Evidence-Based Reviews

Ultra-rapid cycling bipolar disorder: A critical look

Current Psychiatry. 2011 December;10(12):42-55

References

1. Kramlinger KG, Post RM. Ultra-rapid and ultradian cycling in bipolar affective illness. Br J Psychiatry. 1996;168(3):314-323.

2. Leibenluft E. Severe mood dysregulation irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry. 2011;168(2):129-142.

3. Geller B, Tillman R, Bolhofner K. Proposed definitions of bipolar I disorder episodes and daily rapid cycling phenomena in preschoolers school-aged children, adolescents, and adults. J Child Adolesc Psychopharmacol. 2007;17(2):217-222.

4. Feinman JA, Dunner DL. The effect of alcohol and substance abuse on the course of bipolar affective disorder. J Affect Disord. 1996;37(1):43-49.

5. Maj M, Pirozzi R, Formicola AM, et al. Reliability and validity of four alternative definitions of rapid-cycling bipolar disorder. Am J Psychiatry. 1999;156(9):1421-1424.

6. Jenner FA, Gjessing LR, Cox JR, et al. A manic depressive psychotic with a persistent forty-eight hour cycle. Br J Psychiatry. 1967;113(501):895-910.

7. Zwil AS, McAllister TW, Cohen I, et al. Ultra-rapid cycling bipolar affective disorder following a closed-head injury. Brain Inj. 1993;7(2):147-152.

8. Geller B, Tillman R, Craney JL, et al. Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry. 2004;61(5):459-467.

9. Geller B, Sun K, Zimerman B, et al. Complex and rapid-cycling in bipolar children and adolescents: a preliminary study. J Affect Disord. 1995;34(4):259-268.

10. Goldberg JF, Garno JL, Callahan AM, et al. Overdiagnosis of bipolar disorder among substance use disorder inpatients with mood instability. J Clin Psychiatry. 2008;69(11):1751-1757.

11. Zimmerman M, Ruggero CJ, Chelminski I, et al. Psychiatric diagnoses in patients previously overdiagnosed with bipolar disorder. J Clin Psychiatry. 2010;71(1):26-31.

12. MacKinnon DF, Pies R. Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders. Bipolar Disord. 2006;8(1):1-14.

13. Coryell W, Endicott J, Keller M. Rapidly cycling affective disorder. Demographics diagnosis, family history, and course. Arch Gen Psychiatry. 1992;49(2):126-131.

14. Koenigsberg HW, Harvey PD, Mitropoulou V, et al. Characterizing affective instability in borderline personality disorder. Am J Psychiatry. 2002;159(5):784-788.

15. Henry C, Mitropoulou V, New AS, et al. Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences. J Psychiatr Res. 2001;35(6):307-312.

16. Gottschalk A, Bauer MS, Whybrow PC. Evidence of chaotic mood variation in bipolar disorder. Arch Gen Psychiatry. 1995;52(11):947-959.

17. Goldberg JF, Bowden CL, Calabrese JR, et al. Six-month prospective life charting of mood symptoms with lamotrigine monotherapy versus placebo in rapid cycling bipolar disorder. Biol Psychiatry. 2008;63(1):125-130.

18. Schneck CD, Miklowitz DJ, Miyahara S, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008;165(3):370-377.

19. Ghaemi SN, Ostacher MM, El-Mallakh RS, et al. Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety. J Clin Psychiatry. 2010;71(4):372-380.

20. 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(2):179-184.

21. Bauer M, Beaulieu S, Dunner DL, et al. Rapid cycling bipolar disorder—diagnostic concepts. Bipolar Disord. 2008;10(1 Pt 2):153-162.

22. Zavorotnyy M, Diemer J, Patzelt J, et al. Occurrence of ultra-rapid cycling during electroconvulsive therapy in bipolar depression. World J Biol Psychiatry. 2009;10(4 Pt 3):987-990.

23. Lepkifker E, Iancu I, Dannon P, et al. Valproic acid in ultra-rapid cycling: a case report. Clin Neuropharmacol. 1995;18(1):72-75.

24. Woo YS, Chae JH, Jun TY, et al. Lamotrigine added to valproate successfully treated a case of ultra-rapid cycling bipolar disorder. Psychiatry Clin Neurosci. 2007;61(1):130-131.

25. Karama S, Lal S. Adjunctive topiramate in ultradian cycling bipolar disorder: case report with 3-year follow-up. Eur Psychiatry. 2006;21(4):280-281.

26. Pazzaglia PJ, Post RM, Ketter TA, et al. Preliminary controlled trial of nimodipine in ultra-rapid cycling affective dysregulation. Psychiatry Res. 1993;49(3):257-272.

27. Reilly-Harrington NA, Deckersbach T, Knauz R, et al. Cognitive behavioral therapy for rapid-cycling bipolar disorder: a pilot study. J Psychiatr Pract. 2007;13(5):291-297.

