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Psychiatry's Swiss Army Knife

© John McManamy

"In my practice, it has moved up to a number one strategy."

Story number one coming out of May's week-long annual meeting of the American Psychiatric Association had to be - drum roll - today's atypical antipsychotic, a drug for all seasons. The first hint was dropped on a United flight to San Francisco when this writer was brought out of his midtrip stupor by an Abilify ad airing sometime after the movie, obviously intended for the psychiatrists on the plane. In case their 19,000 brethren en route happened to miss the ad, a massive Abilify big top dominated the meeting's Herod's Temple-proportioned exhibit hall. Not to be outdone, the Seroquel, Risperdone, Zyprexa, and Geodon people were out in force, playing host to a veritable psychiatric Disneyland, replete with virtual rides, one involving boarding a subway to experience psychotic thrills and chills. Over at the other end of the convention center, industry-funded studies presented as posters touted atypicals for literally every major mental condition, including psychosis, mania, depression, and the many aspects of anxiety, as well as dementia. Meanwhile, in industry-sponsored symposia, well-respected academic researchers waxed eloquent.

So should we be surprised that the pharmaceuticals are milking their antipsychotics for all their worth? Actually no, given the surprises involved in their discovery. As Samuel Barandes MD of the University of California at San Francisco reminded his audience in a lecture at the APA meeting, the first psychiatric blockbuster Thorazine debuted in the 1940s as a TB drug. Then a Swiss company tried out its own TB med on psychiatric patients and found it worked for depression, instead. That drug was imipramine, which came on the market in 1957 and remains the oldest antidepressant still in service.

The older antipsychotics work by binding tightly to the dopamine receptors. The newer atypical antipsychotics are thought to have a better side effects profile thanks to their affinity for the serotonin 2A receptors, which set in motion a chain of events that results in looser binding of the dopamine receptors. This same blocking of the serotonin 2A receptors also has the effect of acting on SSRIs in a way that results in more dopamine and norepinephrine in the prefrontal cortex., with a corresponding and sometimes dramatic antidepressant effect.

Eli Lilly was the first to get in the act with a series of studies last year looking at OFC (combination six or 12 mg olanzapine and 25 or 50 mg fluoxetine, ie low-mid dose Zyprexa-normal dose Prozac) for psychotic depression, treatment-resistant depression, and bipolar depression. At this year's APA meeting, Eli Lilly presented three large OFC studies, the first showing a 64.8 percent response for bipolar depression after eight weeks, with eight days to partial response. The second found a 77.8 percent response after eight weeks for depressed rapid-cyclers. A third study followed those depressed bipolar patients who had remitted on OFC through an open label maintenance phase over six months, finding 62.5 percent remained free from relapse. The company has an application under review by the FDA for bipolar depression.