Long-acting injectables (LAIs) can provide numerous benefits throughout the continuum of care in certain patients with schizophrenia

LAI antipsychotics (APs) are a treatment option available which help to eliminate uncertainties regarding adherence status while also maintaining stable plasma drug levels over a range of dosing intervals, from every two weeks up to six months.^1,3,4 There is a wide range of evidence from randomized controlled trials, cohort studies, mirror-image studies, and pragmatic studies demonstrating that patients treated with LAIs have improved adherence, lower relapse rates, and lower risk of hospitalization when compared with those treated with oral medications.^2,5 In the past, LAIs have traditionally been recommended for those with frequent recurrences of schizophrenia or adherence issues, however, recent emerging literature, guidelines, and expert opinions suggest that LAIs offer several benefits throughout the continuum of care.¹ 

LAIs may delay and reduce the risk of poor outcomes in early-phase schizophrenia

The consequences of relapse are particularly burdensome for patients in the early phases of their illness diagnosis.⁶ Studies have shown that individuals with early-phase illness who are experiencing a second episode of psychosis have a poorer response to treatment with the same AP than they did during their first psychotic episode.^1,6 LAIs may offer a possible solution to improve treatment adherence rates and reduce the risk of relapse in people living with schizophrenia.¹ In a prospective study of 83 patients with early schizophrenia who were randomly assigned to either LAI or oral APs after a 3-week oral stabilization phase, fewer patients in the LAI group experienced a psychotic exacerbation or relapse and the time to relapse was delayed, compared with the oral AP group.⁷ 

In addition, in a recent randomized trial of 489 participants, the use of LAIs in early-phase schizophrenia treatment substantially improved survival time until first hospitalization.⁶ The mean survival time until first hospitalization of patients treated with LAIs was 83 days longer than those who received the clinician’s choice of medication.⁶ LAIs have also been linked to a significantly lower risk of rehospitalization when compared with equivalent oral formulations of APs.⁸  

LAIs have consistently demonstrated significant benefit compared with oral APs in preventing hospitalization or relapse in studies ranging from restricted research to real-world application.² These data suggest clinicians should more broadly consider LAI treatment for patients with early-phase illness.⁶ Furthermore, despite the commonly-held belief that patients may not want to initiate LAI treatment, data have shown that the majority of patients with early-phase illness readily accept LAIs.^6,7 Studies have also found that with the appropriate training, healthcare providers are able to effectively communicate the advantages of LAIs, resulting in high acceptance rates among patients.⁶

LAIs may delay discontinuation and facilitate treatment continuity in patients with schizophrenia

On account of the chronic nature of schizophrenia, long-term continual AP treatment is crucial to achieve and maintain symptom control in patients with schizophrenia.^1,5 Sustaining an appropriate treatment regimen is a key goal in schizophrenia as treatment discontinuation can result in symptom relapse and puts patients at a greater risk of hospitalization.¹ Additionally, psychotic relapse related to treatment discontinuation has numerous downstream effects on disease course and brain structure, such as potential progressive decline in gray and white matter structure and volume.¹ In a national cohort study of more than 3000 patients with first-episode psychosis who were followed for up to 18 years, patients were 67% less likely to discontinue LAIs compared with other oral formulations of APs.⁵ LAIs have also been proven to have neurobiological benefits in early-phase illness.⁵ These findings may be explained by the improved assurance of continuous treatment with LAIs compared with oral counterparts, as they help to ensure continuous drug delivery and longer treatment periods for the same individual.⁵ LAIs are therefore particularly appropriate and should be considered in patients at risk of treatment interruption, such as those with early-phase illness and those with comorbid substance use disorders.⁵

Treatment with LAIs can also help to rule out pseudo-resistance due to inadequate treatment adherence.⁹ Guidelines have suggested that treatment resistance should be defined by at least one failed trial with an LAI, given for at least 6 weeks after it has achieved steady state (generally at least 4 months from commencing treatment).^9–11

Guidelines recommend LAIs beyond cases of nonadherence

The American Psychiatric Association (APA) recommends that patients receive treatment with an LAI if they prefer such treatment or if they have a history of poor or uncertain adherence.¹² Additionally, the Florida Best Practice Psychotherapeutic Medication Guidelines suggest initial treatment monotherapy with a second-generation oral AP followed by the same second generation LAI.¹³ APA guidelines and growing expert consensus support a wider use of LAIs among patients with schizophrenia, including those with:^12,14 

• Poor insight into their illness and need for treatment
• Homeless or unstable housing situation
• Transitioning between settings of care
• History of multiple (>2) hospitalizations for psychotic relapses
• History of violence to others
• History of suicide attempt
• Substance use disorder
• Young age (18–25 years of age)
• Cognitive impairment
• Good psychosocial support (e.g., from family members)
• Good insight into illness and need for treatment
• Medically unstable patient for whom you are concerned about development of potential side effects

Several factors should be considered when choosing to initiate an LAI 

When making the decision to initiate an LAI, clinicians should review the numerous associated pragmatic factors or ‘amenities of care’ and consider these when developing and communicating the treatment plan with the patient. Patients may also have specific preferences and values regarding the frequency, location, and type of injection. Important considerations for selecting an LAI include:^12,15

• How often are the injections administered?
• Are there different dosing strengths available?
• What is the needle gauge?
• What is the injection volume?
• Is there a choice of injection site? (e.g., intramuscular deltoid or gluteal sites, subcutaneous abdominal site)
• Does this product require reconstitution?
• Does storage of this product require refrigeration?
• Is oral supplementation required?
• Are there any special requirements for post-injection observation?
• Are there any important drug–drug interactions, and can they be remedied?
• Missed doses: what is the grace period?

Early and appropriate use of LAIs may improve individual patient outcomes and provide important benefits for the schizophrenia community as a whole, including increased patient adherence, reduced family and caregiver burden, and improved health economics outcomes.¹²