Bipolar disorder is a lifelong episodic condition characterized by mood swings between mania and depression. The lifetime prevalence of bipolar disorder to be 0.8%. The one month point prevalence for bipolar disorder has been estimated as 0.4%. Acute manic episodes can have devastating consequences. Management of acute mania is directed at rapidly controlling the irritability, agitation, impulsivity, aggression, and psychotic symptoms that characterize the hyperaroused state in manic and mixed episodes (Regier et al, 1984). Several lines of evidence suggest that serotonin is likely to play a pivotal role in the pathophysiology of bipolar disorder. Ritanserin a 5-HT₂ receptor antagonist has been reported to have antipsychotic activity (Mahmood & Silvestone, 2001). In this 6-week double blind, placebo controlled study involving moderate to severe manic patients, we assessed the effects of ritanserin plus haloperidol in combination with lithium. Eligible participations were 45 in patient, age between 21-43 years old and met DSM-IV criteria for a current manic episode, on the basis of a clinical interview by an academician psychiatrist. In addition, a score of at least 20 points on the Young Mania rating Scale was required representing at least a moderate to severe mania. Patients were randomly allocated 23 to lithium (1-1.2mEq/L) + haloperidol (10 mg/day)+ ritanserin (10 mg/day) (Group A) or 22 to lithium (1-1.2 mEq/L)+ haloperidol (10 mg/day) + placebo (Group B) for a 6-week, double-blind, placebo-controlled study. Patients were assessed by a third year resident of psychiatry at baseline and after 3, 7, 14, 21, 28 and 42 days after the medication started. All patients entered the hospital untreated with any medications. The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale. Side effects were systematically recorded throughout the study and were assessed using a checklist. A two-way repeated measures analysis of variance (time- treatment interaction) was used. The two groups as a between-subjects factor (group) and the seven measurements during treatment as the within-subjects factor (time) were considered. In addition, a one-way repeated measures analysis of variance with a two-tailed post-hoc Tukey mean comparison test were performed in the change from baseline in each group. To compare the two groups at baseline and the outcome of two groups at the end of the trial, an unpaired Student's t-test with a two?sided P value was used. To compare the baseline data and frequency of side effects between the protocols, Fisher's exact test was performed.

Young Mania Rating Scale total scores improved with ritanserin. The difference between the two protocols was significant as indicated by the effect of group, the between-subjects factor (F = 5.02, d.f.=1, P = 0.03). The means Extrapyramidal Symptoms Rating Scale scores for the placebo group were higher than the ritanserin group and the difference was significant in day 42 (P=0.001). The difference between the two groups in the frequency of side effects was not significant.

The efficacy of ritanserin to obtain a better improvement in patients with mania seems to support the 5-HT hypothesis of bipolar disorder.

Mahmood, T. & Silvestone, T. (2001) Journal of Affective Disorder,. 66, 1-11.
Regier, D.A. et al. (1984) Archives of General Psychiatry,. 41, 934-941.