Monday, June 23, 2008

When you play with antipsychotics, you play with fire.

Antipsychotic medications have worked wonders to enhance the lives of many people. However, in recent years, antipsychotics have also been used for an increasing number of off-label uses and in progressively younger populations than they ever were before. Before handing these medications out like they are candy, it's important to evaluate the risks associated with using these medications. A recent study suggested that we should be much more careful about choosing our treatment populations than we have been to date.

Before I get to the meat of the study, I'd like to preface this post with an explanation of the study design. The authors of this study are concerned about safety risks in young children and pregnant women when they are given antipsychotic medications. However, they had to develop a research model that did not place young children and pregnant women at risk in the process of looking into this issue. So...rather than give antipsychotics to these two populations, they chose to administer a battery of antipsychotics to a group of roundworms. Roundworms were chosen because they are an accepted research model for investigating matters related to brain and nervous system development. That is definitely a limitation of the study, as most people I know would not say they have much in common with this guy...but that's one of the tough things about studying medications and their to investigate those risks without causing more damage.

Anyway...when the roundworms were given three of these medications, clozapine (Clozaril), fluphenazine (Prolixin), and haloperidol (Haldol), there was less development of neurons in general and axons (a specific anatomical feature of a neuron) in neurons devoted to mechanosensory function (that's touching and registering what you're touching). Neurons that were produced also tended to not migrate to the location where they would be expected to migrate, meaning there might have been neurons there, but they were, so to speak, all dressed up with no place to go.

In some neurons, axons grew past their functional anatomical size. And some had abnormal anatomical features.

Other antipsychotics produced similar results, although not to as significant a degree. The drugs mentioned included: risperidone (Risperdal), aripiprazole (Abilify), quetiapine (Seroquel), trifluoperazine (Stelazine) and olanzapine (Zyprexa).

I'm not going to pontificate about the ethical dilemma encountered when treating a pregnant woman with schizophrenia. The choices made in those situations involve complex risk/benefit considerations that are the responsibility of the patient and her physician.

However, I will say that responsible use of these medications in women of childbearing age is imperative. Forty-nine percent of all pregnancies ending in childbirth in 1994 were unintended, and 48% of all women aged 15-44 in 1994 had had at least one unintended pregnancy at some point in their life. It happens, and it happens a lot.

So if you're a physician and you're handing out prescriptions for antipsychotics for off-label uses to women of childbearing matter how much judgment, education, evaluation, etc. you think you're providing, you really are playing with fire.

Donohoe DR, Weeks K, Aamodt EJ, Dwyer DS. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans. Int J Dev Neurosci. 2008 May-Jun;26(3-4):371-80.

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