Ziprasidone mesylate (Geodon for injection): the first injectable atypical antipsychotic medication

Valerie Sheehan, PHARMD

Symptoms of schizophrenia are usually categorized as positive (including delusions, hallucinations, conceptual disorganization, agitation, and paranoia) or negative (including blunted affect, emotional and social withdrawal, apathy, and anhedonia). The worldwide prevalence of this disease is estimated at 1% (1). Traditionally, antipsychotic medications such as chlorpromazine and haloperidol have been used for the treatment of schizophrenia. These agents block dopamine type 2 (D2) receptors. The major limitations of these agents are their propensity to induce extrapyramidal adverse effects at therapeutic doses and the fact that, in about 30% of patients, the disease is refractory to treatment with these agents or responds inadequately. In addition, these agents have limited efficacy against the negative symptoms of schizophrenia. More recently, novel or "atypical" antipsychotics such as clozapine, olanzapine, risperidone, and quetiapine have become available. These drugs have a tendency to produce fewer extrapyramidal side effects while treating more of the negative symptoms of schizophrenia. These effects are hypothesized to be the result of these drugs' higher affinity for the serotonin 5-HT2A receptors than for the dopamine D2 receptors.
Haloperidol has been available in both short-acting and long-acting (or depot) injectable forms for decades. Long-acting compounds are administered in the maintenance phase of the treatment of schizophrenia and related psychiatric disorders. Ziprasidone is the first atypical antipsychotic available as an intramuscular injection. The Food and Drug Administration approved the intramuscular formulation of ziprasidone on June 21, 2002.