Trazodone (Brand names: Desyrel, Oleptro, Trittico, Molipaxin, amongst others) is an antidepressant of the serotonin antagonist and reuptake inhibitor (SARI) class. Trazodone has also some anxiolytic and hypnotic activity.
In the first days of treatment Trazodone may have a sedative effect which may cause drowsiness.
Trazodone is used to treat symptoms in all types of depression, including when anxiety is also present.
 BRAND NAMES
 MECHANISM OF ACTION
Trazodone possesses antidepressant, and also some anxiolytic and hypnotic activity. Its pharmacological effects are dose-dependent. At low doses trazodone antagonizes 5HT2a receptors while at higher doses (10-50 times the dose required to antagonize 5HT2a receptors) it blocks SERT, 5HT2c and presynaptic α2 receptors.
The serotonin transporter (SERT) is a membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. SERT blockade by Trazodone increases serotonergic tone (action similar to that of SSRI antidepressants). 150–600 mg of Trazodone are required to inhibit SERT in order to obtain an antidepressant effect.
Presynaptic α2-adrenoceptors negatively control noradrenaline and serotonin release. Thus their antagonism increases the release of these two neurotransmitters.
At low-intermediate dosages (25-150 mg) Trazodone exerts an hypnotic action due to its blockade of 5HT2a receptors, as well as H1 histamine receptors and α1 adrenergic receptors.
- Treatment of choice major depressive disorder accompanied by marked agitation, anxiety and insomnia. 
- Trazodone helps in the treatment of chronic pain.
- At low-dosages, Trazodone is effective in treating insomnia associated with SSRI antidepressants use.
- Trazodone may help reducing aggression and agitation in Alzheimer’s disease patients
- Trazodone may help those suffering from lack of erection. it's efficacy appeared greater at higher doses (150-200 vs 50 mg/day)
- Insomnia and sleep disturbance: 50–100 mg at bedtime. Max: 200 mg
- Treatment of depression: The recommended starting dose is 150 mg once daily, to be increased gradually by 75 mg per day every three days. Maximum dose: 375 mg per day. The entire dosage may be taken in one dose at bedtime to prevent daytime somnolence.
- To help reducing aggression and agitation in Alzheimer’s disease patients: 50 mg two times a day.
When discontinued, gradual dose reduction is recommended
- Hypersensitivity to trazodone
- Initial recovery phase of Miocardial infarction
 WARNINGS AND PRECAUTIONS
- Clinical Worsening/Suicide Risk: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Monitor for clinical worsening and suicidal thinking and behavior.
- Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with antidepressants alone and may occur with trazodone treatment, but particularly with concomitant use with other serotonergic agents (including Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOI, both those intended to treat psychiatric disorders and also others, such as Linezolid and intravenous Methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).If such symptoms occur, discontinue Trazodone and initiate supportive treatment. If concomitant use of Trazodone with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
- Orthostatic Hypotension and Syncope: 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.
- QT Prolongation (risk of cardiac arrhythmia): Trazodone Increases the QT interval. Avoid use with drugs that also increase the QT interval, Strong inhibitors of CYP3A4 and in patients with risk factors for prolonged QT interval.
- Use in Patients with Heart Disease: Use with caution in patients with cardiac disease
- Interaction with MAOIs: Do not use concomitantly or within 14 days of Monoamine oxidase inhibitors
- Priapism: Rare cases of priapism were reported. . Men who have an erection lasting greater than 6 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention.
- Potential for Cognitive and Motor Impairment: Trazodone may cause somnolence or sedation and may impair the mental and/or physical ability required for the performance of potentially hazardous tasks. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.
- Discontinuation Symptoms: Withdrawal symptoms including anxiety, agitation and sleep disturbances, have been reported with trazodone. Clinical experience suggests that the dose should be gradually reduced before complete discontinuation of the treatment.
- Concomitant use of Trazodone with other serotoninergic drugs (Triptans, SSRI, SNRI) or drugs that impair metabolism of serotonin (MAOIs) or serotonin precursors (such as tryptophan) can increase the risk of serotonin syndrome.
- Trazodone may enhance effects of alcohol, barbiturates, or other CNS depressants.
- CYP3A4 inhibitors may increase blood concentrations of trazodone.
- CYP3A4 inducers may decrease blood concentrations of trazodone.
- Trazodone increases digoxin and phenytoin serum levels.
- Monitor for increased or decreased prothrombin time if coadministered with Warfarin.
- NSAIDs, Aspirin or other Anticoagulants: Potential for increased risk of bleeding
 PREGNANCY AND LACTATION
- Pregnancy Category C (US). Trazodone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Nursing Mothers: Trazodone and/or its metabolites have been found in the milk of lactating rats, suggesting that the drug may be secreted in human milk. Caution should be exercised when trazodone is administered to a nursing woman.
 SIDE EFFECTS
Drowsiness/sedation, dizziness, dry mouth, headache, orthostatic hypotension, constipation, blurry vision, cardiac arrhythmias and priapism.
 RELATED LINKS
|Tricyclic antidepressants||Amitriptyline (Elavil, Laroxyl) • Clomipramine (Anafranil) • Doxepin (Sinequan) • Imipramine (Tofranil) • Nortriptyline (Aventyl, Pamelor) • Trimipramine (Surmontil)|
|Selective serotonin reuptake inhibitors (SSRIs)||Citalopram (Celexa, Seropram) • Escitalopram (Cipralex, Lexapro) • Fluoxetine (Prozac) • Fluvoxamine (Luvox, Maveral) • Paroxetine (Paxil, Seroxat) • Sertraline (Zoloft)|
|Serotonin–norepinephrine reuptake inhibitors (SNRIs)||Desvenlafaxine (Pristiq) • Duloxetine (Cymbalta, Xeristar) • Venlafaxine (Efexor, Effexor)|
|Serotonin antagonists and reuptake inhibitors (SARIs)||Trazodone (Desyrel, Oleptro)|
|Norepinephrine reuptake inhibitors (NRIs)||Maprotiline (Ludiomil) • Reboxetine (Edronax)|
|Norepinephrine-dopamine reuptake inhibitors (NDRIs)||Bupropion (Wellbutrin)|
|Noradrenergic and specific serotonergic antidepressants (NaSSAs)||Mianserin (Lantanon) • Mirtazapine (Remeron)|
|Norepinephrine-dopamine disinhibitors (NDDIs)||Agomelatine (Valdoxan, Thymanax)|
|Monoamine oxidase inhibitors Nonselective||Tranylcypromine (Parnate)|
|Monoamine oxidase inhibitors B-Selective||Selegiline (Transdermal) (Emsam)|
|Others||5-Hydroxytryptophan • S-Adenosyl methionine • Hypericum (St John's wort)|