Citalopram

Mechanism

Amiodarone is a class III antiarrhythmic, and its SmPC describes QT prolongation as a direct pharmacological effect of the drug. Class IA and III antiarrhythmics open the list of examples in both SSRI labels. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Amiodarone washes out over weeks, so spacing the two drugs apart does not work: QT stays prolonged long after the last dose. Before any decision, potassium and magnesium are corrected and an ECG with QTc is recorded.

Mechanism

Amitriptyline is a tricyclic antidepressant, and tricyclics are named among QT-prolonging drugs in both SSRI labels. Its own SmPC calls for caution with SSRIs because of serotonin syndrome. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions. The kinetic part is weaker here than with escitalopram: the SmPC calls citalopram a weak CYP2D6 inhibitor and notes that with substrates of that enzyme, amitriptyline included, no clinically meaningful changes were seen. QT and serotonin remain the drivers.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope, with torsade at the far end. Serotonin syndrome is tracked separately: agitation, confusion, tremor, myoclonus, sweating, hyperthermia. Arrhythmia risk is higher with hypokalaemia, hypomagnesaemia and bradycardia.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Beyond QT there is kinetics: amitriptyline runs through CYP2D6 and CYP2C19, and inhibiting either path raises its levels. For such combinations the amitriptyline label describes plasma level monitoring and dose adjustment.

Mechanism

Azithromycin is a macrolide, and its SmPC records prolonged cardiac repolarisation and QT with a risk of ventricular arrhythmia and torsade. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A short azithromycin course tempts one to leave things as they are, but the SSRI ban carries no exception for course length. Potassium, magnesium and QTc are checked before the start, and the antibiotic is swapped if they are off.

Mechanism

Ciprofloxacin is a fluoroquinolone, and its SmPC lists concomitant QT-prolonging drugs among the risk factors that call for caution. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Ciprofloxacin's cardiac effect is weaker than moxifloxacin's, yet the SSRI ban makes no exception for weaker effects. Urinary tract infections have replacements outside the fluoroquinolones.

Mechanism

Clarithromycin is a macrolide, and its own SmPC puts concomitant drugs associated with QT prolongation among its contraindications. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions. Clarithromycin inhibits CYP3A4, a minor metabolic path for citalopram, so a small rise in antidepressant levels comes on top of the additive QT.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Both labels carry the ban, so the antibiotic course is planned not to overlap with the antidepressant. H. pylori eradication and respiratory infections have macrolide-free regimens.

Mechanism

Dronedarone is a class III antiarrhythmic. Its SmPC describes a QTc increase of about 10 ms as its own effect and separately contraindicates torsade-inducing drugs alongside it. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. The ban runs both ways: the dronedarone label contraindicates torsade-inducing drugs, the SSRI label contraindicates QT-prolonging ones. Before either drug starts, potassium, magnesium and QTc are checked.

Mechanism

Intravenous erythromycin is named outright in both SSRI labels, and its own SmPC forbids use in patients with a history of QT prolongation or with hypokalaemia and hypomagnesaemia. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. The SSRI labels name the intravenous form, but oral erythromycin works through the same hERG blockade, and the dronedarone label, for one, bans the oral macrolide. The antibiotic is picked outside this group.

Mechanism

Escitalopram is the S-enantiomer of citalopram, the same molecule in purified form. Taking both stacks the dose of one substance, and with it the dose-dependent QT prolongation. The escitalopram SmPC contraindicates any QT-prolonging drug alongside it: the ban is written broadly, and the classes in brackets are examples.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope, with torsade at the far end. Serotonin syndrome is tracked separately: agitation, confusion, tremor, myoclonus, sweating, hyperthermia. Arrhythmia risk is higher with hypokalaemia, hypomagnesaemia and bradycardia.

Management

The pair sits in the escitalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. This pair in a prescription list means an error rather than a regimen: usually the same drug has been written under two brand names. One is kept, and no washout is needed when switching between them, since the substance is the same.

