Tracing the Arc of Progress: A Historical Exploration of Evolving Schizophrenia Treatments and Treatment Goals

What series of small steps can promote and maintain functional recovery in
patients with schizophrenia & BP-I disorder?


During The 27th Emirates Mental Health Society International Congress Cognitive, Behavior & Emotional held in Dubai, UAE (29 September to 1 October 2023)), a symposium titled " What series of small steps can promote and maintain functional recovery in
patients with schizophrenia & BP-I disorder?
" was helmed by Professor Gus Alva, Medical Director, ATP Clinical Research; Assistant Professor, Department of Psychiatry and Neuroscience, University of California, Riverside, CA. The symposium traced schizophrenia treatments from the severe methods of the pre-1950s to modern Long-Acting Injectable therapies, spotlighting a significant transition towards improving life quality for affected individuals. Delving into the PRELAPSE study, the discussion highlighted the potential of LAIs in reducing hospitalization risk, advocating for a value-driven approach in introducing such therapies to patients. The session underscored the persistent advancement in psychiatric medicine, emphasizing a holistic treatment outlook beyond mere symptom alleviation.

The Evolution of Schizophrenia Treatments and Treatment Goals1

The journey of schizophrenia treatment elucidates the continual stride towards enhanced therapeutic strategies over the decades. Pre-1950s, treatment resorted to severe measures like insulin coma and electroconvulsive therapy in the absence of antipsychotics with the goal of treating aggression and self-harm. Post-1950s, the emergence of first-generation antipsychotics offered a pathway to address the positive symptoms of schizophrenia in addition to treating aggression and self-harm. The transition to second-generation antipsychotics during the 1990s fostered a reduced adverse effect profile while addressing negative symptoms primarily, in addition to the previous goals. With the 2000s emerged an inclination towards new mechanisms of action, accentuating a holistic approach beyond mere symptom alleviation. Modern-day strategies now encompass the treatment of aggression, self-harm, and adverse effects alongside core symptoms, aiming for remission, recovery, and an elevated quality of life. The evolution from rudimentary interventions to a more nuanced, patient-centric approach epitomizes the relentless progress in psychiatric medicine, striving not just for symptom control but for a broader enhanced life quality for individuals afflicted with schizophrenia.


Long-term Antipsychotic Use: A Shield Against Relapse and Mortality

Contrary to prevailing beliefs suggesting that relapse risk decreases post the inaugural schizophrenia episode, research from a nationwide Finnish database, spanning 1996-2014, examined outcomes for 8,719 patients after discontinuation of antipsychotic treatment.2 The data showed that patients on continuous antipsychotic medication faced the least risk of rehospitalization or death, whereas risk significantly increased for those discontinuing treatment at varying intervals post first hospital discharge. Strikingly, the risk didn't decline over the initial 8 years post discontinuation, emphasizing that prolonged antipsychotic therapy correlates with improved survival rates. Additionally, the risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years.2


First Impressions: The Impact of Therapy Introduction on LAI Acceptance

Long-acting injectable (LAI) therapy represents a significant advancement in managing chronic conditions like schizophrenia.3 By administering medication in an injectable form at extended intervals—weekly, bi-weekly, or even monthly—LAI therapy helps mitigate the challenges associated with daily oral medication adherence.3,4 However, not all patients accept LAI therapy, and this acceptance is affected by several factors. The manner in which LAI therapy is introduced to patients significantly influences their acceptance of it.5 A mere 33% (n=11/33) of patients agreed to LAI therapy when discussed negatively by psychiatrists, often emphasizing the mode of administration.5 Contrastingly, when more information was shared post-visit, a striking 96% (n=27/28) of those who initially declined were willing to accept LAI therapy.5 This drastic difference underscores the importance of a value-led discussion surrounding LAI therapy, which should highlight the personal benefits and share positive experiences from other patients to foster a better acceptance rate.6


LAIs and Early-Phase Schizophrenia: A Journey to Delayed Hospitalization

The impact of LAI therapy on hospitalization risk was evaluated by the PRELAPSE study,7,8 which was carried out over a span of 2 years across 39 mental health centers in the US, aimed to unravel the impact of LAI antipsychotics on the time to first hospitalization among individuals with early-phase schizophrenia. By conducting a meticulous randomized clinical trial, the study contrasted the outcomes between patients treated with LAIs and those receiving usual care. Remarkably, the data depicted a more extended period before hospitalization in the LAI group, with a mean survival time of 613.7 days as opposed to 530.6 days for the control group. The hazard ratio stood at 0.56, showcasing a statistically significant delay in hospitalization for those on LAI treatment. Additionally, there was a 44% reduction in the incidence rate of first hospitalization. This pivotal finding underscores the potential of LAIs as a compelling treatment alternative in early-phase schizophrenia management. It beckons clinicians to broaden their horizons in treatment options, recognizing the substantial personal and economic benefits tied to delayed hospitalization. The insights from the PRELAPSE study carve a path toward a more informed, value-driven discussion surrounding the adoption of LAIs in early schizophrenia treatment protocols. As discussed in many studies, even in early-phase patients, a higher rate of LAI use can be achieved in community mental health centers than is currently the case.9-11


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