Can Seroquel Get You High?

What Is Seroquel?

Seroquel is the brand name of the prescription drug quetiapine. This drug is available in brand-name and generic versions and has immediate-release and extended-release options. The brand name for the extended-release option is Seroquel XR. Both options usually come in the form of an oral tablet.

When an individual takes this atypical antipsychotic, the chemical activity in their brain is altered. Seroquel releases serotonin and dopamine in the brain, which improves symptoms in individuals with various mental health disorders.

Why People Use Seroquel

Doctors commonly prescribe Seroquel to treat or ease the symptoms of various mental health disorders including schizophrenia, bipolar disorder, and depression. It may be used in combination with therapy and may be prescribed in addition to another medication, like an antidepressant. When used correctly, Seroquel may prevent mood swings, decrease hallucinations (if applicable), improve concentration, increase confidence, and treat depressive or manic episodes. The Seroquel dosage depends on various factors like the specific mental health condition being treated, the age of the individual being treated, and others. 

Does Seroquel Get You High?

If Seroquel is misused, it can cause someone to feel an intense and potentially dangerous high. Abusing Seroquel to improve mood, increase pleasure, or reduce anxiety may result in unpleasant or even fatal side effects. When misused, Seroquel overdoses are possible and may include symptoms like drowsiness/sleepiness, increased heartbeat, dizziness, and fainting.

This prescription drug comes with a high risk of addiction, especially when combined with other medications and drugs. Some individuals who misuse Seroquel may mix it with cocaine, for example. Chances of addiction and dependence also increase when someone snorts or injects Seroquel instead of taking it as an oral tablet. When Seroquel is snorted, it enters the bloodstream more quickly, resulting it an intense high and can lead to a Seroquel overdose.

Side Effects of Seroquel

Seroquel, when misused, comes with complications. It’s still important to be careful when using Seroquel as prescribed, including the Seroquel dosage, while also considering the potential symptoms and risks that come with regular use.

Side effects of Seroquel may include:

• Dry mouth
• Drowsiness
• Constipation
• Stomach pain
• Increased appetite
• Weight gain
• nausea/vomiting
• Sore throat
• Rapid heartbeat
• Weakness
• Trouble moving

Not only can this prescription drug potentially cause undesirable symptoms, but it can also have long-lasting side effects.

Risks of Seroquel Use

Individual risks of taking Seroquel vary from person to person based on their mental health condition, their age, etc., however, some possible risks to consider include:

• Suicidal thoughts/actions

• Increased cholesterol

• High blood sugar

• Low white blood cell count

• Cataracts

• Seizures

• Changes in thyroid levels

• Metabolism changes

• Stroke

• Allergies

• Tremors

Although Seroquel does come with its possible dangers and risks, it’s usually harmless if used as prescribed and responsibly. If you experience any of the issues above while using Seroquel, it’s vital to talk to your doctor to discuss the best next steps.

Responsible Use of Seroquel

Seroquel can interact with other medications. For example, it shouldn’t be combined with anti-arrhythmic drugs, certain antibiotics, antipsychotic drugs, alcohol, or methadone. When mixed with specific drugs, the side effects may increase and become more intense. These drugs include benzodiazepines, muscle relaxants, certain pain medications, antihistamines, and sedatives.

If addiction occurs, residential addiction treatment, like the one we offer at Silver Pines, is likely the best solution. . Our residential addiction treatment program begins with detoxing, allowing individuals to experience the effects in Seroquel withdrawal in a comfortable and healthy environment. Due to the dangers of Seroquel withdrawal, it’s important to speak with your doctor if you’re thinking of stopping the drug.

If you have any questions about the effects of Seroquel and other prescription drugs and if you need to enter a drug detox program, like the one we offer at Silver Pines, call us today at 267. 719.8689. 

Sources

https://www.medicalnewstoday.com/articles/quetiapine-oral-tablet#alternatives

https://www.everydayhealth.com/drugs/quetiapine

The Dangers Of Snorting Seroquel (Insufflation)

Seroquel Addiction | What is Seroquel Used For?

Table of Contents

1. Is Seroquel Addictive?
2. What Type of Drug is It?
3. Is Seroquel Safe?
4. How is It Used?
5. Effects of Seroquel
6. Can You Overdose?
7. How to Stop Using Seroquel
8. Addiction Treatment
9. Key Takeaways

Seroquel, an atypical antipsychotic medication, has been approved by the US Food & Drug Administration (FDA) for the treatment of schizophrenia and certain types of bipolar and depressive disorders. Yet, despite warnings, there’s evidence of widespread off-label use of the drug. Several studies even indicate that Seroquel is the most commonly abused atypical antipsychotic. Abuse can lead to addiction that requires treatment and therapy in a rehab facility.

Is Seroquel Addictive?

Although Seroquel (quetiapine) is not a controlled substance, it does have a potential for misuse or abuse. It has the highest potential for abuse when it’s taken without a prescription or taken in a way other than that suggested by a health professional. Studies state that Seroquel is the most abused atypical antipsychotic.¹

It’s believed that people abuse and misuse Seroquel because of how it reduces anxiety and ease sleep deprivation, not because of its euphoric effects. Despite warnings by their doctors, some people take the drug in higher amounts, more often, and for a longer period of time than their doctors recommend.

