Changing Perceptions: Clozapine no longer a 'last resort'

(Original Post Date: December 7, 2009)
A thanks to one of my wonderful students, for sending along this article about Clozapine. http://www.currentpsychiatry.com/article_pages.asp?AID=8165 We actually just attend the Yale Master Psychopharmacology conference last week, where the speaker on Advances in Schizophrenia, Dr. Cyril D’Souza, was quite clear in his preference to see patients treated with Clozapine. Interesting to see this publicized in this way, given the initial introduction of this drug with such care. When introduced, it was suggested as the drug for those treatment resistant patients, with I believe the understanding that those not responding to other agents might find benefit in the drug vs. the risk of potentially life threatening agranulocytosis. This was later widened to include those with schizophrenia or schizoaffective disorder who were a suicide risk. Use of the drug has led to individuals being treated with clozapine while closely scrutinized for the development of life-threatening side effects. More recent studies have suggested clozapine has antiaggressive properties(per Krakowski et al, 2006) and offers superior symptom management (per CATIE results).This article suggests thinking more broadly about the use of clozapine, given studies showing its efficacy. As I translate the idea: rather than thinking of it as a 'last resort', we should consider it a ‘second choice’ after a first trial of antipsychotic medication is not effective. It seems to me that clozapine needs a new marketing strategy. Although we should expect that if we begin to use clozapine in a larger proportion of the population we will see its side effect, agranulocytosis, occurring in greater numbers (i.e. it will have the same frequency, but if more of your patients are taking it, the likelihood you will see a case of agranulocytosis will increase.) Whenever we do prescribe clozapine, we must carefully attend to the potential it has for this side effect, and be sure that we monitor individuals closely.
Posted by Joanne at 12:57 PM

And thanks also for the comment, which shows your use of this clinical information!

Joanne, I wanted to share a recent and ongoing clinical case (without going into too much detail) that I have been a part of at my current clinical site in a forensic setting. The article that I forwarded to you I had also forwarded to my clinical preceptor, a psychiatrist. Not more than a week or two after this conference and stumbling upon this article did it come to our attention that one of the inmates, had presented a couple of months ago in the midst of an acute psychotic episode. It is likely paranoid schizophrenia but with a mood component thus our differentials of adding a bipolar diagnosis per history or leaning towards schizoaffective. This inmate, prior to arrival, had been misdiagnosed with mood and anxiety disorders only (as far as we could gather from collateral sources). Nonetheless, we started slowly titrating up on Risperdal. First 1mg BID and so on up to 6mg according to response; we also concurrently followed the antipsychotic with adequate amounts of Cogentin, Amantadine and even some Klonopin to aide with anxiety as well as hoping to prevent and treat some already apparent EPS. Along with this titration we slowly introduced Depakote as well to stabilize mood. As we responded to symptoms with the Risperdal increases, the psychosis almost completely cleared. The turn around was rapid and the medications effective. BUT, of course this was too good to be true and by this time EPS and Parkinsonian symptoms had become too much to bear. The inmate was at times unable to eat or take pills because of shaking so badly. We had of course had “the benefits outweigh the risks” talk prior to administering the medication, but it was at this point that we attempted to back off several of the meds. We switched from Risperdal to Abilify to see if this might help decrease the EPS, but no changes were noted. It struck me as we were sitting pondering this difficult case, "Why not Clozaril!?" With its very good side effect profile (except of course the life-threatening agranulocytosis, ha) it would give the antipsychotic and even mood stabilizing properties without the same high risk for EPS. At first my preceptor and the nurses were very hesitant and questioned this high-risk medication yet soon at least my preceptor was on board and telling me the more consideration, the more sure it might work very well for this particular patient. We began a titration down off all meds and did basically a washout (in the safety of an inpatient setting) while keeping low-dose Klonopin onboard. So, the current status is that some Parkinsonian symptoms seemed to have decreased but the resting tremor remains. We are weekly monitoring WBC levels (for agranulocytosis as Joanne mentioned) and titrating the dose up. So far so good! I’ll try and update to let you all know how things are progressing…..Thanks again Joanne for posting on this topic, it’s really interesting as well as clinically applicable. ☺ (Comment Date: January 13, 2010)