Trazodone: MedlinePlus Drug Information

A small number of children, teenagers, and young adults (up to 24 years of age) who took antidepressants (‘mood elevators’) such as trazodone during clinical studies became suicidal (thinking about harming or killing oneself or planning or trying to do so). Children, teenagers, and young adults who take antidepressants to treat depression or other mental illnesses may be more likely to become suicidal than children, teenagers, and young adults who do not take antidepressants to treat these conditions. However, experts are not sure about how great this risk is and how much it should be considered in deciding whether a child or teenager should take an antidepressant. Children younger than 18 years of age should not normally take trazodone, but in some cases, a doctor may decide that trazodone is the best medication to treat a child’s condition.

You should know that your mental health may change in unexpected ways when you take trazodone or other antidepressants even if you are an adult over age 24. You may become suicidal, especially at the beginning of your treatment and any time that your dose is increased or decreased. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: new or worsening depression; thinking about harming or killing yourself, or planning or trying to do so; extreme worry; agitation; panic attacks; difficulty falling asleep or staying asleep; aggressive behavior; irritability; acting without thinking; severe restlessness; and frenzied abnormal excitement. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor when you are unable to seek treatment on your own.

Your healthcare provider will want to see you often while you are taking trazodone, especially at the beginning of your treatment. Be sure to keep all appointments for office visits with your doctor.

The doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with trazodone. Read the information carefully and ask your doctor or pharmacist if you have any questions. You also can obtain the Medication Guide from the FDA website: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm.

No matter your age, before you take an antidepressant, you, your parent, or your caregiver should talk to your doctor about the risks and benefits of treating your condition with an antidepressant or with other treatments. You should also talk about the risks and benefits of not treating your condition. You should know that having depression or another mental illness greatly increases the risk that you will become suicidal. This risk is higher if you or anyone in your family has or has ever had bipolar disorder (mood that changes from depressed to abnormally excited) or mania (frenzied, abnormally excited mood) or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.

Trazodone: Pediatric Medication | Memorial Sloan Kettering Cancer Center

This information from Lexicomp^® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.

Brand Names: Canada

APO-TraZODone; APO-TraZODone D; DOM-TraZODone; Oleptro; PMS-TraZODone; RATIO-TraZODone [DSC]; TEVA-TraZODone; TraZODone-100; TraZODone-150; TraZODone-50

Warning

• Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
• This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.

What is this drug used for?

• It is used to treat low mood (depression).
• It may be given to your child for other reasons. Talk with the doctor.

Extended-release tablets:

• If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.

What do I need to tell the doctor BEFORE my child takes this drug?

• If your child is allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had.
• If your child has had a recent heart attack.
• If your child has ever had a long QT on ECG or other heartbeat that is not normal.
• If your child has any of these health problems: Low potassium levels, low magnesium levels, or slow heartbeat.
• If your child is taking any of these drugs: Linezolid or methylene blue.
• If your child has taken certain drugs for depression or certain other health problems in the last 14 days. This includes isocarboxazid, phenelzine, or tranylcypromine. Very high blood pressure may happen.
• If your child is taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask the doctor or pharmacist if you are not sure.

This is not a list of all drugs or health problems that interact with this drug.

Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe to give this drug with all of your child’s other drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.

What are some things I need to know or do while my child takes this drug?

• Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
• Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
• To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
• Alcohol may interact with this drug. Be sure your child does not drink alcohol.
• Talk with your child’s doctor before your child uses marijuana, other forms of cannabis, or prescription or OTC drugs that may slow your child’s actions.
• An unsafe heartbeat that is not normal (long QT on ECG) has happened with this drug. This may raise the chance of sudden death. Talk with the doctor.
• This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
• Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
• This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death.

If your child is pregnant or breast-feeding a baby:

• Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.

What are some side effects that I need to call my child’s doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
• Signs of bleeding like throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Fast or abnormal heartbeat.
• Swelling.
• Feeling confused.
• Call your child’s doctor right away if your child gets a painful erection (hard penis) or gets an erection that lasts for longer than 4 hours. If this is not treated right away, it may lead to lasting sex problems and your child may not be able to have sex in the future.
• A severe and sometimes deadly problem called serotonin syndrome may happen. The risk may be greater if your child also takes certain other drugs. Call your child’s doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; a fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; severe diarrhea, upset stomach, or throwing up; or very bad headache.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:

• Feeling dizzy, sleepy, tired, or weak.
• Constipation, diarrhea, stomach pain, upset stomach, or throwing up.
• Dry mouth.
• Headache.
• Feeling nervous and excitable.
• Shakiness.
• Muscle pain.
• Stuffy nose.
• Weight gain or loss.

These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.

You may report side effects to your national health agency.

How is this drug best given?

Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.

• Give this drug right after a meal or light snack.
• Tablet may be broken in half.
• Do not let your child chew or crush.
• If your child feels sleepy after taking this drug, talk with your child’s doctor. Your child’s doctor may change your child’s dose or when you give this drug.
• Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
• It may take several weeks to see the full effects.
• Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of seizures. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.

What do I do if my child misses a dose?

• Give a missed dose as soon as you think about it.
• If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
• Do not give 2 doses at the same time or extra doses.

How do I store and/or throw out this drug?

• Store at room temperature protected from light. Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

General drug facts

• If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
• Do not share your child’s drug with others and do not give anyone else’s drug to your child.
• Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider’s examination and assessment of a patient’s specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Last Reviewed Date

2020-04-23

Copyright

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

Trazodone 100mg Capsule – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

Each capsule contains 100mg trazodone hydrochloride

Excipient with known effect

Each capsule contains 155.320 mg of Lactose monohydrate

For the full list of excipients, see section 6.1.

Relief of symptoms in all types of depression, including accompanied by anxiety.

Posology

DEPRESSION:

Adults:

Initially 150mg/day in divided doses after food or as a single dose on retiring. This may be increased up to 300mg/day in single or divided doses. The major portion of a divided dose to be taken on retiring. The dose may be further increased to 600mg/day in divided doses in hospitalised patients.

Elderly:

For very elderly or frail patients the recommended initial starting dose is reduced to 100mg/day given in divided doses or as a single night-time dose (see section 4.4). This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100mg should be avoided in these patients. It is unlikely that 300mg/day will be exceeded.

Paediatric population

There are insufficient data to recommend the use of Trazodone hydrochloride in children below the age of 18 years.

DEPRESSION ACCOMPANIED BY ANXIETY:

As for depression.

ANXIETY:

75mg/day increasing to 300mg/day as necessary.

A decrease in side-effects (increase of the resorption and decrease of the peak plasma concentration) can be reached by taking Trazodone hydrochloride after a meal.

Hepatic Impairment:

Trazodone hydrochloride undergoes extensive hepatic metabolism, see section 5.2 and has also been associated with hepatotoxicity, see sections 4.4 and 4.8. Therefore caution should be exercised when prescribing for patients with hepatic impairment, particularly in cases of severe hepatic impairment. Periodic monitoring of liver function may be considered.

Renal Impairment:

No dosage adjustment is usually necessary, but caution should be exercised when prescribing for patients with severe renal impairment (see also section 4.4 and 5.2).

Method of administration

Oral

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Alcohol intoxication and intoxication with hypnotics.

Acute myocardial infarction.

Use in children and adolescents under 18

Trazodone hydrochloride should not be used in children and adolescents under 18 years old. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behaviour and anger) has been observed in a clinical study on children and adolescents treated with antidepressant more frequently than with placebo. Moreover, long-term safety data on children and adolescents regarding growth, maturation, cognitive and behavioural development are not available.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Trazodone hydrochloride is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder.

The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms are present.

To minimize the potential risk of suicide attempts, particularly at therapy initiation, only restricted quantities of Trazodone hydrochloride should be prescribed at each occasion.

It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions:

– Epilepsy, specifically abrupt increases or decreases of dosage should be avoided

– Patients with hepatic or renal impairment, particularly if severe

– Patients with cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree, recent myocardial infarction

– Hyperthyroidism

– Micturition disorders, such as prostate hypertrophy, although problems would not be anticipated as the anticholinergic effect of Trazodone hydrochloride is only minor

– Acute narrow angle glaucoma, raised intra-ocular pressure, although major changes would not be anticipated due to the minor anticholinergic effect of Trazodone hydrochloride

Should jaundice occur in a patient, Trazodone hydrochloride therapy must be withdrawn.

Severe hepatic disorders with potential fatal outcome have been reported with trazodone use (see adverse reaction section). Patients should be instructed to report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a physician. Investigations including clinical examination and biological assessment of liver function should be undertaken immediately, and withdrawal of trazodone therapy be considered.

Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a possible worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with Trazodone hydrochloride a depressive phase can change from a manic – depressive psychosis into a manic phase. In that case Trazodone hydrochloride must be stopped.

Interactions in terms of serotonin syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of other serotonergically acting substances like other antidepressants (e.g. tricyclic antidepressants, SSRI’s, SNRI’s and MAO-inhibitors) and neuroleptics. Malignant neuroleptic syndromes with fatal outcome have been reported in cases of co-administration with neuroleptics, for which this syndrome is a known possible adverse drug reaction. See Sections 4.5 and 4.8 for further information.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving Trazodone hydrochloride. Concomitant administration of antihypertensive therapy with Trazodone hydrochloride may require a reduction in the dose of the antihypertensive drug.

