Augmentation Therapy for Treatment-Resistant Major Depressive Disorder
The most studied adjunctive strategy involved the use of atypical antipsychotics.
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NEW ORLEANS — Clinicians face a variety of choices when initial treatment of major depressive disorder (MDD) fails. George I. Papakostas, MD, associate professor of psychiatry at Harvard Medical School in Boston, Massachusetts, reviewed augmentation options for treatment-resistant MDD during a presentation at the 2017 Psych Congress.
“Deciding what treatment to use is a complex decision between us and [our] patients that is based on efficacy, safety, which is of paramount importance to clinicians and patients, tolerability, and treatment history,” he said. “A past positive experience is going to fuel a positive future experience.”
Dr Papakostas offered multiple alternatives that favor drug augmentation over switching, especially in cases when switching may cause withdrawal or when the therapeutic benefit of the first-line agent is lost. The most studied augmentation strategy involves the addition of atypical antipsychotics. While randomized studies have shown that atypical antipsychotics are more effective at addressing symptoms in treatment-resistant depression compared with placebo, not all patients can tolerate these drugs. Unfavorable side effects include weight gain and extrapyramidal symptoms.
While the efficacy of adjunctive lithium is greater than that of adjunctive placebo or atypical antipsychotics for treatment-resistant MDD, Dr Papakostas pointed out several limitations, including study duration. “We're talking about lithium being more effective than placebo at weeks 1 and weeks 2,” he explained. “Sustained efficacy is a question that has not yet been answered…we need a definitive study of longer duration.” The second limitation Dr Papakostas cited with lithium is a paucity of studies on newer agents. Additionally, the need for blood monitoring complicates its use a treatment approach.
Mirtazapine is a frequent intervention alternative used by Dr Papakostas, due to strong data backing its efficacy and its proven beneficial effects with regard to insomnia. However, disadvantages include weight gain, sedation, and the infrequent possibility of agranulocytosis.
Omega-3 fatty acids are associated with high acceptability and tolerability, and might offer beneficial cardiovascular benefits. Achieving the optimal dosage for omega-3s, though, may prove difficult. Dr Papakostas recommended that patients take as close to 1 g/d as possible.
Modafinil may resolve depressive symptoms in patients who present with residual somnolence and fatigue, but it failed to show efficacy in patients without fatigue as well as in patients with insomnia. Another augmentation that Dr Papakostas cautioned about was OROS methylphenidate, which can also aid fatigue, apathy, and comorbid attention-deficit hyperactivity disorder (ADHD) but has the potential for abuse and was associated with several negative studies.
“All things being equal, I always prefer to go with a patient's strong choice whenever we come to a decision point,” Dr Papakostas said. “Always question your own diagnoses, always question other people's diagnoses. Your ability to inspire patients and make them feel confident will help your patients improve.”
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Papakostas GI. Update on treatment-resistant major depressive disorder. Presentation at: Psych Congress; September 16-19, 2017; New Orleans, LA.