Treatment of rapid-cycling bipolar disorder: are antidepressants mood destabilizers?

Editorial ajp.psychiatryonline.org A century ago, rapid-cycling bipolar disorder was not observed. Either classic nosol-ogists, such as Kraepelin, simply missed it or it did not exist. The term was first coined in the 1970s to identify lithium nonresponders in randomized clinical trials; thereafter, rapid cycling became the subject of decades of further research, which has confirmed that rapid cycling is a factor in poor prognosis. Rapid-cycling patients do worse in follow up than patients without rapid cycling, and they are also less likely to respond to treatment. The erroneous impression then arose that anticonvulsants, such as carba-mazepine or divalproex, were more effective than lithium in treating rapid cycling. The error came from comparing studies using lithium alone against studies using anticon-vulsants alone, without a direct comparison of the two treatments. Such comparisons need to be made head to head, in randomized studies. When these comparisons are performed with proper methods, anticonvulsants are seen to be about equivalent to lithium (i.e., ineffective) in treating rapid cycling (1, 2). Because rapid cycling was not described until the 1970s, clinicians began speculating that psy-chotropics, such as antidepressants, induce rapid cycling. Is rapid cycling iatrogenic? Do an-tidepressants perhaps increase the risk for rapid cycling or worsen symptoms in some patients? Early reports of a possible link between antidepressants and rapid cycling were made in the 1970s by Kukopulos in Italy (3) and by Wehr et al. at NIMH (4). Later observational studies were contradictory and inconclusive (5). Yet the largest published randomized clinical trial showed that discontinuation of antidepressant medication improved refractory rapid cycling (4). This study found an association between tricyclic antidepressant treatment and rapid cycling in a double-blind, placebo-controlled on-off-on-off design, although the published report was incomplete in many details. Nonetheless , the implication, that antidepressants cause rapid cycling, was intriguing; this finding potentially gives clinicians an important tool to improve outcome in bipolar disorder: discontinuation of antidepressants. Yet this approach goes against some of the tendencies of physicians: giving, not stopping, medications to improve mental illnesses. In this issue of the Journal, Schneck and colleagues report new data from the NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, in which about one-third of the patients with bipolar disorder had rapid cycling ; these patients also had more recurrences in the 1-year follow up. Only 5% of these rapid-cycling patients continued to meet that definition (four or more episodes in a …