Pretreatment Depression Severity Research Articles

Abnormal Electroencephalographic Sleep Profiles in Major Depression

To test the hypothesis that depressed patients with selected neurobiologic disturbances are less responsive to psychotherapy, we examined responses to cognitive behavior therapy in relation to electroencephalographic sleep profiles. Under a prospective, case-control design, 90 outpatients with probable or definite endogenous major depression (Schedule for Affective Disorders and Schizophrenia and Research Diagnostic Criteria) were stratified into abnormal and normal sleep subgroups (on the basis of an empirically validated electroencephalographic sleep profile) and more severe and less severe depression subgroups (on the basis of pretreatment Hamilton scores). Response to 16 weeks of treatment was analyzed for both intention-to-treat and completers (n = 82) samples. Outcomes during a 36-month prospective follow-up were assessed with survival analyses. Abnormal sleep profiles and higher pretreatment depression severity were independently associated with poorer outcomes on several analyses. The association between sleep abnormality and cognitive behavior therapy response was not significant in the completers analyses, however, largely because of differential attrition. During follow-up, pretreatment depression severity was predictive of relapse and a lower recovery rate, whereas sleep abnormality was predictive of a lower recovery rate and a higher risk of recurrence. Depressed patients characterized by higher severity and/or an abnormal electroencephalographic sleep profile were relatively less responsive to cognitive behavior therapy. These associations are hypothesized to result from a constellation of neurophysiologic disturbances that interfere with the acquisition, application, and implementation of the skills emphasized in cognitive behavior therapy.

Evaluating Clinical Response of Open Nortriptyline Pharmacotherapy in Adolescent Major Depression

Adolescents with major depressive disorder (N = 25) were treated with nortriptyline 100 mg for 6 to 10 weeks. Clinical change was assessed by three treatment outcome measures: the Schedule for Affective Disorders and Schizophrenia (K-SADS-III-R) (to assess syndromal recovery, i.e., no longer fulfilling diagnostic criteria for the disorder), the self-rated Beck Depression Inventory, and a clinician-rated 17-item Depression Scale (derived from the KSADS-III-R). At 6 weeks, recovery rates for full response were 44% to 57%, for partial response were 26% to 32%, and for nonresponse were 12% to 28%. Better outcome was not associated with concurrent treatment (hospital or outpatient), endogenous or nonendogenous status, or pretreatment depression severity. A significantly greater number of full and partial responders had plasma nortriptyline levels in the adult range of 50-150 ng/ml. None of the response measures, when analyzed as continuous variables, were curvilinearly associated with plasma nortriptyline levels, a finding which does not support the therapeutic window hypothesis. The 17 adolescents who were treated for 10 weeks continued to improve on all three outcome measures (syndrome, p < 0.07; Beck, p < 0.05; 17-Item, p < 0.004) relative to their response at 6 weeks. By 10 weeks, all three measures suggested clinical improvement, but no conclusions about efficacy can be offered in view of the open-label design, absence of placebo controls, diagnostic subtype heterogeneity, small sample size, and concurrent treatments. These data suggest that apparent improvement in adolescent major depressive disorder may vary, depending on treatment outcome criteria, plasma nortriptyline level, and treatment duration. Clinical recovery appears more rapid when treatment response is defined by the clinician-rating (17-Item Depression Scale) and slower when defined by self-rating (Beck Depression Inventory) or by diagnostic status (syndromal criteria). The clinician-rated scale may be more sensitive to early improvements in adolescents, as in adults. Extending treatment from 6 to 10 weeks increased the response rate by about 50%, so a 10-week trial of nortriptyline might be clinically indicated before nonresponse status in adolescents is established.