Elderly patients may more often experience orthostatic hypotension, somnolence and other anticholinergic effects of trazodone. Careful consideration should be given to the potential for additive effects with concomitant medication use such as with other psychotropics or anti-hypertensives or in the presence of risk factors such as comorbid disease, which may exacerbate these reactions. It is recommended that the patient/carer is informed of the potential for these reactions and monitored closely for such effects following initiation of therapy, prior to and following upward dose titration.

Following therapy with Trazodone hydrochloride, particularly for a prolonged period, an incremental dosage reduction to withdrawal is recommended, to minimise the occurrence of withdrawal symptoms, characterised by nausea, headache, and malaise.

There is no evidence that Trazodone hydrochloride possesses any addictive properties.

As with other antidepressant drugs, cases of QT interval prolongation have been reported with Trazodone hydrochloride very rarely. Caution is advised when prescribing Trazodone hydrochloride with medicinal products known to prolong QT interval. Trazodone hydrochloride should be used with caution in patients with known cardiovascular disease including those associated with prolongation of the QT interval.

Potent CYP3A4 inhibitors may lead to increases in Trazodone hydrochloride serum levels. See section 4.5 for further information.

As with other drugs with alpha-adrenolytic activity, Trazodone hydrochloride has very rarely been associated with priapism. This may be treated with an intracavernosum injection of an alpha-adrenergic agent such as adrenaline or metaraminol. However there are reports of Trazodone hydrochloride induced priapism which have required surgical intervention or led to permanent sexual dysfunction. Patients developing this suspected adverse reaction should cease Trazodone hydrochloride immediately.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose galactose malabsorption should not take this medicine.

General: The sedative effects of antipsychotics, hypnotics, sedatives, anxiolytics, and antihistaminic drugs may be intensified; dosage reduction is recommended in such instances.

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.

In vitro drug metabolism studies suggest that there is a potential for drug interactions when Trazodone hydrochloride is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving Trazodone hydrochloride will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. It has been confirmed in in-vivo studies in healthy volunteers, that a ritonavir dose of 200 mg BID increased the plasma levels of Trazodone hydrochloride by greater than two-fold, leading to nausea, syncope and hypotension. If Trazodone hydrochloride is used with a potent CYP3A4 inhibitor, a lower dose of Trazodone hydrochloride should be considered. However, the co-administration of Trazodone hydrochloride and potent CYP3A4 inhibitors should be avoided where possible.

Carbamazepine reduced plasma concentrations of Trazodone hydrochloride when co-administered. Concomitant use of carbamazepine 400 mg daily led to a decrease of plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine of 76 % and 60 %, respectively. Patients should be closely monitored to see if there is a need for an increased dose of Trazodone hydrochloride when taken with carbamazepine.

Trazodone hydrochloride may enhance the effects of muscle relaxants and volatile anaesthetics. Similar considerations apply to combined administration with sedative and antidepressant drugs, including alcohol. Trazodone hydrochloride intensifies the sedative effects of alcohol. Alcohol should be avoided during Trazodone hydrochloride therapy.

Trazodone hydrochloride has been well tolerated in depressed schizophrenic patients receiving standard phenothiazine therapy and also in depressed parkinsonian patients receiving therapy with levodopa. Antidepressants can accelerate the metabolism of levodopa.

Tricyclic antidepressants: Concurrent administration should be avoided due to the risk of interaction. Serotonin syndrome and cardiovascular side effects should be bewared.

Fluoxetine: Rare cases have been reported of elevated Trazodone hydrochloride plasma levels and adverse effects when Trazodone hydrochloride had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonin syndrome) could not be excluded.

Possible interactions with monoamine oxidase inhibitors have occasionally been reported. Although some clinicians do give both concurrently, use of Trazodone hydrochloride with MAOIs, or within two weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within one week of stopping Trazodone hydrochloride is also not recommended.

Phenothiazines: Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines, like e.g. chlorpromazine, fluphenazine, levomepromazine, perphenazine.

Other

Concomitant use of Trazodone hydrochloride with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are co-administered with Trazodone hydrochloride. Since Trazodone hydrochloride is only a very weak inhibitor of noradrenaline re-uptake and does not modify the blood pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that Trazodone hydrochloride may inhibit most of the acute actions of clonidine. In the case of other types of antihypertensive drug, although no clinical interactions have been reported, the possibility of potentiation should be considered.

Undesirable effects may be more frequent when Trazodone hydrochloride is administered together with preparations containing Hypericum perforatum (St Johns wort).

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

Concurrent use with Trazodone hydrochloride may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients.

Trazodone has had no effect on arterial blood pCO2 or pO2 levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.

Pregnancy

Data on a limited number (< 200) of exposed pregnancies indicate no adverse effects of Trazodone hydrochloride on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. The safety of Trazodone hydrochloride in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided.

Caution should be exercised when prescribing to pregnant women. When Trazodone hydrochloride is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Breast-feeding

Limited data indicate that excretion of Trazodone hydrochloride in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Trazodone Hydrochloride should be made taking into account the benefit of breast-feeding to the child and the benefit of Trazodone hydrochloride therapy to the woman.

Fertility

No fertility data are available.

Trazodone has minor or moderate influence on the ability to drive and use machines. As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states or blurred vision.

Cases of suicidal ideation and suicidal behaviours have been reported during Trazodone hydrochloride therapy or early after treatment discontinuation (see section 4.4).

The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Trazodone hydrochloride therapy.

¹ Fluid and electrolyte status should be monitored in symptomatic patients.

² See also Section 4.4.

³ Trazodone is a sedative antidepressant and drowsiness is sometimes experienced during the first days of treatment, usually disappears on continued therapy.

⁴ Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man. Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.

⁵ Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.

⁶ See also section 4.4.

In contrast to the tricyclic antidepressants, trazodone is devoid of anticholinergic activity. Consequently, troublesome side effects such as dry mouth, blurred vision and urinary hesitancy have occurred no more frequently than in patients receiving placebo therapy. This may be of importance when treating depressed patients who are at risk from conditions such as glaucoma, urinary retention and prostatic hypertrophy.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms

The most frequently reported reactions to overdose have included drowsiness, dizziness, nausea and vomiting. In more serious cases coma, tachycardia, hypotension, hyponatraemia, convulsions and respiratory failure have been reported. Cardiac features may include bradycardia, QT prolongation and torsade de pointes. Symptoms may appear 24 hours or more after overdose.

Overdoses of Trazodone hydrochloride in combination with other antidepressants may cause serotonin syndrome.

Management

There is no specific antidote to trazodone. Activated charcoal should be considered in adults who have ingested more than 1 g trazodone, or in children who have ingested more than 150 mg trazodone within 1 hour of presentation. Alternatively, in adults, gastric lavage may be considered within 1 hour of ingestion of a potentially life-threatening overdose.

Observe for at least 6 hours after ingestion (or 12 hours if a sustained release preparation has been taken). Monitor BP, pulse and Glasgow Coma Scale (GCS). Monitor oxygen saturation if GCS is reduced. Cardiac monitoring is appropriate in symptomatic patients.

Single brief convulsions do not require treatment. Control frequent or prolonged convulsions with intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). If these measures do not control the fits, an intravenous infusion of phenytoin may be useful. Give oxygen and correct acid base and metabolic disturbances as required.

Treatment should be symptomatic and supportive in the case of hypotension and excessive sedation. If severe hypotension persists consider use of inotropes, e.g. dopamine or dobutamine.

Pharmacotherapeutic group: Other antidepressants.

ATC code: N06AX05.

Trazodone is a triazolopyridine derivative which differs chemically from other currently available antidepressants. Although trazodone bears some resemblance to the benzodiazepines, phenothiazines and tricyclic antidepressants, its pharmacological profile differs from each of these classes of drugs. The basic idea for the development of trazodone was the hypothesis that depression involves an imbalance of the mechanism responsible for the emotional integration of unpleasant experiences. Consequently, new animal models of depression consisting of responses to unpleasant or noxious stimuli, instead of the current tests related to the aminergic theory of depression, were used in studying the drug. Trazodone inhibits serotonin uptake into rat brain synaptosomes and by rat platelets at relatively high concentrations and inhibits brain uptake of noradrenaline in vitro only at very high concentrations. It possesses antiserotonin-adrenergic blocking and analgesic effects. The anticholinergic activity of trazodone is less than that of the tricyclic antidepressants in animal studies and this has been confirmed in therapeutic trials in depressed patients.

The electroencephalographic profile of trazodone in humans is distinct from that of the tricyclic antidepressants or the benzodiazepines, although bearing some resemblance to these agents in its effect in certain wavebands. Studies of the cardiovascular effects of trazodone in humans, His bundle and surface electrocardiograms in dogs, and experience with overdosage in man indicate that trazodone is less liable than imipramine to cause important adverse effects on the heart. However, studies in depressed patients with significant cardiac impairment suggest that trazodone may aggravate existing ventricular arrhythmias in a small undefined subgroup of such patients.

Trazodone hydrochloride is a potent antidepressant. It also has anxiety reducing activity. Trazodone hydrochloride is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms. Whilst the mode of action of Trazodone hydrochloride is not known precisely, its antidepressant activity may concern noradrenergic potentiation by mechanisms other than uptake blockade. A central antiserotonin effect may account for the drug’s anxiety reducing properties.

