Intramuscular Preparations of Antipsychotics

Abstract

Intramuscular formulations of antipsychotics can be sub-divided into two groups on the basis of their pharmacokinetic features: short-acting preparations and long-acting or depot preparations. Short-acting intramuscular formulations are used to manage acute psychotic episodes. On the other hand, long-acting compounds, also called "depot", are administered as antipsychotic maintenance treatment to ensure compliance and to eliminate bioavailability problems related to absorption and first pass metabolism. Adverse effects of antipsychotics have been studied with particular respect to oral versus short- and long-acting intramuscular formulations of the different compounds. For short-term intramuscular preparations the main risk with classical compounds are hypotension and extrapyramidal side effects (EPS). Data on the incidence of EPS with depot formulations are controversial: some studies point out that the incidence of EPS is significantly higher in patients receiving depot preparations, whereas others show no difference between oral and depot antipsychotics. Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure is reasonably well tolerated, so that in clinical practice depot antipsychotic therapy is usually begun while the oral treatment is still being administered, with gradual tapering of the oral dose. Efficacy, pharmacodynamics and clinical pharmacokinetics of haloperidol decanoate, fluphenazine enanthate and decanoate, clopenthixol decanoate, zuclopenthixol decanoate and acutard, flupenthixol decanoate, perphenazine enanthate, pipothiazine palmitate and undecylenate, and fluspirilene are reviewed. In addition, the intramuscular preparations of atypical antipsychotics and clinical uses are reviewed. Olanzapine and ziprasidone are available only as short-acting preparations, while risperidone is to date the only novel antipsychotic available as depot formulation. To date, acutely ill, agitated psychotic patients have been treated with high parenteral doses of typical antipsychotics, which often cause serious EPS, especially dystonic reactions. Intramuscular formulations of novel antipsychotics (olanzapine and ziprasidone), which appear to have a better tolerability profile than typical compounds, showed an equivalent efficacy to parenteral typical agents in the acute treatment of psychoses. However, parenteral or depot formulations of atypical antipsychotics are not yet widely available.

Opinions of French patients with schizophrenia regarding injectable medication

“…When patients receive treatment for schizophrenia, long-acting injectable forms of typical antipsychotic medication are an option that has been used to ensure compliance with maintenance therapy 1. However, treatment with typical medication often produces side effects, including weight gain, sedation, hypotension, seizures, acute extrapyramidal symptoms (eg, parkinsonism, akathisia, and dystonia), and chronic motor problems (eg, tardive dyskinesia, chronic akathisia, and tardive dystonia) 2,3.…”

A Meta-Analysis of the Risk of Acute Extrapyramidal Symptoms With Intramuscular Antipsychotics for the Treatment of Agitation

“…Early FGAs, such as chlorpromazine, were effective but often caused hypotension, and have been largely replaced in practice by the high potency FGA haloperidol. 4 However, haloperidol poses a high risk for acute extra-pyramidal symptoms (EPS) such as dystonia. 5 Such symptoms can be distressing, painful, or even life-threatening, and may erode patient trust and compliance.…”

Use of combinatorial pharmacogenomic testing in two cases from community psychiatry

“…While depot medications largely skip first pass metabolism,8 they are still ultimately metabolized by CYP enzymes, which inform steady-state concentrations 9. Additionally, some studies have shown that patients with the G/G genotype at the HTR2A gene may have an increased response to risperidone 10–15.…”