0959 Sleep and Pharmacotherapy in Treatment-Resistant Late-life Depression: Findings from the OPTIMUM Clinical Trial

Abstract Introduction Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems. However, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD or how sleep affects treatment response. We investigated the bidirectional relationship between sleep and treatment outcomes in the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) study, the largest comparative effectiveness trial of pharmacotherapy for TRLLD to date. Methods This analysis examined: (1) occurrence of reduced sleep in 634 participants in the OPTIMUM randomized controlled trial; (2) how their sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with consistent insufficient sleep [n = 164], worsened sleep [n = 62], or with improved sleep [n = 158]). We used item #4 (scale 0 – 6) from the Montgomery-Asberg Depression Rating Scale (MADRS) to assess insufficient sleep, representing reduced sleep duration or depth compared to usual sleep pattern. Scores >2 indicate a meaningful reduction in duration or sleep depth. Patients who scored >2 on item #4 throughout the trial were classified as having consistent insufficient sleep; patients who reported an increased score (and >2 at trial end) were classified as having worsened sleep; and patients who reported a decreased scores (and ≤2 at trial end) were classified as having improved sleep. Treatment response was defined as a > 50% reduction in the total MADRS score (minus item #4 ) at trial end. Results About half (51%, n= 323) of participants with TRLLD reported reduced or insufficient sleep before treatment. At trial end, consistent insufficient sleep and worsened sleep were each associated with treatment non-response. Improve sleep was not a significant predictor of treatment response, however participants with consistent sufficient sleep or improved sleep were three times more likely to experience treatment response compared to patients with insufficient sleep and worsened sleep. Conclusion Insufficient or reduced sleep are modifiable factors that may improve treatment outcomes in TRLLD. Given that sleep complaints including insomnia are associated with greater risk of depressive relapse and treatment non-response, a tailored treatment plan for those at greatest risk of sleep disturbance with concomitant depression may facilitate better outcomes. Support (if any)