Schizophrenia: puttin’ on the pounds

November 6, 2009

Something a little more educational this time: having schizophrenia can make you a lard ass at no fault of your own.  The two drugs that you will hear most often making this a problem are clozapine (Clozaril – and not clonazepam (Klonopin), which is an anxiolytic), and olanzapine (Zyprexa).  The odd part is recognizing that the greater the increase in BMI while taking the antipsychotic, the better the antipsychotic is controlling the psychosis (generally).  There are a lot of mechanisms that are suggested for this weight gain and they are still finding more.

The simplest explanation is caloric intake v. caloric output.  Easy.  We all know that eating more calories than we use will eventually put on the pounds.  Sad but true.  People with schizophrenia are much more often sedentary than people sans schizophrenia for numerous reasons (quickly: paranoia, avolition, anhedonia, drowsiness from meds, etc.).  But there is the opposite side of the above equation: what kind of caloric intake are we talking about, here?

Clozapine and Zyprexa are both serotonin and histamine antagonists, meaning they slow the use of these neurotransmitters down (throwing the Dopamine Hypothesis to the wind).  This is a very effective way to control psychosis, on the other hand, I know of people who have come in Andrew at a standard BMI and live there now at a weight of 350 lbs.  The decrease in serotonin activity increases food intake because it decreases the sense of satiety.  The histamine antagonism increases appetite and actually reverses the effects of another neurotransmitter/hormone called leptin that is released by your fat cells that tells your brain to stop consuming.

There were other mechanisms for why people with schizophrenia continue to gain weight on their antipsychotics, but most of them were poorly researched because they were only recently discovered.  So instead of looking at those, I am going to try to discuss some interventions to the weight gain that I found in the literature, both behavioral and medicinal.

Most of the behavioral mechanisms are pretty straightforward: more exercise.  This is done with strict regimens that include nutrition education, frequent weight measurements and group discussions about weight.  The program has shown some success, but I know many patients at Andrew who just don’t care to exercise more or pay attention to their diets.  As much as we want to control some of these things for them, it is their choice.

Metformin (Glucophage) is a commonly used medication with people who are on anti-psychotics (well, at least with the people I work with).  This is because many of them have non-insulin dependent diabetes mellitus (NIDDM).  But it has turned out in one very controlled study (admittedly small number of subjects though) that metformin has helped to control the weight gain better than a placebo.  In some cases, the subjects even lost a little weight to bring their BMI closer to a normal range.  The authors suggested that they might not gain the weight because the metformin makes the glucose available for use rather than storing it as fat right away as well as reducing the production of glucose by the liver.  This sounds very hopeful, but really, there is only one gold standard study showing this and two others showing no conclusive results.

Amantadine has been used for controlling weight gain as well, but this drug increases the use of dopamine in the brain.  All well and good if the dopamine hypothesis is indeed false, but having two drugs that work to decrease psychosis through serotonin release rather than dopamine is not enough to cast away all the evidence for the dopamine hypothesis.

All together it is a tricky issue.  There are other drugs that can be used, but they might increase the side effects of the antipsychotics or have serious side effects of their own.  I think more research should go into this work on metformin personally.  It’s a cheap drug that might be able to prevent a lot of heart ache in the future for these people, as well as allow them to be more active which could increase mood and decrease psychosis.  More money for metformin, please?

Klein, D.K., Cottingham, E.M., Sorter, M., Barton, B.A., Morrison, J.A. (2006). A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. American Journal of Psychiatry, 163, 2072-2079.

Rege, S. (2008). Antipsychotic induced weight gain in schizophrenia: mechanisms and management. Australian and New Zealand Journal of Psychiatry, 42, 369-381.

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