Aripiprazole, a “Dopamine-Serotonin System Stabilizer” in the Treatment of Psychosis

Aripiprazole, a novel antipsychotic agent, is assumed to be a “dopamine-serotonin system stabilizer”. According to preclinical studies, aripiprazole exerts partial agonistic action on D2 and 5-HT1A receptors. Thus, it may block a receptor if it is overstimulated and stimulate a receptor when activity is needed. It also has antagonist properties at 5-HT2A receptors. In randomized double-blind studies, aripiprazole was significantly more effective than placebo in controlling positive and negative symptoms of schizophrenia. It showed antipsychotic efficacy comparable to haloperidol, olanzapine and risperidone. Negative and depressive symptoms responded better to aripiprazole than to haloperidol. In an open-label study comparing olanzapine to aripiprazole, aripiprazole showed beneficial effects on cognitive dysfunctions in schizophrenic patients. Also, aripiprazole was effective in patients with mania. Under aripiprazole the rate of extrapyramidal side effects was less than under haloperidol treatment, and did not differ from the placebo and risperidone arms. Clinically significant weight gain occurred less frequently with aripiprazole than with olanzapine. Aripiprazole also demonstrated a significant reduction in cholesterol levels, while haloperidol and olanzapine increased cholesterol levels in comparative trials. Prolactin levels increased 5-fold over placebo levels with risperidone, no increase was seen with aripiprazole. While risperidone treatment was associated with a significantly prolonged mean QTC interval when compared with placebo, aripiprazole treatment did not differ from placebo level. The three most common adverse effects attributed to aripiprazole included headache, anxiety and insomnia. Due to its metabolization process, the risk for interactions of aripiprazole with other cytochrome P 450 dependent drugs is minimal (German J Psychiatry 2003; 6: 9-16).