April 2007

Paliperidone (Invega)
Paliperidone (Invega), recently approved to treat schizophrenia, is similar to risperidone (Risperidone) in efficacy and adverse effects.

Methylphenidate for ADHD in Preschool Children
Low doses of methylphenidate (Ritalin and others) are effective and safe for preschool children with ADHD but may cause more side effects than in older children.

A Case of Wernicke's Encephalopathy
Wernicke's encephalopathy is caused by thiamine deficiency, usually due to alcoholism or malnutrition.

In Brief
Taste Altered in Mood Disorders; Reduced Gray Matter May Predict Schizophrenia; FDA Issues Methadone Alert

Two Ineffective Adjuncts for Mania
Olanzapine (Zyprexa) and topiramate (Topamax) add no therapeutic benefit as adjunctive treatments for bipolar disorder.

Schizophrenia, Substance Abuse, and Violence
Substance abuse increases the risk of violent behavior in people with schizophrenia.

Two Ineffective Adjuncts for Mania

April 2007

Most patients with bipolar disorder receive multiple medications simultaneously. Tohen and coworkers studied the combination of carbamazepine (Tegretol and others), used for decades as a mood stabilizer, plus olanzapine (Zyprexa), recently approved by the US Food and Drug Administration for several phases of bipolar disorder, for patients with manic or mixed episodes.1

All 118 patients who were randomized in this double-blind, 6-week study received carbamazepine, 400 to 1200 mg/day. Approximately half were assigned also to take olanzapine, up to 30 mg/day. Olanzapine added no therapeutic benefit in this population but was associated with greater weight gain and elevations in triglycerides and cholesterol. Olanzapine did not affect levels of carbamazepine. However, carbamazepine decreased olanzapine concentrations by about half.

For several decades, doctors have tried various anticonvulsants as mood stabilizers for patients with bipolar disorder. One is topiramate (Topamax). A number of studies have concluded that topiramate by itself is ineffective as a mood stabilizer. Chengappa and coworkers tried topiramate as adjunctive therapy.2

The authors conducted a 12-week, double-blind, placebo-controlled trial of adults with bipolar I disorder who were experiencing a manic or mixed episode. All patients were receiving therapeutic levels of valproate (Depakote and others) or lithium. They were randomly assigned to either adjunctive topiramate or placebo. Topiramate was titrated from 25 to 400 mg over 8 weeks and continued for an additional 4 weeks.

Topiramate produced no added therapeutic benefit over that associated with placebo. Side effects more common with topiramate than with placebo were paresthesias, diarrhea, and anorexia. On a positive note, topiramate patients lost more weight: -2.5 kg (5.6 lb) versus -0.2 kg (0.4 lb) in the placebo group (P < .001).

In conclusion, topiramate seems to confer little benefit as a mood stabilizer, whether employed singly or as an adjunct to other agents. However, it can allow some patients to lose weight, a common problem in patients with bipolar disorder. Olanzapine appears to add no therapeutic benefit to carbamazepine for the treatment of mania or mixed states. It does, however, increase the side effect burden. And carbamazepine can decrease olanzapine levels when administered simultaneously.

1Tohen M, Bowden CL, Smulevich AB, Kryzhanovskaya LA, Bergstrom R, Quinlan T, Osuntokun O, Wang WV, Potts A,Martenyi F: Olanzapine plus carbamazepine versus carbamazepine in the treatment of mania: A 6-week, double-blind, randomized trial. Paper presented at the 45th annual meeting of the American College of Neuropsychopharmacology, Hollywood, FL,December 3-7, 2006.

2Roy Chengappa KN, Schwarzman LK, Hulihan JF, Xiang J, Rosenthal NR, for the Clinical Affairs Product Support Study-168 Investigators: Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: A randomized, placebo-controlled trial. J Clin Psychiatry 2006;67:1698-1706.