Absorption

Peak plasma concentrations are attained about 1.5 hours after oral administration of trazodone. Absorption is delayed and somewhat enhanced by food. The area under the plasma concentration-time curve is directly proportional to dosage after oral administration of 25 to 100mg. Trazodone is rapidly absorbed from the gastro-intestinal tract and extensively metabolised. Paths of metabolism of Trazodone include n-oxidation and hydroxylation. The metabolic m-chlorophenylpiperazine is active. Trazodone is excreted in the urine almost entirely in the form of its metabolites, either in free or in conjugated form. Trazodone is extensively metabolised, less than 1% of an oral dose being excreted unchanged in the urine. The main route of elimination is via the kidneys with 70 to 75% of an oral dose being recovered in the urine within the first 72 hours of ingestion. The elimination of Trazodone is biphasic, with a terminal elimination half-life of 5 to 13 hours. Trazodone is excreted in breast milk.

Biotransformation

In vitro studies in human liver microsomes show that trazodone is metabolised by cytochrome P4503A4 (CYP3A4) to form m-chlorophenylpiperazine. Whilst significant, the role of this pathway in the total clearance of trazodone in vivo has not been fully determined.

Elimination

There was an approximate two-fold increase in terminal phase half-life and significantly higher plasma concentrations of Trazodone in 10 subjects aged 65 to 74 years compared with 12 subjects aged 23 to 30 years following a 100mg dose of Trazodone. It was suggested that there is an age-related reduction in the hepatic metabolism of Trazodone.

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Trazodone 100mg Capsules – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

Trazodone 100 mg Capsules

Capsule containing 100 mg of Trazodone Hydrochloride.

For the full list of excipients, see section 6.1.

Relief of symptoms in all types of depression including depression accompanied by anxiety.

Posology

DEPRESSION:

Adults:

Initially 150mg/day in divided doses. This may be increased to 300mg/day in a single dose or divided doses.

Elderly or Frail

For very elderly or frail patients, the recommended initial starting dose is reduced to 100 mg/day given in divided doses or as a single night-time dose (see section 4.4). This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100 mg should be avoided in these patients. It is unlikely that 300 mg/day will be exceeded.

Pediatric population:

There are insufficient data on safety to recommend the use of trazodone in children below the age of 18 years.

DEPRESSION ACCOMPANIED BY ANXIETY

As for depression.

Hepatic Impairment:

Trazodone undergoes extensive hepatic metabolism, see section 5.2, and has also been associated with hepatotoxicity, see sections 4.4 and 4.8. Therefore caution should be exercised when prescribing for patients with hepatic impairment, particularly in cases of severe hepatic impairment. Periodic monitoring of liver function may be considered.

Renal Impairment:

No dosage adjustment is usually necessary, but caution should be exercised when prescribing for patients with severe renal impairment (see also section 4.4 and 5.2).

Method of administration

Route of administration: oral.

Trazodone capsules should be swallowed whole and not chewed.

Tolerability may be improved by taking trazodone after food.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Alcohol intoxication and intoxication with hypnotics.

• Acute myocardial infarction.

Pediatric population

Trazodone should not be used in children and adolescents under 18 years old. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behavior and anger) has been observed in a clinical study on children and adolescents treated with antidepressant more frequently than with placebo. Moreover, long-term safety data on children and adolescents regarding growth, maturation and cognitive and behavioral development are not available.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Trazodone is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behavior or thoughts and unusual changes in behavior and to seek medical advice immediately if these symptoms present.

To minimise the potential risk of suicide attempts, particularly at therapy initiation, only restricted quantities of Trazodone should be prescribed at each occasion.

It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions:

• Epilepsy, specifically abrupt increases or decreases of dosage should be avoided

• Patients with hepatic or renal impairment, particulary if severe

• Patients with cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree, recent myocardial infarction

• Hyperthyroidism

• Micturition disorders, such as prostate hypertrophy, although problems would not be anticipated as the anticholinergic effect of Trazodone is only minor

• Acute narrow angle glaucoma, raised intra-ocular pressure, although major changes would not be anticipated due to the minor anticholinergic effect of Trazodone

Should jaundice occur in a patient, Trazodone therapy must be withdrawn.

Severe hepatic disorders with potential fatal outcome have been reported with trazodone use (see adverse reaction section). Patients should be instructed to report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a physician. Investigations including clinical examination and biological assessment of liver function should be undertaken immediately, and withdrawal of tradozone therapy be considered.

Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a possible worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with Trazodone a depressive phase can change from a manic – depressive psychosis into a manic phase. In that case Trazodone must be stopped.

Interactions in terms of serotonin syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of other serotonergically acting substances like other antidepressants (e.g. tricyclic antidepressants, SSRI’s, SNRI’s and MAO-inhibitors) and neuroleptics. Malignant neuroleptic syndromes with fatal outcome have been reported in cases of coadministration with neuroleptics, for which this syndrome is a known possible adverse drug reaction. See Sections 4.5 and 4.8 for further information.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving Trazodone. Concomitant administration of antihypertensive therapy with Trazodone may require a reduction in the dose of the antihypertensive drug

Elderly patients may more often experience orthostatic hypotension, somnolence and other anticholinergic effects of trazodone. Careful consideration should be given to the potential for additive effects with concomitant medication use such as with other psychotropics or antihypertensives or in the presence of risk factors such as comorbid disease, which may exacerbate these reactions. It is recommended that the patient/carer is informed of the potential for these reactions and monitored closely for such effects following initiation of therapy, prior to and following upward dose titration.

Following therapy with Trazodone, particularly for a prolonged period, an incremental dosage reduction to withdrawal is recommended, to minimise the occurrence of withdrawal syptoms, characterised by nausea, headache, and malaise.

There is no evidence that Trazodone possesses any addictive properties.

As with other antidepressant drugs, cases of QT interval prolongation have been reported with Trazodone very rarely. Caution is advised when prescribing Trazodone with medicinal products known to prolong QT interval. Trazodone should be used with caution in patients with known cardiovascular disease including those associated with prolongation of the QT interval.

Potent CYP3A4 inhibitors may lead to increases in trazodone serum levels. See section 4.5 for further information.

As with other drugs with alpha-adrenolytic activity, Trazodone has very rarely been associated with priapism. This may be treated with an intracavernosum injection of an alpha-adrenergic agent such as adrenaline or metaraminol. However there are reports of Trazodone -induced priapism which have required surgical intervention or led to permanent sexual dysfunction. Patients developing this suspected adverse reaction should cease Trazodone immediately.

Trazodone contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.

General: The sedative effects of antipsychotics, hypnotics, sedatives, anxiolytics, and antihistaminic drugs may be intensified; dosage reduction is recommended in such instances.

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.

In vitro drug metabolism studies suggest that there is a potential for drug interactions when Trazodone is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving Trazodone will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. It has been confirmed in in- vivo-studies in healthy volunteers, that a ritonavir dose of 200 mg BID increased the plasma levels of Trazodone by greater than two-fold, leading to nausea, syncope and hypotension. If Trazodone is used with a potent CYP3A4 inhibitor, a lower dose of Trazodone should be considered. However, the co-administration of Trazodone and potent CYP3A4 inhibitors should be avoided where possible.

Carbamazepine reduced plasma concentrations of trazodone when coadministered. Concomitant use of carbamazepine 400 mg daily led to a decrease of plasma concentrations of trazadone and its active metabolite m-chlorophenylpiperazine of 76 % and 60 %, respectively.Patients should be closely monitored to see if there is a need for an increased dose of Trazodone when taken with carbamazepine.

Trazodone may enhance the effects of muscle relaxants and volatile anaesthetics, and caution should be exercised in such instances. Similar considerations apply to combined administration with sedative and anti-depressant drugs, including alcohol. Trazodone intensifies the sedative effects of alcohol. Alcohol should be avoided during Trazodone therapy.

Trazodone has been well tolerated in depressed schizophrenic patients receiving standard phenothiazine therapy and also in depressed parkinsonian patients receiving therapy with levodopa.Antidepressants can accelerate the metabolism of levodopa.

Tricyclic antidepressants: Concurrent administration should be avoided due to the risk of interaction. Serotonin syndrome and cardiovascular side effects are possible.

Fluoxetine: Rare cases have been reported of elevated Trazodone plasma levels and adverse effects when Trazodone had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonine syndrome) could not be excluded.

Possible interactions with monoamine oxidase inhibitors have occasionally been reported. Although some clinicians do give both concurrently, use of Trazodone with MAOIs, or within two weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within one week of stopping Trazodone is also not recommeded.

Phenothiazines: Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines, like e.g. chlorpromazine, fluphenazine, levomepromazine, perphenazine.

Other

Concomitant use of Trazodone with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are coadministered with Trazodone.

Since Trazodone is only a very weak inhibitor of noradrenaline re-uptake and does not modify the blood pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that Trazodone may inhibit most of the acute actions of clonidine. In the case of other types of antihypertensive drug, although no clinical interactions have been reported, the possibility of potentiation should be considered.

Undesirable effects may be more frequent when Trazodone is administered together with preparations containing Hypericum perforatum (St John’s Wort).

