• Clinical science



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.


Selective serotonin reuptake inhibitors

The side effects of SSRIs are: Serotonin syndrome, Stimulation of the CNS (agitation), Reproductive dysfunctions in males, and Insomnia.

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


Serotonin-norepinephrine reuptake inhibitors


Serotonin antagonist and reuptake inhibitors

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


Atypical antidepressants

Mirtazapine [6][7]

  • Mechanism of action
    • Selective α2-adrenergic antagonistserotonin and norepinephrine release
    • 5-HT2 and 5-HT3 receptor antagonists↑ effect of serotonin on free 5-HT1 receptor → likely causes antidepressant effects
    • H1 antagonist
  • Indications: major depressive disorder, especially in patients who are underweight and/or who have insomnia
  • Side effects
    • ↑ Appetite and weight gain
    • Sedation (due to H1 antagonism)
    • ↑ Serum cholesterol and triglyceride levels
    • Minimal sexual side effects
    • Dry mouth
  • Drug interactions: risk of serotonin syndrome if used concomitantly with other serotonergic drugs

Mirtazzzapine makes you sleepy (Zzz...).

Bupropion [8]

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

Vilazodone [9]

Vortioxetine [10]


VareniCliNe makes you Very Clean from Nicotine.


Monoamine oxidase inhibitors

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

References: [13]

Tricyclic antidepressants

Physostigmine should not be given to patients with suspected TCA overdose because it can precipitate cardiac arrest!

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 wort

  • Description
    • A flowering plant (Hypericum perforatum) used as a medicinal herb for depression
    • Because of its over-the-counter availability and significant drug interactions, it is important to be familiar with this dietary supplement.
  • Indication: Although not approved by the FDA, which considers it a dietary supplement, there are some studies that support St. John's wort is superior to placebo in treating mild depression.
  • Drug interactions


Antidepressant discontinuation syndrome [18][19]

  • 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).

Serotonin syndrome [20][21]

Serotonin syndrome causes HARM: Hyperthermia, Autonomic instability, Rigidity, and Myoclonus.

Tricyclic antidepressant toxicity [15]

The clinical features of TCA overdose can be remembered with the three Cs of Tri-cyclic poisoning: Convulsions, Coma, and Cardiac conduction abnormalities.

Differential diagnosis of drug-induced hyperthermia

Characteristics Serotonin syndrome Neuroleptic malignant syndrome Malignant hyperthermia Anticholinergic toxicity
Causative agents
  • < 24 h
  • Days to weeks
  • Minutes–24 h
  • < 24 h
Clinical features
Laboratory findings
  • Nonspecific
  • Nonspecific
  • Discontinuation of the causative drugs
  • Dantrolene
  • Cooling