Evidence-Based Reviews

Rapid-cycling bipolar disorder: Which therapies are most effective?

Current Psychiatry. 2002 March;1(3):9-21

References

1. Dunner DL, Fieve RR. Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry. 1974;20:229-233.

2. Calabrese JR, Delucchi GA. Spectrum of efficacy of valproate in 55 rapid-cycling manic depressives. Am J Psychiatry. 1990;147(4):431-434.

3. Calabrese JR, Shelton MD, Bowden CL, et al. Bipolar rapid cycling: Focus on depression as its hallmark. J Clin Psychiatry. 2001;62(Suppl 14):34-41.

4. Kukopulos A, Reginaldi D, Laddomada P, et al. Course of the manic depressive cycle and changes caused by treatment. Pharmacopsychiatry. 1980;13:156-167.

5. Maj M, et al. Long-term outcome of lithium prophylaxis in bipolar disorder: a 5-year prospective study of 402 patients at a lithium clinic. Am J Psychiatry. 1998;155:30-35.

6. Tondo L, Baldessarini RJ, et al. Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders. Am J Psychiatry. 1998;155:638-645.

7. Wehr TA, Sack DA, Rosenthal NE, et al. Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. Am J Psychiatry. 1988;145:179-84.

8. Calabrese JR, Woyshville MJ, Kimmel SE. Rapport DJ: Predictors of valproate response in bipolar rapid cycling. J Clin Psychopharmacology. 1993;13(4):280-283.

9. Sharma V, Persad E, et al. Treatment of rapid cycling bipolar disorder with combination therapy of valproate and lithium. Can J Psychiatry. 1993;38:137-139.

10. Calabrese JR, Suppes T, Bowden CL, et al. for the Lamictal 614 Study Group. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid cycling bipolar disorder. J Clin Psychiatry. 2000;61(11):841-850.

11. Fatemi SH, Rapport DJ, Calabrese JR, et al. Lamotrigine in rapid cycling bipolar disorder. J Clin Psychiatry 1997;58:522-527.

12. Calabrese JR, Bowden CL, et al. for the Lamictal 602 Study Group. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 1999;60(2):79-88.

13. Bowden CL, Calabrese JR, McElroy SL, et al. Comparison of the efficacy of lamotrigine in rapid cycling and non-rapid cycling bipolar disorder. Biol Psychiatry. 1999;45(8):953-958.

14. Frye MA, et al. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000;20:607-614.

15. Calabrese JR, Bowden CL, Sachs GS, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999;60(2):79-88.

16. Calabrese JR, Bowden CL, DeVeaugh-Geiss J, et al. Lamotrigine demonstrates long term mood stabilization in recently manic patients. Annual meeting of the American Psychiatric Association, New Orleans, 2001.

17. Stancer HC, Persad E. Treatment of intractable rapid-cycling manic-depressive disorder with levothyroxine. Clinical observations. Arch Gen Psychiatry. 1982;39(3):311-312.

18. Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study.. Arch Gen Psychiatry. 1990;47(5):435-40.

19. Suppes T, Webb A, Paul B, Carmody T, et al:. Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. Am J Psychiatry. 1999;156:1164-1169.

Other potential uses for gabapentin are being investigated, such as antidepressant augmentation, anxiety, and chronic pain. Thus, patients with RCBD and a comorbid illness may benefit from add-on gabapentin.

ECT: Some limited success

Electroconvulsive therapy (ECT) has been implicated less frequently than antidepressants in the induction of rapid cycling, and when this does occur it is usually in the context of combined ECT/antidepressant therapies.

Berma and Wolpert in 1987 reported a case of successful ECT treatment of rapid cycling in an adolescent who had been treated with trimipramine for depression. Vanelle et al in 1994 suggested that maintenance ECT works well in 22 treatment-resistant bipolar patients, including 4 with rapid cycling, over an 18-month treatment period.

Behavioral intervention: changing sleep routines

NIMH research of 15 rapid cyclers who were studied for 3 months looked at behavioral interventions and their effect on switching (Feldman-Naim 1997). This study suggested that patients were more likely to switch from depression into hypomania/mania during daytime hours and from mania/hypomania into depression during nighttime.

The use of light therapy or activity and exercise during depression and the use of induced sleep or exposure to darkness during mania/hypomania may be therapeutic. Wehr and colleagues supported this in a 1998 report of one patient studied over several years, comparing this rapid-cycling patient’s regular sleep routine with prolonged (10 to 14 hours per night) and enforced bed rest in the dark.⁷ The promotion of sleep by scheduling regular nighttime periods of enforced bed rest in the dark may help prevent mania and stabilize mood in rapid cyclers.

Other add-on possibilities

Haykal in 1990 reported bupropion to be an effective add-on treatment in 5 of 6 patients with refractory, rapid-cycling bipolar II disorder. Benefit has also been reported from clorgyline, clonidine, magnesium, primidone, and acetazolamide.

Calcium-channel blockers may also offer clinical utility, although supportive evidence is limited. Nimodipine was evaluated for efficacy in 30 patients with treatment-refractory affective illness by the NIMH and Passaglia et al in 1998. Patients who improved on this agent had ultradian rapid cycling, defined in the study as those with affective episodes lasting as short as a week.

A recommended treatment strategy

Based on the available data in bipolar I rapid cycling, we recommend initial treatment with divalproex followed by augmentation with lithium if hypomanic or manic episodes persist, lamotrigine if breakthrough episodes are predominantly depressive, and atypical antipsychotics if psychotic symptoms or true mixed states remain.

For patients presenting with bipolar II rapid cycling, we recommend starting with lamotrigine, then augmenting with divalproex or lithium for breakthrough episodes. Lamotrigine shows more promise because of its reportedly greater antidepressant properties and lack of cycle induction or switching, but offers only modest antimanic therapy.

Pending further investigations, current application of the data suggests that when treating patients with RCBD, conventional antidepressants should be avoided and, if first-line therapies are not effective, the clinician should consider moving to combination drug therapy with 2 or more agents.

Related resources

Bauer MS, Calabrese JR, Dunner DL, et al. Multi-site data reanalysis: validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV. Am J Psychiatry. 1994;151:506-515.
Calabrese JR, Kimmel SE, Woyshville MJ, et al. Clozapine in treatment refractory mania. Am J Psychiatry. 1996;153(6):759-764.
Calabrese JR, Bowden CL, McElroy SL, et al. Spectrum of activity of lamotrigine in treatment refractory bipolar disorder. Am J Psychiatry. 1999;156(7):1019-1023.
Sachs GS. Printz DJ. Kahn DA. Carpenter D. Docherty JP. The expert consensus guideline series: medication treatment of bipolar disorder 2000. Postgraduate Medicine. April 2000; Spec No:1-104.

Drug brand names

Buproprion • Wellbutrin
Carbamazepine • Tegretol
Clonidine • Catapres
Clozapine • Clozaril
Divalproex sodium • Depakote
Gabapentin • Neurontin
Lamotrigine • Lamictal
Levothyroxine • Synthroid, Levothroid, Levoxyl
Olanzapine • Zyprexa
Nimodipine • Nimotop
Primidonem • Mysoline
Topiramate • Topamax