Risperdal ConstaTM: The First Long- Acting Atypical Antipsychotic Agent

OVERVIEW OF OLDER AND NEWER AGENTS Schizophrenia, with its accompanying signs and symptoms of delusions, hallucinations, disorganized thoughts, inappropriate affect, and impaired psychosocial functioning, is considered one of the more complex psychiatric disorders to treat.1 One reason for this difficulty is the tendency for patient noncompliance with medication regimens. This trend of nonadherence to therapy is sometimes influenced by “poor insight, negative attitude or subjective response toward medication, previous nonadherence, substance abuse, shorter illness duration, inadequate discharge planning or aftercare environment, and poor therapeutic alliances.”2 Adverse drug effects (ADEs) from medications, especially extrapyramidal symptoms, neuroleptic dysphoria, akathisia, sexual dysfunction, and weight gain, may also have a negative effect on patient adherence.3 In 1993, Weiden and Olfson estimated that the annual cost of schizophrenia relapse, mostly a result of noncompliance, exceeded $2 billion annually.4 Traditionally, noncompliant patients with schizophrenia have been treated with injections of long-acting depot formulations of the conventional (firstgeneration) antipsychotic agents, allowing for scheduled observation of medication delivery at prescribed intervals, typically every two to four weeks, depending on the pharmacokinetics of the agent used. To date, only two conventional antipsychotic agents—haloperidol (e.g., Haldol®, Ortho-McNeil) and fluphenazine (Prolixin®, Apothecon)—have been available in the depot formulations within the U.S.5 Chemically, their formulations are biodegradable esters of the original medication (i.e., pro-drugs) dissolved in an oil-based vehicle that, when injected intramuscularly, is slowly released from the injection site and hydrolyzed.5 The advantages of conventional depot formulations include reduced fluctuations in serum concentration, the avoidance of first-pass metabolism, and the certainty of medication delivery.6,7 Some disadvantages include extrapyramidal symptoms and the need for patients to be stabilized with oral therapy before conversion to the depot product.5 In October 2003, the Food and Drug Administration gave Janssen Pharmaceutica approval to market Risperdal ConstaTM (risperidone), the first secondgeneration (“atypical”) antipsychotic agent available in a long-acting injectable formulation. For many years, both physicians and patients have preferred using the newer agents because of their improved side-effect profile. Risperdal ConstaTM is a novel, delayed-release formulation because it is not an esterified oil-and-water formulation; it is formulated in microspheres contained in an aqueous solution that releases the medication slowly over time.