences, including the aggravation of existing neuropsychiatric diseases.

Medicines for depression

All psychotropic drugs are divided into three groups: antipsychotics, antidepressants and tranquilizers.

Antipsychotics

Neuroleptics are powerful psychotropic drugs that are used to treat psychoses with hallucinations and delusions. Treatment with such drugs is carried out only in hospitals, but in some cases, small doses of the drug can be prescribed for people suffering from insomnia, experiencing weakness and pain, people with obsessive thoughts.

Antipsychotics supplement the treatment regimen for asthenia, shyness, depression.

Antidepressants

Antidepressants are divided into two classes.

The first one is drugs with a pronounced sedative effect. These include drugs such as amitriptyline, anafranil, lyarivon, ludiomil.

The second group includes preparations containing an activating component. These include melipranil and petilil.

Recently, many combination antidepressants such as Prozac have emerged.

The risk of developing dependence on antidepressants is only 15%.

Tranquilizers

Tranquilizers are the most famous and most dangerous drugs in terms of addiction.They are used most often for insomnia, obsessive thoughts, anxiety.

The most powerful tranquilizers are phenazepam, clonazepam, lorazepam, lexotan. Less potent relanium, seduxen, librium, valium, signopam, tazepam. Weak ones – grandaxin, mezapam, rudotel. Tranquilizers with a pronounced hypnotic effect – radedorm and reladorm.

Attention! Do not self-medicate. Prescribing and taking medications for depression is possible only after consulting a specialist.

Nootropics

In addition, there is a group of drugs with a pronounced stimulating effect, used for chronic fatigue syndromes. These are the so-called nootropics – drugs designed to increase cerebral circulation. These include nootropil, encephabol and kogitum.

When taking tranquilizers, you need to strictly observe the dosage and schedule of taking the medicine, otherwise drug dependence may occur, which is very little different from drug dependence.Only a doctor can prescribe medications and a treatment regimen.

When taking, do not expect an immediate effect, it occurs approximately in the second – third week of treatment. At the first sign of relief, do not stop taking the drug. Dose reduction and discontinuation are best discussed with your doctor. If the neurotic disorder is not treated, the disease is likely to return in a more severe and difficult to treat form.

All drugs specified in the article are dispensed strictly on prescription!

Recommendations for the treatment of depression

We recommend that you consult a neurologist.Typically, depression is accompanied by lack of sleep, lack of appetite, distraction and difficulty focusing on something. When diagnosing and treating it is necessary to take into account the totality of the manifestation of the depressive state.
Household injuries, long-term head injuries, active weightlifting can also affect the development of depression.

No need to drink several cups of coffee a day, or try to invigorate yourself with energy drinks – these will only aggravate your condition.Nervous breakdowns are possible, after which it is difficult to restore a normal emotional state.
Neurologists, qualified specialists who have helped many people to recover their condition and get rid of depression, conduct appointments in our clinic.

  • Vasilenko

    Vladimir Vladimirovich

  • Doctor neurologist

  • Experience 33 years

Promethazine and Codeine | Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Warning

For all patients taking this drug:

  • This medicinal product contains an opioid. Opioid drug treatment can carry risks such as dependence, abuse, or inappropriate use of these drugs. Improper use or abuse of this drug can lead to overdose and death. If you have any questions, ask your doctor.
  • This drug may cause very bad and sometimes deadly breathing problems. Call a doctor right away if breathing is slow, shallow, or difficult.
  • Even one dose of this drug, taken by another person or by mistake, can be deadly, especially in children. If this drug has been taken by another person or by mistake, get medical help right away.
  • Store all medicines in a safe place.Keep all medicines out of the reach of children and pets.
  • This medicinal product contains an opioid. Serious side effects have occurred with the use of opioid drugs with benzodiazepines, alcohol, marijuana, or other forms of cannabis, as well as prescription or over-the-counter drugs that can cause drowsiness or slow action. These effects include slowed down or labored breathing and death. Benzodiazepines include drugs such as alprazolam, diazepam, and lorazepam.Benzodiazepines can be used to treat many health conditions such as anxiety, sleep disturbances, or seizures. If you have any questions, please consult your doctor.
  • Many drugs interact with this drug and can increase the risk of side effects, such as deadly breathing problems. Check with your doctor and pharmacist to make sure this drug is safe to use with all your other drugs.
  • Avoid alcohol, marijuana, or other forms of cannabis, or prescription or over-the-counter medications that can slow you down.
  • Get immediate medical attention if you feel very sleepy, dizzy, or pass out. Caregivers or others should seek immediate medical attention if the patient does not respond, does not respond, or does not respond in the usual way, or if he is asleep and does not wake up.
  • Make sure you know how to measure your dose. Dosing error can lead to accidental overdose and death. If you have questions, ask your doctor or pharmacist.
  • Do not take this drug if you are pregnant
  • Long-term use of this drug during pregnancy may cause withdrawal in newborns. This can be life threatening. Consult your doctor.

