Adverse drug reactions from prescription medications are a significant public health problem. It takes several years to establish the safety of prescription drugs newly approved by the U.S. Food and Drug Administration (FDA), because previously unknown or undetected adverse drug reactions only emerge after the drugs are marketed to the general population. In fact, a 2002 study showed 20% of drugs approved by the FDA over the past 25 years were found to subsequently have serious or life-threatening effects that were unknown or undisclosed at the time of approval. Paliperidone, a benzisoxazole derivative, is the major active metabolite of risperidone and is still a relatively new antipsychotic in the United States. It was approved by FDA in December 2006 for the acute and maintenance treatment of schizophrenia and schizoaffective disorder, and may be used as monotherapy or as an adjunct to mood stabilizers and/or antidepressants. Paliperidone was well tolerated in the six-week efficacy and tolerability clinical trials performed prior to FDA approval. Adverse reactions that were reported more commonly than with placebo included tachycardia (9%-22%), hyperkine-sia (3%-11%), hypertonia (1%-6%), extrapyramidal symptoms (EPS) (3%-10%), and somnolence (4%-13%). Similar adverse reactions were seen in risperidone short-term trials, with the exception of less tachycardia (l%-5%) and greater extrapyramidal symptoms in doses above 8 mg per day (17%-20%). Discontinuation due to adverse effects with paliperidone was most commonly related to movement disorder-related adverse effects, tachycardia, and psychosis. Similar to risperidone, dose-related increase in EPS are seen primarily at the 9 and 12 mg per day doses, compared with the 3 and 6 mg daily doses.
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