Patients with bipolar disorder who develop a rapid-cycling pattern suffer substantial depressive morbidity and are at high risk for suicide attempts, according to William Coryell, MD, and colleagues. However, the researchers also noted that their findings do not implicate tricyclic antidepressants or selective serotonin reuptake inhibitors in the promotion of affective instability.

“Bipolar patients who developed a rapid-cycling pattern at any time during follow-up were more likely than those who did not to have had onsets before 17 years of age, were more likely to make serious suicide attempts during follow-up, and were much more likely to have depressive symptoms during any given week,” Dr. Coryell’s team reported in the September issue of Archives of General Psychiatry. Dr. Coryell is a Professor of Psychiatry at the University of Iowa Health Care in Iowa City.

“These results suggest that, in the large majority of cases, rapid cycling does not persist more than several years beyond its onset, though it is associated with an increased level of long-term morbidity,” Dr. Coryell told NEUROPSYCHIATRY REVIEWS. “Currently used antidepressants do not seem to trigger manic episodes nor promote rapid cycling. The presence of rapid cycling should not preclude the use of antidepressants, but care should be taken to optimize the patient’s mood stabilizer regimen.”

IMPLICATIONS FOR PROGNOSIS AND TREATMENT

Rapid cycling among patients with bipolar affective disorders has important implications for long-term prognosis and for the use of antidepressants, noted Dr. Coryell. It has been suggested that antidepressants trigger and prolong rapid cycling, and cycle lengths have been observed to increase after antidepressant treatment was withdrawn. Because the identification of rapid cycling requires a thorough analysis of episodes for at least a year, a description of its natural course requires a lengthy observation period, as well as follow-up regardless of whether the patients remain in treatment. No prior study is known to have described the course of rapid cycling beyond five years.

Dr. Coryell and colleagues evaluated 345 patients with bipolar I or bipolar II disorder and conducted follow-up for a mean of 13.7 years as part of the National Institute of Mental Health Collaborative Depression Study. A total of 89 patients (25.8%) were identified who, during one or more years of follow-up, manifested a pattern that met DSM-IV criteria for rapid cycling. These patients were compared with the remaining patients with bipolar disorder by demographics, overall affective morbidity, morbidity during specific treatment conditions, and the likelihood of suicidal behavior. The researchers then analyzed the data to assess whether the use of tricyclic antidepressants for depressive symptoms was associated with the persistence of rapid cycling or with tendencies to switch from depressive to manic or hypomanic phases.

CHARACTERISTICS OF RAPID-CYCLERS

The investigators found that the 89 patients who showed a rapid-cycling pattern were significantly more likely to have had an illness onset before 17 years of age and were also more likely to make serious suicide attempts. In four of five cases, rapid cycling ended within two years of its onset. In addition, resolutions were not associated with decreases in tricyclic antidepressant use. Throughout follow-up, patients prone to rapid cycling experienced more depressive morbidity than did other patients with bipolar disorder, particularly when lithium carbonate was being used without tricyclic antidepressants. The researchers also found that the use of these antidepressants was not more likely in the weeks preceding shifts from depression to mania or hypomania.

“Early onsets were overrepresented among adult patients prone to rapid cycling, and yet rapid-cycling patients with an onset of bipolar illness before the age of 17 years resembled other rapid-cycling patients in their propensity to switching and in overall manic or depressive morbidity over time,” the investigators reported. “Although these data cannot determine the direct effects of prepubertal and early pubertal periods on the propensity to rapid cycling, they do indicate that the very early onset of bipolar disorder may convey a lifelong propensity to this phenomenon.”

In addition, Dr. Coryell and colleagues stated, “These analyses found no association between the cessation of rapid-cycling patterns and any decrease in the use of tricyclic antidepressants to treat depressive symptoms during lithium maintenance.… Bipolar patients who manifested rapid cycling resembled those who did not by the proportion of follow-up weeks during which they were treated with lithium and/or tricyclic antidepressants. The proportion of weeks with selective serotonin reuptake inhibitor treatment was low in both groups but significantly higher for those with rapid cycling.”

Dr. Coryell added that follow-up of the patients is continuing and that his team will conduct further analyses as the total follow-up period lengthens.

—Colby Stong

Suggested Reading
Coryell W, Solomon D, Turvey C, et al. The long-term course of rapid-cycling bipolar disorder. Arch Gen Psychiatry. 2003;60:914-920.

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