The predictive value of insomnia for the treatment outcome of pharmacotherapy, psychotherapy, and combined therapy in major depressive disorder: A mega-analysis of five randomised clinical trials

Background: Insomnia represents a common sleep disorder in major depressive disorder (MDD) that is associated with unfavourable treatment outcomes. Yet, it is unknown whether this relationship varies between treatment modalities. The present study aimed to evaluate the predictive value of insomnia for remission status following pharmacotherapy, psychotherapy, and combined therapy. Methods: Data were obtained from five randomised clinical trials investigating the efficacy of MDD treatment in a homogeneous study population. Patients with MDD (N = 898) aged between 18 and 65 years were assessed for insomnia (item score ≥ 2) and remission (total score ≤ 7) using the Hamilton depression rating scale (HDRS-17). Logistic regression analyses were performed to evaluate and compare the predictive value of pre-treatment insomnia for remission status following 24 weeks of treatment while controlling for sex, age, and baseline depression severity. Results: Insomnia was associated with significantly lower odds of remission overall (OR = 0.618, 95%CI [0.450–0.849]) as well as for pharmacotherapy (OR = 0.219, 95%CI [0.069–0.692]) and combined therapy (OR = 0.583, 95%CI [0.348–0.976]) but not for psychotherapy. The predictive value was, however, not significantly different between the treatment modalities even though direct comparisons revealed significantly higher odds of remission following psychotherapy compared to pharmacotherapy in the insomnia relative to the control group (OR = 3.414, 95%CI [1.013–11.505]). Conclusion: Insomnia is associated with a decreased likelihood of remission in MDD. The most profound impact is observed for pharmacotherapy and combined therapy whereas the clinical relevance for psychotherapy appears modest.