What do APA’s Schizophrenia Treatment Guidelines say about long-acting injectable antipsychotics?

On September 1, 2020, the American Psychiatric Association released a new evidence-based “Practice Guideline for the Treatment of Patients with Schizophrenia.” [1]  Their last Schizophrenia Treatment Guideline was quite dated (2004), so this is a welcome publication as psychiatric treatment and treatment philosophies have shifted in the past decade.  Specifically, many new LAI formulations have become available, and the benefit of LAIs for relapse-prevention in the treatment of schizophrenia has been shown in clinical trials of second-generation LAIs across a range of clinical situations.

The following guideline statement pertains specifically to the use of long-acting injectable antipsychotics:

“APA suggests that patients receive treatment with a long-acting injectable antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence.” [2]

Regarding this statement, we add the following comments:

  • Note that a patient can only express a preference if LAIs are offered by the clinician as a good alternative to oral antipsychotics. A major barrier to the use of LAIs is lack of inclusion of this option by clinicians when discussing various antipsychotic therapies.
  • While not explicitly noted in the statement, LAIs are a possible choice for any stage of illness, including first-episode psychosis – if patients prefer it.
  • LAIs are specifically suggested if non-adherence is a known concern (by history) or a clinical possibility. Consideration of the possibility of non-adherence is important to avoid mistakenly labeling a patient as treatment-resistant.  A time-limited LAI trial can resolve this uncertainty around adherence.  This is a critical point if clozapine is considered for treatment-resistance.
  • The statement does not specifically outline clinical situations where LAI should be strongly considered. Clinical examples may include patients with forensic histories due to untreated psychosis and patients with co-morbidities or symptoms that increase the probability of non-adherence (e.g., active substance use or anosognosia, respectively).
  • The APA adds that LAIs (like other pharmacological treatments) “should be implemented in the context of a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments for schizophrenia.” This deserves emphasis: simply prescribing a LAI does not constitute good psychiatric care.
  • The APA Guideline with regards to LAIs is consistent with a recent, extensively revised German Schizophrenia Guideline. The German Guideline emphasizes that LAIs are an evidence-based and effective choice for patients who require antipsychotic maintenance treatment in order to prevent a relapse.  The German Guideline adds that choosing a LAI is guided by side effects and injection interval, not efficacy differences. [3]



[1] The APA Guideline is available for free here.

[2] Using the GRADE (Grading of Recommendations Assessment Development and Evaluation) approach, the confidence of the statement is rated as a 2B suggestion (suggestion = balance of benefits and harms less clear compared with a recommendation; B = moderate strength of supporting evidence).

[3] The German Guideline (in an English version) is available for free here.

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