Michael E. Thase, MD


May 23, 2012

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My name is Michael Thase. I'm a professor of psychiatry at the University of Pennsylvania, the Perelman School of Medicine, here in the beautiful city of Philadelphia. We're host this year -- the city of Philadelphia -- to the American Psychiatric Association (APA) meeting.

I've been asked to talk for a few minutes about some of the interesting things I've seen in the therapeutics of mood disorders. I think, importantly, we're coming off a period of 5-10 years where there have been no truly novel antidepressant medications introduced. We've had a few newer medications introduced, but they've generally been variants of or logical successors to existing medications.

I think we're starting to see evidence of this pattern changing at this meeting. Indeed, there have been reports further evaluating the remarkable antidepressant properties of ketamine.[1] I think most important, this is not a monamine-active treatment. In fact, it's a medicine initially introduced as an anesthetic.

The fact that it has abuse potential and has psychomimetic and dissociative effects really prevents it from being considered as a potentially useful antidepressant. But its novel mechanism, rapid action, and utility for people who haven't benefited from conventional first- and-second-line medications do warrant ongoing interest. Importantly, the antidepressant effects being uncoupled from, or not invariably associated with, the psychomimetic or the dissociative properties does suggest that different aspects of the N-methyl-D-aspartate (NMDA) receptor can be targeted -- hopefully, with retaining the antidepressant effects without the abuse potential, or dissociative or psychomimetic properties -- remains a very viable hypothesis.

We also saw some poster data on soon-to-be-approved antidepressants. I think the one that is the closest to being introduced in the United States is levomilnacipran,[2,3] which will be the fourth entry into the serotonin-norepinephrine reuptake inhibitor (SNRI) class of medications. I think it's now clear that this is an effective medication. That was established for the parent drug, milnacipran, outside of the United States, but was not clearly demonstrated for milnacipran in the United States. It's only available here for treatment of fibromyalgia. Levomilnacipran has a longer half-life, and in the controlled-release formulation, it will be once-a-day dosing.

I think the thing that distinguishes this from the other members of the SNRI class is that at low therapeutic dose, the drug is much more of a norepinephrine reuptake inhibitor than a serotonin reuptake inhibitor, making it clearly different from venlafaxine, desvenlafaxine, and duloxetine.

We saw evidence of further proof that a novel antidepressant known as 21004,[3] which is under development by a couple of companies in a shared partnership, has measurable or real antidepressant effects and good tolerability. This medicine is not truly novel, in the sense that it does target monoamines, primarily serotonin, but is different from current available medications, in the sense that it is not a strong serotonin reuptake inhibitor. So, it is a multiaction neuromodulator from that standpoint, but it may be a useful or better-tolerated medication for patients who aren't helped by reuptake inhibitors or have too many side effects.

Lastly, one of the most exciting things I saw for bipolar disorder was evidence that a more recently introduced, second-generation antipsychotic -- lurasidone -- had reliable, effective antidepressant effects for bipolar depression.[4] Lurasidone may well have a better tolerability profile, or at least less sedation and less risk for weight gain, than the only currently approved monotherapy for bipolar depression, quetiapine. There aren't many treatments with proven efficacy in bipolar depression, so having another medication approved (even if tolerability turns out to be comparable) is a good thing. And of course, demonstrating benefit sets the stage for comparisons of comparative effectiveness and comparative tolerability, which will be a target or an aim for the next generation of research.

I participated in several classes, courses, and workshops about the role of cognitive-behavioral therapy in the treatment of depression and in severe depressive disorders. Of course, when thinking about comprehensive or integrated treatment plans (which was one of the themes of this year's APA meeting), it is always important to think about the role of psychosocial interventions in combination with, or as an alternative to, pharmacologic strategies as well. In the quest for better drug development, it is always important not to forget the biopsychosocial nature of depression and the lives that our depressed patients live, and the benefit that they can derive from focused, practical psychotherapy.

Thanks for tuning in.


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