Abuse in People with Histories of Drug Use

According to several case reports, Seroquel abuse is most common in people with some history of multi-substance abuse. Some case reports are about inmates in jails or prisons, who may take Seroquel because obtaining controlled substances like opioids and benzodiazepines in restrictive environments is not an option. ²

Potential for Addiction

The Korean Society of Applied Pharmacology tried to determine the drug’s potential for causing physical and psychological dependence. Their findings show that quetiapine affects the neurological systems related to abuse liability. They also found that it has the potential to lead to psychological dependence.

Developing Tolerance

Seroquel can make life more bearable for people who have severe mental illnesses. People without mental illnesses may find that the drug helps them experience feelings of pleasure and relaxation. The more they abuse the drug, the more prone they are to developing tolerance. To experience the same high, they’ll need progressively higher doses. Not every person who abuses Seroquel will become addicted. But abuse is the first step toward addiction.

Easy to Abuse

The drug has a potential for misuse, as it comes in a format that’s easy to abuse. People can take the pill orally or crush it and snort the powder. When snorted or used intravenously, the drug creates a large dopamine surge, which can lead to addiction.

More About Other Drugs

Baclofen

Gabapentin

K2-Spice

Marijuana

Meloxicam

Seroquel

Valium

Weight Loss Pills

What Type of Drug is Seroquel?

Seroquel is the brand name for the generic drug quetiapine, which was approved in 1997 by the Food and Drug Administration. It’s a second-generation and atypical antipsychotic used in the treatment of:

Schizophrenia: Doctors often prescribe Seroquel for adult and pediatric schizophrenia.

Bipolar disorder: Seroquel is an approved drug for the treatment of acute depressive episodes in bipolar disorder. It is also used in combination with lithium to enhance treatment for bipolar depressive episodes. Doctors often prescribe it for the long-term management of bipolar disorder and its symptoms.

Major depressive disorder: Seroquel is not the primary drug in the treatment for major depressive disorder, but it can be added to increase the effects of the primary medication.

Seroquel is part of a newer generation of antipsychotic drugs known as atypical antipsychotics (AAs). They are designed to help patients suffering from a psychiatric condition known as psychosis. The first generation of antipsychotic drugs was known to cause Parkinson’s-like side effects. The second-generation antipsychotics come with fewer adverse effects. The most common side effects of the new drugs include weight gain, metabolic problems, and sexual symptoms, among others.

Prescribed to Treat Withdrawal from Other Drugs

Doctors also prescribe AAs for the treatment of withdrawal symptoms from abused substances such as:

Cocaine

Opioids

Alcohol

Benzodiazepines

Antipsychotics may either reduce or increase the level of neurotransmitters in the brain. The affected neurotransmitters include dopamine, serotonin, and noradrenaline. The drugs primarily affect the levels of dopamine in the brain, as an overactive dopamine system may be one cause of the delusions and hallucinations people experience during psychosis.

Positive Effects

This class of drugs helps patients suffering from mental/mood conditions by restoring the balance of certain neurotransmitters in the brain. Some of the positive effects include:

Decreasing hallucinations

Improving concentration

Enhancing positive thought

Reducing nervousness

Raising levels of activity in everyday life

Improving sleep, appetite, and energy levels

Preventing severe mood swings or reducing their number

Is Seroquel a Controlled Substance?

Seroquel is not a controlled substance, as it’s believed not to cause addiction. But studies from recent years report widespread off-label use of the drug.

Little knowledge exists about the reasons for off-label prescribing of Seroquel. Experts argue that Seroquel is a more attractive treatment option than other antipsychotics. It has low dystonia and extrapyramidal side effects.

Some people abuse it due to its sedative effects, either alone or in combination with other substances. Other people take the drug to boost the effects of illicit substances or to prevent their negative effects.

Is Seroquel Safe?

According to the FDA’s Adverse Event Reporting System, Seroquel was the primary or secondary suspect in 20,000 cases of adverse events in 2017. That number included 1,754 deaths in which the drug was a primary suspect and 2,309 deaths in which the drug was a secondary suspect. In 93% of the cases, the cause for the incident was an off-label prescribing of the medication.

In recent years, an increasing number of doctors have been prescribing the drug off-label for the treatment of insomnia. Many of these doctors have minimal training in psychiatry and limited understanding of the adverse effects. According to the University of Pennsylvania School of Medicine, 25% of Americans have acute insomnia each year.³ Even though many medical experts have warned of the pill’s side effects, Seroquel continues to be prescribed to many Americans. The majority of these people are not even aware that the drug is primarily aimed at aiding mental/mood conditions.

Many drugs can affect the side effects of Seroquel and make them more severe. Some drugs that interact with Seroquel and can cause problems include:

Illegal substances, or “street drugs”

Cold, cough, and allergy drugs

Drugs that treat mental illness, such as antidepressants

Drugs used to treat HIV/AIDS

Some types of antibiotics

Heart medications

Fungal disease medications

Seizure medications

Methadone

Steroids that are taken orally

Drugs used to treat Parkinson’s disease

What are the Street Names for Seroquel?

The most common street names for Seroquel include:

Snoozeberries

Susie-Q

Q-ball (when combined with cocaine)

How do People Use Seroquel?

Seroquel can be used in various ways. Most commonly, it’s taken orally as a pill or a tablet on its own. Some people crush the pill or tablet and snort its contents.

