In young people with moderate to severe depression, the addition of fluoxetine to cognitive behavioral therapy (CBT) does not appear to decrease depressive symptoms, according to study results published in Lancet Psychiatry. However, exploratory post-hoc analyses found adjunctive fluoxetine might be beneficial for comorbid anxiety symptoms in adolescents and young adults.
A randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical study on the topic — the Youth Depression Alleviation–Combined Treatment trial — was conducted in Australia. The investigators explored whether combination treatment with CBT and fluoxetine was more effective than the use of CBT and placebo in young patients with moderate to severe major depressive disorder. Study participants, who were between 15 and 25 years of age (mean age, 19.6 ± 2.7 years), had sought treatment at 1 of 4 clinical centers in Melbourne, Australia. Participants were randomly assigned in a 1:1 ratio to receive CBT for 12 weeks, along with either placebo or fluoxetine. At study onset, patients received either 1 fluoxetine 20-mg capsule or 1 placebo pill per day. All of the study participants received CBT, which was delivered by a therapist in 50-minute weekly sessions. Patients also underwent interviews at baseline and at weeks 4, 8, and 12, during which time they completed assessments with research assistants. The primary study outcome was change in interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks.
A total of 153 participants were enrolled in the study between February 20, 2013, and December 13, 2016. Among the enrollees, 77 were assigned to CBT plus placebo and 76 were assigned to CBT plus fluoxetine. At baseline, participants had severe depression (mean MADRS score, 33.6 ± 5.1 in the CBT plus placebo group and 32.2 ± 5.6 in the CBT plus fluoxetine group). Moreover, high proportions of patients in both groups had a comorbid anxiety disorder (61% in the CBT plus placebo group and 64% in the CBT plus fluoxetine group), as well as past-month suicidal ideation (71% in the CBT plus placebo group and 78% in the CBT plus fluoxetine group).
Overall, 77% of those in the CBT plus placebo arm and 84% of participants in the CBT plus fluoxetine arm completed the follow-up at 12 weeks. After 12 weeks of therapy, patients in both groups demonstrated a reduction in MADRS score (-13.7; 95% CI, -16.0 to -11.4 in the CBT plus placebo group vs -15.1; 95% CI, -17.4 to -12.9 in the CBT plus fluoxetine group). No significant between-group difference in MADRS score was observed (-1.4, 95% CI, -4.7 to 1.8; P =.39). Moreover, 5 suicide attempts were reported in the CBT plus placebo arm and 1 suicide attempt was reported in the CBT plus fluoxetine arm (odds ratio, 0.2; 95% CI, 0.0-1.8; P =.21).
In exploratory post-hoc analyses, researchers determined that patients who were aged 18 years and older in the CBT plus fluoxetine group showed some evidence for a greater reduction in MADRS scores compared with the CBT plus placebo group. In addition, researchers found evidence of a reduction in anxiety symptoms, as measured by the Generalized Anxiety Disorder 7-item scale, in the CBT plus fluoxetine group compared with the CBT plus placebo group (-2·1, 95% CI, -3·9 to -0·3; P =0·02).
The investigators concluded that the current study did not find any evidence that the addition of fluoxetine vs placebo to CBT helps to reduce depressive symptoms among young persons with moderate to severe major depressive disorder. Based on exploratory analyses, the addition of antidepressant medication might be beneficial in patients with comorbid anxiety symptoms, as well as in older youth.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Davey CG, Chanen AM, Hetrick SE, et al. The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial. Lancet Psychiatry. 2019;6(9):735-744.