citalopram

Mechanism

Dual QT-prolongation risk. Citalopram carries an FDA boxed warning about dose-dependent QT effect (FDA Celexa caps at 40 mg/day); amiodarone is a potent QT-prolonging drug.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antidepressants: mirtazapine or agomelatine (minimal QT effect). If citalopram is needed, cap at 20 mg/day; ECG before start and at 2 weeks.

Mechanism

Both drugs prolong QT and are serotonergic. Citalopram weakly blocks CYP2D6, a partial amitriptyline route, so amitriptyline levels rise modestly.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antidepressants if citalopram fails: mirtazapine or agomelatine. For neuropathic pain, replace amitriptyline with gabapentin or pregabalin.

Mechanism

Additive QT prolongation. Less dangerous than citalopram with clarithromycin (azithromycin prolongs QT less), but risk persists, especially with risk factors.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In atrial fibrillation, hypokalaemia, or prior QT prolongation, alternative antibiotics (doxycycline, a cephalosporin).

Mechanism

Additive seizure threshold reduction (both drugs do this). Weak additional serotonergic risk (bupropion has minimal serotonergic activity). Citalopram itself prolongs QT.

Symptoms

Seizures (especially with prior epilepsy or eating disorders), QT prolongation on ECG, dizziness. Serotonin syndrome when other serotonergics are added.

Management

The combination is used for antidepressant augmentation (bupropion added to SSRI). Cap citalopram at 20 mg, bupropion at 300 mg/day. Avoid in prior epilepsy or eating disorders.

Mechanism

Additive QT prolongation (both prolong QT). Ciprofloxacin weakly blocks CYP1A2; citalopram is metabolised by CYP2C19, so the pharmacokinetic effect is minimal. The main risk is additive QT.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Alternative antibiotics: a cephalosporin or nitrofurantoin (no QT effect). If ciprofloxacin is needed: ECG before start, maintain potassium and magnesium, keep citalopram at 20 mg.

Mechanism

Clarithromycin prolongs QT and is a potent CYP3A4 inhibitor. Citalopram is metabolised by CYP3A4 only minorly, so pharmacokinetic effect is small, but QT prolongation adds up.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antibiotics: azithromycin (weaker QT effect) or doxycycline/a cephalosporin. If clarithromycin is needed: do not increase citalopram; ECG before start and every 3 days during therapy.

Mechanism

Dronedarone prolongs QT (FDA Multaq carries a boxed warning). Citalopram does so dose-dependently. Additive torsades de pointes risk.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine. Alternative antiarrhythmic: a beta-blocker for rate control.

Mechanism

SSRI + SNRI – serotonergic load rises, serotonin syndrome risk. Duloxetine also prolongs QT at high doses, summing with citalopram's QT effect.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is not prescribed. When switching antidepressants, allow a 2-week washout. Alternative monotherapy: mirtazapine or agomelatine.

Mechanism

Escitalopram is the S-enantiomer of citalopram. Combined use is a doubling of the same drug without therapeutic purpose. Additive QT prolongation and serotonin syndrome risk.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

The combination is not prescribed. Choose one: escitalopram (more selective and active) is preferable. When switching, allow a 1-week washout.

Mechanism

Esomeprazole is the S-isomer of omeprazole, the same CYP2C19 inhibitor. Citalopram plasma levels rise by 40–50%. The FDA caps citalopram at 20 mg/day with CYP2C19 inhibitors.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Cap citalopram at 20 mg/day when combined. Alternative PPIs without CYP2C19 effect: pantoprazole or rabeprazole.

Mechanism

Dual risk. Fluconazole blocks CYP2C19 (strongly) and CYP3A4 (moderately) and prolongs QT itself. Citalopram plasma levels rise, plus additive QT prolongation.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Cap citalopram at 20 mg/day when combined. ECG before start and every 3 days during therapy. Alternative antifungals: echinocandins for systemic mycoses or terbinafine for dermatophytosis.

