European Neuropsychopharmacology, 2 (1992) 463 465 ~ 1992 Elsevier Science Publishers B.V. All rights reserved 0924-977X/92/$05.00


NEUPSY 00073

Sleep deprivation in rapid-cycling bipolar affective disorder: case report Jonathan Benjamin a and Joseph Zohar b ~Division qf Psychiatry, Ben Gurion University of the Negev. and bDivision q1Psychiatry, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel (Received 4 March, 1991) (Revised, received 27 July, 1992) (Accepted 17 August, 1992)

Key words." Sleep deprivation; Bipolar disorder; Hypomania Summary We describe a 4-month long hypomanic response to sleep deprivation in a patient with consistent (20-day cycles) rapid cycling. He subsequently reverted to very rapid cycling; however, sleep deprivation remained effective for each attack of depression. Sleep deprivation treatment, its immediate but short-lived beneficial effect, may have a role in the treatment of the ultra-short depressions encountered in very rapid cycling.


Case report

'Rapid-cycling' bipolar affective disorder, conventionally defined as bipolar disorder with four or more episodes of depression and/or mania per year, is widely acknowledged as difficult to treat (Wehr et al., 1988). Sleep deprivation is a recognized alternative for certain cases of depression, but its use is limited because its effects disappear after a day or two (Nolen, 1987). However, in very rapid cycling affective disorder, where the depression itself only lasts a few days, the brief action of sleep deprivation may be particularly suitable. Here we report on combination of discontinuation of medications and sleep deprivation in a case of very rapid cycling. We are not aware of previous reports of sleep deprivation in rapid cycling.

A 45-year-old father of 3 children with longstanding affective disorder had a recent history of uncontrolled cycles of hypomania and depression lasting roughly 20 days. At age 17 he suffered a crisis of confidence, feelings of worthlessness, and stopped school attendance. Imipramine was ineffective, but he responded rapidly to 2 ECT treatments. In the ensuing 10 years he had 5 further depressive episodes which responded on each occasion to 2 ECT treatments (see Fig. 1). At age 27 lithium carbonate 1200 mg/day was begun. He did well on this regimen, sustaining only one attack in 1975 (after 1 '/2 years without medication), and two 10day bouts of mild dysphoria in 1977 and 1979. In his 40th year, after a trial of clomipramine, he suffered 5 episodes of depression, lasting 15 30 days each, and this pattern was to persist for 3 years. Each period of depression was followed by a few days of mild euphoria. Discontinuation of lithium was unsuccessful, as were combinations of

Correspondence to: J. Zohar, M.D., Division of Psychiatry, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. Tel.: 972-3-5303300; Fax: 972-3-5352788.








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Fig. I. Lines next to n a m e s o f t r e a t m e n t represent d u r a t i o n o f treatment, imi - i m i p r a m i n e ; cmi - c l o m i p r a m i n e ; thy thyroxine" car - c a r b a m a z e p i n e : phe - phenelzine; clo clonidine: des - desipramine. T h e small circle p i n p o i n t s a week o f extremely rapid cycling while off lithium. T h e period within the larger circle is s h o w n in m o r e detail in Fig. 2. Sleep deprivations are s h o w n by vertical arrows. T h e thick line represents persistent h y p o m a n i a after sleep deprivation.

lithium and: thyroxine 100 #g, carbamazepine 600 mg and phenelzine. A second attempt to discontinue lithium (shown by the small circle in Fig. 1) resulted in three 48-h cycles of depression and hypomania within a week, and was abandoned. This period of active illness was ended by the addition of a proprietary medicine containing folic acid 5 mg and vitamin B]2 100 Itg, and his remission lasted about a year, until a recurrence of depression, at which point he was started on imipramine. There now began a phase of illness in which 10 days of depression were typically followed by 2 3 days of hypomania and 7 days of euthymia. The hypomania manifested itself as hyperactivity at home and at work, increased libido, and poor judgement. The cessation of the vitamins, the addition of clonidine 50 /~g, and the substitution of desipramine for imipramine were to no avail. He began psychotherapy and had 3 months respite: then the very rapid cycling returned, but, with one exception, without the hypomanic phases (see the large circle in Fig. 1). On admission (Fig. 2) he was quiet, despondent and soft-spoken. He disparaged his genuine achievements in the face of adversity and had suicidal ideation. There were no other positive findings in the mental status, physical or routine laboratory examinations. His medications were tapered over 2 days, and on the next evening total










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sleep deprivation was employed, during which he was under constant nursing observation. The following day he was euthymic and showed a more optimistic outlook, and a day later he was frankly hypomanic and remained so for a full 4 months (Fig. 2). This was the first time hypomania had lasted more than a few days. He subsequently had a number of further episodes of depression. One was aborted by a night flight while on holiday, one aborted spontaneously after 2 days, and 2 were relieved by planned total sleep deprivation on the 4th day. During the 5th episode, in order to evaluate the importance of the sleep deprivation, it was deliberately withheld lk)l" 8 days. The episode persisted for that period, at which point the patient insisted on sleep deprivation and the depression resolved. However, on further l\)llow-up, although sleep deprivation was still effective in curtailing depressive phases, the patient reverted to his previous pattern of rapid cycling. Sleep deprivation was then stopped, and ECT was introduced. Unlike the immediate responses to sleep deprivation, the patient remained depressed during 6 ECT lrealments spread over 3 weeks, at the end of which he gradually achieved a euthymic remission.


