PracticeUpdate Conference Series European Congress of Psychiatry 2019

Baseline Depression Severity Does Not Affect Benefits of Antidepressant Therapy Study evaluates available data on five new-generation antidepressant medications.

D oes degree of severity of major depression affect the benefits derived from antide- pressants? The answer is no, according to research led by Andrea Cipriani, MD, PhD, from the University of Oxford in the United Kingdom. Dr. Cipriani stated in his abstract that the role of baseline severity as an effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This can be observed in the case of major depressive disorder, where clinical practice guidelines for prescribing antidepressants vary. For instance, the National Institute for Health and Care Excellence (NICE) and the American Psychiatric Association recommend pharmacother- apy for even mild degrees of depression, whereas the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the Royal Australian and New Zealand College of Psychiatrists do not necessarily support this approach. In their study, Dr. Cipriani and colleagues examined whether the baseline severity of major depres- sive disorder modifies the efficacy of various antidepressants. They did this through individual participant data (IPD) meta-analysis. The researchers identified all placebo-controlled, double-blind, randomized trials of new-generation antidepressants in the acute-phase treatment of major depression conducted in Japan. They requested the studies’ IPD through the public- private partnerships between the relevant academic societies and the pharmaceutical companies. They examined how baseline depression severity could modify the effects of antidepressants, using six increasingly complex, competing, mixed-effects models for repeated measures. The researchers identified 11 eligible trials and obtained IPD from six. In a related journal article, they specify that participants were largely in their 30s and 40s, there were slightly more females than males, and the average baseline Hamilton Rating

Scale for Depression (HDRS) was approximately 22 to 23. The trials lasted 6 to 8 weeks. The six trials compared duloxetine, escitalopram, mirtazapine, paroxetine, or bupropion against pla- cebo (n=2464). The best-fitting model revealed no interaction between baseline severity and treat- ment (coefficient = –0.04, 95% confidence interval –0.16 to 0.08, P = .49). Several sensitivity analyses confirmed these findings. In their journal article, the researchers note that the findings reflect earlier research on the use of fluoxetine and venlafaxine as well as cognitive behavior therapy for depression. Their analysis did not include tricyclic antidepressants or monoamine oxidase inhibitors, however, so the findings may not be generalizable to those classes. In the abstract, Dr. Cipriani and colleagues con- clude that “we may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.” In a comment on the study for Elsevier’s PracticeUpdate , Dennis Butler, PhD, Professor Emeritus of Family Medicine at the Medical College of Wisconsin in Milwaukee, pointed out

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