Chapter 11: Long-Acting Injectable Antipsychotics

DRUG CLASS OVERVIEW

Antipsychotics are the mainstay of drug treatment for the management of schizophrenia and other psychotic disorders. The mechanism of action of the medication depends on the type of antipsychotic with the older “typical” antipsychotics focusing on the antagonism of postsynaptic dopamine type-2 (D₂) receptors. The newer “atypical” drugs antagonizing both D₂ and serotonin type-2A receptors elicit a comparable antipsychotic effect but with the potential for lessening iatrogenic movement disorders and improving negative symptoms (e.g., anhedonia, flattened affect, cognitive impairment).¹ The option of using depot formulations of these medications allows for a number of benefits including consistent drug delivery, assured patient compliance, predicable bioavailability, and avoidance of intentional or accidental overdose.² Available depot formulations exist for the typical antipsychotics haloperidol and fluphenazine and the atypical antipsychotics risperidone, paliperidone, and olanzapine. Dosing parameters vary due to different drug release mechanisms and intended time to response. (see Table 11-1) Their role in therapy has been established and they are recommended for patients who would prefer this method of treatment with the simplification of medication administration, who have a history of relapse due to noncompliance, and when avoiding noncompliance is a clinical priority.^{2, 3, and 4} Although patients on depot antipsychotics receive treatment on a more consistent and monitored basis, data are still limited on whether depot injections reduce relapse rates or long-term adverse drug events compared to oral antipsychotics.^5,6

TYPICAL ANTIPSYCHOTICS

HALOPERIDOL AND FLUPHENAZINE

Haloperidol and fluphenazine are the two typical, or first-generation, antipsychotics available in a long-acting injectable form. Both are synthesized via esterification to a long chain fatty acid, decanoate. Previously, ethanate had been utilized as a lipid chain for fluphenazine but this formulation is no longer available in the United States. The esters are then dissolved in purified sesame oil for final preparation in the standard concentrations of 50 mg/mL and 100 mg/mL for haloperidol decanoate and 25 mg/mL for fluphenazine decanoate.^7,8,9 After intramuscular injection, the availability of the drug is presumed to be dependant on diffusion from the sesame oil because it has been observed that the hydrolysis of the ester is ...