Abstract
With more long-acting injectable (LAI) antipsychotics available for treating schizophrenia, each with variable durations of action (2 weeks to 3 months), it is important to have clear management strategies for patients developing breakthrough psychotic symptoms or experiencing symptomatic worsening on LAIs. However, no treatment guidelines or clinical practice pathways exist; health-care providers must rely on their own clinical judgment to manage these patients. This article provides practical recommendations-based on a framework of clinical, pharmacokinetic, and dosing considerations-to guide clinicians' decisions regarding management of breakthrough psychotic symptoms. Management options include ruling out/addressing medical illness or substance abuse/misuse as a contributing factor, addressing stressors, optimizing nonpharmacologic treatments, treating medical/psychiatric comorbidities, ensuring proper LAI administration technique, addressing missed LAI doses or lack of steady-state attainment, and increasing LAI dose directly or indirectly by shortening the injection interval (off-label). If these strategies do not work sufficiently with frequent monitoring, the LAI could be supplemented with a low dose of the corresponding oral formulation for fast symptom control (off-label). However, caution should be exercised with this strategy, because data on the safety of concomitant use of LAI and oral antipsychotics (OAPs) are limited, especially over extended periods. If symptoms abate, therapy optimization could be continued and slow discontinuation of the OAP could be considered. For persistent/worsening symptoms, the OAP should be increased to optimum effective dose while intensifying the initial steps used before it was added. If this fails, switching the OAP or LAI could be considered. We believe that these strategies will help clinicians manage breakthrough psychotic symptoms during LAI treatment and improve overall outcomes among those who can benefit from LAIs.
Highlights
Earlier data estimated that long-acting injectable (LAI) antipsychotics were prescribed to between one-quarter and one-third of patients with schizophrenia in the United States, Australia, and Europe[3,4]; more recent data (2016) from the United States indicate that 11% of patients are prescribed LAI antipsychotics
This article provides a framework and action plan for health-care providers (HCPs) who manage patients treated with LAI antipsychotics who present with breakthrough psychosis and symptomatic worsening
Management options aimed at optimizing the disease prognosis and patient outcome include first ruling out or addressing medical or substance use as a contributing factor, identifying and addressing potential stressors, optimizing nonpharmacologic treatments, treating medical and psychiatric comorbidities, ensuring proper LAI administration technique, addressing missed LAI doses or lack of steady state, and increasing the dose of LAIs or shortening their injection intervals
Summary
The use of long-acting injectable (LAI) antipsychotics for the treatment of patients with schizophrenia decreased significantly after oral formulations of second-generation. We provide practical solutions based on a framework of clinical, pharmacokinetic (PK), and dosing considerations to help HCPs make well-informed decisions regarding management strategies for patients presenting with breakthrough psychotic symptoms or symptomatic worsening while being treated with LAI antipsychotics. 1064 mg every 2 months; for ∙ For patients taking 882 mg monthly (or every 6 weeks), with oral aripiprazole for 21 those stabilized on 20 mg/d if the length of time since the last injection consecutive days. Potential causes of breakthrough psychotic symptoms that may need to be addressed can include treatment nonadherence to LAIs, OAPs, non-antipsychotic comedications, and inappropriate or inadequate dosing, including initiating treatment incorrectly and other medication errors. The benefit of adding a different antipsychotic, done frequently in clinical care, is not supported by highlevel evidence based on randomized controlled trials.[31,32,33] This even seems to apply to clozapine, for which there is limited and inconsistent evidence of benefit when included as part of a polypharmacy
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