Adjunctive Aripiprazole Treatment Can Improve Outcomes in MDD

Early identification of non-responders to escitalopram monotherapy and providing adjunctive aripiprazole treatment can improve outcomes in major depressive disorder (MDD), according to a study published in The Journal of Clinical Psychiatry.

Canadian researchers conducted a study where participants (N=211) between 18 and 60 years of age, scoring 24 or more in the Montgomery-Ashberg Depression Rating Scale (MADRS) were recruited. The study involved 2 phases. In phase 1, participants were treated with open-label escitalopram 10 to 20 mg/day for 8 weeks. At baseline and at other defined points, they were administered questionnaires. Participants also underwent neuroimaging, blood testing, and electroencephalography at baseline, week 2, and week 8. After 8 weeks, patients were classified as responders (≥50% decrease in MADRS score) and non-responders (<50% decrease in MADRS score from baseline). In phase 2, responders continued escitalopram monotherapy at the same dose, and non-responders received adjunctive aripiprazole at 2 to 10 mg/day. Dose adjustments were made according to tolerability and side effects.

The outcome measures used in this study were MADRS, Quick Inventory of Depressive Symptomatology, Clinical Global Impressions-Severity of Illness Scale, Sheehan Disability Scale, and Lam Employment Absence and Productivity Scale.

Of the evaluable cohort, 180 participants completed phase 1 and 85 were responders. Among the 47% responders in phase 1, 91% had sustained response at the end of phase 2. Among non-responders in phase 1, 61% achieved response in week 16 and exhibited significant reduction on major clinical and functional measures. In regard to functional, symptomatic and combined outcomes, 18% in phase 1 achieved remission. In phase 2, 52% of the escitalopram group and 19% of the aripiprazole group achieved remission.

Thresholds set at 20%, 30%, and 40% for early improvement after 2 weeks were measured for escitalopram at 8 weeks and to adjunctive aripiprazole at 16 weeks. The 20% threshold showed the best balance for sensitivity and specificity for escitalopram, whereas the 40% threshold had high sensitivity and positive predictive value but lower sensitivity and negative predictive value. Positive predictive value and specificity were highest at 40% threshold for adjunct aripiprazole group.

An evaluation of areas under the receiver operating characteristic curve for escitalopram showed 0.69 and 0.74 for response and remission at week 8. Escitalopram and aripiprazole showed AUC at 0.66 and 0.70 for response and remission at week 16.

Of note, this study had a high retention rate. However, lack of a placebo-controlled group for the non-responders in phase 2 limits assessment.

The researchers of the study concluded that response and remission rates to escitalopram after 8 weeks of treatment were modest, though response to escitalopram after 8 weeks was sustained in majority of patients at 16 weeks. There was also an overlap between functional and symptomatic outcomes by end of phase 2. More than 50% of non-responders had positive response to adjunctive aripiprazole at 16 weeks, and in both the phases, early assessment of symptomatic change at 2 weeks helped predict subsequent response rates.

Combined use of clinical, neuroimaging, electroencephalography, and molecular data can provide an earlier prediction of response to therapy, thus helping in better therapeutic decision making.

Multiple authors declared affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors’ disclosures.

Reference

Kennedy SH, Lam RW, Rotzinger S, et al; CAN-BIND Investigator Team. Symptomatic and functional outcomes and early prediction of response to escitalopram monotherapy and sequential adjunctive aripiprazole therapy in patients with major depressive disorder: A CAN-BIND-1 Report. J Clin Psychiatry. 2019;80(2).