Risperidone carbamazepine

Mula M, Monaco F. Carbamazepine-risperidone interactions in patients with epilepsy. Clin Neuropharmacol 2002 25(2) 97-100. 

Risperidone Aripiprazole 2D6 > 3A4 2D6, 3A4 Carbamazepine and phenytoin topiramate hypericum (St. John s Wort). Paroxetine, fluoxetine, sertraline (high dose) grapefruit juice 2D6 or 3A4 substrates acting as competitive inhibitors. 

CYP3A4 TCAs, risperidone, carbamazepine, benzodiazepines, haloperidol, fluoxetine,... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Mood stabilizers (e.g., lithium, valproic acid, and carbamazepine) used as augmentation agents may improve labile affect and agitated behavior. A placebo-controlled trial supports fast symptom improvement when divalproex is combined with either olanzapine or risperidone. 

Among these choices, bnspirone is preferred if the patient is also experiencing anxiety. If the patient is depressed and agitated, a SSRI should be tried first. Second line choices inclnde carbamazepine (Tegretol) or one of the atypical antipsychot-ics—ziprasidone (Geodon), risperidone (Risperdal), olanzapine (Zyprexa), quetiap-ine (Seroquel), or aripiprazole (Abilify) can be tried. If psychotic symptoms are present, one of the atypical antipsychotics should be tried first. 

A child with attention-deficit hyperactivity disorder [ADHD] and conduct disorder is treated with 45 mg/d of methylphenidate and 2 mg/d of risperidone. A new diagnosis of complex partial seizures is made and the child is started on carbamazepine. About 10 days after the initiation of carbamazepine, the child develops withdrawal dyskinesias of mouth and tongue. After discontinuation of carbamazepine, the movements last for 1 week. 

In the Expert Consensus survey (Rush and Frances, 2000), respondents were asked to rate which classes of medication may be helpful for treating patients with severe and persistent physical aggression and those who destroyed property. The atypical antipsychotics were rated most highly, followed by anticonvulsant/ mood stabilizer. These were followed (with much lower priority) by antidepressants and beta-blockers. Among the atypical antipsychotics, risperidone was rated most highly, followed by olanzapine others had much lower ratings. Divalproex or valproic acid and carbamazepine were rated highest of the mood stabi-... 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

In a 6-week open study of risperidone (mean dosage 4.7 mg/day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3% were completely symptom-free (35). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n = 13), exacerbation of mania ( n = 5), drowsiness (n = 3), and impotence (n = 2). 

Carbamazepine induces CYP3A, and the metabolism of risperidone, which mainly involves CYP2D6, may also involve CYP3A. Carbamazepine can therefore reduce risperidone plasma concentrations (SEDA-22, 71). However, since carbamazepine alters the biotransformation of many agents, non-specific enzyme induction has been suggested for the risperidone and carbamazepine interaction (240). 

Plasma concentrations of risperidone and 9-hydroxyr-isperidone were measured in 44 patients (aged 26-63 years) treated with risperidone alone (n = 23) or co-medi-cated with carbamazepine (n = 11) (241). Carbamazepine markedly reduced the plasma concentrations of risperidone and 9-hydroxyrisperidone. 

Mean plasma concentrations of risperidone and 9-hydroxyrisperidone (5 ng/ml and 35 ng/ml) fell significantly during carbamazepine co-administration (2.5 ng/ ml and 19 ng/ml) in 11 schizophrenic patients taking risperidone 6 mg/day and then carbamazepine 400 mg/day for 1 week the changes in risperidone concentrations... 

Conversely, carbamazepine concentrations can increase when risperidone is added when risperidone 1 mg/day was added in eight patients taking carbamaze-pine (mean dose 625 mg/day) carbamazepine plasma concentrations increased from 6.7 pg/ml at baseline to 8.0 pg/ ml 2 weeks later (243). 

In a 50-year-old man with deficient CYP2D6 activity, the addition of carbamazepine to pre-existing risperidone therapy resulted in a marked reduction in the plasma concentrations of risperidone and 9-hydroxyrisperidone and an acute exacerbation of his psychosis (245). 

Lane HY, Chang WH. Risperidone-carbamazepine interactions is cytochrome P450 3A involved J Clin Psychiatry 1998 59(8) 430-1. 

Spina E, Avenoso A, Facciola G, Salemi M, Scordo MG, Giacobello T, Madia AG, Perucca E. Plasma concentrations of risperidone and 9-hydroxyrisperidone effect of comedication with carbamazepine or valproate. Ther Drug Monit 2000 22(4) 481-5. 

Ono S, Mihara K, Suzuki A, Kondo T, Yasui-Furukori N, Furukori H, de Vries R, Kaneko S. Significant pharmacokinetic interaction between risperidone and carbamazepine its relationship with CYP2D6 genotypes. Psychopharmacology (Berl) 2002 162(1) 50 1. 

Spina E, Scordo MG, Avenoso A, Perucca E. Adverse drug interaction between risperidone and carbamazepine in a patient with chronic schizophrenia and deficient CYP2D6 activity. J Clin Psychopharmacol 2001 21(l) 108-9. 

Alfaro CL, Nicolson R, Lenane M, Rapoport JL. Carbamazepine and/or fluvoxamine drug interaction with risperidone in a patient on multiple psychotropic medications. Ann Pharmacother 2000 34(l) 122-3. 

The cause of death in both cases was thought to have been acute zolpidem overdose, but it is not clear how risperidone and carbamazepine could have been excluded as possible contributors. 

ANTIPSYCHOTICS CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, PRIMIDONE 1 levels of apiprazole (all), haloperidol (carbamazepine, phenobarbital), clozapine, quetiapine, sertindole (carbamazepine, phenytoin), risperidone and olanzapine (carbamazepine) Induction of metabolism Watch for poor response to these antipsychotics, and consider increasing the dose... 

Co-administration with carbamazepine may decrease plasma levels of risperidone > Co-administration with fluoxetine and paroxetine may increase plasma levels of risperidone... 

Risperidone significantly increases serum carbamazepine concentrations (106) and carbamazepine significantly reduces serum risperidone concentrations (107). The clinical relevance of these changes is uncertain. 

Steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone have been measured in 23 patients taking risperidone alone and in 11 patients co-medicated with carbamazepine (108). Carbamazepine markedly reduced the concentrations of both compounds, although the difference was significant only for the metabolite. 

Carbamazepine markedly reduced the plasma concentrations of risperidone and 9-hydroxyrisperidone. 

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