title: Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropsychiatric Sciences, Scientific Institute and University Vita-Salute San Raffaele, San Raffaele Turro, Via Stamira d'Ancona 20, Milan, Italy. benedetti.francesco@hsr.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbini
authors.forename: Mara Cigala
authors.initials: MC
authors.lastname: Fulgosi
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.forename: Sara
authors.initials: S
authors.lastname: Dallaspezia
authors.forename: Adriana
authors.initials: A
authors.lastname: Pontiggia
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006760:Hospitalization; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010789:Phototherapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D012892:Sleep Deprivation; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D008094:Lithium