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Original Investigation
July 8, 2020

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

Author Affiliations
  • 1École de psychologie, Université Laval, Québec City, Québec, Canada
  • 2Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Institut universitaire en santé mentale de Québec, Québec City, Québec, Canada
  • 3National Jewish Health, Denver, Colorado
  • 4University of California, San Francisco
  • 5University of Colorado, Denver
JAMA Psychiatry. 2020;77(11):1107-1115. doi:10.1001/jamapsychiatry.2020.1767
Key Points

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

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    1 Comment for this article
    Insomnia treatment with Zolpidem
    Helen P-B, MD, PhD, DCH, FRACP | Ryde Hospital, Sydney, NSW, Australia
    The study by Morin et al. 1 investigated the effect of psychological and pharmacological therapies for insomnia. In this study, half of the patients were randomised to receive Zolpidem medication as the first line of treatment, and 63% (68/107) of this group were women. All participants started Zolpidem with an initial dose of 5mg, and dosage was not increased in women. However, dosage for men was titrated up to 10mg based on the therapeutic response, adverse effects, and participant’s age. As there is a dose-dependent effect of the medication, and Zolpidem was capped at 5mg for women, it is pertinent to know whether the improvement in the time taken to fall asleep (sleep onset latency) and time awake after sleep onset (wake after sleep onset), was lower in women compared to participating men whose final dose was 10mg. Likewise, such a gender discrepancy might partially explain the noted significant differences between improvement in the behaviour therapy first-line treatment group, versus the Zolpidem medication group (sleep onset latency reduction of 21.1 and 11.7 minutes respectively; wake after sleep onset reduction of 33.0 and 16.6 minutes respectively), as both groups comprised of more women than men.

    Kathryn Hadley Bed(Hons)PrimEd, PGDipPsych, GradDipPsychAdv1, Ben Benazzouz BSC(Hons)Psych1; Helen Puusepp-Benazzouz MD, PhD2
    1. University of New England, Armidale, NSW, Australia
    2. Ryde Hospital, Sydney, NSW, Australia