Table 21. Antipsychotic Drug Interactions29,30,61–79,86.
| Interacting Medication | Mechanism | Clinical Effect | ||
| Drug interactions assessed to have major severity | ||||
| Anticholinergics | Pharmacodynamic effects Additive anticholinergic effect | Decreased antipsychotic effect | ||
| Barbiturates | Phenobarbital induces antipsychotic metabolism | Decreased antipsychotic concentrations | ||
| Beta-blockers | Synergistic pharmacologic effect; antipsychotic inhibits metabolism of propranolol; antipsychotic increases plasma concentrations | Severe hypotension | ||
| Carbamazepine | Induces antipsychotic metabolism | Up to 50% reduction in antipsychotic concentrations | ||
| Charcoal | Reduces GI absorption of antipsychotic and absorbs drug during enterohepatic circulation | May reduce antipsychotic effect or cause toxicity when used during overdose or for GI disturbances | ||
| Cigarette smoking | Induction of microsomal enzymes | Reduced plasma concentrations of antipsychotic agents | ||
| Epinephrine, norepinephrine | Antipsychotic antagonizes pressor effect | Hypotension | ||
| Ethanol | Additive CNS depression | Impaired psychomotor skills | ||
| Fluvoxamine | Fluvoxamine inhibits metabolism of haloperidol and clozapine | Increased concentrations of haloperidol and clozapine | ||
| Guanethidine | Antipsychotic antagonizes guanethidine neuronal uptake | Impaired antihypertensive effect | ||
| Lithium | Unknown | Rare reports of neurotoxicity | ||
| Meperidine | Additive CNS depression | Hypotension and sedation | ||
| Interacting Medication | Mechanism | Clinical Effect | ||
| Amphetamines, anorexiants | Decrease pharmacologic effect of amphetamine; drug-disease state interaction | Diminished weight-loss effect; amphetamines may exacerbate psychosis; treatment-refractory patients may improve | ||
| ACE inhibitors | Additive hypotensive effect | Hypotension, postural intolerance | ||
| Antacids containing aluminum | Insoluble complex in GI tract formed | Possible reduced antipsychotic effect | ||
| Antidepressants (antidepressant, nonspecific) |
Decreases metabolism of antidepressant through competitive inhibition | Increased antidepressant concentration | ||
| Benzodiazepines | Increases pharmacologic effect of benzodiazepine | Respiratory depression, stupor, hypotension | ||
| Bromocriptine | Antipsychotic antagonizes dopamine receptor stimulation | Increased prolactin | ||
| Caffeinated beverages | Form precipitate with antipsychotic solutions | Possible diminished antipsychotic effect | ||
| Cimetidine | Reduces antipsychotic absorption and inhibits clearance | Increased or decreased antipsychotic effect | ||
| Clonidine | Antipsychotic potentiates α-2-adrenergic hypotensive effect | Hypotension | ||
| Disulfiram | Impairs antipsychotic metabolism | Increased antipsychotic concentrations | ||
| Methyldopa | Unknown | Blood pressure elevations | ||
| Phenytoin | Induction of antipsychotic metabolism; increases phenytoin metabolism | Decreased antipsychotic concentrations; decreased phenytoin levels | ||
| SSRIs | Impair antipsychotic metabolism; pharmacodynamic interaction | Sudden onset of extrapyramidal symptoms | ||
| Valproic acid | Antipsychotic inhibits valproic acid metabolism | Increased valproic acid half-life and levels | ||
ACE=angiotensin-converting enzyme; GI=gastrointestinal; CNS=central nervous system SSRIs=selective serotonin reuptake inhibitors.