Last updated: September 11, 2023

Summarytoggle arrow icon

Antidepressants are used primarily to treat major depressive disorder (MDD), although they are also indicated for the treatment of many other neuropsychiatric conditions. The most widely used classes of antidepressants are selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs). Most of these drugs work by increasing levels of serotonin, norepinephrine, or dopamine within the synaptic cleft. SSRIs are the first-line treatment for the vast majority of patients with depression because of their efficacy and favorable side-effect profile. While MAOIs and TCAs also have a high degree of efficacy, they are no longer widely used because of their undesirable side-effect profiles. Serotonin syndrome may occur as a complication of serotonergic antidepressant use; TCA toxicity is also possible, as is antidepressant discontinuation syndrome, which is caused by abrupt withdrawal or dose reduction of an antidepressant taken for ≥ 4 weeks.

Overviewtoggle arrow icon

Overview of antidepressants
Agents Indications Mechanism of action Adverse effects Contraindications Interactions
St. John's Wort
Selective serotonin reuptake inhibitors (SSRIs; e.g., fluoxetine, sertraline, citalopram)
Serotonin norepinephrine reuptake inhibitors (SNRIs; e.g., venlafaxine, duloxetine)
Tricyclic antidepressants (TCAs) Secondary amines (e.g., nortriptyline, desipramine)
  • Tertiary amines should be avoided in elderly individuals.
Tertiary amines (e.g., amitriptyline, imipramine)
Serotonin antagonist and reuptake inhibitors (SARIs; e.g., trazodone)
Monoamine oxidase inhibitors (MAOIs; e.g., tranylcypromine, phenelzine, selegiline)
Atypical antidepressants Mirtazapine
  • Hypersensitivity [4]
Bupropion [5]
  • Concomitant MAOI use [6]
  • Hypersensitivity
  • Sleep disturbances
  • Transdermal nicotine: ↑ adverse events

Antidepressants increase the risk of suicidal thoughts and suicidality in children, adolescents, and young adults < 24 years with major depressive disorder.

Selective serotonin reuptake inhibitorstoggle arrow icon

The long-term side effects of SSRIs include: Serotonin syndrome, SIADH, Rocking (movement disorders), Insomnia (stimulating effects), and Sexual dysfunction.

To avoid serotonin syndrome, SSRIs should be discontinued at least two weeks before starting an MAOI. Particular caution is warranted with fluoxetine, which should be discontinued at least five weeks before starting a MAOI.

Serotonin-norepinephrine reuptake inhibitorstoggle arrow icon

Serotonin antagonist and reuptake inhibitorstoggle arrow icon

Think “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and priapism!

Atypical antidepressantstoggle arrow icon

Mirtazapine [11]

Mirtazzzapine makes you sleepy (Zzz...).

Bupropion [12]

Buproprion is not associated with sexual dysfunction or weight gain. It is contraindicated in patients with seizure and eating disorders.

Vilazodone [13]

Vortioxetine [14]



VareniCliNe makes you Very Clean from Nicotine.

Monoamine oxidase inhibitorstoggle arrow icon

To remember the members of the MAO inhibitor class, think: “MAO thought capitalism was the PITS” (Phenelzine, Isocarboxazid, Tranylcypromine, Selegiline).

Tricyclic antidepressantstoggle arrow icon

Secondary amines are generally better tolerated than tertiary amines, especially in elderly patients.

The side effects of TCAs are: Tremor, Cardiovascular adverse effects, Anticholinergic adverse effects, Sedation, and Seizures.

St. John's worttoggle arrow icon

Complicationstoggle arrow icon

For the management of toxic effects due to overdose, see “Antidepressant overdose.”

Antidepressant discontinuation syndrome [17][18]

  • Description: symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks
  • Clinical features
  • Timing
    • Typically occurs within 3 days after drug cessation
    • Symptoms usually subside within 1–2 weeks
  • Diagnosis: is primarily based on history and clinical features.
  • Treatment: Restart antidepressant therapy at the original dose and begin tapering slowly.

