Elsevier

Biological Psychiatry

Volume 66, Issue 3, 1 August 2009, Pages 298-301
Biological Psychiatry

Brief Report
Rapid and Sustained Antidepressant Response with Sleep Deprivation and Chronotherapy in Bipolar Disorder

https://doi.org/10.1016/j.biopsych.2009.02.018Get rights and content

Background

The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD) depression has been a goal for decades. The most widely documented rapid-onset antidepressant therapy is sleep deprivation (SD), which acts within 24–48 hours in 40%–60% of depressed patients. Conventional antidepressants usually require 2–8 weeks to meet response criteria. The delay, which may prolong suffering and increase suicidal risk, underlines the urgency of alternative treatment strategies. This study evaluates the combined efficacy of three established circadian-related treatments (SD, bright light [BL]), sleep phase advance [SPA]) as adjunctive treatment to lithium and antidepressants.

Methods

Forty-nine BPD patients were randomly assigned to a chronotherapeutic augmentation (CAT; SD+ BL+ SPA) or to a medication-only (MED) group. Clinical outcome was assessed using the Hamilton Rating Scale for Depression.

Results

Significant decreases in depression in the CAT versus MED patients were seen within 48 hours of SD and were sustained over a 7-week period.

Conclusions

This is the first study to demonstrate the benefit of adding three noninvasive circadian-related interventions to SD in medicated patients to accelerate and sustain antidepressant responses and provides a strategy for the safe, fast-acting, and sustainable treatment of BPD.

Section snippets

Participants

Forty-nine BPD outpatients (29 men and 20 women) meeting DSM-IV (10) criteria for BPD major depressive episode based on the Structured Clinical Interview for DSM-IV (SCID) were entered into the study. All patients met the minimum intake inclusion score of 18 on the Hamilton Rating Scale for Depression—24 (HRSD-24) (Table 1). Exclusion criteria included a history of suicidal behavior, neurological disorders (e.g., epilepsy, dementia), current substance abuse (within the previous 6 months), sleep

Results

During follow-up, five patients in the CAT group terminated early because of relocation (n = 1), intolerance to medications (n = 2), or failure to adhere to protocol during follow-up (n = 2). None in the MED group terminated early. All CAT patients received chronotherapy. As seen in Table 1, the CAT and MED groups did not significantly differ in terms of age, sex, severity of depression, or medication use. Also, there were no significant differences between cohorts for drug-naive status,

Discussion

The adjunctive noninvasive interventions of SD, BL, and SPA produced robust decreases in depression as early as 48 hours post-SD that were sustainable for at least 7 weeks. A dramatic improvement by Week 7 in the CAT over the MED patients provided further support for the long-term benefit of CAT interventions. These differences cannot be attributed to prior drug history or to responsiveness to medications because there were no significant differences between the groups at baseline. The

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JCG is deceased.

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