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The INTEGRATE project offers a concise, algorithmic guideline for schizophrenia pharmacotherapy, co-designed by global experts and those with lived experience.
Schizophrenia affects almost 1% of Australians. It remains one of the most severe and complex psychiatric conditions, with high levels of disability, early mortality and comorbidity. While effective treatments exist, they are often delayed, inconsistently applied or poorly tolerated. Existing guidelines are generally country-specific, lengthy and not always easy to navigate at the point of care. In response, the international INTEGRATE collaboration has developed a concise, algorithmic and evidence-based guide to the pharmacological treatment of schizophrenia.
This new guideline is particularly relevant to Australian clinicians. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) last updated its schizophrenia guideline in 2016, and while still clinically useful, it lacks structured recommendations for stepped care, shared decision making, and management of side effects using an algorithmic format. Moreover, Australian clinicians are dealing with a fragmented system, where state governments provide public psychiatric hospital services and some outpatient care for people with schizophrenia, while primary care and private psychiatry and allied health are funded by the federal government, where transitions between hospital and community settings can compromise continuity of care. A user-friendly tool that supports consistent decision making may help ensure consistency of care.
What we did
The INTEGRATE guideline was co-developed by experts from 30 countries and all UN regions, including Australian psychiatrists and lived experience advocates. Our goal was to produce a globally relevant yet locally applicable algorithm to guide pharmacological treatment of schizophrenia — from first episode to treatment resistance — while accounting for side effects, comorbidities, and the preferences of the person receiving care.
We conducted an umbrella review of meta-analyses and clinical trials, which informed a two-stage Delphi-style consensus survey, expert workshops (including at the 2024 Schizophrenia International Research Society meeting), and iterative input from people with lived experience of schizophrenia. Over 70 experts contributed to the surveys, and the guideline was endorsed by representatives from high, middle, and low-income countries.
What we found
The guideline is structured around shared decision making and early, personalised intervention. Initial pharmacotherapy should be guided by side effect profile, prior treatment history, and patient preference, with low-dose initiation and proactive titration. The guideline recommends first-line treatment with an antipsychotic with a lower overall side effect burden, such as a D2 partial agonist (eg, aripiprazole). If two antipsychotics are ineffective at therapeutic doses for 4–6 weeks, clozapine is recommended, with plasma monitoring and adjunctive metformin to reduce metabolic risk. If clozapine is not feasible, switching to olanzapine or augmentation strategies (eg, with aripiprazole or electroconvulsive therapy) may be appropriate.
The algorithm offers tailored approaches for different symptom domains. For persistent negative symptoms, strategies include switching to cariprazine or aripiprazole, cautious dose reduction, or antidepressant augmentation. For depressive symptoms, both psychosocial and pharmacological treatments are considered. Cognitive symptoms should prompt a review of anticholinergic burden and a trial of cognitive remediation therapy.
Importantly, the guideline recommends active metabolic health monitoring and management at all stages. Baseline and follow-up testing includes BMI, blood pressure, glucose, lipids and prolactin. Interventions such as statins, antihypertensives, metformin and GLP-1 receptor agonists are incorporated into the treatment algorithm based on thresholds familiar to general practitioners and primary care teams.
An accompanying open-access digital tool allows clinicians to input patient-specific data and receive step-by-step guidance from the algorithm.
These guidelines differed from a GRADE approach, which may be a limitation and a strength. Rather than using GRADE criteria, findings of the umbrella reviews were validated using a Delphi consensus approach. This is important in areas where there is low quality GRADE evidence, such as management of akathisia or hyperprolactinaemia.
What needs to happen next?
Mental health treatment in Australia needs to move to a more collaborative approach for the care of people with schizophrenia. The INTEGRATE guidelines offer a tool that is not only evidence-based and consensus-driven, but can be applied in both primary care and specialist mental health services. We believe this tool has the potential to support more consistent prescribing, reduce inappropriate polypharmacy, and address the high rates of untreated side effects and metabolic complications that plague our current practice.
We would like to see health services, particularly in public mental health, adopt algorithmic prescribing tools into routine care. Electronic medical records could integrate these algorithms and link them to prescribing alerts. Registrars and early-career psychiatrists would benefit from structured clinical decision support — especially in rural or after-hours settings where senior supervision may be less available.
In addition, the digital tool could also be embedded in primary care settings, where much of the ongoing physical and mental health care occurs.
Finally, further implementation research is needed to evaluate the real-world impact of the guideline on patient outcomes, treatment satisfaction and health system performance. Living updates of the guideline are planned every five years, ensuring that the tool remains responsive to emerging treatments — like novel antipsychotics, GLP-1 agonists or digital interventions.
Conclusion
Schizophrenia remains one of the most serious challenges in mental health care. We now have a roadmap, grounded in evidence and consensus, to guide clinicians through the pharmacological treatment of this complex condition. It is time to put that roadmap into the hands of every psychiatrist, registrar and GP who cares for people with schizophrenia.
Dan Siskind is a psychiatrist and Professor of Psychiatry at The University of Queensland. He works clinically at Metro South Addiction and Mental Health Services in Brisbane.
Rob McCutcheon is a psychiatrist and Associate Professor of Psychiatry at the University of Oxford.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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