Consideration of Long-Acting Injectable Antipsychotics for Polypharmacy Regimen in the Treatment of Schizophrenia: Put It on the Table or Not?

Abstract

Antipsychotic monotherapy (APM) is considered best-acceptable treatment option regardless of antipsychotic class and formulation types for treating schizophrenia. However, antipsychotic polypharmacy (APP) has been also widely utilized in routine clinical practice. Despite APP has some clinical benefits it has also numerous pitfalls in relation with increased total number and doses of APs leading to adverse events as well as decrease of treatment adherence and persistence resulting in poor clinical outcomes. Recent introduction of long-acting injectable antipsychotics (LAIs) to the market has offered a chance for better medication adherence/persistence and also provided a simplification of treatment regime leading to more stabilized treatment for schizophrenia patients. When we cannot stay away from APP in the treatment of schizophrenia, clinicians need to find more proper APP regimens and thereby utilization of APP in efficient way should be a practical strategy to benefit schizophrenia patient in a real world treatment setting. With this regard, LAIs can be one of available APP regimen for treatment of schizophrenia in routine practice since their clinical utility and pharmacokinetic stability over oral APs have been well-elaborated today. However, when we have to commence LAIs as a part of APP with oral APs or other LAIs, every effort should be made before doing so whether or not validated and available treatment options or other clinical factors were not done or evaluated yet. Any treatment guidelines do not support APP regardless of the formulation of APP regimen or address two or more LAIs for treatment of schizophrenia till today.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study

“…Although not the focus of this study, we also found that the proportion of individuals who had used an oral SGA was quite high in the pre- and post-index period, while those who used a FGA both oral or LAI was low. These findings may reflect prescribing practices where individuals are generally initiated on a LAI formulation of the corresponding current oral antipsychotic, and while polypharmacy between different types and formulations of antipsychotics is not uncommon, the same type of LAI and oral are generally prescribed together [ 24 – 26 ]. These findings may warrant inquiry in future work examining antipsychotic medication treatment patterns and prescribing practices among individuals initiating LAIs; for those also under an active CTO, understanding which antipsychotics, if any, are included within the treatment plan would provide additional insight.…”

Exploring Hidden Issues in the Use of Antipsychotic Polypharmacy in the Treatment of Schizophrenia

“…Most treatment guidelines state that APM should be the first-line treatment and APP should be a treatment strategy of last resort for treatment-resistant schizophrenia [ 2 - 10 ]. They stated that clozapine should be tried in the first place to overcome inadequate treatment response from different APM trials.…”

“…However, the efficacy of antipsychotic therapy is not satisfactory in real world by which many next treatment strategies have been utilized in routine practice for offering better treatment outcomes for patients with schizophrenia, although some second treatment options such as antipsychotic polypharmacy (APP) are not officially recommended by major treatment guidelines or fully supported by evidence-based data from randomized controlled, clinical trials (RCTs), cohort study and adequately-powered, well-designed practical trials [ 3 - 10 ].…”

The dilemma of polypharmacy in psychosis: is it worth combining partial and full dopamine modulation?

“…Despite this, at least 20% of patients with schizophrenia do not have a sufficient response to APM ( Asenjo Lobos et al , 2010 ; Okhuijsen-Pfeifer et al , 2018 ). Approximately 34% of patients with schizophrenia do not respond to the first- and second-line treatment with antipsychotics, and they are therefore classified as treatment-resistant schizophrenia (TRS) cases ( Pae et al , 2021 ). This is one of the reasons why antipsychotic polypharmacy (APP) is commonly prescribed in clinical practice (i.e.…”