Drug Interactions between maprotiline and risperidone

MONITOR: Coadministration with risperidone may increase the plasma concentrations of maprotiline. The exact mechanism is unknown but may involve competitive inhibition of maprotiline metabolism, possibly via CYP450 2D6. In a case report of 3 patients treated with maprotiline (150 to 175 mg/day), addition of risperidone led to increases in maprotiline plasma levels by 40% to 60% within 10 days to several weeks. One patient gradually developed anticholinergic adverse effects, including dry mouth, constipation, blurred vision, and urinary retention, all of which attenuated with lower dosages of both drugs. Excessive anticholinergic effects can also result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Other adverse effects that may be increased with this combination include CNS depression and orthostatic hypotension.

MANAGEMENT: Pharmacologic response and maprotiline plasma levels should be monitored more closely whenever risperidone is added to or withdrawn from therapy, and the maprotiline dosage adjusted as necessary. Caution is advised when prescribing this combination, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.