A patient with very rapid cycling who had tried a number of remedies, including lithium and carbamazepine and a period without lnedication in the past, showed a marked, albeit temporary,

465 response when discontinuation of drugs was combined with sleep deprivation. Sleep deprivation also proved effective on subsequent occasions, one of them fortuitous. When the intervention was withheld the attack prolonged itself until sleep deprivation was administered. A potential difficulty in interpreting these results is due to the fact that sleep deprivation was initially combined with cessation of medication, a standard treatment for rapid cycling (Wehr et al., 1988). However, during follow-up, obvious responses to sleep deprivation alone, together with failure to respond when it was withheld, seem to support the role of sleep deprivation in influencing the course of events. Moreover, previous cessations of medication had not helped this patient. Alternatively, one might argue that the effect of sleep deprivation in this patient was not specific, since he had previously responded to vitamins and to psychotherapy. Moreover, the stabilizing effect of sleep deprivation appeared to wane after 4 months in a manner reminiscent of his previous responses. However, the immediate emergence from depression is typical of responses to sleep deprivation (Nolen, 1987), and was not observed during his subsequent treatment with ECT. In addition, hypomania following depression was observed after sleep deprivation but not with vitamin therapy or commencement of psychotherapy. Sleep deprivation has been reported to induce hypomania in 20-30% of affective patients (Wu and Bunney, 1990). This result is of course less than ideal; the therapist's paramount goal continues to be sustained euthymia. Thus, we make no claim to have 'cured' this patient, nor even to have induced a convincing remission; we aim only to draw attention to an arresting phenomenon. Sleep deprivation is reported to have been temporarily effective in 59% of over 1700 depressed patients (Wu and Bunney, 1990); several theories attempt to explain its mechanism of action. Wehr and Wirz-Justice (1982) proposed a euphorogenic substance synthesized during wakefulness. Synthesis is slow, at least in those who benefit from sleep deprivation, so a day or more without sleep are needed for its effect to become apparent. Wu and Bunney (1990) have recently suggested the converse, i.e. that a depressogenic substance is formed during sleep, at least in susceptible subjects when depressed, and metabolized slowly during prolonged wakefulness (as in sleep deprivation). None of these theories explains the phenomenon

of a sustained response to sleep deprivation, as occurred in this patient, and in about 10% of patients generally (Nolen, 1987). If sleep deprivation works by inactivating a depression switch each morning, it is hard to understand why the effect should persist for more than a day, let alone four months. Similarly, the proposed euphorogenic effect of a day's wakefulness should be short-lived. Various explanations for recurrent affective illness have been offered. Post (1990) suggested that a 'kindling' model, as in epilepsy, can explain recurrent depression. This model could presumably be invoked to explain rapid cycling depression, but perhaps not rapid cycling bipolar illness. We are not aware of previous reports of sleep deprivation in rapid cycling, so it would be premature to indulge in speculation about the particular effectiveness of this manoeuvre in this condition. Yet rapid cyclers are occasionally 'blessed' with extremely regular cycles, and therefore with predictability. A possible clinical strategy would thus be to plan sleep deprivation to coincide with expected depressions in individual patients. In addition, the very brevity of action of sleep deprivation, considered a disadvantage in typical depression (which usually persists for some months), might make it a highly focused and useful treatment for the recurrent, brief, disruptive depressions seen in very rapid cycling affective disorders.

References Borbely, A.A. and Wirz-Justice, A. (1982) Sleep, sleep deprivation and depression: a hypothesis derived from a model of sleep regulation. Hum. Neurobiol. 1, 205 210. Nolen, W.A. (1987) Sleep deprivation in resistant depression. In: J. Zohar and R.H. Belmaker (Eds.), Treating Resistant Depression, PMA Publishing Corp., New York, pp. 307 317. Post, R.M. (1990) Sensitization and kindling perspectives for the course of affective illness: towards a new treatment with the anticonvulsant carbamazepine. Pharmacopsychiatry 23, 3 17. Wehr, T.A., Sack, D.A., Rosenthal, N.E. et at. (1988) Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. Am. J. Psychiat. 145, 179 184. Wehr, T.A. and Wirz-Justice, A. (1982) Internal coincidence model for sleep deprivation and depression. Hum. Neurobiol. 1. Wu, J.C. and Bunney, W.E. (1990) The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am. J. Psychiat. 147, 14~21.

Sleep deprivation in rapid-cycling bipolar affective disorder: case report.

We describe a 4-month long hypomanic response to sleep deprivation in a patient with consistent (20-day cycles) rapid cycling. He subsequently reverte...
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