Those who don’t want to snort the pill dissolve it in a water-based liquid and inject the content into their veins. Abusing Seroquel intravenously carries the highest risk for overdose. It also increases the risk of transmission of HIV and hepatitis.

Seroquel might also be abused in combination with other substances such as cocaine. Mixing prescription medications with illicit drugs has been a common practice. Some people take the mix to enhance the intoxication effects from the illicit substances and lower their adverse effects. For example, Seroquel is, dangerously, mixed with cocaine to mitigate the dysphoria effects related to cocaine withdrawal.

Injecting the drug into the veins increases the risk of developing pulmonary complications. Moreover, Seroquel can amplify the cardiovascular and arrhythmogenic properties of cocaine.

Effects of Seroquel

Short-Term Effects

The first-generation antipsychotics have a larger number of side effects. But the atypical psychotics also come with a few side effects. A person taking Seroquel will experience these effects for about six hours. Common short-term side effects of Seroquel can include:

Fatigue

Dizziness

Dry mouth

Sore throat

Nervousness

Depression

Headache

Abdominal pain

Upset stomach

Irritability

Numbness in arms or legs

Missed menstrual periods

Increased appetite

Moreover, mixing Seroquel with alcohol comes with another set of side effects. Drinking alcohol while taking the antipsychotic can worsen the side effects of the drug and lead to:

Mood changes

Constipation

Nausea

Vomiting

Drowsiness

Lightheadedness

Fatigue

Changes in appetite

Weight changes

Changes in liver function

Long-Term Effects

The most common long-term effects of Seroquel include:

Sexual dysfunction

Increased risk of diabetes

Tardive dyskinesia

Weight gain

High cholesterol

Cataracts

Suicidal thoughts and behaviors

Thyroid problems

Seizures

Cardiac problems

Can You Overdose on Seroquel?

The Medical Expenditure Panel Survey (MEPS) found that 39. 5% of total prescriptions in 2017 were written for Seroquel. The increase in Seroquel prescriptions has led to a rise in overdoses and problems with dependence. According to the US Drug Abuse Warning Network, there has been a 90% increase in the number of Seroquel-related emergency department visits between 2005 and 2011.⁴ It was found that the recreational use of the drug poses health risks for users, especially women and polydrug users.

Although the drug has positive effects for people with mental illness, recreational use is dangerous. Injecting Seroquel has many risks associated with it, including increased risk for HIV and hepatitis transmission.

Seroquel blocks histamine, muscarinic, and alpha receptors. An overdose might lead to CNS depression, tachycardia, orthostatic hypotension, or delirium.⁵

The most common symptoms of a Seroquel overdose include:

• Drowsiness
• Vomiting
• Dizziness
• Rapid heartbeat
• Seizure
• Fainting

Apart from overdosing, other life-threatening side effects include delirium, seizures, and cardiac dysrhythmias.

How Do I Stop Using Seroquel?

People who have been taking Seroquel for a prolonged period and in high doses will experience withdrawal symptoms when they stop. The most common side effects might include:

Irritability

Anxiety

Insomnia

Nausea

Headache

Diarrhea

Vomiting

Dizziness

Hypersensitivity

Mood swings

Difficulty sleeping

Suicidal thoughts

The best method for getting clean is entering a substance abuse rehab center and undergoing detox, where a team of medical professionals can care for the person in recovery and attend to their needs.

What are the Withdrawal Symptoms of Seroquel?

Regular use of Seroquel for a long period of time can lead to a discontinuation syndrome. Antipsychotic discontinuation syndrome is the set of symptoms that may happen when a person:

• Suddenly stops taking an antipsychotic, or
• Drastically lowers the dose

According to the International Journal of Mental Health Counseling, nearly 40% of people who stop taking antipsychotics may experience discontinuation syndrome. ⁶ The symptoms generally appear within the first few days after stopping. They tend to be the most severe one week after stopping and fade away after that.

Discontinuation symptoms have been reported to happen very often and can include:

Headaches

Insomnia

Dizziness

Irritability

Nausea and vomiting

Diarrhea

The withdrawal symptoms of Seroquel vary significantly from person to person. They depend on the doses taken, the period of time, and the method of use.

For example, a person who has been taking low doses of the drug might experience minimal withdrawal symptoms that might last a week or two. If the person has been taking higher doses for a longer time, the symptoms might be more severe.

Additional factors could be at play, including the person’s underlying mental health issues.

The best treatment involves tapering the dose slowly under the supervision of a medical professional. Gradual withdrawal over a period of one to two weeks is recommended.

Treatment for Seroquel Addiction

Co-occurring Disorder Treatment

In some people, addiction is the result of an underlying mental health issue. In others, addiction develops first, and mental health symptoms appear later. Sometimes, mental health symptoms may be worsened by drug use.

Although there is no one cause for addiction, a mental health issue may increase the likelihood of developing an addiction and vice versa.

People who are suffering from an addiction and a mental health problem should seek treatment for a co-occurring disorder. According to the Substance Abuse and Mental Health Services Administration, this type of treatment can:

• Lower the relapse rate
• Reduce the number of suicide attempts
• Lead to long-term sobriety

Many rehab centers offer an integrated approach to co-occurring disorder treatment. Patients receive all the medical, therapeutic, and holistic care they need to heal mentally, physically, emotionally, and spiritually.

