Notable Side Effects

• Sexual dysfunction (men: delayed ejaculation, erectile dysfunction; men and women: decreased sexual desire, anorgasmia)

• Gastrointestinal (decreased appetite, nausea, diarrhea, constipation, dry mouth)

• Mostly central nervous system (insomnia but also sedation, agitation, tremors, headache, dizziness)

• Note: patients with diagnosed or undiagnosed bipolar or psychotic disorders may be more vulnerable to CNS-activating actions of SSRIs

• Autonomic (sweating)

• Bruising and rare bleeding

• Rare hyponatremia (mostly in elderly patients and generally reversible on discontinuation of citalopram)

• SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Life-Threatening or Dangerous Side Effects

• Rare seizures

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

Weight Gain

• Reported but not expected

• Citalopram has been associated with both weight gain and weight loss in various studies, but is relatively weight neutral overall

Sedation

• Occurs in significant minority

What to Do About Side Effects

• Wait

• Wait

• Wait

• Take in the morning if nighttime insomnia

• Take at night if daytime sedation

• In a few weeks, switch to another agent or add other drugs

Best Augmenting Agents for Side Effects

• Often best to try another SSRI or another antidepressant monotherapy prior to resorting to augmentation strategies to treat side effects

• Trazodone or a hypnotic for insomnia

• Bupropion, sildenafil, vardenafil, or tadalafil for sexual dysfunction

• Bupropion for emotional flattening, cognitive slowing, or apathy

• Mirtazapine for insomnia, agitation, and gastrointestinal side effects

• Benzodiazepines for jitteriness and anxiety, especially at initiation of treatment and especially for anxious patients

• Many side effects are dose-dependent (i.e., they increase as dose increases, or they reemerge until tolerance redevelops)

• Many side effects are time-dependent (i.e., they start immediately upon dosing and upon each dose increase, but go away with time)

• Activation and agitation may represent the induction of a bipolar state, especially a mixed dysphoric bipolar II condition sometimes associated with suicidal ideation, and require the addition of lithium, a mood stabilizer or an atypical antipsychotic, and/or discontinuation of citalopram

CITALOPRAM: DOSING AND USE

Usual Dosage Range

• 20–40 mg/day

Dosage Forms

• Tablets 10 mg, 20 mg scored, 40 mg scored

• Orally disintegrating tablet 10 mg, 20 mg, 40 mg

• Capsule 10 mg, 20 mg, 40 mg

How to Dose

• Initial 20 mg/day; increase by 20 mg/day after 1 or more weeks; maximum 40 mg/day; single dose administration, morning or evening

Dosing Tips

• Citalopram should no longer be prescribed at doses greater than 40 mg/day because if can cause abnormal changes in the electrical activity of the heart

• Some controversy with FDA dosage limit of 40 mg/day, and higher doses may be prescribed by experts

• Tablets are scored, so to save costs, give 10 mg as half of 20-mg tablet or 20 mg as half of 40-mg tablet, since the tablets cost about the same in many markets

• Many patients respond better to 40 mg than to 20 mg

• Given once daily, any time of day when best tolerated by the individual

• If intolerable anxiety, insomnia, agitation, akathisia, or activation occur either upon dosing initiation or discontinuation, consider the possibility of activated bipolar disorder and switch to a mood stabilizer or an atypical antipsychotic

Overdose

• Rare fatalities have been reported with citalopram overdose, both alone and in combination with other drugs

• Vomiting, sedation, heart rhythm disturbances, dizziness, sweating, nausea, tremor

• Rarely amnesia, confusion, coma, convulsions

Long-Term Use

• Safe

Habit Forming

• No

How to Stop

• Taper not usually necessary

• However, tapering to avoid potential withdrawal reactions generally prudent

• Many patients tolerate 50% dose reduction for 3 days, then another 50% reduction for 3 days, then discontinuation

• If withdrawal symptoms emerge during discontinuation, raise dose to stop symptoms and then restart withdrawal much more slowly

Pharmacokinetics

• Parent drug has 23–45 hour half-life

• Weak inhibitor of CYP450 2D6

• Metabolized by CYP450 3A4 and 2C19

Drug Interactions

• Tramadol increases the risk of seizures in patients taking an antidepressant

• Can increase tricyclic antidepressant levels; use with caution with tricyclic antidepressants

• Can cause a fatal “serotonin syndrome” when combined with MAO inhibitors, so do not use with MAO inhibitors or at least for 14 days after MAOIs are stopped

• Do not start an MAO inhibitor for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing citalopram

• May displace highly protein bound drugs (e.g., warfarin)

• Can rarely cause weakness, hyperreflexia, and incoordination when combined with sumatriptan or possibly other triptans, requiring careful monitoring of patient

• Possible increased risk of bleeding especially when combined with anticoagulants (e.g., warfarin, NSAIDs)

• NSAIDs may impair effectiveness of SSRIs

• Should not be dosed above 20 mg/day in patients taking a CYP450 2C19 inhibitor (e.g., cimetidine) due to risk of QT prolongation

• Via CYP450 2D6 inhibition, citalopram could theoretically interfere with the analgesic actions of codeine, and increase the plasma levels of some beta blockers and of atomoxetine

• Via CYP450 2D6 inhibition, citalopram could theoretically increase concentrations of thioridazine and cause dangerous cardiac arrhythmias