Antidepressants and lithium
Tricyclic antidepressants + fluoxetine, paroxetine or sertraline ! increased pharmacological and toxicological effects of the tricyclic due to decreased hepatic metabolism. This is a potentially hazardous combination.
Tricyclic antidepressants + MAOIs ! stroke, hyperpyrexia and convulsions can occur. Potentially a hazardous combination.
Tricyclic antidepressants + directly acting sympathomimetic amines (e.g. noradrenaline, adrenaline) ! hypertension and arrhythmias due to enhancement of the sympathomimetic effects.
Tricyclic antidepressants + phenothiazines ! additive anticholinergic effects that can cause psychosis and agitation.
Tricyclic antidepressants + phenytoin ! reduction in phenytoin metabolism can increase phenytoin toxicity.
Tricyclic antidepressants + warfarin ! increased bleeding due to reduced metabolism of warfarin.
Tricyclic antidepressants + barbiturates, carbamazepine ! increased metabolism of the tricyclic due to enzyme induction leading to a reduced antidepressant effect.
Irreversible MAOIs + tricyclic antidepressants ! as above, plus hypertension.
Irreversible MAOIs + SSRIs ! serotonin syndrome (see p. 171).
Irreversible MAOIs + pethidine ! severe excitation, hypertension and coma that can lead to death. This is a very hazardous combination.
Irreversible MAOIs + oral hypoglycaemic drugs ! increased hypoglycaemic effect.
Lithium + diuretics ! reduced lithium clearance and raised plasma lithium concentration thereby enhancing toxicity.
Lithium + non-steroidal anti-inflammatory drugs ! decreased lithium clearance and raised plasma lithium concentration thereby enhancing toxicity.
Lithium + typical neuroleptics ! increased extrapyramidal side effects and possibly increased neurotoxicity.
Lithium + antiarrhythmic drugs ! potentiation of the cardiac conduction effects of the antiarrhythmic drugs.
Lithium + carbamazepine, valproate ! enhanced therapeutic effects of lithium.
Lithium + tetracycline antibiotics ! enhanced toxicity of lithium due to increased lithium absorption and impaired excretion.
Lithium + succinylcholine ! prolonged muscle paralysis; synergic effect of the drugs at the neuromuscular junction.
Venlafaxine + cimetidine ! increased plasma venlafaxine concentration due to impaired metabolism. ?Increased side effects.
Venlafaxine + MAOIs ! serotonin syndrome likely.
Mirtazepine + diazepam, alcohol ! increased sedation and possible cognitive impairment.
Nefazodone + triazolam ! increased effect of triazolam due to impaired hepatic metabolism.
Nefazodone + digoxin ! increased plasma digoxin concentration due to impaired metabolism.
Nefazodone + morphine ! increased analgesic effect of morphine due to impaired metabolism.
Trazodone + CNS depressants ! enhanced sedation.
Trazodone + SSRIs, buspirone, MAOIs ! serotonin syndrome possible due to additive serotonergic effects.
Bupropion + MAOIs ! hypertensive crisis.
Bupropion + L-dopa ! enhanced therapeutic and toxic effects of L-dopa; can cause hallucinations, confusion and dyskinesias. Changes due to additive dopaminergic effects.
Bupropion + fluoxetine (?other SSRIs) ! delirium and possible grand-mal seizures. Bupropion + lithium ! seizures can occur.
Bupropion + valproate ! increased plasma valproate concentrations.
Benzodiazepines + cimetidine, disulfiram ! inhibition of benzodiazepine metabolism causing increased sedation.
Benzodiazepines + antacids ! reduced absorption of benzodiazepines leading to reduced therapeutic effects.
Benzodiazepines + digoxin ! reduced metabolism of digoxin leading to prolonged action and increased toxicity.
Benzodiazepines + smoking, rifampicin ! due to enzyme induction, plasma concentration of the benzodiazepine is reduced.
Buspirone + MAOIs ! hypertension due to increased serotonergic effect.
Buspirone + haloperidol ! elevated plasma haloperidol concentration leading to increased side effects.
Buspirone + cyclosporin A ! elevated cyclosporin concentrations leading to renal toxicity.
Carbamazepine + phenytoin, tricyclic antidepressants, typical neuroleptics, valproate, clonazepam, warfarin, nefazodone and propoxyphene ! reduced plasma concentration of carbamazepine due to increased metabolism.
Carbamazepine + antiarrhythmic drugs ! additive effect on cardiac conduction time can cause increased cardiotoxicity.
Carbamazepine + erythromycin ! increased toxicity of carbamazepine due to reduced metabolism.
Carbamazepine + oral contraceptives ! reduced contraceptive efficacy due to enhanced hepatic metabolism.
Phenytoin + oral anticoagulants ! decreased anticoagulant effect due to increased hepatic metabolism.
Barbiturates + phenytoin ! decreased anticonvulsant effect due to hepatic enzyme induction; enhanced phenytoin toxicity on abruptly stopping barbiturate.
Barbiturates + oral anticoagulants ! decreased anticoagulant effects due to hepatic enzyme induction.
All antipsychotics + L-dopa ! decreased therapeutic effect of L-dopa due to dopamine receptor blockade.
All antipsychotics + anticholinergic drugs ! decreased absorption resulting in decreased plasma concentrations.
Phenothiazine neuroleptics (e.g. chlorpromazine, thioridazine) + vasodilators and antihypertensive drugs ! increased hypotensive effects due to increased peripheral vasodilation.
Atypical antipsychotics: interactions with the cytochrome P450 system (see p. 89).
Cyt 1A2 metabolizes clozapine: common substrates - amitriptyline, clomipramine, propranolol, theophylline, warfarin, caffeine. Common inhibitors - fluvoxamine, paroxetine.
Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine: common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine.
Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine: common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole.
Summary of some amine-containing foods which could interact with MAOIs, particularly irreversible inhibitors (e.g. phenelzine, isocarboxazid, tranycypromine, selegiline)
Cheeses, particularly any type of ripe cheese
Broad beans (fava beans)
Beef, chicken or other types of liver
Any fermented products, e.g. red wine, beers (including non-alcoholic beers) Food containing monosodium glutamate
Note: This list is only intended as a brief guideline and is based largely on the types of food commonly available in Europe.
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