Staff members at these treatment centers have specialized training and qualifications for dual diagnosis treatment. They possess the knowledge and experience to help patients achieve long-term health.

Medical Detox

A person suffering from an addiction will experience a range of withdrawal symptoms when they stop taking the drug. This is known as the detox period, and it may last a few days or a couple of weeks. These withdrawal symptoms can be uncomfortable, harmful, and even life-threatening, and medical detox at a rehab center is recommended. People who enter a medical detox facility can withdraw from drugs safely in a comfortable and secure environment.

Inpatient Care

Inpatient care lasts anywhere from 21 days to several months. It’s a suitable treatment option for people who are battling with a severe case of addiction. They will be monitored 24/7 by a team of medical professionals who understand addiction and its underlying issues. Patients will live on-site and attend a wide range of activities, including:

• 12-step meetings
• One-on-one therapy sessions
• Group therapy sessions

There’s a broad array of inpatient centers to choose from, ranging from those that use the 12-step method to those that offer a more holistic approach. However, all types of centers have the same focus, and that is to help the patient learn healthier habits, attitudes, and behaviors.

Outpatient Care

Outpatient care is intended for people who are suffering from a milder form of addiction. It’s also more suitable for patients who have a safe place to live in, and who have other people to attend to their needs. If the person requires minimal care and has daily responsibilities they can’t miss, then outpatient care is the best option.

A person receiving outpatient treatment lives off-site but comes to the rehab center for on-site meetings. Similar to inpatient care, the patient participates in 12-step meetings and one-on-one therapy sessions. Depending on the rehab center, they might also attend holistic classes such as meditation and yoga.

Aftercare

Before leaving inpatient/outpatient treatment, patients are encouraged to work with a therapist to develop an aftercare plan. The purpose of an aftercare plan is to help patients maintain their sobriety, find purpose in life, and create healthy relationships with themselves, friends, and family.

Although each person receives a customized plan, some common components of a typical aftercare treatment plan include:

Ongoing counseling

Family therapy

Participation in a 12-step or alternative support group

Vocational rehabilitation

Educational assistance

Legal assistance

Maintenance medication

Relapse prevention programming

Key Takeaways

Seroquel belongs to the class of drugs known as atypical antipsychotics. The drugs were initially invented as a safer alternative to first-generation antipsychotics. However, recent studies and reports suggest an alarming increase in their off-label use. Seroquel has been named as the most commonly abused atypical antipsychotic.

Seroquel abuse is related to its potent sedative effect rather than its euphoric effects. When it’s used for recreational/self-medication purposes without medical supervision, it can result in adverse side effects, including potential substance abuse and dependence.

People who are taking the drug must follow their doctor’s recommendations precisely. If a Seroquel addiction develops, the safest way to long-term abstinence is medical detox and comprehensive inpatient/outpatient care. Ongoing recovery efforts, including aftercare, are also critical for a successful and long-term recovery.

This information should not replace a visit to a doctor or treatment center. If you are concerned that you or your loved one might be suffering from Seroquel addiction, ask for professional help today.

Resources

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348850/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819904/
3. https://www.samhsa.gov/data/sites/default/files/DAWN2k11ED/DAWN2k11ED/DAWN2k11ED.htm
4. Sarah L. Anderson and Joseph P. Vande Griends, “Quetiapine for insomnia: A review of the literature,” American Journal of Health-System Pharmacy, Vol. 71, March 2014
5. https://www.ncbi.nlm. nih.gov/pmc/articles/PMC4444129/
6. https://journals.lww.com/em-news/fulltext/2012/11000/toxicology_rounds__atypical_antipsychotic.7.aspx

Additional Drug Education

Alcohol

• Alcoholism
• Alcoholism in Your Twenties
• Alcohol Awareness Month
• Autism and Alcohol
• How to Stop Binge Drinking
• Rising Alcohol Consumption

Benzodiazepines

• Ativan
• Benzodiazepines
• Clonazepam
• Xanax

Hallucinogens

• DMT
• Ketamine
• Kratom
• LSD

Opiates

• Deadly Heroin Epidemic
• Heroin Abuse Rates
• Heroin Addiction
• Heroin and Depression
• Heroin Effects on the Brain
• 27 Overdoses in 24 Hours
• Ohio Heroin Epidemic
• Opiates vs. Opioids

Opioids

• Churches Address Opioids
• Commission to Fight Opioids
• Fentanyl
• Hydrocodone
• Methadone
• Opioid Addiction
• Opioid Abuse
• Opioid Deaths Increase
• Oxycodone
• Percocet
• Percodan
• Prescribing Opioids Survey
• Taking Charge of Opioids
• Tramadol
• Vicodin

Other Drugs

• Baclofen
• Gabapentin
• K2-Spice
• Marijuana
• Meloxicam
• Narcan
• Seroquel
• Valium
• Weight Loss Pills

Stimulants

• Adderall
• Amphetamines
• Betel Nut
• Cocaine
• Meth and Anxiety
• Stimulants

Side effects of neuroleptics and excess weight

Author Masha Pushkina, psychoeducator Views 914 02 Antipsychotics and excess weight is a problem that worries many. As you know, antipsychotics affect weight gain. According to statistics, more than 80% of people with severe mental disorders are overweight. A patient taking olonzapine gains an average of 2.3 kg per month, clozapine – 1.7 kg, quetiapine – 1.8 kg, zotepine – 2.3 kg.

