SEATTLE, WA—Cognitive behavioral therapy for insomnia (CBT-I) did not appear to abrogate the frequency or burden of antidepressant side effects in patients with comorbid major depressive disorder (MDD), results from the multi-site Treatment of Insomnia and Depression (TRIAD) study presented at SLEEP 2015 have shown.

These higher effects were observed even though participants in the two comparative groups received the same medications at the highest doses, stated Rachel Manber, PhD, of Stanford University, Stanford, CA.

“One possible explanation for this finding is that the sleep restriction component of CBT-I might have led to a transient partial sleep deprivation, which could have amplified the side effects of the antidepressants directly or indirectly, by decreasing tolerance to the side effects,” she added.

Noting that “little is known about determinants of antidepressant side effects,” the TRIAD study provided “a unique opportunity to explore whether insomnia severity and insomnia treatment predict treatment side effects.”

A total of 148 patients with insomnia and comorbid MDD were randomized to 16 weeks of treatment comprising seven sessions of CBT-I or control (CTRL) with a concomitant two-step medication algorithm, in which escitalopram, sertraline, and desvenlafaxine were administered in a prescribed sequence. The majority of the patients were female (73.3%); age was 46.6±12.6 years.

“Other medications that could impact sleep or depression were proscribed,” Dr. Manber stated.

Side effects of each of the medications were measured using the Frequency, Intensity, and Burden of Side Effects Rating scale. Patients were instructed to rate the side effects of “the medication you have taken within the past week for your depression.” Sleep measures included the Insomnia Severity Index (ISI) and sleep diary.

The starting antidepressant medications were escitalopram (78%), sertraline (14%), and desvenlafaxine (8%). There was no significant group difference in starting antidepressants (P=0.44). Average maximum doses were: 16.9mg (4.8mg for escitalopram, 109.0±60.4 for sertraline, and 75.0±28.4 for desvenlafaxine; P>0.52).

“Baseline ISI, mean latency to sleep onset, and time awake in the middle of the night did not predict frequency, intensity, or burden of antidepressant side effects,” Dr. Manber noted, with all P-values greater than 0.1.

However, participants who received CBT-I reported significantly greater maximum frequency and burden of medication side effects compared to the CTRL group (P≤0.03), she concluded.