Effectiveness of Sequential Psychological and Medication Therapies for Insomnia DisorderA Randomized Clinical Trial

Questions  What should be first-line treatment in the management of insomnia disorder, and is there an added value to providing a second treatment for those who fail initial therapy?

Findings  In a randomized clinical trial of 211 adults with insomnia disorder, first-stage treatment involving behavior therapy or zolpidem medication produced similar response and remission rates. Adding a second-stage therapy significantly increased the percentage of responders and remitters among patients treated initially with behavior therapy but not among those treated initially with medication.

Meaning  Sequential treatments involving cognitive behavioral therapy and medication are an effective strategy for insomnia management.

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