Weight gain with antipsychotics

Weight gain is a very common side effect of many antipsychotics, especially some second-generation (newer) drugs.

This may be due to the fact that neuroleptics increase appetite, so you want to eat more than usual. They can also make you less active and feel tired, so you move less and burn fewer calories.

If you gain a lot of weight, it can increase your risk of developing diabetes and other health problems.

Changes in weight can have a negative effect on mood and self-esteem.

What can be done to keep from getting fat?

If the problem becomes significant, it should be discussed with your psychiatrist and possibly switched to another antipsychotic. You should also eat a healthy diet and increase your level of physical activity.

Weight gain often causes patients to resist taking pills, and it also creates additional psychological or physiological problems that then have to be sorted out. Weight gain due to psychotropic drugs is not the only reason why people with mental disorders gain weight, but let’s look at this problem.

What is considered overweight?

In clinical practice, to assess body weight, physicians are usually guided by the concept of body mass index (BMI), which was developed by the Belgian sociologist and statistician Adolphe Quetelet back in 1869. This is a value that allows you to assess the degree of correspondence between a person’s mass and his height, and thereby indirectly assess whether the mass is insufficient, normal or excessive.

Body mass index is calculated by the formula: body weight / height in meters squared (kg/m²).

BMI between 18. 5 and 24.9 is considered normal, BMI between 25 and 29.9 indicates overweight, BMI between 30 and 39.9 indicates obesity of I and II degrees, BMI above 40 indicates morbid obesity, that is, condition of the body that interferes with the normal functioning of the body.

The interpretation of BMI indicators recommended by the World Health Organization does not take into account the sex and age of the person, and this is a flaw in the system, but the US Department of Health, for example, collects statistics on anthropometric data on BMI. These data show that BMI is generally higher in men than in women. In addition, BMI is higher in middle-aged people than in young and old people.

Which drugs make you gain weight. Whether only from neuroleptics?

There are a number of studies that have examined the relationship between weight gain and certain groups of drugs. Metabolic disorders are most often associated with the use of antipsychotics.

A patient taking olonzapine gains on average 2. 3 kg per month, clozapine 1.7 kg, quetiapine 1.8 kg, zotepine 2.3 kg. Changes in weight during the course of the studies were also observed in those taking risperidone (1.0 kg per month) and ziprasidone (0.8 kg per month).

Also gaining weight are patients taking antidepressants and lithium, which is used in the treatment of mood disorders, in particular the manic and hypomanic phases of bipolar disorder, as well as in the prevention of its exacerbations and in the treatment of severe and resistant depression. Here, research data diverge, but if you measure the average values, then in the course of observations it turned out that people on antidepressants can add from 0.57 to 1.37 kg per month. With regard to lithium, 20% of patients on long-term treatment with this drug gain more than 10 kg of weight.

What is it about these medicines that causes weight gain?

There is no unequivocal opinion on this issue among scientists. However, this issue is being studied. Scientists at the National Institute of Mental Health in 2007 conducted an experiment on mice, during which they found that neuroleptics block the brain receptors responsible for controlling appetite. Another study, conducted already in 2012 by the staff of the Feinstein Institute for Medical Research, suggests that the problem of weight gain when taking antipsychotics is associated with a genetic predisposition in certain patients to gain excess weight in principle.

Are there drugs that don’t make you fat?

Yes, there certainly are. Not all psychotropic drugs lead to weight gain. There is evidence that taking some selective serotonin reuptake inhibitors even leads to a decrease in it during the first weeks after the start of administration. The same is written about the antiepileptic drugs felbamate and topiramate. But still, when prescribing drugs, the doctor is primarily guided not by the danger of gaining excess weight, but by improving your general well-being, because this, in any case, is more important than the number on the scales.

Sources:

• Bodyweight gain with atypical antipsychotics, Wetterling, 2001
• Weight gain and antidepressants, Fava, 2000
• Lithium: a review of its metabolic adverse effects, Livingstone and Rampes, 2006
• Weight Gain From Antipsychotics Traced to Appetite-Regulating Enzyme, Receptor, Science Update, 2007
• Gene Variants Implicated in Extreme Weight Gain Associated with Antipsychotics, Science Update, 2012
• Interruption of selective serotonin reuptake inhibitor treatment, Michelson, 2000
• Clozapine weight gain, plus topiramate weight loss, Dursun and Devarajan, 2000

The aim of the current publication is to review more recent clinical data on the use of trazodone for depression, focusing on the approved dose of 300 mg/day, and to discuss its place in current treatment strategies for depression and related conditions, as well as for off-label indications – insomnia and anxiety.

Trazodone is available in many countries around the world in a variety of formulations, including immediate release (IR) tablets, extended release tablets and, in some countries, even as oral drops and injection.

Recently, a new once-daily extended-release formulation of trazodone (150 mg and 300 mg halved tablets) has been developed. This patented delivery technology is able to control the release of trazodone within 24 hours and was developed in an attempt to improve patient adherence to therapy without loss of efficacy and improve tolerability by avoiding the early high plasma concentration peaks seen with conventional IR drugs. Trazadone extended release was approved in the US in early 2010 for the treatment of patients with depression and is in the process of being approved in many European countries.