Mechanism

Fluconazole prolongs QT by directly blocking the Ikr potassium current, in the words of its SmPC, which also contraindicates QT-prolonging drugs metabolised through CYP3A4. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions. Kinetics adds a second layer: fluconazole inhibits CYP2C19, the main path for citalopram. The citalopram SmPC caps the dose at 20 mg a day in poor CYP2C19 metabolisers, and an enzyme inhibitor turns any patient into one.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. In superficial mycoses topical forms give almost no systemic absorption and the question disappears. In systemic mycosis an echinocandin is chosen: caspofungin, micafungin or anidulafungin. Swapping fluconazole for another azole does not solve the problem, because the voriconazole and posaconazole SmPCs also describe QTc prolongation. If the pair continues anyway, potassium, magnesium and QTc stay under watch.

Mechanism

Haloperidol is a typical antipsychotic, and its own SmPC outright forbids giving it with QTc-prolonging drugs. The SSRI labels name it as their antipsychotic example. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. The ban stands on both sides, and parenteral haloperidol carries more risk than oral. If an antipsychotic is needed, the question is settled on that side, not by trimming the antidepressant dose.

Mechanism

Levofloxacin is a fluoroquinolone, and its SmPC devotes a section to caution in patients already taking QT-prolonging drugs. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. The fluoroquinolone label says caution, the SSRI label says contraindication, and the stricter document sets the severity. For a community infection the antibiotic is picked outside this group.

Mechanism

Citalopram (SSRI) raises synaptic serotonin. Linezolid reversibly inhibits MAO. Co-administration sharply amplifies serotonergic transmission. The FDA carries a boxed warning.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.

Management

The combination is not prescribed. Stop citalopram at least 2 weeks before linezolid. Alternative antibiotics: vancomycin, daptomycin, ceftaroline by susceptibility.

Mechanism

Methadone prolongs QT, and its SmPC ties torsade mainly to doses above 100 mg a day. The same label warns about serotonin syndrome with SSRIs. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope, with torsade at the far end. Serotonin syndrome is tracked separately: agitation, confusion, tremor, myoclonus, sweating, hyperthermia. Arrhythmia risk is higher with hypokalaemia, hypomagnesaemia and bradycardia.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Opioid substitution is not interrupted for an antidepressant, so the question is settled on the antidepressant side. If the pair is already running, an ECG with QTc is taken before the start and at every methadone dose increase, with potassium and magnesium kept normal.

Mechanism

Moxifloxacin is named outright in both SSRI labels. Its own SmPC forbids concomitant use with other QT-prolonging drugs and quotes the measured QTc increase of about 6 ms. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Moxifloxacin is the most cardiac of the fluoroquinolones, and respiratory infections have replacements outside that group. This pair is resolved on the antibiotic side.

Mechanism

Ondansetron prolongs QT in a dose-dependent way, as its SmPC states, and the same label describes serotonin syndrome when it is given with SSRIs. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope, with torsade at the far end. Serotonin syndrome is tracked separately: agitation, confusion, tremor, myoclonus, sweating, hyperthermia. Arrhythmia risk is higher with hypokalaemia, hypomagnesaemia and bradycardia.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A single intravenous dose is capped at 16 mg in the label precisely because of QT. Post-operative and chemotherapy nausea have antiemetics outside the setron group, and on citalopram those are the ones chosen.

Mechanism

Citalopram is an SSRI. Combined with phenelzine causes serotonin syndrome. FDA Nardil Section 4 strict contraindication.

Symptoms

Hyperthermia, myoclonus, tachycardia, hypertension.

Management

Combination contraindicated. 2-week washout.

Mechanism

Both drugs prolong the QT interval, and both labels assume the effects add up. Both labels cite the same study: in subjects on citalopram 40 mg once daily for 11 days, a single 2 mg dose of pimozide increased QTc by a mean of about 10 ms compared with pimozide alone. The labels differ on pharmacokinetics. The pimozide label states that citalopram did not change pimozide AUC or Cmax; the Spanish citalopram label reports a rise that was not consistent through the study. The pimozide label calls the mechanism of this pharmacodynamic interaction unknown.

Symptoms

QT prolongation itself causes no symptoms and shows only on the ECG. The danger is ventricular arrhythmia, above all torsade de pointes. Both labels report such cases, and the pimozide label also reports ventricular tachycardia, ventricular fibrillation and sudden death, including at therapeutic doses. Arrhythmia presents as dizziness, palpitations or syncope (citalopram label, FDA). The citalopram label reports torsade de pointes mainly in women and in patients with hypokalaemia, a pre-existing long QT interval or heart disease.

