CNS, Psychiatry & Neurology

Selectively inhibit presynaptic serotonin (5-HT) reuptake transporter (SERT), increasing synaptic serotonin; minimal effect on norepinephrine/dopamine reuptake. First-line for major depression and most anxiety disorders.

GI upset/nausea, headache, insomnia or somnolence, sexual dysfunction (decreased libido, delayed orgasm), hyponatremia/SIADH (esp. elderly), increased bleeding risk (impaired platelet aggregation), and initial increase in anxiety.

Longest half-life of the SSRIs; active metabolite norfluoxetine has a half-life of ~1-2 weeks. Self-tapering reduces discontinuation syndrome but prolongs drug interactions; potent CYP2D6 inhibitor.

Most anticholinergic and most sedating SSRI; shortest half-life with no active metabolite, so highest risk of discontinuation syndrome; potent CYP2D6 inhibitor; associated with weight gain; avoid in pregnancy (cardiac malformation signal).

Citalopram prolongs QT dose-dependently; max 40 mg/day (20 mg if >60 yr, hepatic impairment, or CYP2C19 poor metabolizers/interacting drugs). Escitalopram is the active S-enantiomer with less QT risk.

Abrupt stop of short-half-life serotonergics causes flu-like symptoms, dizziness, insomnia, irritability, and 'brain zaps' (electric-shock sensations). Worst with paroxetine; taper to avoid. Distinguish from relapse by rapid onset and resolution on restart.