Some antipsychotic medicines commonly used to treat a type of bipolar disorder may not have clear benefits after six months of use, researchers have found.

There are different types of bipolar disorder. Bipolar I — what most people associate with the illness — is characterized by periods of mania (intense elevated mood, increased energy and speed of thinking, reduced sleep etc) and severe depression (low mood, no interest or motivation, lack of pleasure, suicidal thoughts etc) . This new study is the first to compare the effectiveness of certain antipsychotics in treating this type of bipolar disorder longer-term, following a period of mania.

Publishing their findings online October 13 in Molecular Psychiatry, the research team was led by Lakshmi N. Yatham, M.D., of the University of British Columbia, a 1996 NARSAD Young Investigator (YI) grantee who went on to receive Independent Investigator (II) grants in 1999 and 2003.

The study focused on people with Bipolar I being treated with a combination of an antipsychotic (risperidone or olanzapine) and a mood stabilizer (lithium or valproate). The patients enrolled in the study had recently experienced manic episodes. To compare how the antipsychotics worked over long periods, some patients continued on whichever antipsychotic they were already taking, for another six months or one year in conjunction with lithium or valproate. Others, serving as controls, took placebos (or dummy pills) instead of antipsychotics along with lithium or valproate. Then, the three groups were compared: How long did it take before each patient experienced another depressive or manic episode?

Overall, the researchers found, patients were less likely to have a mood episode if they continued on antipsychotics for 24 weeks rather than taking placebos . However, the benefits of continuing antipsychotics beyond 24 weeks were not apparent as the proportion of patients that had a mood episode was not different between 24 and 52 groups.

The team noted that extended use of both antipsychotics was accompanied by weight gain in patients — clinically significant weight gain on olanzapine in 35% of patients after a year of use, and some weight gain in 15%-17% of patients on risperidone with any length of use. This suggests that the relief provided by these drugs should be considered against the potential for significant weight gain.

The researchers also observed some differences between the two types of antipsychotics as regards their longer-term usefulness, and the types of mood episodes each antipsychotic medicine helped to prevent , although they caution that these findings must be considered preliminary . For instance, beyond six months of use, those taking risperidone experienced manic or depressive episodes as frequently as the placebo group. Those taking olanzapine, on the other hand, had the fewest episodes when using the medication over a whole year rather than stopping use after 24 weeks, making the year-long treatment most effective for that drug. Risperidone tended to delay mania, while olanzapine tended to delay depression. To unpack the effects of different treatments, the researchers say, future work should examine other types of antipsychotics as well as non-antipsychotic treatments like psychotherapy, and do so in a larger patient group.

In addition to Dr. Yatham, the research team also included other past NARSAD grant recipients: 1998 YI and 2007 II grantee Serge Beaulieu, M.D., Ph.D.; 2007 II grantee Flavio P. Kapczinski, M.D., Ph.D.; 2013 II grantee Beny Lafer, M.D., Ph.D.; 1997 II grantee Peter H. Silverstone, M.D.; and 1989 YI and 1995 II L. Trevor Young, M.D., Ph.D.

Read the paper.