Do long-acting injectable antipsychotics have a role in early-phase schizophrenia?

Early intervention and continuous treatment in schizophrenia are key to ensuring good outcomes. This includes determining patient’s treatment goals, developing a relapse prevention plan, and acknowledging adherence issues, but is there a role for long-acting injectable antipsychotics (LAIs)? The case was put forward in this ECNP2020 Satellite symposium.

The need for early intervention

Management of the first psychotic episode has long-term implications, proposed Tara Niendam (University of California, USA). Duration of untreated psychosis, from first episode to accurate diagnosis, strongly predicts long-term outcome1. ‘Early’ psychosis (first 5 years after onset of symptoms) is the critical period when treatment has its biggest impact2.  Focus on maintaining functioning rather than recovering lost functioning.

Early psychosis is the critical period when treatment has its biggest impact


Reducing the risk of relapse

Potential courses of illness are heterogeneous, and early comprehensive treatment can reduce long-term disability3. Early functioning is the best predictor of later functioning. Give the patient the message that recovery is possible, and focus on the wider treatment goals and roles they wish to pursue, alongside controlling symptoms. Developing a ‘patient relapse prevention plan’ helps them recognize early signs of relapse and respond quickly and appropriately.

Unawareness of illness is an important feature of schizophrenia, said Robin Emsley (Stellenbosch University, Cape Town, South Africa). Insight often remains impaired despite a favorable treatment response4, and impacts on ability to be involved in treatment-making decisions.

Stopping medication is the most powerful predictor of relapse

Stopping medication is the most powerful predictor of relapse5. Even short periods of antipsychotic discontinuation can lead to relapse and the abrupt return of florid symptoms, often with few early warning signs6. Consequences of relapse can be severe, involving psychosocial7 and biological effects6. The latter include emergent refractoriness6, brain volume reduction8, and increased mortality9.


LAIs can be used to reduce relapse rates

Prof Emsley suggested LAIs should be used to reduce relapse rates. In a meta-analysis, LAIs were associated with a 64% lower risk of rehospitalization than oral medication10. How the physician presents the option of an LAI can greatly affect the likelihood of acceptance11. Focusing on the treatment benefits for the patient, and not just the modality, is important. Incorporating motivational interviewing allows incorrect treatment beliefs to be challenged.

An LAI, in a clinical trial, significantly delayed the time to first hospitalization in individuals with early-phase schizophrenia, compared to standard care

LAIs are not widely used in the early-phase of schizophrenia, with reasons including overestimation of degree of adherence with oral medication and bias against injections12. John Kane (Donald and Barbara Zucker School of Medicine, New York, USA) stressed that difficulty in adhering to chronic treatments is a normal human characteristic and should not be stigmatized. Many barriers to the use of LAIs can be overcome with education and training12. A very recent clinical trial results showed that an LAI significantly delayed the time to first hospitalization in individuals with early-phase schizophrenia, compared to standard care13.


Benefits of early-intervention program

Charlotte Emborg Mafi (Aarhus University Hospital, Denmark) discussed the intensive early-intervention program for first episode psychosis introduced in Denmark, with an ‘assertive’ approach to optimizing patient engagement.  Teams have a low staff to patient ratio, allowing home visits and frequent contact. Total direct and indirect medical costs per patient were reduced with this approach, as well as increased adherence to treatment14,15.


Educational financial support for this Satellite symposium was provided by Lundbeck.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Perkins DO, et al. Am J Psychiatry 2005;162:1785-804.
  2. McGorry PD, et al. World Psychiatry 2008;7:148-56.
  3. Volavka J, Vevera J. Int J Clin Pract 2018;72:e13094.
  4. Phahladira L. et al. Schizophr Res 2019;206:394-9.
  5. Robinson D, et al. Arch Gen Psychiatry 1999;56:241-7.
  6. Emsley R, et al. BMC Psychiatry 2013;13:50.
  7. Kane JM. J Clin Psychiatry 2007;68 Suppl 14:27-30.
  8. Andreasen NC, et al. Am J Psychiatry 2013;170:609-15.
  9. Taipale H, et al. World Psychiatry 2020;19:61-8.
  10. Tiihonen J, et al. Am J Psychiatry 2011;168:603-9.
  11. Weiden PJ, et al. J Clin Psychiatry 2015;76:684-90.
  12. Kane JM, et al. J Clin Psychiatry 2019;80:18m12546.
  13. Kane JM, et al. JAMA Psychiatry 2020;e202076.
  14. Hastrup LH, et al. Br J Psychiatry 2013;202:35-41.
  15. Nordentoft M, et al. Early Interv Psychiatry 2015;9:156-162.
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