Merck Manual

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Drugs Used to Treat Depression

Drugs Used to Treat Depression


Some Side Effects


Selective serotonin reuptake inhibitors (SSRIs)








Sexual dysfunction (primarily, delayed orgasm but also loss of desire and erectile dysfunction in some people), nausea, diarrhea, headache, weight loss (short-term), weight gain (long-term), discontinuation syndrome*, forgetfulness, blunting of emotions, and easy bruising

SSRIs are the most commonly used class of antidepressants. They are also effective for generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, phobic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and bulimia.

Toxicity due to overdosage is less serious than that with other antidepressants.

Norepinephrine- dopamine reuptake inhibitors


Headache, agitation, discontinuation syndrome*, high blood pressure in a few people, and rarely seizures

Bupropion is useful for depressed people who also have attention-deficit/hyperactivity disorder or cocaine use disorder and those trying to stop smoking. Bupropion does not cause sexual dysfunction.

Serotonin modulators (5-HT2 blockers)


Drowsiness and weight gain

Mirtazapine does not cause nausea or sexual dysfunction.


Prolonged drowsiness, painful and persistent erection (priapism), and an excessive decrease in blood pressure when a person stands

Trazodone is most often given at bedtime to people who have both depression and insomnia.

Serotonin- norepinephrine reuptake inhibitors





Nausea, dry mouth, discontinuation syndrome*, and, if high doses are taken, an increase in blood pressure

Most of the side effects can be prevented or minimized when low doses are used and when changes in dosages are made slowly.

Heterocyclic (including tricyclic) antidepressants

  • Amitriptyline

  • Amoxapine

  • Clomipramine

  • Desipramine

  • Doxepin

  • Imipramine

  • Maprotiline

  • Nortriptyline

  • Protriptyline

  • Trimipramine

Drowsiness, weight gain, increased heart rate and decreased blood pressure when a person stands (orthostatic hypotension), dry mouth, confusion, blurred vision, constipation, difficulty starting to urinate, delayed orgasm, and discontinuation syndrome*

With clomipramine and maprotiline, seizures

These drugs are usually not prescribed for older people because side effects are usually more pronounced in them.

Overdosage can cause serious, potentially life-threatening toxicity.

Monoamine oxidase inhibitors (MAOIs)

  • Isocarboxazid

  • Phenelzine

  • Selegiline

  • Tranylcypromine

Insomnia, nausea, weight gain, sexual dysfunction (loss of desire, delayed orgasm, and erectile dysfunction), pins-and-needles sensation, dizziness, decreased blood pressure (particularly when a person stands), and discontinuation syndrome*

People who take these drugs must follow dietary restrictions and avoid using certain drugs to avoid a serious reaction involving a sudden, severe increase in blood pressure with a severe, throbbing headache (hypertensive crisis).

Selegiline is available as a patch. With the patch, people do not have to follow the dietary restrictions unless the patch contains a high dose.


  • Dextroamphetamine

  • Methylphenidate

Nervousness, tremor, insomnia, and dry mouth

These drugs are usually used with antidepressants. Used alone, they are usually ineffective as antidepressants.

Melatonergic antidepressant


Headache, nausea, and diarrhea

Agomelatine has fewer side effects than most antidepressants. It does not cause daytime drowsiness, insomnia, weight gain, or sexual dysfunction.

Agomelatine may increase liver enzyme levels. These levels should be measured before therapy is started and every 6 weeks thereafter.

Ketamine-like drug


Dizziness, increased blood pressure, feeling of detachment

Esketamine is related to the anesthetic ketamine.

Esketamine is used in combination with other oral antidepressants for treatment-resistant depression.

Esketamine is available as a nasal spray

* Discontinuation syndrome consists of dizziness, anxiety, irritability, fatigue, nausea, chills, and muscle aches that occur when a drug is stopped abruptly.