Supplemental CBT Plus Antidepressant Therapy Benefits Treatment-Resistant Depression

man sitting in chair, woman taking notes
man sitting in chair, woman taking notes
No prior randomized controlled trials have tested supplementing routine medication management with CBT in patients with drug-resistant depression.

Patients with drug-resistant depression in psychiatric hospitals may benefit from cognitive-behavioral therapy (CBT) given in addition to usual medication management, according to results from a study published in the Journal of Clinical Psychiatry.

Atsuo Nakagawa, MD, PhD, of the Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan, and colleagues noted that no prior randomized controlled trials have tested the benefits of supplementing routine medication management with CBT in patients with drug-resistant depression who receive psychiatric specialty care.

The 16-week, assessor-masked, controlled trial with a 12-month follow-up randomly assigned 80 patients to either CBT plus treatment-as-usual (TAU) or TAU alone. 

The study included outpatients age 20 to 65 with DSM-IV criteria for major depressive disorder (MDD) who were deemed treatment-resistant after at least 8 weeks of antidepressant medication, a 17-item GRID-Hamilton Depression Rating Scale (GRID-HDRS17) score ≥16, and a Maudsley Staging Method for treatment-resistant depression score ≥3.  The primary outcome was the alleviation of depressive symptoms as measured by change in the total GRID-HDRS17 score from baseline to week 16. Patients received one 50-minute CBT session a week for 16 weeks. If deemed necessary, patients could receive up to 4 additional sessions.

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Of the original 80 patients, 78 were assessed for the primary outcome and 73 were followed up for 12 months. Compared with the control therapy supplemental CBT significantly improved depressive symptoms at 16 weeks. Greater least squares mean changes in GRID-HDRS17 were observed in the intervention group compared with the control group (–12.7 vs -7.4; difference = –5.4; P <.001). Treatment benefit was maintained at 12-month follow-up (–15.4 vs -11.0; difference = –4.4; P =.002).  In contrast, self-rated secondary outcome measures (Beck Depression Inventory-II and QIDS-SR score) showed non-significant differences in both groups.

Study limitations include a relatively small sample size, a highly motivated patient population that may limit the generalizability of these findings, and the inability to control antidepressant medication. Nonetheless, the investigators argue that these results are promising and that additional research is warranted.


Nakagawa A, Mitsuda D, Sado M, et al. Effectiveness of supplementary cognitive-behavioral therapy for pharmacotherapy-resistant depression: a randomized controlled trial. J Clin Psychiatry. 2017;78(8):1126-1135.