Psychiatry Practice Changers 2014

Bret S. Stetka, MD; Cristoph U. Correll, MD


December 08, 2014

In This Article

Long-acting Injectables: Defining Their Role

Antipsychotic nonadherence is estimated to be as high as 40%, greatly increasing the risk for relapse in patients with psychosis. The worrisome epidemiology comes with enormous potential costs to patients and their families—financial stress, worsening mental and medical health, and, most seriously, increased risk for suicide among them. Long-acting injectable (LAI) antipsychotic formulations were developed to hopefully address the problems of nonadherence and relapse.

Less frequent dosing can encourage and enable patients to better adhere to the medication schedule. From the clinician's perspective, the exact knowledge of if and when a patient stops taking the scheduled medication allows for a timely outreach during a window of opportunity where the blood level does not drop precipitously, and patients and/or caregivers can be reached to get the patients back on treatment that they require to stay stable. However, the question of the potential benefits of LAIs in research settings and real-world patients still has experts debating on page and podium.

Two recent randomized controlled trials[8,9] reported no advantage of LAI risperidone (Risperdal®) over oral antipsychotics, a finding echoed by previous work. But as the authors concluded and Donald C. Goff pointed out in a JAMA editorial[10] earlier this year, this lack of a difference could be partly due to the fact that schizophrenia patients willing to enroll in clinical trials may have better adherence patterns and receive different interventions inherent to a research study that enhance adherence behaviors vs in real-world settings, so they benefit more from oral agents than do often nonadherent patients followed in usual care settings.

This interpretation of the results is in line with findings from mirror-image studies[11] published in 2013 showing that LAIs are significantly more effective in preventing hospitalizations compared with oral antipsychotics. Mirror studies compare periods of different treatments in the same patients. Despite a potential observation bias during the often prospective LAI period, these studies may provide a more real-world comparison of two agents as observed in clinical care where clinicians also compare different approaches in the same patient and in those who are clinically eligible for a switch to an LAI having problems with adherence and relapses on oral agents.

Relatedly, findings from the ACLAIMS (A Comparison of Long-acting Medications for Schizophrenia) trial[12]—the first randomized comparison of a first- vs a second-generation LAI antipsychotic—were reported in JAMA this year. ACLAIMS included patients at high risk for relapse, better representing a real-world sample. The investigators found no statistically significant difference in the rate of efficacy failure for paliperidone (Invega® Sustenna®) compared with haloperidol (Haldol®), though the long-acting paliperidone was associated with more weight gain and increases in prolactin, while more akathisia was seen with the long-acting haloperidol.

LAI use varies greatly across countries and cultures despite the fact that different degrees of nonadherence are universal and common in patients with severe psychotic disorders. As data are emerging that repeated relapses may reduce treatment responsiveness, clinicians should consider the use of LAIs earlier in the treatment algorithm, offering their use to patients in a nonpunitive, proactive, and preventive fashion.


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