Management

The combination is contraindicated in all four labels. The Spanish pimozide label names citalopram in its contraindications (pimozide label, AEMPS). The Spanish citalopram label bans concomitant use in a dedicated paragraph because the interaction appeared at a low pimozide dose (citalopram label). The US labels of both drugs repeat the ban (citalopram and pimozide labels, FDA). Do not give citalopram to a patient on pimozide who needs an antidepressant; if a patient already takes both, stop one of the drugs. The ban also covers other serotonin reuptake inhibitors, named as sertraline, paroxetine and escitalopram (pimozide label), and any drug that prolongs the QT interval (pimozide and citalopram labels). Choose the replacement outside those lists. For any pimozide treatment, take an ECG before the start and repeat it during treatment, correct potassium and magnesium, and stop pimozide if QT or QTc exceeds 500 ms (pimozide label).

Mechanism

Quetiapine is an atypical antipsychotic, and antipsychotics appear among the QT examples in both SSRI labels. Post-marketing reports describe QT prolongation at therapeutic doses, and the quetiapine SmPC calls for caution with any QT-prolonging drug. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Quetiapine is often added to an antidepressant in resistant depression, which is exactly why this pair deserves attention up front: the SSRI label files antipsychotics under contraindicated combinations. If the regimen is assembled anyway, an ECG with QTc is taken before the start and two weeks in, with potassium and magnesium kept normal.

Mechanism

Sotalol is a class III antiarrhythmic, and its SmPC contraindicates concomitant QT-prolonging drugs. That list names SSRIs explicitly, citalopram and escitalopram among them. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A rare case where both labels name each other outright: sotalol lists SSRIs by name, the citalopram label bans class III antiarrhythmics. Sotalol, meanwhile, is prescribed for vital indications more often than the antidepressant is.

Mechanism

Tacrolimus can prolong QT and cause torsade, in the words of its SmPC, which also calls for caution in patients already on QT-prolonging drugs. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Tacrolimus is not withdrawn after transplantation, so the antidepressant is chosen around it rather than the other way round. With QT-prolonging co-medication the tacrolimus label explicitly requires ECG monitoring and blood level control.

Mechanism

Citalopram, like other selective serotonin reuptake inhibitors (SSRIs), blocks serotonin uptake into platelets, and platelets need serotonin to stop bleeding. Aspirin irreversibly blocks platelet cyclooxygenase and injures the stomach lining. Together they raise the risk of bleeding, above all from the upper gastrointestinal tract (aspirin and citalopram labels).

Symptoms

Gum bleeding, epistaxis, bruising without trauma. Severe cases: GI bleeding.

Management

Aspirin SmPCs, including those for 100 mg products, advise avoiding selective serotonin reuptake inhibitors (SSRIs) with aspirin whenever possible because of the bleeding risk, especially from the upper gastrointestinal tract (aspirin 100 mg SmPCs). If the combination is needed, use it with caution (aspirin and citalopram SmPCs) and explain the signs of bleeding to the patient in advance: black stools, vomiting blood, low blood pressure, cold sweat, abdominal pain, dizziness. If they appear, the patient stops treatment and sees a doctor at once (aspirin 100 mg SmPC). The US Food and Drug Administration (FDA) also asks prescribers to inform patients about the higher bleeding risk when citalopram is combined with aspirin and other antiplatelet drugs (citalopram FDA label).

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

Start bupropion at a low dose and increase it gradually (FDA label). Bupropion raises citalopram exposure: AUC by 40% and Cmax by 30%. So when bupropion is added to citalopram, the Spanish bupropion SmPC calls for reviewing whether the citalopram dose should be lowered. If bupropion is prescribed for smoking cessation to someone taking an antidepressant, the Zyntabac SmPC advises considering a ceiling of 150 mg/day. Bupropion is contraindicated with a history of seizures, bulimia or anorexia nervosa.

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

Esomeprazole is the S-isomer of omeprazole and the same CYP2C19 inhibitor; CYP2C19 handles about 38% of citalopram metabolism. In therapeutic drug monitoring data, citalopram serum levels were about a third higher with esomeprazole (+33%). The FDA caps citalopram at 20 mg/day with CYP2C19 inhibitors.