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

Concurrent use with trazodone may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients.

Pregnancy:

Data on a limited number (< 200) of exposed pregnancies indicate no adverse effects of Trazodone on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data area available. The safety of Trazodone in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided.

Caution should be exercised when prescribing to pregnant women. When Trazodone is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Breastfeeding:

Limited data indicate that excretion of Trazodone in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Trazodone should be made taking into account the benefit of breast-feeding to the child and the benefit of Trazodone therapy to the woman.

Trazodone has minor or moderate influence on the ability to drive and use machines. As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.

Cases of suicidal ideation and suicidal behaviours have been reported during Trazodone therapy or early after treatment discontinuation (see section 4.4).

Trazodone has had no effect on arterial blood pCO2 or pO2 levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.

The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Trazodone therapy.

1 Fluid and electrolyte status should be monitored in symptomatic patients.

2 See also Section 4.4.

3 Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy.

4 Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man. Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.

5 Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.

6 See also section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

Features of toxicity:

The most frequently reported reactions to overdose have included drowsiness, dizziness, nausea and vomiting.

In more serious cases coma, tachycardia, hypotension, hyponatraemia, convulsions and respiratory failure have been reported. Cardiac features may include bradycardia, QT prolongation and torsade de pointes. Symptoms may appear 24 hours or more after overdose.

Overdoses of Trazodone in combination with other antidepressants may cause serotonin syndrome.

Management:

There is no specific antidote to trazodone. Activated charcoal should be considered in adults who have ingested more than 1 g trazodone, or in children who have ingested more than 150 mg trazodone within 1 hour of presentation. Alternatively, in adults, gastric lavage may be considered within 1 hour of ingestion of a potentially life threatening overdose.

Observe for at least 6 hours after ingestion (or 12 hours if a sustained release preparation has been taken). Monitor BP, pulse and Glasgow Coma Scale (GCS). Monitor oxygen if GCS is reduced. Cardiac monitoring is appropriate in symptomatic patients.

Single brief convulsions do not require treatment. Control frequent or prolonged convulsions with intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). If these measures do not control the fits, an intravenous infusion of phenytoin may be useful. Give oxygen and correct acid base and metabolic disturbances as required.

Treatment should be symptomatic and supportive in the case of hypotension and excessive sedation. If severe hypotension persists consider use of inotropes, e.g. dopamine or dobutamine.

Pharmacotherapeutic group: other antidepressants, ATC code: N06A X05.

Trazodone is a potent antidepressant. It also has anxiety reducing activity. Trazodone is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms. Whilst the mode of action of trazodone is not known precisely, its antidepressant activity may concern noradrenergic potentiation by mechanisms other than uptake blockade. A central antiserotonin effect may account for the drug’s anxiety reducing properties.

Trazodone is rapidly absorbed from the gastro-intestinal tract and extensively metabolised. Paths of metabolism of Trazodone include n-oxidation and hydroxylation. The metabolic m-chlorophenylpiperazine is active. Trazodone is excreted in the urine almost entirely in the form of its metabolites, either in free or in conjugated form. The elimination of Trazodone is biphasic, with a terminal elimination half-life of 5 to 13 hours. Trazodone is excreted in breast milk.

There was an approximate two-fold increase in terminal phase half-life and significantly higher plasma concentrations of Trazodone in 10 subjects aged 65 to 74 years compared with 12 subjects aged 23 to 30 years following a 100mg dose of Trazodone. It was suggested that there is an age-related reduction in the hepatic metabolism of Trazodone.

In vitro studies in human liver microsomes show that trazodone is metabolised by cytochrome P4503A4 (CYP3A4) to form m-chlorophenylpiperazine. Whilst significant, the role of this pathway in the total clearance of trazodone in vivo has not been fully determined.

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Trazodone – StatPearls – NCBI Bookshelf

Continuing Education Activity

Trazodone is a medication used in the management and treatment of major depressive disorder. It is in the serotonin-antagonist-and-reuptake-inhibitor class of medications. This activity reviews the indications, action, and contraindications for trazodone as a valuable agent in managing major depression. This activity will highlight the mechanism of actions, adverse effects, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions), pertinent for members of the interprofessional team in the treatment of patients with depression and related conditions.

Objectives:

• Identify the indications for trazodone, including off-label indications.

• Describe the common adverse effects associated with trazodone use.

• Review the treatment considerations for patients with monoamine oxidase inhibitors use

• Explain the importance of collaboration and communication amongst interprofessional team members to improve outcomes for patients affected by severe hepatic impairment who are candidates for trazodone use.

Access free multiple choice questions on this topic.

Indications

Trazodone is an FDA-approved antidepressant for treating major depressive disorders.[1] It can be used as part of combination therapy with other drugs or psychotherapies or used by itself for treating depression. Non-FDA-approved use is to induce sedation in patients with sleep problems. These patients may or may not have concurrent depression. Because of a lack of sufficient clinical data for justifying its use as a sleep aid, trazodone is not FDA-approved for sleep disorders. Trazodone is also used off-label for anxiety, Alzheimer disease, substance abuse, bulimia, and fibromyalgia due to its serotonergic receptor antagonism and serotonin reuptake inhibiting effects. Trazodone has also been used for post-traumatic stress disorder (PTSD) if the first-line treatment use of SSRIs does not show efficacy. The dose of 50 mg to 200 mg of trazodone has been demonstrated to reduce episodes of nightmares as well as improving sleep habits in studies involving PTSD patients. However, various studies show panic symptoms have suffered exacerbation in some instances, which is why SSRIs, instead of trazodone, are preferred as the first-line treatment for PTSD. Additionally, research has shown trazodone to improve apnea and hypopnea episodes in patients with obstructive sleep apnea (OSA), and the drug does not worsen hypoxemic episodes.[2] It raises the respiratory threshold, lowering the risk of respiratory instability.[3]

Mechanism of Action

Trazodone is an antidepressant that works by inhibiting both serotonin transporter and serotonin type 2 receptors. It is a triazolopyridine derivative. Trazodone inhibits the reuptake of serotonin and blocks the histamine and alpha-1-adrenergic receptors. It also induces significant changes in 5-HT presynaptic receptor adrenoreceptors. The full spectrum of trazodone’s mechanism of action is not fully understood, which could explain its off-label uses. Trazodone is in the category of SARI drugs (serotonin antagonist and reuptake inhibitors), with other members being phenylpiperazine, etoperidone, lorpiprazole, and mepiprazole.[4]

Clinical studies have shown trazodone to be comparable in efficacy to other drug classes, such as TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors), and SNRIs (serotonin-norepinephrine receptor inhibitor) in treating major depressive disorders. Also, trazodone has better tolerance than second-generation SSRIs, which are highly associated with insomnia, anxiety, and sexual dysfunction.[5] The unique property of trazodone, where it simultaneously inhibits SERT, 5-HT2A, and 5-HT2C receptors, avoids the issue of sexual dysfunction, insomnia, and anxiety that commonly presents with SSRIs and SNRIs therapy. Trazodone reduces levels of neurotransmitters associated with arousal effects, such as serotonin, noradrenaline, dopamine, acetylcholine, and histamine. Low-dose trazodone use exerts a sedative effect for sleep through antagonism of 5-HT-2A receptor, h2 receptor, and alpha-1-adrenergic receptors. 

Furthermore, a recent study on human astrocytes showed trazodone helps decrease inflammatory mediator release and helps normalize trophic and metabolic support during inflammation of neurons, which is associated with major depression.

Administration

Trazodone administration is via the oral route. It may be administered after meals to decrease lightheadedness and postural hypotension. Begin with evening administration of 75 mg to 150 mg before bedtime, as a prolonged-release once a day administration. This regiment helps to optimize its purpose as an antidepressant, and it elicits higher compliance.[6] The dose may be increased every third day, up to 300 mg per day. The dose may be up to 600 mg/day in hospitalized patients. The dose in the elderly should be down to 100 mg/day. Results of multi-drug regiment studies showed the use of citalopram and fluoxetine with trazodone had no significant impact on any alteration of serum level and no increased risk of headache, sedation, or serotonin syndrome.

Studies showed that administering 50 mg to 100 mg per day of trazodone helped nonorganic insomnia due to depressive disorder, with 100 mg dosage as most effective to improve sleep. Trazodone may be available as immediate-release (IR) tablets, prolonged-release tablets, and in some cases, oral drops and injection solutions.

Adverse Effects

The primary adverse effects of trazodone include headaches, fatigue, dizziness, and drowsiness/somnolence. Other risks include anticholinergic effects (dry mouth), orthostatic hypotension, QT prolongation, torsades, priapism, and an increase in suicidal thoughts. QT prolongation and arrhythmia risks are due to the interaction of trazodone with hERG potassium channels. Antidepressants are associated with an increased risk of suicidal thinking, especially in younger adults, adolescents, and children. Despite the presence of anticholinergic side effects, the risk is less than tricyclic antidepressants, such as imipramine or amitriptyline. The risk for orthostatic hypotension is higher in the elderly, especially in those with pre-existing heart conditions, and it is due to the adrenergic α1-receptor blockade. Patients show adverse effects of somnolence and hypotension during the first week of administration. Special care is necessary for men who have sickle cell anemia, multiple myeloma, leukemia, autonomic dysfunction, hypercoagulable state, or those who have a penile anatomic variation as angulation, cavernosal fibrosis, or Peyronie disease, as it can cause priapism.

