Both the beneficial and adverse effects of antipsychotic drugs are known to fluctuate over time even after steady state blood levels of the drug are achieved. This suggests that such effects are influenced, at least temporarily, by a number of endogenous (e.g. mood, stress level, circadian cycle) and exogenous (e.g. diet, interpersonal encounter, environmental change) factors, which may, when taken together, help to explain the significant placebo rate in antipsychotic drug trials [1]. Exercise is one factor that has been shown to temporarily enhance treatment effects in schizophrenia [2][3][4][5][6][7][8]. Whether side effects are enhanced or dampened after exercise, however, has not been addressed in these studies. The following case example suggests that physical activity can sometimes increase the side effects of drugs. Case ExampleTed was a young patient diagnosed with schizophrenia and treated for many years with antipsychotic fluphenazine enanthate depot injections administered every three weeks. Periodically and always unexpectedly, he would knock loudly on my office door, demanding to be seen at once. The complaint was always the same -that his muscles were stiff, a parkinsonian side effect of fluphenazine. The timing of these knocks was mysterious. They did not correspond to the time since last injection. They did not appear to correspond to any particular life event or emotional upset. Months would pass without any knocks and then there could be three in the same week.Ted was the one who finally figured it out. The knocks occurred during the months that he played soccer. His injection was in the upper outer quadrant of the buttock, the dorsogluteal muscle, and whenever those muscles were strongly activated as in soccer, blood flow to and from the depot site increased so much that his blood stream was inundated, his brain received more drug, more dopamine receptors were blocked [the mechanism of action of antipsychotic drugs, and, subsequently, his muscles became stiff, an effect of dopamine blockade [9,10]. Clinical experience reinforces the observation that side effects to depot intramuscular antipsychotic injection increase after exercise. This motivated a literature review of exercise effects on side effects of antipsychotic drugs, however administered. Exercise and Antipsychotic DrugsMary V. Seeman* Department of Psychiatry, University of Toronto, Canada Abstract Background: Exercise has been shown to reduce symptoms in patients with schizophrenia.