Mechanism

Two SSRIs simultaneously. Fluoxetine is a potent CYP2D6 inhibitor and weak CYP2C19 inhibitor, so citalopram levels may rise. Additive serotonin syndrome and QT prolongation risk.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is not prescribed. When switching from fluoxetine to citalopram, allow at least 5 weeks of washout (due to norfluoxetine). From citalopram to fluoxetine, 2 weeks suffice.

Mechanism

Two SSRIs simultaneously – serotonin syndrome without therapeutic purpose. Fluvoxamine also blocks CYP1A2 (a minor citalopram route).

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is not prescribed. When switching SSRIs, allow a 2-week washout. Alternative monotherapy: mirtazapine or agomelatine.

Mechanism

Additive QT prolongation. Haloperidol is one of the strongest QT prolongers among typical antipsychotics, especially parenterally. Citalopram does so dose-dependently.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants: mirtazapine or agomelatine.

Mechanism

Ketoconazole is a potent CYP3A4 inhibitor. Effect on citalopram is moderate (CYP3A4 is a minor route), but ketoconazole itself prolongs QT, so additive torsades de pointes risk persists.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed: ECG before start and at day 3 of therapy.

Mechanism

Additive serotonergic effect of SSRIs and lithium (lithium enhances synaptic serotonergic transmission). SSRI-related lithium level rises have also been reported.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is possible with careful monitoring. Check lithium level at 2 and 4 weeks after starting citalopram. If agitation, tremor, or diarrhoea appears, reassess lithium level and serotonergic status.

Mechanism

Mirtazapine increases serotonergic transmission via α2-adrenergic blockade and blocks 5-HT2A/2C. Serotonin syndrome is rare with citalopram but possible at high doses. Citalopram itself prolongs QT.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is used for antidepressant augmentation. Cap citalopram at 20 mg and mirtazapine at 30 mg/day. Monitor blood pressure, pulse, and mental status in the early weeks.

Mechanism

Omeprazole is a potent CYP2C19 inhibitor, the main citalopram metabolic route. Citalopram plasma levels rise by 40–50%. The FDA capped citalopram at 20 mg/day with CYP2C19 inhibitors in 2012 because of dose-dependent QT risk.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Cap citalopram at 20 mg/day when combined. Alternative PPIs without CYP2C19 effect: pantoprazole or rabeprazole.

Mechanism

Quetiapine prolongs QT at high doses. Citalopram does so dose-dependently. Quetiapine depends on CYP3A4, citalopram on CYP2C19 and CYP3A4, so direct pharmacokinetic interaction is absent. The main risk is additive QT.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

The combination is acceptable at low doses of both (citalopram ≤20 mg, quetiapine ≤300 mg). ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.

Mechanism

Two SSRIs simultaneously – serotonin syndrome without therapeutic rationale. Citalopram itself prolongs QT.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.

Management

The combination is not prescribed. When switching SSRIs, allow a 1-week washout. For augmentation: mirtazapine or agomelatine (different class).

Mechanism

Tacrolimus prolongs the QT interval, especially with hypomagnesaemia (common on calcineurin inhibitors). Citalopram also prolongs QT dose-dependently (FDA caps at 40 mg/day). Effects add up.

Symptoms

QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk rises with hypokalaemia and hypomagnesaemia.

Management

Avoid the combination. Alternative antidepressants with minimal QT effect post-transplant: mirtazapine, agomelatine, sertraline (up to 100 mg/day). ECG before start and at 2 weeks; maintain potassium and magnesium.

Mechanism

Dual risk. Citalopram (SSRI) raises synaptic serotonin and prolongs QT. Tramadol blocks serotonin and norepinephrine reuptake and lowers seizure threshold. Effects add up.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

Avoid the combination. For analgesia on citalopram, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.

Mechanism

SSRI + SNRI – serotonin syndrome, additive QT prolongation at high venlafaxine doses.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.

Management

The combination is not prescribed. When switching antidepressants, allow a 1-week washout. For augmentation, use mirtazapine or agomelatine.