In some cases, trazodone use has correlated with visual hallucinations.[7] Hallucinations generally resolve with discontinuation of trazodone, and physicians should switch the patient to another antidepressant medication.

Contraindications

Trazodone therapy requires careful consideration for patients treated with any class of monoamine oxidase inhibitors (MAOIs), including linezolid or IV methylene blue. MAO inhibitors impair the metabolism of serotonin, and concurrent administration increases serum levels of serotonin. One must have 14 days of the MAOI-free period to reduce the risk of serotonin syndrome before initiating treatment with trazodone. Concomitant use of other serotonergic drugs, such as triptans, TCA, or fentanyl, will also increase serotonin levels. 

Trazodone use requires caution in patients with compromised liver function and renal function.[8]

Monitoring

Baseline liver functions require monitoring before, or periodically during, therapy in patients taking trazodone. Patients receiving trazodone should also be monitored for suicide ideation, especially at the beginning of the treatment or when the dose is modified. Monitor also for signs or symptoms of serotonin syndrome. In addition, concomitant administration of CYP 3A4 inhibitors can lead to an increase in drug levels of trazodone, increasing the risk of serotonin syndrome and cardiovascular adverse effects.[9]

Toxicity

Due to the hepatic and renal metabolism of trazodone, special care is necessary for patients with severe hepatic impairment and severe renal impairment.

Serotonin syndrome, while rare, is potentially life-threatening, presenting as a triad of mental status alteration, neuromuscular abnormality, and autonomic instability.[10] Initial clinical suspicion varies from presenting tremor, clonus, or akathisia. The first step to address this should be discontinuation of serotonergic agents, hydration, and control of agitation with anxiolytics. The risk is higher with a certain antidepressant, antibiotics, migraine medications, antiemetic, and analgesics.

The idiopathic drug-induced liver injury may result from trazodone administration. The timeframe typically is three months, but reported cases require liver transplantation. 

Enhancing Healthcare Team Outcomes

To properly administer medications for the appropriate population, the presence of clear communication and instruction is necessary. In addition to healthcare providers being able to communicate with each other, patients must feel comfortable enough to be involved in the treatment process. Providers having appropriate empathy for patients is necessary for patients to disclose their needs to providers.[11] An interprofessional healthcare team incorporating clinicians, mid-level practitioners, nurses, psychological professionals, and pharmacists will lead to optimal patient care with minimal adverse events. [Level 5]

References

1.

Schwasinger-Schmidt TE, Macaluso M. Other Antidepressants. Handb Exp Pharmacol. 2019;250:325-355. [PubMed: 30194544]

2.

Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez A, Owens R, Orr JE, Malhotra A. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc. 2015 May;12(5):758-64. [PMC free article: PMC4418332] [PubMed: 25719754]

3.

Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 01;37(4):811-9. [PMC free article: PMC4044741] [PubMed: 24899767]

4.

Mandrioli R, Protti M, Mercolini L. New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs. Curr Med Chem. 2018;25(7):772-792. [PubMed: 28707591]

5.

Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. [PMC free article: PMC3693429] [PubMed: 23192413]

6.

Fiorentini A, Rovera C, Caldiroli A, Arici C, Prunas C, Di Pace C, Paletta S, Pozzoli SM, Buoli M, Altamura AC. Efficacy of oral trazodone slow release following intravenous administration in depressed patients: a naturalistic study. Riv Psichiatr. 2018 Sep-Oct;53(5):261-266. [PubMed: 30353201]

7.

Santos G, Moreira AM. Distressing Visual Hallucinations after Treatment with Trazodone. Case Rep Psychiatry. 2017;2017:6136914. [PMC free article: PMC5494093] [PubMed: 28702268]

8.

Carvalhana S, Oliveira A, Ferreira P, Resende M, Perdigoto R, Barroso E. Acute Liver Failure due to Trazodone and Diazepam. GE Port J Gastroenterol. 2017 Jan;24(1):40-42. [PMC free article: PMC5553376] [PubMed: 28848778]

9.

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jabłońska J, Rybakowski J. [Trazodon–the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [PubMed: 22232986]

10.

Jurek L, Nourredine M, Megarbane B, d’Amato T, Dorey JM, Rolland B. [The serotonin syndrome: An updated literature review]. Rev Med Interne. 2019 Feb;40(2):98-104. [PubMed: 30243558]

11.

Nichol JR, Sundjaja JH, Nelson G. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Sep 7, 2020. Medical History. [PubMed: 30484996]

Teva-Trazodone – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Trazodone belongs to the class of medications called antidepressants. It is used to treat symptoms of depression. It works by affecting the balance of chemicals in the brain that are associated with depression. It may take up to 4 weeks before the full beneficial effects of this medication are seen.  

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

50 mg
Each round, light orange, coated tablet marked with “50” above the tablet scoreline on one side and “Novo” on the other contains 50 mg of trazodone. Nonmedicinal ingredients: colloidal silicon dioxide, FD&C Yellow No. 6 Lake, hydroxyproplyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch, and sodium starch glycolate. This medication does not contain gluten or tartrazine.

100 mg
Each round, white, coated tablet marked with “100” above the tablet scoreline on one side and “Novo” on the other contains 100 mg of trazodone. Nonmedicinal ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch, and sodium starch glycolate. This medication does not contain gluten or tartrazine.

150 mg
Each rectangular-shaped, light orange tablet marked with “Novo” on one side and marked with”50/50/50″ in a triangular pattern on the other contains 150 mg of trazodone. Nonmedicinal ingredients: croscarmellose sodium, FD&C Yellow No. 6 Lake, lactose, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. This medication does not contain gluten or tartrazine.

How should I use this medication?

The recommended adult dose of trazodone ranges from 150 mg to 300 mg daily, taken in 2 or 3 divided doses with a meal or light snack.

The dose is usually started at 150 mg to 200 mg daily and increased gradually until the best dose is found.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you are allergic to trazodone or any ingredients of the medication.

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• constipation
• decreased sexual desire or ability
• diarrhea
• dizziness or lightheadedness
• drowsiness
• dry mouth
• fatigue
• headache
• nausea
• nervousness
• vomiting
• weakness

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• blurred vision
• breast enlargement (for men)
• breast leakage of milk (for women, even if not pregnant)
• changes in menstrual cycle
• confusion
• dizziness when rising from a sitting or lying position
• new or worsened emotional problems
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• symptoms of glaucoma (e.g., blurred vision, seeing halos of bright colours around lights, red eyes, increased pressure in your eyes, eye pain or discomfort)
• symptoms of low sodium levels in the blood (e.g., achy, stiff or uncoordinated muscles; confusion; tiredness; weakness)
• symptoms of mania (e.g., elevated or irritable mood, reduced need for sleep, racing thoughts)
• vision changes

Stop taking the medication and seek immediate medical attention if any of the following occur:

• painful, prolonged erection of the penis (lasting more than 4 hours)
• seizures
• symptoms of a serious allergic reaction (swelling of the face or throat, difficulty breathing, wheezing, or itchy skin rash)
• symptoms of serotonin syndrome (e.g., confusion, fast heartbeat, hallucinations, restlessness, shaking, shivering, sudden jerking of muscles, sweating)
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools; spitting up of blood; vomiting blood or material that looks like coffee grounds)
• thoughts of self-harm or suicide

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Alcohol and other medications that cause drowsiness: Do not combine this medication with alcohol or other medications (e.g., antidepressants, sleeping pills, anxiety medications) that cause drowsiness since additional drowsiness can occur and be dangerous.

Behaviour changes and suicidal thoughts: This medication may worsen symptoms of depression, including thoughts of suicide or wanting to harm themselves or others. It may also cause agitated or aggressive behaviour. If you experience these symptoms or any other behaviour change while taking this medication, contact your doctor immediately. Family members or caregivers of people who are taking this medication should contact the person’s doctor immediately if they notice unusual behaviour changes.

Bleeding: Trazodone may cause a reduced number of platelets in the blood, which can make it difficult to stop cuts from bleeding. If you notice any signs of bleeding, such as frequent nosebleeds, unexplained bruising, or black and tarry stools, notify your doctor as soon as possible. Your doctor will order routine blood tests to make sure potential problems are caught early.

Blood pressure: Trazodone may cause low blood pressure and possibly cause a feeling of lightheadedness when moving from a sitting or lying position to a standing position.

Dizziness: Trazodone can cause severe dizziness, especially when rising from a sitting or lying position. People taking medications that can cause dizziness should rise slowly from sitting or lying down to reduce the possibility of severe dizziness or fainting.

Drowsiness/reduced alertness: Trazodone may impair the mental or physical abilities required for potentially hazardous tasks, such as driving or operating machinery. Avoid driving, operating machinery, or performing other hazardous tasks until you have determined how this medication affects you.

