Delayed Sleep-Wake Phase Disorder May Predict Relapse in Euthymic Bipolar Disorder

man sitting edge of bed not able to sleep
man sitting edge of bed not able to sleep
Delayed sleep-wake phase disorder may be a predictor of relapse in euthymic patients with bipolar disorder.

Delayed sleep-wake phase disorder may be a predictor of relapse in euthymic patients with bipolar disorder, according to a prospective study recently published in the Journal of Clinical Psychiatry.1

Up to half of patients with bipolar disorder experience recurrence or relapse each year, despite adhering to treatment, thus calling for preventive strategies.2 Among previously identified factors found to predict such relapse are presence of residual depressive or manic symptoms at initial recovery, number of days of elevated mood in the preceding year, mixed urban/rural area living setting, and early age of onset.2-4 The presence of subsyndromal symptoms was also found to predict relapse/recurrence of bipolar disorder.5,6

Accumulating evidence indicates that dysregulation of the circadian rhythm is a frequent comorbidity of bipolar disorder.7 In a previous study, the authors of the current article found a prevalence of 32.4% for circadian rhythm sleep-wake disorder (CRSWD) in a cohort of 104 patients with bipolar disorder (vs 0.13% and 0.17% in the general population in Japan and Norway, respectively), leading them to speculate “that there are underlying common pathophysiological backgrounds between [bipolar disorder] and CRSWD.”8 In this follow-up study, the researchers sought to determine whether disruptions in an individual’s circadian rhythm would affect clinical outcomes in bipolar disorder (ie, relapse from euthymia).

They enrolled 104 euthymic patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Revision, criteria for bipolar disorder I (n=40) or II (n=64) who visited Tokyo Medical Hospital, Japan, as outpatients between 2014 and 2015. Study participants had to be euthymic (ie, with a score <7 points on the Young Mania Rating Scale and a score <13 points on the Montgomery-Åsberg Depression Rating Scale [MADRS]) for >8 weeks at study initiation. Exclusion criteria included current affective episodes, substance abuse, and suicidal risk.

At baseline, 34 (32.7%) of the study participants met the criteria for CRSWD (delayed sleep-wake phase disorder, n=27; non-24-hour sleep-wake rhythm disorder, n=6; or irregular sleep-wake rhythm disorder, n=1). Patients were followed for a period of 48 weeks, during which 51 (49.0%) experienced relapse (depressive episodes, n=32; manic/hypomanic episodes, n=19).

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Study participants who experienced relapse vs no relapse had lower age at baseline (43.9±12.5 vs 49.5±15.5; P =.042) and earlier disease onset (age, 26.3±12.0 vs 32.8±12.7; P =.007). In addition, patients who relapsed during the study period vs those who did not had higher MADRS scores (4.9±4.1 vs 3.3±3.6; P =.028), higher scores on the Pittsburgh Sleep Quality Index (PSQI; 8.7±3.6 vs 7.0±3.5; P =.018), higher rates of ≥2 mood episodes in the past year (47.1% vs 13.2%; P <.001), and higher rates of comorbid CRSWD (52.9% vs 13.2%; P <.001).

Patients with vs without CRSWD had lower age at baseline and lower age at onset of bipolar disorder (P <.001 for both), higher total PSQI scores (P =.007), and higher rates of ≥2 mood episodes in the previous year (P <.001). Proportional hazard regression analyses indicated an association between time to relapse of mood episodes and comorbid CRSWD (P =.039), as well as with ≥2 mood episodes in the previous year (P =.010).

“[C]ircadian rhythm dysfunction, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in [bipolar disorder] patients,” concluded the researchers, emphasizing the importance for clinicians to focus on such dysregulations when treating these patients.


  1. Takaesu Y, Inoue Y, Ono K, et al. Circadian rhythm sleep-wake disorders predict shorter time to relapse of mood episodes in euthymic patients with bipolar disorder: A prospective 48-week study. J Clin Psychiatry. 2017;79(1):17m11565.
  2. Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2006;163(2):217-224.
  3. De dios C, González-pinto A, Montes JM, et al. Predictors of recurrence in bipolar disorders in Spain (PREBIS study data). J Affect Disord. 2012;141(2-3):406-414.
  4. Yatham LN, Kauer-sant’anna M, Bond DJ, Lam RW, Torres I. Course and outcome after the first manic episode in patients with bipolar disorder: prospective 12-month data from the Systematic Treatment Optimization Program For Early Mania project. Can J Psychiatry. 2009;54(2):105-112.
  5. Tohen M, Bowden CL, Calabrese JR, et al. Influence of sub-syndromal symptoms after remission from manic or mixed episodes. Br J Psychiatry. 2006;189:515-519.
  6. De dios C, Ezquiaga E, Agud JL, Vieta E, Soler B, García-lópez A. Subthreshold symptoms and time to relapse/recurrence in a community cohort of bipolar disorder outpatients. J Affect Disord. 2012;143(1-3):160-165.
  7. Melo MCA, Abreu RLC, Linhares neto VB, De bruin PFC, De bruin VMS. Chronotype and circadian rhythm in bipolar disorder: A systematic review. Sleep Med Rev. 2017;34:46-58.
  8. Takaesu Y, Inoue Y, Murakoshi A, et al. Prevalence of circadian rhythm sleep-wake disorders and associated factors in euthymic patients with bipolar disorder. PLoS ONE. 2016;11(7):e0159578.