Due to the combined antagonism of serotonergic receptors and inhibiting the reverse capture of serotonin (AIOOS), trazodon also demonstrated unique therapeutic flexibility, which led to its potential use of concomitant diseases associated with depression, as well as in the appointment of indications, including insomnia, anxiety, anxiety, anxiety, anxiety, anxiety Dementia, Alzheimer’s disease, abuse of psychoactive substances, schizophrenia, bulimia and fibromyalgia.

PubMed/MEDLINE searched the literature using the following keywords: “trazodone” and “major depressive disorder” as free text. The search was limited to fully published randomized controlled trials, in English only. Each article was assessed for relevance, and only articles published after 1981 (US approval date) were included. Separate searches have been made for the use of trazodone for other indications, including insomnia and anxiety. Again, only fully published randomized controlled trials were included.

Mechanisms of action and pharmacological properties of trazodone

Trazodone is a derivative of triazolopyridine. Although its pharmacological effects in humans are not fully understood, trazodone is believed to have more than one mechanism of therapeutic action, making it a multifunctional drug.

Trazodone: antidepressant, antagonist, serotonin reuptake inhibitor (SSRI)

Trazodone is the first antidepressant with a dual mechanism of action involving serotonin transporter (SERT) inhibition and serotonin type 2 (5-HT2) receptor antagonism (both 5-HT2A and 5-HT2C receptors). Preclinical evidence suggests that the antidepressant activity of SSRIs and SNRIs is most likely due to blockade of serotonin, whereby serotonin exerts its 5-HT1A receptor agonist action. However, this serotonin agonist effect also affects other serotonin receptor subtypes, such as the 5-HT2A and 5-HT2C receptors, which are thought to be responsible for the side effects often associated with SSRI and SNRI therapy, including insomnia, sexual dysfunction, and anxiety. Unlike SSRIs and SNRIs, serotonin antagonist/reuptake inhibitors (SSRIs) such as trazodone provide simultaneous inhibition of SERT and 5-HT2A and 5-HT2C receptor antagonism, thus avoiding the tolerability problems often associated with 5-HT2C stimulation. NT 2A/2C. In addition, there have been suggestions that concurrent 5-HT2A/2C antagonism and serotonin inhibition may have a synergistic effect that enhances the antidepressant activity of SARIs and may improve treatment tolerability.

Moreover, trazodone exhibits α1- and α2-adrenergic and histamine H1 receptor antagonistic properties with minimal anticholinergic effects. It is also well known that at low doses (25-100 mg) trazodone has therapeutic activity as a hypnotic. It is known that the action of several neurotransmitter systems, including serotonin, norepinephrine, dopamine, acetylcholine and histamine, are involved in the excitation mechanism. Thus, arousal can be effectively disrupted and sleep induced by inhibition of several of these neurotransmitter systems. The effectiveness of trazodone in this regard may be explained by its ability to inhibit H1 receptors, and the sleep-inducing effect of H1 receptor blockade may be enhanced by simultaneous antagonism of 5-HT2A and α-adrenergic receptors.

Dosage and method of administration

According to the relevant summary of the characteristics of the drug trazodone, therapy should be started with an evening dose (initial dose of 75-150 mg at bedtime). Subsequently, the dose can be increased every 3 days to 300 mg/day, administered in repeated doses after meals (trazodone IR), twice daily (extended release trazodone) or once daily, preferably at bedtime. In hospitalized patients, the dose may be further increased to 600 mg/day on repeated doses. For elderly patients, the initial dose should be reduced to 100 mg/day.

Extended release formulations

In the 1980s, extended-release tablets of trazodone (Roussel Laboratories Ltd., Guildford, UK) [75 and 150 mg tablets] were developed to limit the early and relatively high peak plasma concentrations that are observed with IR tablets. This high peak plasma concentration may be associated with side effects such as drowsiness or hypotension, especially during the first week of treatment. These side effects may limit treatment tolerability and adherence, thereby limiting the use of the therapeutic dose (up to 300 mg/day) in depressed patients.

As reported in the SPC, after a single oral dose of 100 mg of fast-release trazodone, a maximum plasma concentration (max) of 1.2 μg / ml of the drug is achieved, and the time to reach the maximum plasma concentration (t max) is 1 hour. With prolonged release of trazodone after a single oral dose of 75 mg, a maximum concentration of about 0.7 μg / ml is reached with a maximum duration of 4 hours. 4 hours after ingestion. The half-life is approximately 12 hours.

The half-life of trazodone IR is relatively short (6.6 hours after a single 100 mg dose), so repeated daily dosing is often used to achieve sufficient dose levels for depressed patients, but this dosing regimen can be inconvenient and may result in missed doses and decrease in compliance.

More recently, a new once-daily extended-release formulation of trazodone has been developed to further improve adherence to treatment at therapeutic doses and reduce peak plasma concentration and dosing frequency compared to the conventional fast-release formulation. Extended-release trazodone was developed in two doses (tablets scored at 150 and 300 mg) to ensure proper titration, starting at 150 mg/day, in increments of 75 mg every 3 days.

