Small steps for big impact in treatment of schizophrenia

Functional recovery is an important goal in treating schizophrenia, but one that can be hard to achieve. At the ECNP 2021 hybrid meeting, Professor Jose Manuel Olivares of the University of Santiago de Compostela, Spain, explained how small steps may make a big difference.

Functional recovery is an important outcome for schizophrenia treatment. Goals should be personalized and optimized to each patient and can include:1,2

  • reducing or eliminating and controlling symptoms
  • monitoring for adverse events
  • preventing relapse
  • maximizing quality of life and adaptive functioning
  • enabling and maintaining recovery
  • helping patients to achieve their own life goals


Step 1: Identifying psychosis early promotes functional and clinical remission

Functional remission is closely coupled with clinical remission, particularly early in schizophrenia. In a real-world setting analysis of 220 patients who achieved functional remission, there was a significant association with clinical remission (odds ratio [OR] 14.74; p < 0.0001). What’s more, the relationship was strongest in patients with duration of psychosis under 5 years (n = 80; OR 23.73; p < 0.0001).3

Early detection of psychosis leads to higher recovery rates

This underlines the importance of identifying psychosis early, which was investigated in the 10-year follow-up of the Treatment and Intervention in Psychosis Study (TIPS). Significantly higher proportions of patients who had early detection of psychosis had recovered (p = 0.017) or were in full-time work (p = 0.007).4


Step 2: Early intervention improves outcomes

Simply identifying psychosis earlier is not enough; it must also be treated earlier. When the duration of untreated psychosis (DUP) was less than 1 year, significantly more patients, in an Italian study, showed a ‘favorable’ clinical course than those with a DUP of more than 1 year (p = 0.049).5

Similarly, a 12-month follow-up from the Northwick Park Study of First Episodes showed rates of relapse were halved if the duration of untreated illness (DUI) was less than 44 days, compared with DUI of more than 365 days (p = 0.004).6

Early intervention was better than treatment-as-usual in all meta-analyzable outcomes

Early intervention was better than treatment-as-usual in all meta-analyzable outcomes in a meta-analysis of 10 studies totaling 2176 patients. This included global functioning (p = 0.001), general symptom severity (p = 0.001), involvement at school or work (p =0.01), and risk of relapse (p = 0.01).7


Step 3: Long-acting injectables reduce hospitalizations

Only half of patients in one study took their medication for at least a month after first hospitalization

Even if the clinician identifies psychosis early and prescribes medications, it counts for nothing if the patient does not take them. In a study of 2588 patients at their first hospitalization in Finland, 54.3% of patients did not collect a prescribed antipsychotic within 30 days of discharge, or used the medication for less than 30 days.8

How can clinicians try to improve treatment adherence? One option is to consider a long-acting injectable (LAI) antipsychotic. A cluster randomized study, in the US, tested whether LAIs delayed hospitalization in early-phase schizophrenia compared with clinicians’ choice in a real-world setting.9

In a study, long-acting injectable improved adherence and delayed time to hospitalization

The study showed there was a 44% decrease in incidence rate of first hospitalization after treatment with an LAI compared with clinician’s choice.9 The number-needed-to-treat with the LAI to prevent one additional hospitalization was 7 patients.9

The benefits of LAIs hold across studies. According to a meta-analysis of 42 studies, patients treated with LAIs had a significantly lower hospitalization rate than patients receiving oral antipsychotics (p < 0.001), despite having more severe or chronic illness (p = 0.01). Risk of discontinuation from any cause was also significantly lower with LAIs (p = 0.001).10


Educational financial support for this Satellite symposium was provided by Otsuka Pharmaceutical Europe Ltd and H. Lundbeck A/S.

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. Hasan et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013;14(1):2-44
  2. Lehman et al. APA practice guideline for the treatment of patients with schizophrenia. 2nd edition, 2010
  3. Gorwood et al. Predictive factors of functional remission in patients with early to mid-stage schizophrenia treated by long acting antipsychotics and the specific role of clinical remission. Psychiatry Res 2019;281:112560
  4. Hegelstad et al. Long-term follow-up of the TIPS early detection in psychosis study: effects on 10-year outcome. Am J Psychiatry 2012;169(4):374-80
  5. Primavera et al. Does duration of untreated psychosis predict very long term outcome of schizophrenic disorders? Results of a retrospective study. Ann Gen Psychiatry 2012;11(1):21
  6. Owens et al. Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk. Br J Psychiatry 2010;196(4):296-301
  7. Correll et al. Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. JAMA Psychiatry 2018;75(6):555-65
  8. Tiihonen et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011;168(6):603-9
  9. Kane et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry 2020;77(12):1217-24
  10. Kishimoto et al. Effectiveness of Long-Acting Injectable vs Oral Antipsychotics in Patients With Schizophrenia: A Meta-analysis of Prospective and Retrospective Cohort Studies. Schizophr Bull 2018;44(3):603-19