Drug interactions between Paxil and Risperdal

MONITOR: The coadministration with paroxetine may increase the plasma concentrations of certain neuroleptic agents such as phenothiazines and others that are thought to be metabolized by CYP450 2D6. The mechanism is decreased neuroleptic clearance due to inhibition of the isoenzyme by paroxetine. The interaction has been studied with risperidone. In 10 patients stabilized on risperidone (4 to 8 mg/day) for schizophrenia or schizoaffective disorder, paroxetine (20 mg/day for 4 weeks) increased the mean plasma concentration of risperidone by 388% after two weeks and 453% after four weeks compared to baseline. After four weeks, the sum of the concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, increased significantly (45% over baseline), as was the mean plasma risperidone to 9-hydroxyrisperidone ratio. One patient developed Parkinsonian symptoms in the second week. In this patient, total plasma levels of risperidone and its active metabolite increased by 62% during paroxetine coadministration. The interaction has also been cited in a clinical study with perphenazine and a case report of a 29-year-old man treated with trifluoperazine who developed severe extrapyramidal adverse effects following addition of paroxetine. The symptoms resolved after withdrawal of medication and did not recur following reinstitution of trifluoperazine.

MANAGEMENT: Caution is advised if neuroleptic agents such as phenothiazines, haloperidol, risperidone, or zuclopenthixol must be used concomitantly with paroxetine. Pharmacologic response and plasma neuroleptic levels should be monitored more closely whenever paroxetine is added to or withdrawn from therapy, and the neuroleptic dosage adjusted as necessary. Patients should be monitored for the development of extrapyramidal symptoms (e.g., tremor, shuffling gait, drooling, mask-like face, tongue stiffness, muscle spasms or rigidity, involuntary movements) and changes in mental status.