Glaucoma: Trazodone may worsen symptoms of glaucoma (increased pressure in the eyes), such as blurred vision or eye pain or pressure. If you have glaucoma, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart rhythm: Trazodone can cause changes to the normal rhythm of the heart, including an irregular heartbeat called QT prolongation. QT prolongation is a serious life-threatening condition that can cause fainting, seizures, and sudden death. If you are at risk for heart rhythm problems (e.g., people with heart failure, angina, low potassium or magnesium levels), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Priapism: Trazodone has been associated with prolonged or inappropriate erections (priapism) for a number of men taking this medication. If this occurs, stop taking the medication immediately and contact your doctor.

Seizures: Seizures have been reported for a small number of people taking trazodone. Most of these people were already taking medications for a previously diagnosed seizure disorder. If you have a history of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Serotonin syndrome: Rarely, severe, life-threatening reactions are possible when trazodone is combined with other medications that act on serotonin, such as tricyclic antidepressants and serotonin reuptake inhibitors, which are other medications used to treat depression. This is called serotonin syndrome. These combinations should be avoided. Symptoms of a reaction may include muscle rigidity and spasms, difficulty moving, changes in mental state including delirium and agitation. Coma and death are possible.

Stopping the medication: If this medication needs to be stopped, it should be done gradually, under the supervision of your doctor. Suddenly stopping trazodone can cause anxiety, agitation, or sleep problems.

Pregnancy: The safety of trazodone for use during pregnancy has not been established. It should not be used by women who may become pregnant unless, in the opinion of their doctor, the expected benefits outweigh the potential risks. If you are or may be pregnant, talk to your doctor about the risks and benefits of this medication.

Breast-feeding: This medication may pass into breast milk. If you are breast-feeding and are taking trazodone, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children and adolescents: The safety and effectiveness of trazodone have not been established for people less than 18 years of age.

Seniors: People over the age of 65 years may be more at risk of side effects from this medication and may require lower treatment doses.

What other drugs could interact with this medication?

There may be an interaction between trazodone and any of the following:

• alcohol
• antiarrhythmic medications (e.g., amiodarone, disopyramide, procainamide, sotalol, quinidine, flecainide)
• antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine, olopatadine, rupatadine)
• anti-Parkinson’s medications (e.g., bromocriptine, entacapone, pramipexole, rasagiline, safinamide, selegiline)
• amphetamines (e.g., dextroamphetamine, lisdexamfetamine)
• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• apalutamide
• aprepitant
• azelastine
• “azole” antifungals (e.g., itraconazole, ketoconazole, posaconazole, voriconazole)
• benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• bosentan
• brimonidine
• buprenorphine
• buspirone
• butorphanol
• cabergoline
• cannabis
• chloral hydrate
• clonidine
• cobicistat
• conivaptan
• deferasirox
• dexmethylphenidate
• dextromethorphan
• diltiazem
• elagolix
• enzalutamide
• ergotamine-like medications (e.g., dihydroergotamine, ergotamine, methylergonovine)
• esketamine
• flibanserin
• grapefruit juice
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
• lemborexant
• linezolid
• lithium
• lumacaftor and ivacaftor
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• methadone
• methylene blue
• methylphenidate
• metoclopramide
• mifepristone
• mirtazapine
• mitotane
• modafinil
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, tranylcypromine) muscle relaxants (e.g., baclofen,  cyclobenzaprine, methocarbamol, tizanidine)
• opioid pain medications (e.g., codeine, morphine)
• ozanimod
• pomalidomide
• protein kinase inhibitors (e.g., dasatinib, imatinib, lapatinib, pazopanib, sunitinib)
• quinine
• rifabutin
• rifampin
• ropinirole
• rotigotine
• St. John’s wort
• sarilumab
• scopolamine
• seizure medications (e.g., clobazam, gabapentin, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
• serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
• serotonin/norepinephrine reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine, levomilnacipran, venlafaxine)
• siltuximab
• tapentadol
• tetrabenazine
• tocilizumab
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, desipramine, trimipramine)
• “triptan” migraine medications (e.g., sumatriptan, zolmitriptan)
• tryptophan
• verapamil
• warfarin
• zolpidem
• zopiclone

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2021. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Teva-Trazodone

Trazodone Dosages by Use – Sleep, Anxiety & More

Trazodone is a medication that is FDA-approved for depression treatment. However, it can also be prescribed off-label to treat problems like insomnia and anxiety. Trazodone has a wide dosing range, so there are many different dosages people take when they are prescribed the drug. It is only available as a generic prescription, though it was previously available under brand names like Oleptro.

Article at a Glance:

• Trazodone is an antidepressant that is FDA-approved for depression.
• Off-label uses for trazodone are common and include insomnia and anxiety.
• Because trazodone is not a controlled substance, some doctors consider it safer than other alternatives for insomnia and anxiety.

Trazodone Dosage Overview

Trazodone is available as a tablet in several dosages. The lowest tablet strength is 50 mg, while higher strengths include 100 mg, 150 mg and 300 mg tablets. The tablets can be split to get a lower dose when needed; for example, someone may split a 50 mg tab to get a 25 mg dose.

Physicians usually start patients on the lowest effective dose, increasing the dose as needed.

Trazodone for Depression

Although trazodone is only FDA-approved for depression, it is rarely prescribed for that reason. Selective-serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft), escitalopram (Lexapro) and fluoxetine (Prozac) are more common and are generally considered some of the gold standards for depression treatment. Trazodone is more popular as an off-label drug for other medical issues, such as insomnia.

When someone starts taking a medication like trazodone for depression, it can take several weeks for the drug’s full effectiveness to begin. For the treatment of depression, trazodone may start to help improve symptoms in one to two weeks. The maximum effects may take anywhere from four to six weeks to show. If you have been taking trazodone for depression without improvement after this time, it is important to tell your doctor.

Dosage for Depression

Compared to when it’s used off-label for other conditions, trazodone for depression treatment typically requires higher doses. The starting dose of trazodone for depression is 150 mg daily. It can then be increased to a max dose of 600 mg daily, which may be split across multiple doses during the day.

Because trazodone is used at high doses in depression, it is important not to stop the drug cold turkey. Instead, if you are stopping trazodone, your dose should be slowly tapered over two to four weeks to avoid withdrawal symptoms.

Trazodone for Anxiety

Trazodone is not FDA-approved for anxiety, but it can be prescribed off-label for this reason. However, first-line anxiety treatments — including other antidepressants — are more likely to be used first. Trazodone is believed to help with anxiety because it influences neurotransmitters that are linked to excitability, such as serotonin, noradrenaline, dopamine, acetylcholine and histamine.

Trazodone Dosage for Anxiety

To treat anxiety, trazodone can be taken at a dose of 50 mg to 100 mg, two to three times daily. The total daily dosage should not exceed 400 mg.

Related Topic: Moderate anxiety treatment

Is Trazodone Like Xanax?

Trazodone and Xanax are very different from one another. Unlike trazodone, Xanax is not classified as an antidepressant; instead, it is a benzodiazepine. Xanax is a short-acting drug that enhances brain neurotransmitters like GABA, which may be imbalanced in people with anxiety or panic disorders.

Another big difference between trazodone and Xanax is the fact that Xanax is a Schedule IV controlled substance. Xanax may not be an ideal option if a patient is prone to drug abuse, but trazodone may be appropriate because it is not a controlled substance.

Side effects of trazodone and Xanax, such as drowsiness, can be similar because both drugs are central nervous system depressants.

Using Trazodone for Sleep

When trazodone is used to treat a condition like depression, the drowsiness side effect can be problematic. However, this side effect is what causes trazodone to be prescribed for insomnia. That said, sleep medicine doctors do not recommend it for insomnia treatment due to unclear evidence of its effectiveness. Regardless, trazodone is a popular drug for sleep due to its reputation as a safer alternative to other sleep medications; unlike trazodone, many of these other medications are controlled substances.

Trazodone Dosage for Sleep

When prescribed for sleep, trazodone can be taken as a 50 mg to 100 mg dose at bedtime. If needed, the dose can be increased to up to 200 mg at bedtime to help with sleep. Those with both depression and sleep problems may need a higher dose in some cases — up to 300 mg at bedtime.

Trazodone vs. Ambien

Ambien is a brand name of zolpidem, a popular prescription sleep aid. Unlike trazodone, Ambien is a sedative-hypnotic and a Schedule IV controlled substance, meaning that it has a risk of abuse, dependence and addiction.

Although sleep medicine guidelines recommend Ambien for insomnia, some people are hesitant to take Ambien because of its side effects. Aside from its addiction risk, side effects include complex sleep behaviors like sleepwalking and sleep-driving. The FDA has even issued a Black Box Warning for these effects.

Find the Help You Need

Although trazodone is not a controlled substance, it is still possible to become addicted to it. If you struggle with taking too much trazodone and are unable to stop, The Recovery Village can help. Contact our experts today to learn more about treatment plans that can work well for your situation.

• Sources

  U.S. National Library of Medicine. “Trazodone.” November 19, 2019. Accessed November 11, 2020.

  Anxiety and Depression Association of America. “Clinical Practice Review for GAD.” July 2, 2015. Accessed November 11, 2020.

  Drug Enforcement Administration. “Controlled Substances.” August 20, 2020. Accessed November 11, 2020.

  Sateia, Michael J.; Buysse, Daniel J.; Krystal, Andrew D.; et al. “Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.” Journal of Clinical Sleep Medicine, February 15, 2017. Accessed November 11, 2020.

