title: Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course.
abstract: The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone-corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (> or = 50% decrease in score on Hamilton Rating Scale for Depression [HRS]) was 55% (N = 42). The response rate in the group with trimipramine monotherapy (N = 14) was 79%, whereas in the groups with adjunct SD (N = 14) and BL (N = 14), respectively, it was only 43%. All three groups showed significant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders (p < .05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The non-responders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) (p < .01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome.
authors.affiliation: Department of Psychiatry, University of Basle, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Holsboer-Trachsler
authors.forename: U
authors.initials: U
authors.lastname: Hemmeter
authors.forename: M
authors.initials: M
authors.lastname: Hatzinger
authors.forename: E
authors.initials: E
authors.lastname: Seifritz
authors.forename: U
authors.initials: U
authors.lastname: Gerhard
authors.forename: V
authors.initials: V
authors.lastname: Hobi
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D003346:Corticotropin-Releasing Hormone; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy*; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010789:Phototherapy; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D017286:Polysomnography; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D012892:Sleep Deprivation; D014299:Trimipramine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014299:Trimipramine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone