Article website: https://pmc.ncbi.nlm.nih.gov/articles/PMC11117856/pdf/brainsci-14-00433.pdf

 

Citation: Cipolla, S., Catapano, P., D’Amico, D., Monda, R., Sallusto, N. P., Perris, F., De Santis, V., Catapano, F., Luciano, M., & Fiorillo, A. (2024). Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review. Brain sciences, 14(5), 433. https://doi.org/10.3390/brainsci14050433

 

 

What is the definition of treatment-resistant schizophrenia (TRS)?

  • Persistence of symptoms despite ≥2 trials of antipsychotic medications of adequate dose and duration with documented adherence (the Treatment Response and Resistance in Psychosis (TRRIP) working group)

 

What is the treatment for TRS?

  • The Food and Drug Administration (FDA) indicated clozapine as an atypical antipsychotic drug for TRS
  • However, up to 60% of patients do not respond to adequate treatment with clozapine
  • Furthermore, its adverse effects and the need for frequent blood monitoring can make compliance an issue

 

What are the other treatment strategies for TRS?

  • Dual LAI APs – this combination may be promising, effective, and relatively safe therapeutic strategy
  • Oral polypharmacy – however, the supporting evidence on the efficacy and safety of oral polypharmacy is inconsistent, and it can greatly reduce patient adherence to treatment
  • Non-pharmacological treatments – Electroconvulsive therapy

 

What is the study method of this systematic review?

  • Literature search for articles regarding combination of two LAI APs from inception up to 9 February 2024, on PubMed, Scopus and APA PsychInfo, according to the PRISMA statement.

 

What are the types of articles included in this systematic review?

  • 9 case reports, 4 case series, 2 observational retrospective studies

 

Below are key points (in discussion section) regarding the use of dual LAI APs in treating schizophrenia spectrum disorders:

  • Growing Use: The use of two LAI APs is increasing in clinical practice despite a lack of specific guideline recommendations. This approach is used across a range of ages and illness durations, including stable schizophrenia and first psychotic episodes.
  • Efficacy: Patients treated with dual LAI APs generally show a good response, with improvements in symptoms and scores on psychopathological scales. The number and length of hospitalisations also tend to decrease.
  • Causation: It remains uncertain whether reduced hospitalisation rates result from switching from oral to long-acting drugs or from the combined use of two LAI APs. The dual LAI APs regimen appears to be effective even after unsuccessful attempts with oral drugs, including clozapine.
  • Adherence: LAI APs can improve adherence, reducing hospital readmissions in patients with psychosis who have a history of poor adherence.
  • Combination rationale: Some clinicians combine first- and second-generation antipsychotics to target different receptors, but combinations of two first-generation or two second-generation drugs are also possible.
  • Patient Consent: The willingness of patients to take two LAI APs is rarely mentioned, yet is important. Achieving shared decision-making (SDM) in clinical practice is a moral and ethical priority.
  • Safety: No new or unexpected adverse effects have been reported due to the combination of two LAI APs. The treatment is considered to be as safe as using one long-acting drug, without increasing the risk of adverse events.
  • Decision-Making: The decision to administer two LAI APs has advantages, such as improved compliance and control over medication levels, but also presents disadvantages such as discomfort from injections and difficulty managing side effects.
  • Reserved for Specific Patients: Dual LAI APs should be reserved for patients who have not benefited from previous adequate antipsychotic treatment, particularly those with poor compliance and when other strategies have failed

 

What are the limitations of this systematic review?

  • The review is limited by the inclusion of mainly case reports, the heterogeneity of samples, and the absence of randomised controlled trials

 

In this article, what is the recommended administration of two LAI APs?

  • The two intramuscular injections can be administered simultaneously or alternately on a weekly/bi-weekly basis. This choice doesn’t seem to affect the treatment’s effectiveness or the occurrence of adverse events. Clinicians should consider the pharmacokinetic properties of the LAI APs to maximise their clinical impact and avoid concentration peaks that could lead to adverse effects. It is important to avoid concentration peaks in the hours following administration, thus limiting excessive receptor occupancy and the consequent onset of adverse effects, such as extra-pyramidal symptoms, sedation, and hyperprolactinemia. To minimize pain or injury, it is recommended to alternate the muscle used for each drug administration