Sequential Addition of CBT or Antidepressants Effective in Nonremitting Depression

Researchers compared data from several studies finding the effectiveness in adding cognitive behavioral therapy and antidepressant medication to the treatment of nonremitting depression.

According to a study published in The American Journal of Psychiatry, the sequential addition of psychotherapy or antidepressant medication for treating patients with remitting depression was effective to prevent the recurrence of symptoms.

The investigators of this study sought to evaluate the acute and long-term outcomes of sequential combination therapy — adding either cognitive-behavioral therapy (CBT) or antidepressant medication following monotherapy — in adults with nonremitting major depressive disorder.

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The phase 1 study sample included 251 adults with major depression who were previously untreated. Participants were initially randomized in a 1:1:1 ratio to receive escitalopram, duloxetine, or CBT monotherapy for 12 weeks. Patients who did not achieve remission or respond to monotherapy (n=112) were eligible for phase 2, receiving an additional 12 weeks of combination therapy divided into 2 treatment arms: CBT plus medication (when medication was added, n=37) or medication plus CBT (when CBT was added, n=75). To assess the risk of recurrence, patients who responded to the combination treatment were then followed for an additional 18 months. Using Hamilton Rating Scales (HAM-D and HAM-A), the severity of depression and anxiety was assessed at week 13 to 18, week 20, 22, and 24. The primary outcomes were remission at the end of phase 2 and relapse/recurrence during follow-up.

Of the 112 patients who entered combination therapy, 54 (48.2%) achieved remission: 54.1% of the CBT plus medication group and 45.1% of the medication plus CBT group. Overall phase 2 remission rates were higher in patients who in phase 1 responded to monotherapy, but did not achieve remission vs patients who did not respond to monotherapy at all (61% vs 41%). Among the patients who responded to monotherapy but did not achieve remission 89% who entered the CBT plus medication group achieved remission vs 53% who entered the medication plus CBT group. However, rates of response and remission in patients who did not respond to initial monotherapy were similar between treatment arms. In either group, the severity of depression or anxiety disorder — measured by baseline HAM-D and HAM-A scores — was found to be a strong predictor of nonremission during any phase.

Limitations to the study included the sample population, which had not previously received treatment for depression and represented only a small scope of comorbidities, preventing the ability to generalize the results. Another limitation was the small number of patients in the subgroup CBT plus medication; the intensity of the phase 2 booster CBT sessions for this group may have been less than needed to achieve full effects of combination treatment.

Regardless of the order, the sequential addition of CBT or antidepressant medication to treat patients who did not achieve remission on monotherapy alone is an effective approach for preventing the relapse or recurrence of depression in this population.


Dunlop BW, LoParo D, Kinkead B, et al. Benefits of sequentially adding cognitive-behavioral therapy or antidepressant medication for adults with nonremitting depression [published online February 15, 2019]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.18091075