29.17 Dopamine Receptor Antagonists (First-Generation Antipsychotics)
977
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
Decreased antipsychotic effect
Additive anticholinergic effect
Anticholinergic toxicity
Barbiturates
Phenobarbital induces antipsychotic metabolism
Decreased antipsychotic concentrations
Carbamazepine
Induces antipsychotic metabolism
Up to 50% reduction in antipsychotic
concentrations
Charcoal
Reduces GI absorption of antipsychotic and adsorbs
drug during enterohepatic circulation
May reduce antipsychotic effect or cause
toxicity when used to treat 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 status
Fluvoxamine
Fluvoxamine inhibits metabolism of haloperidol and
clozapine
Increased concentrations of haloperidol and
clozapine
Guanethidine
Antipsychotic antagonizes guanethidine reuptake
Impaired antihypertensive effect
Lithium
Unknown
Rare reports of neurotoxicity
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
Antacids containing
aluminum
Insoluble complex formed in GI tract
Possible reduced antipsychotic effect
AD nonspecific
Decreased metabolism of AD through competitive
inhibition
Increased AD concentration
Benzodiazepines
Increased pharmacologic effect of the 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
Reduced antipsychotic absorption and clearance
Decreased antipsychotic effect
Clonidine
Antipsychotic potentiates
a
-adrenergic hypotensive
effect
Hypotension or hypertension
Disulfiram
Impairs antipsychotic metabolism
Increased antipsychotic concentrations
Methyldopa
Unknown
BP elevations
Phenytoin
Induction of antipsychotic metabolism; decreased
phenytoin metabolism
Decreased antipsychotic concentrations: increased
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
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.)
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.
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