Efficacy and tolerability of trazodone in depression

Several direct studies have demonstrated comparable efficacy of trazodone with other drug classes, including TCAs (amitriptyline and imipramine), SSRIs (fluoxetine, paroxetine, sertraline, citalopram and escitalopram), SNRIs (venlafaxine and mirtazapine) and norepinephrine and dopamine reuptake inhibitors (bupropion). ) . Randomized controlled trials of trazodone in elderly people with depression published since 1981 years old

Trazodone versus tricyclic antidepressants (TCAs)

In a series of comparative trials conducted in the 1980s, short-term therapy (4–6 weeks) with trazodone (100–400 mg) was found to be comparable in efficacy to TCAs such as amitriptyline and imipramine. An early randomized, double-blind, placebo-controlled study of elderly patients with unipolar depression demonstrated that the therapeutic efficacy of trazodone was superior to placebo and comparable to that of imipramine after 4 weeks of treatment. A double-blind, randomized trial of trazodone in elderly patients with severe depression reported significant improvements in both the Hamilton Depression Rating Scale (HAM-D) and the Geriatric Depression Scale (GDS), which were similar to those observed in patients treated with amitriptyline and mianserin. In addition, HAM-D and visual analogue scale (VAS) scores were similar between trazodone and amitriptyline in a study of elderly depressed patients.

Trazodone (Trittico) versus second-generation antidepressants

There have been several direct trials of trazodone (dose range 150-450 mg) and second-generation antidepressants in patients with depression. An analysis of head-to-head trials comparing different second-generation antidepressants found that the relative benefit in terms of response was comparable between trazodone and other second-generation antidepressants, including SSRIs, SNRIs, and bupropion.

A small study (n = 27) comparing the antidepressant efficacy and safety of trazodone and the SSRI fluoxetine in elderly depressed patients reported similar improvements in HAM-D scores after 6 weeks of treatment. Significant improvement in HAM-D scores from baseline was also observed with trazodone IR (dose range 50-400 mg/day) and fluoxetine (dose range 20-40 mg/day) in a larger, randomized, double-blind study (n = 126) outpatients with depression – these improvements in clinical performance were similar in the two treatment groups, but HAM-D sleep disturbance scores improved significantly in the trazodone group than in the fluoxetine group (-2. 7 vs 1.6; p = 0.001).

More recently, two similar European multicentre, double-blind, randomized trials compared twice-daily long-acting trazodone with paroxetine and sertraline in patients with depression. Efficacy was assessed by measuring change from baseline in the HAM-D, Montgomery Osberg Depression Rating Scale (MADRS) and Clinical Global Impression Severity (CGI-S) after 6 weeks of treatment. The results of these two studies showed that extended release trazodone was as effective as paroxetine and sertraline in reducing depressive symptoms and promoting remission; trazodone may also be of benefit to patients with major depression who have difficulty sleeping or exhibit common sleep disturbances.

The efficacy of venlafaxine SNRIs was compared with that of trazodone in a double-blind, randomized, placebo-controlled trial in 225 patients with depression. Overall, both trazodone (dose range 150-400 mg/day after the titration phase) and venlafaxine (dose range 75-200 mg/day) were significantly more effective than placebo, as measured by changes in HAM-D scores. However, trazodone was associated with greater improvement in HAM-D-associated sleep disturbance factor than venlafaxine, while greater improvement in cognitive impairment and developmental delay was observed with venlafaxine.

In contrast to these results, a double-blind, randomized trial of patients with moderate to severe depression demonstrated that mirtazapine and SNRIs were associated with greater improvement in HAM-D scores compared with trazodone after 6 weeks of treatment.

Trazodone was compared with the norepinephrine-dopamine reuptake inhibitor bupropion in a double-blind, randomized study of outpatients with moderate to severe depression. After 6 weeks, overall efficacy in terms of HAM-D and CGI-S was similar between the trazodone IR and bupropion groups. However, improvements in HAM-D and CGI-S scores at day 7 were significantly greater with trazodone compared with bupropion due to the beneficial effects of trazodone on sleep. At the end of treatment, 46% and 58% of patients were considered to have improved significantly/very much in the trazodone and bupropion groups, respectively.

Trazodone extended release preparations

An extended release formulation (Roussel Laboratories Ltd.) was compared with standard trazodone IR in a double-blind, randomized study of 347 general practitioner patients with MDD. After 6 weeks of treatment (150 mg/day at bedtime for both treatment groups), both treatment groups showed significant improvements from baseline in overall severity, overall improvement, and HAM-D scores. The difference in these improvements was not statistically significant between extended-release trazodone and trazodone IR, but small differences in treatment response rates were in favor of patients receiving extended-release trazodone. Safety, tolerability, and compliance did not differ significantly between the two treatment groups, demonstrating that the new formulation was effective and safe.

The efficacy and safety of extended release trazodone was evaluated in a double-blind, randomized, placebo-controlled trial in 412 patients with MDD (treatment course 6 weeks, dose range 150 to 375 mg/day). The mean maximum daily dose of trazodone administered during the study was 310 mg. The improvement in HAM-D scores was significantly greater with trazodone than with placebo, a difference that was statistically significant after the first week of treatment and persisted throughout the study. Moreover, there was a higher percentage of HAMD-17 responders and a greater decrease in deviations from baseline on the HAMD-17 Depressed Mood Scale, CGI-S, and MADRS total score. In the HAM-D group, the greatest improvement was observed in insomnia, guilt, and depressed mood, while in the MADR group, the greatest improvement was seen in reduced sleep, internal tension, reports of sadness, and suicidal thoughts. Notably, the antidepressant efficacy of trazodone was independent of baseline severity of insomnia and improvement in insomnia. Trazodone was also well tolerated; The most common adverse events were headache and drowsiness. There were no serious treatment-related adverse events or clinically significant ECG or laboratory abnormalities. These results suggest that once-daily long-acting trazodone may be an effective monotherapy option in patients with DMD when administered at an appropriate therapeutic dose (up to 375 mg/day).