Children:

  • Children may have a higher risk of very serious side effects.This risk may be more likely in children with breathing problems. Deadly breathing problems have occurred in some children with codeine. Consult your doctor.
  • This medicinal product is not intended for use in children under 18 years of age. The benefits of using this drug for an allergic cough, cold, or other infection do not outweigh the risks to a child. If your child has received treatment with this drug, or if you have any questions, talk to your child’s doctor.

What is this drug used for?

  • Used to relieve coughs.
  • Used to relieve allergy symptoms.
  • Used to relieve cold symptoms.

What do I need to tell my doctor BEFORE taking this drug?

  • If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.
  • If you have any of the following health conditions: Lung or breathing problems such as bronchial asthma, difficulty breathing or sleep apnea; high levels of carbon dioxide in the blood; gastrointestinal obstruction or narrowing.
  • If you have a cough with a lot of phlegm, a prolonged cough from smoking or inhalation of cigarette smoke, or lung problems such as asthma or emphysema.
  • If you have recently suffered a head injury, brain injury, or have recently developed a tumor or increased intracranial pressure.
  • If you have taken a drug for depression or Parkinson’s disease in the past 14 days. These include isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline. An episode of very high blood pressure may occur.
  • If you are taking any of the following drugs: buprenorphine, butorphanol, linezolid, methylene blue, nalbuphine, or pentazocine.
  • If your doctor has told you that the metabolism of certain drugs is accelerated in your body.
  • If you are breastfeeding. Do not breast-feed while taking this drug.

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all the medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems.You need to make sure that this drug is safe for your medical condition and in combination with other drugs you are already taking. Do not start or stop taking any medication or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

  • Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
  • Do not take the drug in higher doses than the doctor prescribed. Taking more than the prescribed amount of the drug increases the risk of serious side effects.
  • Do not take this drug for longer than your doctor prescribed.
  • Avoid driving or other activities that require increased attention until you see how this drug affects you.
  • To reduce the risk of dizziness or loss of consciousness, get up slowly from a lying or sitting position. Use caution when climbing and descending stairs.
  • Do not take this drug with any other strong pain reliever or with a pain reliever patch without first talking to your doctor.
  • Abruptly stopping this drug after regular use may cause withdrawal.Do not stop taking this drug abruptly without talking to your doctor. Tell your doctor if you experience any unwanted effects.
  • This drug may increase the risk of seizures in some people, including people with a history of seizures. Talk to your doctor to see if you are at increased risk of seizures with this drug.
  • If you have high blood sugar (diabetes), your blood sugar should be checked regularly.
  • Some pregnancy tests may not give results when taking this drug. Consult your doctor.
  • This drug may interfere with some laboratory tests. Tell all healthcare providers and laboratory staff that you are taking this drug.
  • You can easily get sunburn with this drug. Be careful if you are in the sun.If you get sunburn easily with this drug, talk to your doctor.
  • Occasionally, this type of opioid can cause very severe adrenal dysfunction. Call your doctor right away if you experience very severe dizziness or fainting, very severe nausea or vomiting, decreased appetite, feeling very tired or weak.
  • Long-term use of an opioid drug can lead to a decrease in the level of sex hormones.If you have a decreased interest in sex, impaired fertility, missing menstrual periods, or trouble ejaculating, see your doctor.
  • If you are 65 years of age or older, use this drug with caution. You may have more side effects.
  • If used during pregnancy, the drug may have a harmful effect on the fetus. If you are pregnant or become pregnant while taking this drug, call your doctor right away.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor or get medical help right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

  • Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
  • Difficulty, slow or shallow breathing.
  • Noisy breathing.
  • Disturbed breathing during sleep (sleep apnea syndrome).
  • Severe constipation or abdominal pain. These may be signs of a severe bowel disorder.
  • Severe dizziness or fainting.
  • Confusion of consciousness.
  • Obstruction of the urinary tract.
  • Yellowness of the skin or eyes.
  • Uncontrolled body movements, convulsive movements, imbalance, difficulty swallowing or speaking.
  • Hallucinations (a person sees or hears something that is not in reality).
  • Mood swings.
  • Anxiety.
  • Ringing in the ears.
  • Convulsions.
  • Any unexplained bruising or bleeding.
  • Change in vision.
  • A very severe, sometimes fatal, disorder, neuroleptic malignant syndrome (NMS), can occur. Call your doctor right away if you have a fever, muscle cramps or stiffness, dizziness, severe headache, confusion, changes in thinking, tachycardia, an abnormal heartbeat, or excessive sweating.
  • Low white blood cell counts have rarely happened with this drug. This can lead to an increased risk of infection. If you have ever had a low white blood cell count, talk to your doctor. See your doctor right away if you have symptoms of an infection such as fever, chills, or sore throat.

What are some other side effects of this drug?

Any medicine can have side effects.However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

  • Feeling dizzy, sleepy, tired, or weak.
  • Nervous tension and agitation.
  • Constipation, abdominal pain, nausea, vomiting, or decreased appetite.
  • Dry mouth.
  • Headache.
  • Hyperemia (blush).
  • Excessive sweating.

This list of potential side effects is not exhaustive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https: // www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

  • Take with or without food. Take with food if the medicine causes nausea.
  • Doses of liquid preparation should be measured with caution. Use the dispenser that comes with the medicine. If a dispenser is not included in the package, ask your pharmacist for a dosing product for this drug.

What to do if a dose of a drug is missed?

  • If you are taking this medication regularly, take the missed dose as soon as you can.
  • If it is time for your next dose, do not take the missed dose and then return to your normal dose schedule.
  • Do not take 2 doses at the same time or an additional dose.
  • In most cases, this drug is taken as needed.Do not take this medicine more often than prescribed by your doctor.

How do I store and / or discard this drug?

  • Store at room temperature, protected from light. Store in a dry place. Do not store in the bathroom.
  • Protect from heat.
  • Store this medication in a protected place, out of the reach of children, and out of the reach of other people. A box or room, which is locked with a key, can act as a protected storage location for the drug.Keep all medicines out of the reach of pets.
  • Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. Your area may have drug recycling programs.

General information on medicinal products

  • If your health does not improve or even worsens, see your doctor.
  • You should not give your medicine to anyone and take other people’s medicines.
  • Some medicines may come with other patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • A separate patient instruction sheet is attached to the product. Please read this information carefully. Reread it every time you replenish your supply.If you have questions about this drug, talk with your doctor, pharmacist, or other healthcare professional.
  • If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by consumer and limitation of liability

This information should not be used to make decisions about taking this or any other drug.Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are suitable for a particular patient. This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug.This information should not be construed as a guide to treatment and does not replace the information provided to you by your healthcare professional. Check with your doctor for complete information on the possible risks and benefits of taking this drug. Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

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© UpToDate, Inc.and its affiliates and / or licensors, 2021. All rights reserved.

Lorazepam – instructions for use, contraindications, side effects

Indications: The agent is prescribed to eliminate neuroses and neurotic conditions, which are accompanied by the appearance of feelings of anxiety, anxiety, excitement. This also applies to psychological and emotional stress. Also, an indication for use is a psychoactive state, depressive symptoms, schizophrenia.In addition, the drug is used in a manic state, psychosomatic disorders, and sleep problems. For status epilepticus, the drug is also used. In addition, the medicine treats bouts of vomiting and headaches that were caused by alcohol-type delirium or chemotherapy.

Contraindications: Do not take the drug if a person has an increased susceptibility to it. This will cause an allergic reaction of varying complexity.In addition, a contraindication is closed-type glaucoma, acute intoxication, myasthenia gravis, neuroses caused by depression. It is forbidden to give such a drug to pregnant women and during lactation. In addition, pills are not recommended for children under 12 years old, and injections are contraindicated in adolescents under 18 years old.

