Improving long-term outcomes in schizophrenia — translating evidence into practice

The long-term goals of treatment to optimize outcomes for patients with schizophrenia are relapse prevention, management of comorbid medical conditions, and minimization of adverse events, said Rajiv Tandon (Professor of Psychiatry, Department of Psychiatry, University of Florida, FL), and Ilan Melnick (Chief Medical Officer, Miami, FL), at a breakfast symposium at Psych Congress. Relapses cause brain damage and disease progression and are prevented by antipsychotic therapy. Adherence to a daily oral antipsychotic (OAP) regimen can, however, be difficult, particularly for those with cognitive impairment. Long-acting injectable atypical antipsychotics (LAIs) provide the assurance of adherence and are associated with significantly lower relapse rates for individuals experiencing a first episode of psychosis.

Professor Tandon highlighted that the three principles underpinning the long-term management of patients with schizophrenia are knowledge of:

  • the nature of the illness, including identification of treatment targets and goals
  • the therapies available, and their effectiveness and adverse events
  • the tools to measure and monitor outcomes, and to enable targeted and individualized care

Antipsychotics have different adverse-effect profiles

Choosing the best antipsychotic for each patient

Antipsychotics are the mainstay of pharmacotherapy for treatment of schizophrenia. Treatment with antipsychotics are broadly effective against psychotic symptoms, but have perhaps limited efficacy in treating negative and cognitive symptoms. Each has unique pharmacokinetic and adverse event profiles, and individual patient responses to different medications may vary,1,2 Professor Tandon explained.

Significant adverse events vary for different antipsychotics and include extrapyramidal symptoms (EPS) and tardive dyskinesia (TD); metabolic symptoms, e.g. weight gain, dyslipidemia, and diabetes; sedation, hypotension, and hyperprolactinemia; and anticholinergic effects.2

Atypical antipsychotics have been shown to cause less extrapyramidal symptoms (EPS) and tardive dyskinesia than first-generation antipsychotics3

Second-generation atypical antipsychotics are a better treatment choice than first-generation antipsychotics for many individuals with schizophrenia, Professor Tandon continued, because their use is associated with:3

  • fewer negative symptoms
  • less TD
  • fewer EPS
  • better cognition
  • less depression
  • less nonadherence

The goal of pharmacotherapy is to optimize individual outcomes, said Professor Tandon. In the long-term; relapse prevention, management of comorbid medical conditions, and minimization of adverse events are key, based on targeted, individualized, and measurement-based treatment.3

Antipsychotic nonadherence increases the risk of relapse

Nonadherence leads to a threefold increase in risk of relapse3 and prevention of relapse is critical to optimizing outcome

Difficulties in adhering to an OAP treatment regimen are to be expected when patients are required to take a medication every day, particularly if they are experiencing cognitive impairment, said Professor Tandon. However, nonadherence leads to a threefold increase in risk of relapse.3

Each relapse causes brain damage marked by progressive ventricular enlargement and disease progression; impaired symptomatic recovery, functional recovery, and quality of life; increased treatment costs; and higher mortality,2,3 explained Professor Tandon. In addition, pharmacotherapies become less effective with each relapse.

Much of the deterioration in schizophrenia occurs early in the illness, within the first 5 years, he added.

LAIs provide the assurance of adherence and improve outcomes

Early use of an LAI can improve quality of life and prognosis

Dr Melnick explained that early use of an LAI, if possible from the first episode of psychosis, can:

  • reduce number of future relapses, and number and duration of rehospitalizations
  • improve cognition, quality of life and prognosis4

LAIs not only provide the assurance of adherence but significantly lower relapse rates (p<0.001) for patients experiencing a first episode of psychosis,5 he added.

LAIs are a valuable tool to simplify treatment of schizophrenia and address adherence and outcomes

Dr Melnick also discussed a systematic review/meta-analysis of 21 randomized controlled trials (RCTs) (n = 5176) comparing LAIs and OAPs, which demonstrated that pooled LAIs did not reduce relapse compared with OAPs in patients with schizophrenia.6 However, Dr Melnick advised, RCTs might enroll a disproportionate number of patients with better treatment adherence and lower disease severity than in the real world. Mirror-image studies that compare periods of OAP versus LAI treatment in the same patients, might therefore better reflect the population receiving LAIs in clinical practice.7

He described an analysis of 25 mirror-image studies from 28 countries that followed 5940 patients with schizophrenia for at least 12 months (≥6 months each on OAP and LAI). LAIs showed strong superiority over OAPs in preventing hospitalization (p<0.001) and in decreasing the number of hospitalizations (p<0.001).7

LAIs are a valuable tool to simplify treatment of schizophrenia and address adherence and outcomes, said Dr Melnick, and some guidelines now recommend that most patients who require long-term antipsychotic treatment should be offered an LAI.8

To change the lives and treatment outcomes of patients with schizophrenia it is necessary to target the critical years and to start LAIs early

Dr Melnick concluded that to change the lives and treatment outcomes of patients with schizophrenia it is necessary to target the critical years and to start LAIs early.

Educational financial support provided by Alkermes, Inc., Indivior Inc, and Otsuka America Pharmaceutical, Inc. and Lundbeck.

  1. Bruijnzeel D, et al. Asian J Psych 2014;11:3–7.
  2. Keshavan M, et al. Prog Neurobiol 2017; 152:3–20.
  3. Tandon R, et al. Schizophr Res 2010;122(1-3):1–23.
  4. Viala A, et al. Schizo Res Treat 2012:Article ID 368687.
  5. Subotnik K, et al. JAMA Psychiatry 2015;72(8):822–9.
  6. Kishimoto T, et al. Schizophr Bull 2014;40(1):192–213.
  7. Kishimoto T, et al. J Clin Psychiatry 2013;74(10):957–65.
  8. Llorca P, et al. BMC Psychiatry 2013;13:340–57.
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