Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions: A Randomized Clinical Trial.

Importance: Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted. Objectives: To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted. Design, Setting, and Participants: In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023. Interventions: Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone). Main Outcomes and Measures: Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components. Results: Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, -3.5 [95% CI, -4.7 to -2.3] vs -4.3 [95% CI, -5.7 to -2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, -4.7 [95% CI, -7.3 to -2.2] vs -5.2 [95% CI, -7.9 to -2.5]), functional impairments (Work and Social Adjustment Scale mean score change, -5.0 [95% CI, -6.7 to -3.3] vs -5.1 [95% CI, -7.2 to -2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, -4.1 [95% CI, -5.8 to -2.4] vs -1.2 [95% CI, -3.0 to 0.5]; P = .02; Cohen d = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, -3.8 [95% CI, -7.1 to -0.4]; zolpidem plus trazodone, -3.7 [95% CI, -6.3 to -1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, -3.7 [95% CI, -6.4 to -1.0]; zolpidem plus trazodone, -3.3 [95% CI, -5.9 to -0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences. Conclusions and Relevance: In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions. Trial Registration: ClinicalTrials.gov Identifier: NCT01651442.

Effectiveness of Sequential Psychological and Medication Therapies for Insomnia Disorder: A Randomized Clinical Trial.

Importance: Despite evidence of efficacious psychological and pharmacologic therapies for insomnia, there is little information about what first-line treatment should be and how best to proceed when initial treatment fails. Objective: To evaluate the comparative efficacy of 4 treatment sequences involving psychological and medication therapies for insomnia and examine the moderating effect of psychiatric disorders on insomnia outcomes. Design, Setting, and Participants: In a sequential multiple-assignment randomized trial, patients were assigned to first-stage therapy involving either behavioral therapy (BT; n = 104) or zolpidem (zolpidem; n = 107), and patients who did not remit received a second treatment involving either medication (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy [CT]). The study took place at Institut Universitaire en Santé Mentale de Québec, Université Laval, Québec City, Québec, Canada, and at National Jewish Health, Denver, Colorado, and enrollment of patients took place from August 2012 through July 2017. Main Outcomes and Measures: The primary end points were the treatment response and remission rates, defined by the Insomnia Severity Index total score. Results: Patients included 211 adults (132 women; mean [SD] age, 45.6 [14.9] years) with a chronic insomnia disorder, including 74 patients with a comorbid anxiety or mood disorder. First-stage therapy with BT or zolpidem produced equivalent weighted percentages of responders (BT, 45.5%; zolpidem, 49.7%; OR, 1.18; 95% CI, 0.60-2.33) and remitters (BT, 38.03%; zolpidem, 30.3%; OR, 1.41; 95% CI, 0.75-2.65). Second-stage therapy produced significant increases in responders for the 2 conditions, starting with BT (BT to zolpidem, 40.6% to 62.7%; OR, 2.46; 95% CI, 1.14-5.30; BT to CT, 50.1% to 68.2%; OR, 2.09; 95% CI, 1.01-4.35) but no significant change following zolpidem treatment. Significant increase in percentage of remitters was observed in 2 of 4 therapy sequences (BT to zolpidem, 38.1% to 55.9%; OR, 2.06; 95% CI, 1.04-4.11; zolpidem to trazodone, 31.4% to 49.4%; OR, 2.13; 95% CI, 0.91-5.00). Although response/remission rates were lower among patients with psychiatric comorbidity, treatment sequences that involved BT followed by CT or zolpidem followed by trazodone yielded better outcomes for patients with comorbid insomnia. Response and remission rates were well sustained through the 12-month follow-up. Conclusions and Relevance: Behavioral therapy and zolpidem medication produced equivalent response and remission rates. Adding a second treatment produced an added value for those whose insomnia failed to remit with initial therapies. Trial Registration: ClinicalTrials.gov Identifier: NCT01651442.