Adjunctive Medication Selection in Depression To Match Each Patient

Weighing the benefit of adjunctive treatment against adverse effects is central to managing major depressive disorder (MDD) when the underlying antidepressant could not be changed, according to Manish Zinzuvadia. Among the 5 medications approved for adjunctive treatment of MDD, selection depended on each atypical antipsychotic's propensity to cause somnolence, akathisia, or weight gain, as well as the patient's overall medical status.¹ "You have to carefully select from these options because you don't want to solve one thing and create another problem," Zinzuvadia said. Fitting the agent to the patient's circumstances was the means of avoiding new problems while still treating residual symptoms.

Augmentation may be indicated when patients could not tolerate a higher dose of the underlying antidepressant because of weight gain, sedation, or metabolic or electrolyte abnormalities from otherwise innocuous medications, yet residual depressive symptoms persist despite medical stability. Starting from a new baseline was necessary when the underlying treatment was not foundational and did not produce enough benefit. Partial response and response that stalled were the key distinctions between these 2 approaches.

Older patients with unremitted depressive symptoms were often medically complicated, which sometimes required adjunctive doses outside the range of typical phase 3 study data.² "We might have to use a lower dose because they're more likely to have higher fall risk, dizziness or sedation," Zinzuvadia said. Early discontinuation because of adverse effects often eliminated benefit, so titration was slower, and patients were told explicitly how the plan differed and that the time to treatment end point might extend beyond that observed in studies. Slower titration preserved the chance of benefit in patients at higher risk for falls, and that conversation made a longer wait for response easier to accept, Zinzuvadia shared.

Zinzuvadia said in his practice he treated patients with inadequate response to conventional antidepressants with all approved options first, then with intravenous ketamine infusions, used with or sometimes in lieu of more conventional treatments. More medications and interventions are expected to emerge, and remaining at the forefront of these developments is important for clinicians treating patients who had not responded to standard therapy, he said.

Dr Zinzuvadia is the medical director and chief executive officer of Park Avenue Wellness Center in New York

References

1. Spielmans GI, Berman MI, Linardatos E, et al. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403.

2. Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(10011):2404-2412.