Symptoms

QT prolongation on the ECG. Clinically: dizziness, palpitations, syncope. Severe cases progress to torsade de pointes. The risk is higher with bradycardia, hypokalaemia, hypomagnesaemia, congenital long QT syndrome, recent myocardial infarction and decompensated heart failure.

Management

The pair is not banned, but the citalopram dose is capped: with esomeprazole or another CYP2C19 inhibitor, no more than 20 mg/day (US Food and Drug Administration (FDA) citalopram label). The esomeprazole SmPC names citalopram among drugs that may need a lower dose, especially when esomeprazole is taken on demand, and the Spanish citalopram SmPC asks for caution with this combination. Potassium and magnesium are corrected before citalopram is started, and in patients at risk of electrolyte disturbances they are checked at baseline and periodically (citalopram labels). If signs of arrhythmia appear, citalopram is stopped and an electrocardiogram (ECG) is done (citalopram SmPC).

Mechanism

Fluoxetine belongs to the same class, and its SmPC warns about serotonergic reactions when it is combined with other serotonergic agents. Two SSRIs bring no added benefit, while the serotonergic effect stacks.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

Stopping fluoxetine does not end the interaction at once: its SmPC gives a half-life of 4-6 days, and 4-16 days for the active metabolite norfluoxetine. A switch is measured in weeks, and the same label requires this to be taken into account when changing antidepressant.

Mechanism

Fluvoxamine strongly inhibits CYP2C19 and, to a lesser degree, CYP3A4 and CYP2D6 (fluvoxamine SmPC), and citalopram is cleared by all three: about 38% via CYP2C19, 31% via CYP3A4 and 31% via CYP2D6 (citalopram SmPC). Citalopram levels rise, and its QT prolongation is dose-dependent, so the US Food and Drug Administration (FDA) caps citalopram at 20 mg/day with any CYP2C19 inhibitor. Both drugs are serotonergic, and the fluvoxamine SmPC warns that the combination can lead to a life-threatening serotonin syndrome.

Symptoms

Serotonin syndrome: agitation, hallucinations, delirium up to coma; tachycardia, labile blood pressure, dizziness, sweating, hyperthermia; tremor, rigidity, myoclonus, hyperreflexia, incoordination; seizures; nausea, vomiting, diarrhoea. Higher citalopram levels prolong the QT interval: dizziness, palpitations, syncope and, in severe cases, torsade de pointes.

Management

The labels do not ban the pair, but it is used with limits. While the patient takes fluvoxamine, the citalopram dose stays at or below 20 mg/day (US Food and Drug Administration (FDA) citalopram label). The fluvoxamine SmPC requires such drugs to be started at the lower end of the dose range with monitoring for adverse effects, and the Spanish citalopram SmPC asks for caution with fluvoxamine. Potassium and magnesium are corrected before citalopram is started (citalopram SmPC). If serotonin syndrome develops, both drugs are stopped at once and supportive treatment is started (citalopram FDA label). If signs of arrhythmia appear, citalopram is stopped and an electrocardiogram (ECG) is done (citalopram SmPC).

Mechanism

SSRI + NSAID – GI bleeding.

Symptoms

GI bleeding.

Management

PPI or paracetamol.

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

Lithium enhances serotonergic transmission, and its SmPC names SSRIs among the drugs that can bring on serotonin syndrome. The second layer is cardiac: the same label advises avoiding lithium in patients already taking QT-prolonging drugs, while the citalopram label files such combinations under contraindications.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

Lithium is added to an antidepressant on purpose in treatment-resistant depression, and the NICE guideline includes this strategy. So the combination is not forbidden, but it needs monitoring. Before lithium is started, renal, cardiac and thyroid function are assessed (lithium label), and potassium and magnesium are corrected before citalopram is started (citalopram label). Lithium levels are checked 1–2 times a week at the start of treatment until they are stable, then every 1–2 months (lithium label). An extra level is taken after vomiting, diarrhoea, dehydration or an infection, and after starting a diuretic, an ACE inhibitor, an angiotensin receptor blocker or an NSAID. In people with cardiovascular disease or high cardiovascular risk, NICE advises considering ECG monitoring. If signs of arrhythmia appear, such as palpitations, skipped beats or fainting, citalopram is stopped and an ECG is done (citalopram label).

