OBJECTIVE:Insomnia and major depressive disorders (MDD) often co-occur, and such comorbidity has been associated with poorer outcomes for both conditions. However, individual differences in depressive symptom trajectories during and after treatment are poorly understood in comorbid insomnia and depression. This study explored the heterogeneity in long-term depression change trajectories, and examined their correlates, particularly insomnia-related characteristics. METHOD:Participants were 148 adults (age M ± SD = 46.6 ± 12.6, 73.0% female) with insomnia and MDD who received antidepressant pharmacotherapy, and were randomized to 7-session Cognitive Behavioral Therapy for Insomnia or control conditions over 16 weeks with 2-year follow-ups. Depression and insomnia severity were assessed at baseline, biweekly during treatment, and every 4 months thereafter. Sleep effort and beliefs about sleep were also assessed. RESULTS:Growth mixture modeling revealed three trajectories: (a) Partial-Responders (68.9%) had moderate symptom reduction during early treatment (p value < .001) and maintained mild depression during follow-ups. (b) Initial-Responders (17.6%) had marked symptom reduction during treatment (p values < .001) and low depression severity at posttreatment, but increased severity over follow-up (p value < .001). (c) Optimal-Responders (13.5%) achieved most gains during early treatment (p value < .001), continued to improve (p value < .01) and maintained minimal depression during follow-ups. The classes did not differ significantly on baseline measures or treatment received, but differed on insomnia-related measures after treatment began (p values < .05): Optimal-Responders consistently endorsed the lowest insomnia severity, sleep effort, and unhelpful beliefs about sleep. CONCLUSIONS:Three depression symptom trajectories were observed among patients with comorbid insomnia and MDD. These trajectories were associated with insomnia-related constructs after commencing treatment. Early changes in insomnia characteristics may predict long-term depression outcomes. (PsycINFO Database Record