Topiramate clozapine

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Dursun SM, Devarajan S. Clozapine weight gain, plus topiramate weight loss. Can J Psychiatry 2000 45(2) 198. 

Leukopenia has been reported after combination treatment with two leukopenic agents, clozapine and topiramate (307). 

A 28-year-old man with type I bipolar manic disorder was treated with clozapine 550 mg /day he gained 25 kg, and topiramate, a mood stabilizer increasingly used as a weight suppressor, was added (25 mg bd for 1 week increased to 200 mg bd for 5 weeks). His white blood cell count had been 9-10 xl09/l for 2 years while he was taking clozapine, and his complete blood counts were normal for 4 weeks after the addition of topiramate however, but at 5 weeks his white blood cell count was 3.7 xl09/l. 

Chen CK, Shiah IS, Yeh CB, Mao WC, Chang CC. Combination treatment of clozapine and topiramate in resistant rapid-cycling bipolar disorder. Clin Neuropharmacol 2005 28 136-8. 

Behar D, Schaller JL. Topiramate leukopenia on clozapine. Eur Child Adolesc Psychiatry 2004 13 51-2. 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

Clozapine In a 12-week open study of the potential benefits of topiramate in 16 clozapine-treated individuals with schizophrenia, including 5 individuab with type 2 diabetes, there was a 14% improvement in total BPRS scores and a statistically significant 2.5% reduction in body weight paresthesia was the most common adverse reaction [39 ]. 

Hahn MK, Remington G, Bois D, Cohn T. Topiramate augmentation in clozapine-treated patients with schizophrenia clinical and metabolic effects. J Clin Psychopharmacol 2010 30 706-10. 

In 20 subjects in a 12-week, open study in clozapine-treated individuals with schizophrenia the initial dose of topiramate was 25 mg bd and the dose was titrated weekly, as tolerated, up to a maximum of 200 mg/ day [282 ]. There was paresthesia, the most common adverse reaction, in 10 patients and it resolved or abated with topiramate dosage reduction. Other adverse reaction scales showed no significant changes. 

---