Combined Total Sleep Deprivation and Light Therapy in the Treatment of Drug-Resistant Bipolar Depression: Acute Response and Long-Term Remission Rates

Francesco Benedetti, M.D.; Barbara Barbini, M.D.; Mara Cigala Fulgosi, M.D.; Cristina Colombo, M.D.; Sara Dallaspezia, M.D.; Adriana Pontiggia, M.D.; and Enrico Smeraldi, M.D.

Background: Drug resistance remains a persistent source of morbidity and mortality for patients with bipolar depression. A growing number of clinical studies support the usefulness of chronotherapeutic interventions, such as total sleep deprivation (TSD) and light therapy (LT), in the treatment of nonresistant bipolar depression.

Method: To investigate the clinical usefulness of TSD plus LT in the treatment of drug-resistant bipolar depression, we treated 60 inpatients for 1 week with repeated TSD and LT combined with ongoing antidepressants and lithium salts. All patients had a DSM-IV diagnosis of bipolar I disorder. Drug resistance was rated according to Thase and Rush criteria. The pattern of relapses and recurrences was assessed during a prospective 9-month follow-up. Data were gathered from September 2002 to July 2004.

Results: A 2-way repeated-measures analysis of variance with changes in self-rated perceived mood scores as dependent variable and with time and group (history of drug resistance) as independent factors confirmed significant time-by-group interaction (p = .0339). A logistic regression on rates of achievement of response (50% reduction in Hamilton Rating Scale for Depression ratings) confirmed the significance of observed differences: overall, 70% (23/33) of nonresistant versus 44% (12/27) of drug-resistant patients achieved response (p = .045). A survival time analysis (Cox proportional hazards model) showed that history of drug resistance significantly influenced the pattern of relapses and recurrences, with 57% (13/23) of nonresistant responders and 17% (2/12) of drug-resistant responders being euthymic after 9 months (p = .0212).

Discussion: The combination of repeated TSD and LT in drug-resistant patients was useful in triggering an acute response. Further clinical research is needed to optimize this treatment option for drug-resistant patients in the long term.

(J Clin Psychiatry 2005;66:1535-1540)

Received June 7, 2005; accepted Aug. 15, 2005. From the Department of Neuropsychiatric Sciences, Scientific Institute and University Vita-Salute San Raffaele (all authors), and CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele (Drs. Benedetti, Colombo, and Smeraldi), Milan, Italy.

In the spirit of full disclosure and in compliance with all ACCME Essential Areas and Policies, the faculty for this CME article were asked to complete a statement regarding all relevant financial relationships between themselves or their spouse/partner and any commercial interest (i.e., a proprietary entity producing health care goods or services) occurring within at least 12 months prior to joining this activity. The CME Institute has resolved any conflicts of interest that were identified. The disclosures are as follows: Dr. Smeraldi has been a consultant for Janssen-Cilag and Schering. Drs. Benedetti, Barbini, Cigala Fulgosi, Colombo, Dallaspezia, and Pontiggia have no significant commercial relationships to disclose relative to the presentation.

Corresponding author and reprints: Francesco Benedetti, M.D., Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, San Raffaele Turro, Via Stamira d'Ancona 20, Milano, Italy (e-mail: benedetti.francesco@hsr.it).