  Drugs.com. “Trazodone.” August 17, 2020. Accessed November 11, 2020.

  U.S. National Library of Medicine. “Ambien.” July 22, 2020. Accessed November 11, 2020.

  Gelenberg, Alan J.; Freeman, Marlene P.; Markowitz, John C.; et al. “Practice Guideline for the Treatment of Patients With Major Depressive Disorder.” American Psychiatric Association, October 2010. Accessed November 11, 2020.

  Shin, Justin J.; Saadabadi, Abdolreza. “Trazodone.” StatPearls, May 28, 2020. Accessed November 11, 2020.

Medical Disclaimer: The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.

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.

Trade names: Canada

APO-TraZODone; APO-TraZODone D; DOM-TraZODone; Oleptro; PMS-TraZODone; RATIO-TraZODone [DSC]; TEVA-TraZODone; TraZODone-100; TraZODone-150; TraZODone-50

Warning

For all patients taking this drug:

• Drugs like this have increased the likelihood of suicidal thoughts or actions in children and young people.This risk may be higher in people who have attempted suicide or have had suicidal thoughts in the past. All people taking this drug must be closely monitored. Call your doctor right away if you have signs such as depressed mood (depression), nervousness, anxiety, grumpiness, or anxiety attacks, or if other mood or behavior changes occur or worsen. Call your doctor immediately if you have suicidal thoughts or attempted suicides.

Children:

• This drug is not approved for use in children. However, your doctor may decide that the benefits of using this drug outweigh the risks associated with it. If your child has received this drug, ask the doctor about the benefits and risks. Talk to your doctor if you have any questions about how your child is using this drug.

What is this drug used for?

• The drug is used to treat depression.
• This medicinal product can be used for other indications. Consult your doctor.

What should I 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 recently had a myocardial infarction.
• If you have ever had an increase in the duration of the QT interval on the ECG or other heart rhythm disturbances.
• If you have any of the following health problems: low magnesium, low potassium, or bradycardia.
• If you are taking any of the following drugs: linezolid or methylene blue.
• 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 medications that can cause certain types of heart rhythm disturbances (prolonged QT interval). There are many medications that can cause these problems. If you are unsure, check with your doctor or pharmacist.

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 drug 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.
• 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.
• Consult your doctor before using alcohol, marijuana or other forms of cannabis, or prescription and over-the-counter drugs that may slow you down.
• A dangerous heart rhythm disorder (prolonged QT interval on the ECG) has happened with this drug. This may increase the likelihood of sudden death. Consult your doctor.
• This drug may increase the risk of bleeding. Sometimes bleeding can be life-threatening. Consult your doctor.
• The risk of eye problems may be increased in some patients with this drug. Your doctor may order you to see an ophthalmologist to see if you are at increased risk of developing these eye problems.Call your doctor right away if you have eye pain, change in vision, swelling, or redness around the eye.
• This drug may lower sodium levels. Very low sodium levels can be life-threatening, leading to seizures, fainting, difficulty breathing, or death.
• If you are 65 years of age or older, use this drug with caution. You may have more side effects.
• Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding.The benefits and risks for you and your child will need to be discussed.

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 right away or get medical help 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.
• Signs of low sodium levels such as headache, trouble concentrating, memory impairment, confused thinking, weakness, seizures, and balance problems.
• Signs of bleeding such as vomiting or coughing up blood; vomiting of the type of coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; non-cyclic vaginal bleeding; bruising that occurs or increases for no reason; bleeding that you cannot stop.
• Signs of high or low blood pressure, such as very severe headache or dizziness, fainting, or vision changes.
• Increased or abnormal heart rhythm.
• Inflammation.
• Confusion of consciousness.
• Call your doctor immediately if you have a painful erection or if an erection lasts more than 4 hours. This can happen even if you are not having sex at the time. If not addressed immediately, it can lead to long-term erection problems and you may not be able to have sex.
• A serious and sometimes fatal complication called serotonin syndrome can occur. This risk may increase with the concomitant use of certain other drugs. Call your doctor right away if you have anxiety, imbalance, confusion, hallucinations, fever, tachycardia or irregular heartbeat, flushing, muscle twitching or stiffness, seizures, tremors or tremors, excessive sweating, severe diarrhea, nausea or vomiting , very severe headache.

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.
• Constipation, diarrhea, abdominal pain, nausea or vomiting.
• Dry mouth.
• Headache.
• Nervous tension and agitation.
• Shiver.
• Muscle pain.
• stuffy nose.
• Weight gain or loss.

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.

All forms of issue:

• If you feel drowsy after using this drug, talk to your doctor.Your doctor may change the dose or schedule for this drug.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.
• It may take several weeks to achieve full effect.
• Do not stop taking this drug abruptly without talking to your doctor. This can increase the risk of side effects. If necessary, this drug should be stopped gradually as directed by your doctor.

Immediate-release tablets:

• This drug should be taken right after a meal or light snack.
• The tablet can be broken in half.
• Do not chew or crush.

Extended release tablets:

• Take this medicine on an empty stomach.
• Swallow whole. Do not chew or crush.
• Long-acting tablets can be split in half.

What should I do if a dose of a drug is missed?

• 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.

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.
• Store all medicines in a safe place. Keep all medicines out of the reach of children and 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 have different 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.
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Trazodonum – PsyAndNeuro.ru

Trade names in Russia

Trittico, Azona

Form of issue

Tablets: 150 mg

Pharmacological group

Antidepressant

Nomenclature NbN

Serotonin receptor antagonist [2]

Readings

◊ Recommendations of the Ministry of Health of Russia

F32 Depressive episode

F52 Sexual dysfunction not due to organic disorders or diseases

R52.2 Other persistent pain

Y47.1 Adverse reactions in the therapeutic use of benzodiazepines

Z50.2 Rehabilitation for alcoholism

Z50.3 Drug addiction rehabilitation

◊ FDA recommendation

Depression

◊ Recommendations UK Medicines and Healthcare Products Regulatory Agency

• Anxiety
• Depression

Target symptoms

• Depression
• Anxiety
• Insomnia

Mechanism of action and pharmacokinetics

Trazodone, being a triazolopyridine derivative, has the ability to selectively inhibit the reuptake of serotonin in the brain, the drug acts as an antagonist of 5-HT2A / 2C receptors.It has no anticholinergic effect, does not inhibit MAO.

• After oral administration, absorption from the gastrointestinal tract is high.
• Time to reach C _max in blood plasma – 1-2 h
• Half-life: 1st phase 3-6 hours, 2nd phase 5-9 hours
• CYP3A4, CYP3A5 and CYP3A7 isoenzymes are involved in metabolism.

Treatment regimen

◊ Dosage and dose selection

• 150-600 mg / day
• Depression (as monotherapy): start with 150 mg in two divided doses, if necessary increase every 3-4 days by 50 mg, maximum 400 mg (outpatient), 600 mg (inpatient).
• Insomnia: start with 25-50 mg at bedtime, then, if well tolerated, increase to 50-100 mg
• No need to rush to increase doses [1]
• At the beginning of treatment, sedation may be very noticeable
• If a dose of less than 50 mg does not work, it is not necessary to quit treatment, it is better to increase it to 150-300 mg
• Due to the short half-life, the daily dose should be taken in two divided doses

◊ How quickly does it work

• In some patients with insomnia, when the dosage is correct, begins to act immediately.
• With depression, begins to act after 2-4 weeks.
• If there is no effect after 6-8 weeks, it is necessary to increase the dose or switch to another drug.
• Can be taken for many years to prevent relapse.

◊ Expected Result

• In the treatment of depression: complete remission.
• After the disappearance of symptoms of depression, you should continue taking it for 1 year if it was the treatment of the first episode.If this treatment is a recurrent episode, the treatment can be extended indefinitely.
• Use in the treatment of anxiety may be indefinite.
• For insomnia, the use may be indefinite, since there is no data on the formation of tolerance, dependence or withdrawal syndrome [1].

◊ If not working

• Change dose, change medication, or add ancillary medication;
• Connect psychotherapy;
• Reconsider the diagnosis to clarify comorbid conditions;
• In patients with undiagnosed bipolar disorder, the effectiveness of treatment may be low, in which case you should switch to a Mood stabilizer [1].

◊ How to stop taking

It is possible to gradually reduce the dose, although there is no evidence of a withdrawal syndrome [1].

◊ Treatment combinations

• Trazodone is rarely used as monotherapy for insomnia, in severe cases it can be combined with benzodiazepines
• Trazodone is the most common drug in combination with antidepressants, it not only treats insomnia, but also enhances the antidepressant effect

Warnings and contraindications

• Stop taking if the erection becomes unusually long – there is a risk of erectile dysfunction;
• If an erection lasts more than 1 hour – urgently consult a doctor;
• Use caution if patient has had convulsions;
• Use caution if patient has bipolar disorder;
• Do not use if allergic to trazodone [1].

Special patient groups

◊ Patients with kidney problems

No special selection of doses is required [1].

◊ Patients with liver disease

With care [1].

◊ Patients with heart disease

• May cause arrhythmias.
• Closely observe the patient.
• Not recommended after a heart attack.

◊ Elderly patients

In the elderly, side effects are more common.

