Other augmentation options include lithium, buspirone and pindolol, as well as naturally occurring agents such as l-methylfolate, S-adenosylmethionine, creatine, omega-3 fatty acids, and cycloserine.
Combination strategies for MDD involve pairing two FDA-approved antidepressants. According to Dr. Alpert, the most common combinations are an SSRI or SNRI plus bupropion, or an SNRI plus mirtazapine, an approach “which I personally like very much.”
New approaches
There are some new approaches to treating MDD in the pipeline. “Since the 1950s, when antidepressants were discovered, we’ve focused on developing new agents that can better affect the monoamine, norepinephrine, and dopamine [pathways],” he said. “Much of our thinking has had to do with modulating monoaminergic mechanisms. Our animal models are geared toward testing monoamine drugs. It’s exciting that we’re on the cusp of looking at nonmonoaminergic mechanisms.”
Recent targets in the development of new antidepressants include mitochondrial function, inflammation processes, and neurogenesis, he said. Nonmonoaminergic mechanisms including kappa-opioid and neurokinin-1 receptor antagonists and a range of glutamatergic-modulating agents are a growing focus. In addition, rapid-acting antidepressants such as intravenous ketamine and scopolamine promise novel strategies for jump-starting treatment. “This could change the paradigm for how we think about depression treatment,” he said.
Dr. Alpert reported that in the past 12 months he has served as a consultant to Luye Pharma.