Extended test for bipolar drugs

Lithium chloride has long stood as the standard drug treatment for bipolar disorder. Other medications, such as the anticonvulsant valproate, also show promise in quelling the condition’s emotional ups and downs, at least in the short run.

A study that recruited bipolar patients from psychiatric clinics in the United States and Canada now offers a rare look at how lithium and valproate stack up against placebos over the long haul. No long-term, placebo-controlled study of any drug for bipolar disorder had been conducted in more than 25 years.

Bipolar patients randomly assigned to 1 year of placebo treatment typically remained free of serious mood symptoms for 7 months of that year, about as long as those who received either lithium or valproate, reports a team led by psychiatrist Charles L. Bowden of the University of Texas Health Science Center at San Antonio.

Participants entered the study within 3 months of suffering a bout of mania; some had not fully recovered, but none displayed signs of depression when they entered the study.

Despite the surprisingly good showing by the placebo pill, valproate proved superior to it and lithium at staving off symptom flare-ups severe enough to make participants drop out of the study, the scientists say. Valproate also kept mild feelings of depression under control better than either of its rivals.

Overall, lithium offered fewer benefits than reported in many previous studies. The lithium group contained the highest proportion of patients who dropped out of the study, often because of treatment side effects. Those losses may have diluted the study’s ability to reveal lithium’s long-term effects.

After weaning 372 bipolar patients off psychoactive drugs already prescribed for them, the researchers randomly assigned valproate to 187, lithium to 91, and the placebo to 91. Each volunteer’s condition was evaluated at least once a month. Physicians and clinic workers also gave support and advice to patients and their families.

The study, described in the May Archives Of General Psychiatry, was funded by a pharmaceutical company that markets a version of valproate.

In a comment published in the same journal, Harvard Medical School psychiatrist Ross J. Baldessarini and his colleagues call the investigation “an extraordinary undertaking” that still leaves much unknown. For instance, the desire to include a placebo led the researchers to exclude bipolar patients with particularly severe symptoms. They, however, may show the most improvement on active medications (SN: 4/29/00, p. 278: Placebos for depression attract scrutiny).

Further studies should follow treated patients for 2 to 3 years and look for links between symptom improvement and the use of specific drug doses, Baldessarini’s group suggests.