Mechanism

Mirtazapine acts on serotonergic transmission through a different mechanism, and its SmPC names SSRIs among the drugs that can bring on serotonin syndrome. Reports of QT prolongation and torsade with mirtazapine come mainly from overdose and from patients with other risk factors.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

The mirtazapine label does not forbid the combination. It asks for watching serotonergic symptoms in the first days after the start and after every dose increase. An ECG with QTc is for those who already carry cardiac risk factors.

Mechanism

Omeprazole inhibits CYP2C19, which handles about 38% of citalopram metabolism. In therapeutic drug monitoring data, citalopram serum levels were about a third higher with omeprazole (+35%). The FDA caps citalopram at 20 mg/day with CYP2C19 inhibitors because QT prolongation is dose-dependent.

Symptoms

QT prolongation on the ECG. Clinically: dizziness, palpitations, syncope. Severe cases progress to torsade de pointes. The risk is higher with bradycardia, hypokalaemia, hypomagnesaemia, congenital long QT syndrome, recent myocardial infarction and decompensated heart failure.

Management

The pair is not banned, but the citalopram dose is capped: with omeprazole or another CYP2C19 inhibitor, no more than 20 mg/day (US Food and Drug Administration (FDA) citalopram label). The Spanish citalopram SmPC asks for caution with omeprazole, and the omeprazole SmPC warns that it can raise levels of drugs cleared through CYP2C19. Potassium and magnesium are corrected before citalopram is started, and in patients at risk of electrolyte disturbances they are checked at baseline and periodically (citalopram labels). If signs of arrhythmia appear, citalopram is stopped and an electrocardiogram (ECG) is done (citalopram SmPC).

Mechanism

Sertraline belongs to the same class. Its SmPC states outright that the risk of serotonin syndrome and neuroleptic malignant syndrome rises with concomitant serotonergic drugs, other antidepressants included. Post-marketing reports also describe QTc prolongation with torsade, mostly in patients with other risk factors.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

Two SSRIs together add no effect while their risks stack. Most often the pair is the trace of an unfinished switch, and one drug stays in the regimen.

Mechanism

Tramadol inhibits serotonin reuptake, and so does citalopram, so together they raise the risk of serotonin syndrome. Both drugs lower the seizure threshold. Pharmacokinetics play little part: citalopram is only a weak CYP2D6 inhibitor, the enzyme that forms tramadol's active metabolite.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

The Spanish citalopram label states that citalopram should not be used with serotonergic drugs, opioids and tramadol included. For pain relief in a patient taking citalopram, choose paracetamol. If tramadol is still needed, warn the patient about serotonin syndrome and watch for agitation, tremor, myoclonus, sweating and fever during the first days and after each dose increase. Stop both drugs if serotonin syndrome is suspected. Keep tramadol at or below 400 mg a day per the label, and use it in patients with epilepsy only when the circumstances require it.

Mechanism

Venlafaxine blocks serotonin and noradrenaline reuptake, so the serotonergic effect stacks with an SSRI. Its SmPC bans only irreversible MAOIs, describing other serotonergic combinations as ones to be watched. QTc prolongation and torsade were recorded post-marketing, mostly in overdose.

Symptoms

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

Management

The pair usually appears while switching from one antidepressant to another, and the overlap is kept short. Agitation, tremor, sweating and hyperthermia in the first days after a dose change are the warning signs.

Mechanism

Additive CNS depression. Citalopram does not inhibit CYP3A4 — no pharmacokinetic interaction with alprazolam. The effect adds up at GABA and serotonin receptors.

Symptoms

Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk.

Management

On starting the combination, begin alprazolam at the minimum dose. In older patients, cap citalopram at 20 mg/day (QT risk) and alprazolam at 0.5 mg/day. For long-term anxiety treatment, plan CBT as the core therapy with gradual benzodiazepine taper.

Mechanism

Citalopram, like other SSRIs, impairs primary haemostasis by inhibiting platelet serotonin reuptake. Additively with apixaban, bleeding risk rises, mainly GI.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.

Management

The combination is acceptable. In patients over 65 or with prior peptic ulcer: pantoprazole 20 mg/day. Citalopram also prolongs QT, so cap older patients at 20 mg/day.