To remember the main clinical features of antidepressant discontinuation syndrome, think: FINISH (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal).

Drug-induced hyperthermia

Differential diagnosis of drug-induced hyperthermia [19][20]
Characteristics Serotonin syndrome Neuroleptic malignant syndrome Malignant hyperthermia Anticholinergic toxicity
Causative agents
  • < 24 h
  • Days to weeks
  • Minutes–24 h
  • < 24 h
Clinical features Symptoms of autonomic dysfunction
Changes in neuromuscular activity
  • None: normal reflexes and tone
Altered mental status
  • Confusion possible
Laboratory findings
  • Nonspecific
  • Nonspecific

To differentiate between serotonin syndrome and the rest of drug-induced hyperthermia conditions remember that only SErotonin Shakes your Extremities (myoclonus and hyperreflexia, mostly of the lower limbs)

Referencestoggle arrow icon

  1. Revet A, Montastruc F, Roussin A, Raynaud JP, Lapeyre-Mestre M, Nguyen TTH. Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database. BMC Psychiatry. 2020; 20 (1).doi: 10.1186/s12888-020-02711-z . | Open in Read by QxMD
  2. Schmidt M, Butterweck V. The mechanisms of action of St. John’s wort: an update. Wiener Medizinische Wochenschrift. 2015; 165 (11-12): p.229-235.doi: 10.1007/s10354-015-0372-7 . | Open in Read by QxMD
  3. $DESYREL® (trazodone hydrochloride) tablets, for oral use.
  4. $PARNATE® (tranylcypromine) tablets, for oral use.
  5. $REMERON (mirtazapine) tablets.
  6. $WELLBUTRIN XL (bupropion hydrochloride extended-release) tablets for oral use.
  7. $VIIBRYD (vilazodone HCl) Tablets for oral administration.
  8. $BuSpar® (buspirone HCl, USP).
  9. $Antidepressant Discontinuation Syndrome.
  10. Gabriel M, Sharma V. Antidepressant discontinuation syndrome. CMAJ. 2017; 189 (21).doi: 10.1503/cmaj.160991 . | Open in Read by QxMD
  11. Perry PJ, Wilborn CA. Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management.. Ann Clin Psychiatry. 2012; 24 (2): p.155-162.
  12. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013; 13 (4): p.533-540.
  13. Anglin RE, Rosebush PI, Mazurek MF. Neuroleptic malignant syndrome: a neuroimmunologic hypothesis.. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2010; 182 (18): p.E834-8.doi: 10.1503/cmaj.091442 . | Open in Read by QxMD
  14. Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W. Effects of Antidepressants on Sleep. Curr Psychiatry Rep. 2017; 19 (9).doi: 10.1007/s11920-017-0816-4 . | Open in Read by QxMD
  15. Ramar K, Olson EJ. Management of common sleep disorders. Am Fam Physician. 2013; 88 (4): p.231-238.
  16. Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Therapeutic Advances in Psychopharmacology. 2016; 6 (2): p.99-144.doi: 10.1177/2045125316629071 . | Open in Read by QxMD
  17. Wang S-M, Han C, Lee S-J, Patkar AA, Masand PS, Pae C-U. Vilazodone for the Treatment of Depression: An Update. Chonnam Med J. 2016; 52 (2): p.91.doi: 10.4068/cmj.2016.52.2.91 . | Open in Read by QxMD
  18. D'Agostino A, English CD, Rey JA. Vortioxetine (brintellix): a new serotonergic antidepressant.. P T. 2015; 40 (1): p.36-40.
  19. $Trazodone.
  20. Amitriptyline. Updated: December 1, 2017. Accessed: April 10, 2018.
  21. Schatzberg AF, Nemeroff CB. The American Psychiatric Association Publishing Textbook of Psychopharmacology. American Psychiatric Association Publishing ; 2017

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