CIRCADIAN INTERVENTIONS IN PATIENTS WITH RAPID-CYCLING BIPOLAR DISORDER

快速循环双相情感障碍（RCBD）患者至少经历过

Patients with rapid cycling bipolar disorder (RCBD) experience at least four episodes of affective illness (depression, hypomania, and/or mania) in a year. They suffer significant morbidity and are frequently resistant to conventional treatments. An unstable sleep/wake cycle is characteristic of the illness, and data from ZO1 MH 0264-01 CPB indicate that these patients may also have unstable circadian rhythms that tend to be phase-delayed (shifted later). If so, then the use of bright light, dark, or exogenous melatonin to shift and/or stabilize circadian rhythms may have beneficial clinical effects in this population. We are currently testing the clinical effects of four different interventions in patients with RCBD: daily bright light for three months, exogenous melatonin for three months, extending the dark period of the patient's day, and the acute effects of bright or dim light. The first three interventions are all designed to stabilize the patients' circadian rhythms. The bright light and exogenous melatonin trials are both randomized order, cross-over, add-on outpatient trials with three month treatment phases. Our pilot work with bright light indicated that morning light might destabilize mood, while midday light appeared to have mood-stabilizing effects. Based on these data, we are now conducting a controlled trial comparing the effects of midday (i.e. 10 hours before sleep onset) light with those of midday negative ion generator. Patients' melatonin profiles are measured after three months of each of these treatments. In our initial work with exogenous melatonin, we administered 10 mg daily at 10:00 p.m. to five patients with RCBD. The intervention had no beneficial clinical effects, although several patients did experience phase-delayed sleep onset, decreased sleep duration and increased hypomania when the melatonin was withdrawn. Plasma melatonin levels indicate that the high dose may have obliterated the "on-off" quality of the melatonin signal, so we are now doing further pilot work with a lower (5.0 mg) dose. It is important for us to continue our work with exogenous melatonin because patients in the community frequently take it to improve their sleep, but there are no controlled trials of its effects. The third intervention designed to stabilize rhythms involves putting patients on a schedule that includes "long-nights" (i.e. 11-12 hours of dark). Pilot work in two patients indicates that this intervention may stabilize mood. In addition to these long-term treatment trials, we are also interested in the acute clinical effects of bright and dim light. Therefore, we are conducting a study in which patients in the hypomanic and depressed states are exposed to eight hours of bright or dim light. Preliminary results from this study indicate that dim light may dampen hypomania, while bright light has no effect on hypomania; neither bright nor dim light have clinical effects on depression. This result, if confirmed in a larger sample, would suggest that manic patients might benefit from exposure to dim light.