Table

Rapid cycling and ultra-rapid cycling BD: A comparison

Construct	Rapid cycling	Ultra-rapid cycling
Bipolar I vs II	Predominantly BD II^a	No systematic data
Sex	Predominantly women	No systematic data
Longitudinal course	May be a transient phenomenon that can occur at any time^b or an enduring phenomenon that may persist for years^c	Ultradian patterns may be more common across the first several episodes among pediatric BD patients^d
Age at onset	Associated with younger age at onset^e	May be more evident in prepubescent onset mood disorders^d; ultradian cycling more likely when onset occurs before age 13 than in adulthood^e
Diurnal variation in mood	Morning-to-evening mood switches usually involve depression to mania/hypomania, with the opposite typifying evening-to-morning mood switches^f	Not reported
Relationship to environmental stresses	Life stresses may precede initial affective episodes but may be less important as subsequent episodes arise with increasing automaticity	No systematic data
Relationship to menstrual cycle	Despite case reports and self-reported links between RC and menstrual mood exacerbations, prospective data do not identify associations between RC and menstrual patterns^g,^h	No systematic data
Subclinical hypothyroidism	Bauer and Whybrow identified hypothyroidism independent of lithium use in 60% of 30 rapidly cycling BD patients, with evidence of improvement in a separate study of 11 RC patients given suprametabolic levothyroxine (reviewed by Bauer et alⁱ)	No systematic data
Relationship to psychosis	None^a	No systematic data
Relationship to antidepressant use	Naturalistic observations suggest RC may occur later in the illness course as a result of antidepressant use.^c Small open case series data suggest shorter intermorbid intervals on antidepressants with longer intervals off antidepressants.^j RC patients often receive antidepressants, but causal relationships are not well-documented.^k Some case-control data dispute links between antidepressant use and RC^l	No specific published cases
Considerations for suicide risk	RC linked with more serious suicide attempts^l	Suicide attempts may be associated with cycling within an episode^m or rapid shifting in moodⁿ
Time course for judging treatment efficacy	Efforts to diminish acute affective instability may be measured over the course of days to weeks	By definition, treatment of RC involves relapse prevention over the course of 1 year
BD: bipolar disorder; RC: rapid cycling
References a. Schneck CD, Miklowitz DJ, Calabrese JR, et al. Phenomenology of rapid-cycling bipolar disorder: data from the first 500 participants in the Systematic Treatment Enhancement Program. Am J Psychiatry. 2004;161(10):1902-1908. b. Coryell W, Endicott J, Keller M. Rapidly cycling affective disorder. Demographics, diagnosis, family history, and course. Arch Gen Psychiatry. 1992;49(2):126-131. c. Koukopoulos A, Sani G, Koukopoulos AE, et al. Duration and stability of the rapid-cycling course: a long-term personal follow-up of 109 patients. J Affect Disord. 2003;73(1-2):75-85. d. Geller B, Tillman R, Bolhofner K, et al. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome. Arch Gen Psychiatry. 2008;65(10):1125-1133. e. Post RM, Leverich GS, Kupka RW, et al. Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood. J Clin Psychiatry. 2010;71(7):864-872. f. Feldman-Naim S, Turner EH, Leibenluft E. Diurnal variation in the direction of mood switches in patients with rapid-cycling bipolar disorder. J Clin Psychiatry. 1997;58(2):79-84. g. Leibenluft E, Ashman SB, Feldman-Naim S, et al. Lack of relationship between menstrual cycle phase and mood in a sample of women with rapid cycling bipolar disorder. Biol Psychiatry. 1999;46(4):577-580. h. 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(2):179-184. i. Bauer M, Beaulieu S, Dunner DL, et al. Rapid cycling bipolar disorder—diagnostic concepts. Bipolar Disord. 2008;10(1 Pt 2):153-162. j. Wehr TA, Goodwin FK. Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiatry. 1987;144(11):1403-1411. k. Schneck CD, Miklowitz DJ, Miyahara S, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008;165(3):370-377. l. Coryell W, Solomon D, Turvey C, et al. The long-term course of rapid-cycling bipolar disorder. Arch Gen Psychiatry. 2003;60(9):914-920. m. Fawcett J, Scheftner W, Clark D, et al. Clinical predictors of suicide in patients with major affective disorders: a controlled prospective study. Am J Psychiatry. 1987;144(1):35-40. n. MacKinnon DF, Potash JB, McMahon FJ, et al. Rapid mood switching and suicidality in familial bipolar disorder. Bipolar Disord. 2005;7(5):441-448.

Box

Biologic correlates of ultra-rapid cycling

From a biologic perspective, a handful of preliminary studies have examined genetic markers or familial patterns that might be related to rapid cycling (RC) or ultra-rapid cycling (URC). These include a reported link between URC and the low activity variant of the catechol-o-methyltransferase gene polymorphism in a small group of patients with velo-cardio-facial syndrome,^a although this finding was not replicated in a larger sample.^a Other preliminary reports on RC have implicated both the long (l) and short (s) allelic variants of the serotonin transporter gene (SLC6A4), the val66met variant of the brain-derived neurotrophic factor gene, and the circadian cryptochrome 2 (CRY2) gene (reviewed by Bauer et al^b). These candidate loci have been examined in RC but not URC.

URC has not been examined as a familial entity, although in the National Institute of Mental Health Collaborative Depression Study, DSM-IV-TR RC did not occur with elevated frequency in bipolar pedigrees.^c Rapid mood switches—abrupt rather than gradual transitions from one affective pole to another—appear to be only slightly, nonsignificantly more common in first-degree bipolar relatives of BD patients who themselves have rapid rather than gradual transitions from one affective pole to the other.^d

Neuroimaging studies in BD seldom focus on subpopulations with RC or URC, and have been confined mainly to case reports that have yielded limited, non-generalizable observations, such as state-dependent variations in prefrontal activity during tasks of facial recognition (reviewed by Bauer et al^b).

References

a. Papolos DF, Veit S, Faedda GL, et al. Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele. Mol Psychiatry. 1998;3(4):346-349.

b. Bauer M, Beaulieu S, Dunner DL, et al. Rapid cycling bipolar disorder—diagnostic concepts. Bipolar Disord. 2008;10(1 Pt 2):153-162.

c. Coryell W, Endicott J, Keller M. Rapidly cycling affective disorder. Demographics, diagnosis, family history, and course. Arch Gen Psychiatry. 1992;49(2):126-131.

d. MacKinnon DF, Potash JB, McMahon FJ, et al. Rapid mood switching and suicidality in familial bipolar disorder. Bipolar Disord. 2005;7(5):441-448.