Psych Tidbits

1. Phase II trials are starting on a first-order metabolite of clozapine which does not cause agranulocytosis. If you know what that means, you can skip the next two paragraphs.

As your body metabolises medication, it breaks it down into smaller molecules. In some cases, the breakdown products have similar effects to the original medication. In fluphenazine - Prozac - for example, the body breaks down the original Prozac into a series of Prozac-like chemicals, many of which also have SSRI effect. These breakdowns occur slowly, so as you take the medication over days, you get an additive effect. This is why it takes a few weeks to build up a blood level and get the desired effect. If you took enough of a medication to affect you in a few hours, tomorrow your blood would contain whole bunches of these breakdown products, or metabolites, which would keep compounding as you took more.

First order metabolites, being more similar to the original chemical, are most likely to have similar effect. Clozapine is a tremendous antipsychotic medication, that magic one that made the magazine covers around 1990 because it worked on folks who had not been treatable with typical antipsychotics. I knew a few Clozaril miracle patients, who had lived in hospitals or groups homes for years, fairly quickly returned to non-psychotic thinking and something very near full functionality. I watched a new one last month when I covered on a long-term unit for two-plus weeks. Amazing. Unfortunately, clozapine has the potential side-effect of killing you by causing agranulocytosis, and so has to be monitored uber-carefully. Lots of folks can't tolerate it. So a clozapine derivative that doesn't have this side-effect is very, very good news. My group may get to be part of this next phase of trials. Very cool.

2. Increasing evidence for atypical antipsychotics having a subtle but good effect on personality disorders. We kiddingly call it "a little brain glue," but it seems to work, not only with PTSD/BPD in acute distress, which we have seen for several years, but for avoidant, schizotypal, and schizoid personalities. Because the Asperger's diagnosis is capturing out many previously seen as schizoid and the atypicals are reducing specific symptoms but not whole conditions in the other Axis II diagnoses, we are going to be rethinking the whole batch of Personality disorders over the next decade or so.