Kaplan + Sadock's Synopsis of Psychiatry, 11e

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29.17 Dopamine Receptor Antagonists (First-Generation Antipsychotics)

Table 29.17-4 Antipsychotic Drug Interactions

Interacting Medication

Mechanism

Clinical Effect

Drug interactions assessed to have major severity b -Adrenergic receptor antagonists

Synergistic pharmacologic effect; antipsychotic inhibits metabolism of propranolol; antipsychotic increases plasma concentrations

Severe hypotension

Anticholinergics

Pharmacodynamic effects Additive anticholinergic effect

Decreased antipsychotic effect

Anticholinergic toxicity

Barbiturates

Phenobarbital induces antipsychotic metabolism

Decreased antipsychotic concentrations Up to 50% reduction in antipsychotic concentrations May reduce antipsychotic effect or cause toxicity when used to treat overdose or for GI disturbances Reduced plasma concentrations of antipsychotic agents

Carbamazepine

Induces antipsychotic metabolism

Charcoal

Reduces GI absorption of antipsychotic and adsorbs drug during enterohepatic circulation

Cigarette smoking

Induction of microsomal enzymes

Epinephrine,

Antipsychotic antagonizes pressor effect

Hypotension

norepinephrine

Ethanol

Additive CNS depression

Impaired psychomotor status

Fluvoxamine

Fluvoxamine inhibits metabolism of haloperidol and clozapine Antipsychotic antagonizes guanethidine reuptake

Increased concentrations of haloperidol and clozapine

Guanethidine

Impaired antihypertensive effect Rare reports of neurotoxicity

Lithium

Unknown

Meperidine

Additive CNS depression

Hypotension and sedation

Drug interactions assessed to have minor or moderate severity Amphetamines, anorexiants

Decreased pharmacologic effect of amphetamine

Diminished weight loss effect; amphetamines may exacerbate psychosis

ACEIs

Additive hypotensive crisis

Hypotension, postural intolerance Possible reduced antipsychotic effect

Antacids containing aluminum

Insoluble complex formed in GI tract

AD nonspecific

Decreased metabolism of AD through competitive inhibition

Increased AD concentration

Benzodiazepines Bromocriptine

Increased pharmacologic effect of the benzodiazepine Respiratory depression, stupor, hypotension

Antipsychotic antagonizes dopamine receptor stimulation

Increased prolactin

Caffeinated beverages Form precipitate with antipsychotic solutions

Possible diminished antipsychotic effect

Cimetidine Clonidine

Reduced antipsychotic absorption and clearance Antipsychotic potentiates a -adrenergic hypotensive effect

Decreased antipsychotic effect Hypotension or hypertension

Disulfiram Methyldopa Phenytoin

Impairs antipsychotic metabolism

Increased antipsychotic concentrations

Unknown

BP elevations

Induction of antipsychotic metabolism; decreased phenytoin metabolism Impair antipsychotic metabolism; pharmacodynamic interaction Antipsychotic inhibits valproic acid metabolism

Decreased antipsychotic concentrations: increased phenytoin levels Sudden onset of extrapyramidal symptoms

SSRIs

Valproic acid

Increased valproic acid half-life and levels

ACEI, angiotensin-converting enzyme inhibitor; AD, antidepressant; BP, blood pressure; CNS, central nervous system; GI, gastrointestinal; SSRI, selective serotonin reuptake inhibitor. (From Ereshosky L, Overman GP, Karp JK. Current psychotropic dosing and monitoring guidelines. Prim Psychiatry , 1996, 3:21, with permission.)

Typical antipsychotics may inhibit the hypotensive effects of a -methyldopa (Aldomet). Conversely, typical antipsychotics may have an additive effect on some hypotensive drugs. Anti- psychotic drugs have a variable effect on the hypotensive effects of clonidine. Propranolol (Inderal) coadministration increases the blood concentrations of both drugs. The DRAs potentiate the CNS-depressant effects of the sed- atives, antihistamines, opiates, opioids, and alcohol, particu- larly in persons with impaired respiratory status. When these

Phenothiazines, especially thioridazine, may decrease the metabolism of and cause toxic concentrations of phenytoin. Barbiturates may increase the metabolism of DRAs. Tricyclic drugs and selective serotonin reuptake inhibitors (SSRIs) that inhibit CYP2D6—paroxetine (Paxil), fluoxetine (Prozac), and fluvoxamine (Luvox)—interact with DRAs, resulting in increased plasma concentrations of both drugs. The anticholinergic, sedative, and hypotensive effects of the drugs may also be additive.