◊ Children and adolescents

• The patient’s condition should be checked regularly and personally, especially during the first weeks of treatment.
• Inform adults about risks.
• Start with low doses.
• Boys have a higher risk of priapism than adult men

◊ Pregnant

• Not recommended for pregnant women, especially in the first trimester
• All risks should be weighed and compared
• Bleeding can be expected during childbirth

◊ Breastfeeding

• The drug passes into breast milk.
• If infant shows signs of irritation or sedation, stop feeding or taking sertraline
• However, postpartum treatment may be necessary, so all risks should be weighed.

Interaction with other substances

• Tramadol increases the risk of seizures when taken with antidepressants
• Cannot be used with MAO inhibitors. After you stop taking MAO inhibitors, 14 days should pass.Start treatment with MAO inhibitors 7 days after you stop taking vortioxetine.
• Trazodone may reduce the effect of antihypertensive drugs [1].

Analyzes during treatment

Not required.

Side effects and other risks

◊ Mechanism of side effects

• Sedation likely due to antihistamines
• Most side effects occur immediately after starting treatment and go away over time.

◊ Side effects

• Nausea, vomiting, constipation, dry mouth
• Sedation, fatigue, headache
• Reduced pressure
• Dangerous side effects : rarely priapism, rarely convulsions, rarely mania, rarely suicidal ideation
• Weight gain : rare
• Sedation : often
• Sexual dysfunction: no

◊ What to do with side effects

1. Wait
2. If heavily sedated, take at night.
3. Change drug [1]

◊ Long-term use

Safe

◊ Addictive

No.

◊ Overdose

• Rare cases of fatal overdoses.
• Priapism.

Benefits

• Good for the treatment of insomnia when you do not want to use drugs with a dependent potential;
• Good as an additive to anti-pressure drugs to relieve anxiety and insomnia;
• Good in cases where the absence of side effects in the sexual sphere and the absence of the risk of weight gain are essential [1].

Weakness

• Not suitable for tiredness and sleepiness.
• Not suitable if patient does not tolerate sedation.

Expert Advice

Less likely to cause mania than other antidepressants [1]

Footnotes

1. Stephen Stahl “Prescriber’s Guide”, 6th edition, 2017

2. Neuroscience-Based Nomenclature (https: //www.nbn2.com / taskforce)

90,000 TRAZODON is … What is TRAZODON?

Trittico (trazodone) – an unique serotonergic antidepressant with some interesting properties

PSYCHIATRY AND PSYCHOPHARMACOTHERAPY Vol. 20, №3–4, 2018 / PSYCHICHIHOTHERAPY.20, No. 3-4, 2018

IN OUR FRIENDS / FROM OUR FRIENDS

52

transmissions, while the impairment of noradrenergic neurotransmission

plays a lesser role, pharmaceutical chemists

were synthesized by kologami in the 1960s and 70s the first

selective serotonin reuptake inhibitors

(SSRIs) – zimelidine, brompheniramine, etc. These preparations

were practically devoid of interactions with M-cho

linergic, h2-histamine and a1-adrenergic

receptors and therefore had a low level of corresponding AEs (S.Stahl, 2013).

Already at the beginning of the clinical use of these first

SSRIs, it was revealed that SSRIs, as a class of blood pressure, are not devoid of

of their specific PE. So, in particular, it turned out that

SSRIs, being, in contrast to TCAs, are practically devoid of se-

dative effect, often cause insomnia, nightmares,

dreams, psychomotor agitation or exacerbation of anxiety and anxiety , especially at the beginning of te-

rapia.Other common problems associated with

with the use of SSRIs were sexual dysfunctions

(decreased libido and brightness of orgasm up to complete

anorgasmia in both sexes, erectile dysfunction or ejaculation

in men), as well as gastrointestinal disturbances. –

intestinal tract (GIT): decreased appetite, nausea, vomiting;

that, diarrhea. Common to all SSRIs PE (sexual, dissom-

nic, anxious and from the gastrointestinal tract) to varying degrees

are characteristic of all modern, clinically used –

to this day, SSRIs – from the historically first fluoxe –

tin and fluvoxamine until the most recent

in the SSRI group escitalopram (S.Stahl, 2013).

Studies have shown that the reason for the development of the indicated

PE when using SSRIs is the non-selective

stimulation of various subtypes of serotonin re-

receptors, primarily 5-HT2A, 5-HT2C, 5-HT3, to a lesser extent

at least – 5-HT6 and 5-HT7 with an increase under the influence of

SSRIs in the serotonin content in synapses. At the same time,

but it turned out that for the implementation of the antidepressant effect

of the most different classes of blood pressure (not only TCAs, but

and MAOIs, and SSRIs) is the most important and, in general,

stimulation of only 5-HT1A subtype of serotonin recipes –

tori.At the same time, studies have shown that

the mentioned “undesirable” subtypes of serotonin

receptors (5-HT2A / C, 5-HT3, 5-HT6, 5-HT7) are more expedient than

not to stimulate, but, on the contrary, to block … Moreover,

it was shown that blockade of, for example, 5-HT2A / C or

5-HT3-serotonin receptors is associated not only with

ko with a decrease in sexual PE, nausea, anorexia,

anxiety and dyssomnic disorders, but also with an independent

antidepressant effect or with an increase in the

antidepressant effect from the reuptake of mono

amines (S.Stahl, 2013).

From the second generation of antidepressants (selective

monoamine reuptake inhibitors)

to the third generation (drugs of receptor action,

and in particular Trittico)

All this together led to the emergence of the idea back in

1960s to synthesize a blood pressure that would

simultaneously and inhibit the reuptake of serotonium

on, like TCAs or the first SSRIs (zimelidine, bromo

feniramine), and had the properties of a strong blocker

5-HT2A / C and a number of other undesirable subtypes of seroton-

new receptors, similar to some TCAs, but

did not have unwanted M-anticholinergic blocking PE.

Scientists who put forward such an idea believed that the drug

with such receptor properties would not only be better tolerated and give on average less PE in comparison with

nii with the then available SSRIs (zimelidine, bromphe-

niramine) and even more so compared to TCAs, but it will also be

more effective than SSRIs. As time has shown, these

a priori expectations have largely come true during the subsequent

clinical study and comparison with other blood pressure

of the drug Trittico (trazodone), synthesized by specialists of the research laboratory

“Angelini Research Laboratory” in Italy at the end of the 1960s

precisely within the framework of the implementation of the mentioned idea

(S.Stahl, 2013).

In the English-language classifications of types of blood pressure Trittico

(trazodone) is called an antagonist of serotonin re-

type 2 receptors and at the same time an inhibitor of serotonin reuptake

(Serotonin-2 receptor anta-

/

) [I.V. Zabozlaeva, E.V. Mali –

nina, 2011; S. Stahl, 2013]. In the Russian-language classifications of

types of blood pressure, trazodone is usually called “specific

serotonergic blood pressure” or “atypical blood pressure”

(I.V. Zabozlaeva, E. V. Malinina, 2011; Yu.V. Bykov et al,

2013). The complex complex and atypical mechanism

of Trittico’s action determines both its uniqueness

among all other blood pressure, and the frequent effectiveness of

Trittico in cases resistant to various other

HELL (E. Freshska, 2013).

Trazodone under the trade names Trittico and Trittico

was used and applied in Europe and the USSR (and now in

post-Soviet countries) for the treatment of depressive, tre-

anxiety and dyssomnic disorders since the early 1970s

(J.Feighner, W. Boyer, 1988). In the United States, however, the Food and Drug Administration

(Food and Drug Administration, FDA) issued trazodone a solution for use under the trade name Desyrel®

in 1981 only. American-

market, already in the early 1980s trazodone in the USA

became the best-selling and most frequently prescribed of

of all blood pressure used clinically at that time,

even ahead of the one that had just appeared at that time, very

popular and widely advertised “1st modern-

mens SSRI” – fluoxetine.The reason for such a wide

popularity and commercial success of trazodone in the USA

was its good tolerance, a small amount of PE,

in particular, the absence of M-anticholinergic action,

pronounced hypnotic and anti-anxiety effect,

its absence, in contrast fluoxetine and

other SSRIs, a tendency to give sexual AEs (against

against, trazodone often improves sexual function,

, impaired with depression or due to the use of other blood pressure

), his lack of tendency to cause

or aggravate insomnia, anorexia, anxiety at the end of treatment

(E.Freshska, 2013).

It is interesting to note that the idea of ​​combining in one preparation

the ability to inhibit the reuptake of mono-

amines (primarily serotonin) and selectively stimulate the “desired” subtype of serotonin receptors

(5-HT1A) and / or block “unnecessary” subtypes (before

only 5-HT2A / C, 5-HT3, but also 5-HT6, 5-HT7), first realized in the synthesis of trazodone, was very fruitful

creative and currently implemented in such co-

temporary multimodal blood pressure (blood pressure IV generation), as

vilazodone (Viibryd), vortioxetine (Brintellix).Thus,

, trazodone can be considered a drug, in many ways

ahead of its time. Despite the fact that trazodone

appeared on the market earlier than modern SSRIs (but later

of the short-term appearance on the market of zimelidine and

brompheniramine), it is legitimate to consider it AD III, and not

II generation, devoid of a number of PEs inherent in all

SSRIs as a class, while SSRIs can be considered as

HELL II generation (S.