Trazodone in special patient populations

Trazodone has been studied for the treatment of depression in a variety of patient populations, including the elderly, pediatric patients, and patients with renal insufficiency.

In elderly depressed patients, comparable efficacy has been reported between trazodone and amitriptyline TCAs. Two double-blind, randomized trials comparing trazodone and the SSRI fluoxetine also reported similar antidepressant efficacy between the two treatments studied. In addition, fluoxetine was associated with a higher incidence of activating side effects (arousal, anxiety, nervousness, insomnia) compared to trazodone. In contrast, sedative effects were reported more frequently with trazodone than with fluoxetine.

Trazodone extended release (Roussel Laboratories Ltd. ) has been evaluated in depressed elderly patients. After 4 weeks of treatment, both trazodone controlled-release formulations and conventional formulations (both given at night as single daily doses starting at 100 mg and increased to 200 mg/day depending on tolerability) were similar in efficacy as measured by change from baseline on the HAM-D scale and the global assessment of the severity of depression. During the first week of treatment, fewer side effects were reported in patients treated with the controlled release drug.

Patients often experience their first episode of depression in early childhood, before the onset of puberty or adolescence. To date, there are no data on the use of trazodone in children and adolescents with depression. In a small open-label study of ten children with chronic tics and Tourette’s syndrome, the combination of haloperidol and trazodone was shown to be effective in improving clinical symptoms. At the end of the study, the Yale Global Tic Severity Scale score was significantly reduced from baseline, and no side effects were reported. However, it should be noted that trazodone is not recommended for use in children under 18 years of age.

Trazodone is extensively metabolized in the liver, but the effects of trazodone in patients with renal or hepatic insufficiency are not well understood. An early study in the late 1970s evaluated the effects of a 12-day treatment with trazodone (75 mg) in patients with mixed neurosis and normal or impaired renal function. Although higher serum concentrations of trazodone were observed in patients with impaired renal function compared with patients with normal renal function, these differences were not statistically significant. As a result, the authors concluded that impaired renal function is not a contraindication to treatment with low doses of trazodone. A recent case of severe liver toxicity leading to fulminant liver failure has been reported following treatment with venlafaxine and trazodone for 4 months.

Given the available data on the use of trazodone in patients with renal or hepatic impairment, the labeling of trazodone recommends careful dosing and regular monitoring in patients with hepatic impairment, especially in cases of severe hepatic impairment and severe renal impairment (usually in mild or moderate renal impairment, dose adjustment is not required).

Trazodone tolerance

Trazodone is generally well tolerated in the treatment of depression, with the most common side effects being drowsiness (hypnotics/sedation), headache, dizziness, and dry mouth.

Drowsiness is the most common side effect of trazodone, with incidence in depressed patients ranging from 5.6% to 22.5% (last estimate shown in the figure).

Trazodone has minimal anticholinergic activity. However, an increased risk of orthostatic hypotension may be associated with trazodone, especially in elderly patients or patients with pre-existing heart disease. This effect, due to the blockade of adrenergic α 1 receptors, is temporary and is associated with the plasma concentration of the drug.

At toxic plasma levels, trazodone may be associated with prolongation of the corrected QT interval (QTc) and torsades de pointes. Even at therapeutic doses, several cases of life-threatening cardiac arrhythmias, including ventricular tachycardia, have been reported in clinical and preclinical studies. Evidence suggests that QT interval prolongation is due to the interaction of trazodone with hERG potassium channels. Concomitant use of trazodone with drugs known to cause cardiac toxicity or prolong the QT interval should be avoided as this may increase the risk of ventricular arrhythmias, including torso de pointe arrhythmia.

Trazodone may also be associated with rare cases of priapism. For this reason, trazodone should be used with caution in men with conditions that may predispose them to priapism (eg, sickle cell anemia, multiple myeloma, leukemia, autonomic nervous system dysfunction, and hypercoagulable states) or in men with an anatomical deformity of the penis (eg, angulation, cavernous fibrosis or Peyronie’s disease).

Drug interactions have been reported with inhibitors of the cytochrome P450 (CYP) 3A4 enzyme, such as erythromycin, ketoconazole and ritonavir, resulting in increased plasma concentrations of trazodone; conversely, carbamazepine may reduce plasma concentrations of trazodone. Concomitant use with other antidepressants such as TCAs, MAOs or fluoxetine should be avoided due to the risk of serotonin syndrome and cardiovascular side effects. Interactions between trazodone, citalopram and fluoxetine have been studied in 97 patients with depressive syndrome within 1 year. The results showed that the use of citalopram and fluoxetine in combination with trazodone did not significantly affect the concentration of trazodone in the blood serum, and no cases of headache, daytime sedation, fatigue or serotonin syndrome were reported during the study.

Antidepressants increase the risk of suicidal ideation and behavior (suicidality) in children, adolescents, and young adults compared with placebo in short-term studies of MDD and other psychiatric disorders. Cases of suicidal thoughts and suicidal behavior have been reported during trazodone therapy or shortly after cessation of treatment.

Side effects of the antidepressant Trittiko

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