Directions for use: The preparation is intended for internal use. It is assumed 1 mg no more than 3 times a day. To fall asleep better, you need 2 mg half an hour before bedtime.If the state of anxiety is very pronounced, then the dosage is increased to 5-6 mg, but not more, per day. One hour before the operation, you can take 0.05 mg for children and 3-5 mg for adult patients. If a person has renal or hepatic impairment, then the dosage must be reduced.

Special instructions (warnings): May increase the effect of analgesics. With prolonged use, drug dependence may occur.

Side effects: A person may complain of side effects.For example, headache, nausea, apathy occurs. Drowsiness, indigestion, dizziness may occur.

Product form: The drug can be purchased in the form of tablets of 1, 2 and 5 mg, as well as in the form of a solution for injection.

Medicinal effects | Autism FRC

Medication is carried out taking into account not only the nature of the painful manifestations, but also the child’s working capacity. The selection of doses is always difficult because of the high sensitivity of children to antipsychotics, as well as a small gradation in doses that cause the necessary therapeutic and undesirable somnolent, inhibitory effect.In children, when taking antipsychotics, side effects easily occur in the form of akathisia (anxiety, restlessness, the need to change the posture), salivation, hyperkinesis. If during the period of exacerbation, preference is given to antipsychotics, antidepressants, tranquilizers, iminostilbens, valproates, vascular agents, diuretics, then in the period of remission and persistent autistic defect, nootropics, amino acids, cerebrolysin, vitamins are used more often, and only in 30% of cases antidepressants, tranquilizers and other drugs mentioned.

Pharmacotherapy is aimed at relieving positive and negative psychopathological disorders that determine the patient’s condition, easing mental tension, and activating the child.

1. Neuroleptics (tisercin, neuleptil, sonapax, haloperidol, teralen, chlorprothixene, eglonil, rispolept, etc.) are used according to indications, in small doses, mainly in the active period of the course of the disease, when it is necessary to stop deceptions of perception, excitement , anxiety, affective and other symptoms of the disease.To overcome and correct cognitive impairments, stelazine and etaperazine are used. Treatment with neuroleptic drugs is carried out taking into account the condition of the child, flexibly introducing them for short periods and canceling drugs as soon as the need for it disappears.

2. Antidepressants are widely used (azafen, pyrazidol, amitriptyline, ludiamil, etc.) for relief of affective disorders.

3. For the prevention and treatment of phase affective disorders, iminostilbens (carbamazepine and its analogs – finlepsin, tegretol), valproates (depakin, konvuleks) are introduced into therapy.

4. Tranquilizers (nozepam, tazepam, lorazepam, mezapam, relanium, phenazepam, etc.) are rarely used, for short periods, preferably for sleep disorders and to relieve acute agitation. It is advisable not to give these funds in the morning hours due to their pronounced somnolent and muscle relaxant effect. Caution in the administration of these drugs is also associated with the often caused reverse action in early childhood and preschool age (agitation, motor restlessness).

5. In stable states of persistent autistic defect, with minimal severity of residual positive disorders, much attention is paid to treatment with nootropics (nootropil, pantogam, picamilon) and amino acids (cogitum, glycine, glutamic acid, etc.). Particular attention is paid to cerebrolysin. The drug has a versatile neurotropic effect: a regulatory effect on brain metabolism, neuroprotective properties and neurotrophic activity.Cerebrolysin oligopeptides are able to overcome the blood-brain barrier and have a direct effect on the neuronal structures of the brain under conditions of peripheral administration of the drug. Cerebrolysin is used to relieve, smooth out mental retardation, and hence some mitigation of autistic disorders.

6. Vitamins , especially group B (B1, B6, B12, B15), C, E, multivitamins (“Undevit”, “Glutamevit”) are used in all cases of the disease.

7. Means that improve cerebral circulation (Cavinton-Vinpocetine, Stugerone-Cinnarizine) are administered in courses.

8. Diuretics (furosemide, diacarb, triampur, magnesium sulfate, etc.) are used for hypertensive syndrome and acute states of excitement.

Written N.V.

The following literature was used: Bashina V.M. Autism in childhood. – Moscow. – “Medicine”. – 1999; V.V. Kovalev Child psychiatry. – Moscow. – “Medicine”. – 1995; Nikolskaya O.S., Baenskaya E.R., Liebling M.M. Autistic child. Ways to help. – Moscow. – “Terevinf”. – 1997

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