imipramine and Disease-Progression

Acute worsening of depression can negatively impact the outcomes of clinical trials of antidepressants and patient compliance to treatment. We hypothesized that acute worsenings would be more frequent in premenopausal women, relative to men or postmenopausal women, and in women who had demonstrated premenstrual symptom exacerbations (PMEs) prior to treatment, relative to those who had demonstrated no PMEs.. Subjects diagnosed with DSM-III-R chronic major depressive disorder or double depression (dysthymia with concurrent major depressive episode) were randomly assigned between February 1993 and December 1994 to 12 weeks of double-blind treatment with flexibly-dosed sertraline or imipramine, with crossover to the alternate drug in the absence of response. A 6-point or more increase in the 17-item Hamilton Rating Scale for Depression relative to the (7-14 day) previous visit defined worsening. PME was assessed through daily diaries prior to treatment.. There were 3582 evaluable visits attended by 554 subjects. Premenopausal women had a deteriorating depressive presentation at a greater proportion of their visits (8.6%) than did postmenopausal women (4.5%, p < .01) or men (5.9%, p < .01). The presence of PME at baseline was associated with more worsenings than the absence of PME (12.0% vs. 7.3%, p < .05). Results were similar whether the subject was treated with sertraline or imipramine. Nonresponse at treatment completion was more likely among subjects with worsening (p < .01). Dropouts were more likely than completers to have had an exacerbation at their terminal visit (p < .05).. Acute worsening of depression was associated with reproductive variables and negatively affected clinical trial outcomes including early treatment discontinuation and nonresponse.

Topics: Adult; Cross-Over Studies; Depressive Disorder, Major; Disease Progression; Double-Blind Method; Dysthymic Disorder; Female; Humans; Imipramine; Male; Menopause; Middle Aged; Patient Dropouts; Sertraline; Sex Factors; Treatment Outcome

Dynamic systems theory provides a conceptual framework for the study of change in psychotherapy that is consistent with that used in other sciences. A dynamic systems model of change was proposed and evaluated in the context of cognitive therapy for depression. Consistent with this model, less client protection and more destabilization of depressive patterns predicted more improvement at the end of treatment. Less protection was associated with more therapist support/stabilization. More destabilization was associated with more affective intensity in the session and with more of a therapist focus on the historical antecedents of current problems, exposure to multiple sources of corrective information, and repeated practice of new skills. Although preliminary, this pattern of findings is consistent with the model proposed and with principles of dynamic systems from other sciences.

Topics: Adolescent; Adult; Antidepressive Agents, Tricyclic; Cognitive Behavioral Therapy; Depressive Disorder; Disease Progression; Female; Follow-Up Studies; Humans; Imipramine; Male; Middle Aged; Models, Psychological; Observer Variation; Predictive Value of Tests; Psychiatric Status Rating Scales; Reproducibility of Results; Systems Theory; Time Factors; Treatment Outcome