INTEGRATE: International guidelines for the algorithmic treatment of schizophrenia

Quick reference guide

Context

Schizophrenia affects approximately 0.7% of the global population and is associated with substantial morbidity, reduced life expectancy, and high cardiometabolic burden. A 2022 systematic review identified that existing guidelines are largely country-specific, lack structured algorithmic approaches, and provide insufficient guidance on early non-response management, maintenance treatment duration, and negative symptoms (Correll et al., Schizophrenia, 2022). INTEGRATE was developed between May 2023 and January 2025 through an umbrella review of 83 meta-analyses, two international consensus surveys with 70 experts from 30 countries, lived experience focus groups, and an expert workshop attended by 255 clinicians. The guidelines align with the ANZJP GRADE Guidelines for Schizophrenia (2026) and complement other key references including the Maudsley Prescribing Guidelines, providing greater algorithmic specificity for day-to-day clinical decision-making in Australian and international settings.

Key recommendations

The five key recommendations below are derived from the INTEGRATE guidelines. Each should be applied using shared decision-making, with treatment individualised to patient preferences, side-effect profile, and clinical context.

Recommendation 1: Use shared decision-making and individualised prescribing. 

Involve patients and carers in all prescribing decisions. Select antipsychotics based on individual side-effect profiles, efficacy, route of administration, and pharmacokinetic factors (age, sex, comorbidities, tobacco use, renal/hepatic function). Use digital decision-support tools where available (e.g., antipsychotic side-effect comparison tools, PsyMetRiC cardiometabolic risk calculator). Act promptly on inadequate response or poor tolerability.

Recommendation 2: Follow a structured, algorithmic treatment sequence. 

In first-episode psychosis, initiate with a low side-effect burden antipsychotic such as a D2-partial agonist (e.g., aripiprazole 10 mg if no patient preference). Assess response at 1 week and titrate accordingly. If significant positive symptoms persist after a therapeutic trial of ≥4 weeks at an adequate dose (with confirmed adherence), switch to an agent with a different pharmacodynamic profile (e.g., amisulpride, or risperidone). If two adequate antipsychotic trials fail, promptly initiate a clozapine trial aiming for plasma levels of 350–500 ng/mL. Discuss long-acting injectable formulations early. Assess adherence regularly using plasma drug levels, pill counts, or carer and staff reports.

Recommendation 3: Begin metabolic monitoring at treatment initiation. 

Obtain at baseline: BMI, waist circumference, blood pressure, HbA1c, fasting glucose (repeat at 4 weeks), lipids, prolactin, LFTs, U&Es, FBC, and ECG. Monitor BMI, waist circumference, and blood pressure weekly for the first 6 weeks. Repeat the full panel at 3 months and annually thereafter. Follow the same schedule when switching antipsychotics.

Recommendation 4: Proactively manage cardiometabolic risk.

Provide lifestyle advice (diet, physical activity, smoking cessation) to all patients. Co-initiate metformin (start 500 mg XR daily, titrate to 1 g twice daily as tolerated; check B12 annually) when prescribing olanzapine or clozapine. Consider a GLP-1 receptor agonist for: ≥5% weight gain within 3 months on any antipsychotic; BMI ≥30 kg/m² (or ≥27.5 kg/m² for South/East Asian, Middle Eastern, Black African, or African-Caribbean backgrounds); or BMI ≥27 kg/m² with ≥1 metabolic syndrome criterion. Offer statins for raised cholesterol; antihypertensives for BP >140/90 mmHg; and arrange diabetes/endocrinology review for HbA1c ≥6.5%, random glucose ≥11 mmol/L, or fasting glucose ≥7 mmol/L.

Recommendation 5: Promptly identify and manage antipsychotic side-effects. 

Tardive dyskinesia: switch to clozapine, quetiapine, olanzapine, or a D2 partial agonist; add a VMAT2 inhibitor (if available) if switching is not feasible. Akathisia: consider dose reduction, switch to quetiapine or olanzapine, or add propranolol 10–30 mg 2–3 times daily or mirtazapine 15 mg nocte.

Symptomatic hyperprolactinaemia: switch to a D2 partial agonist or add adjunctive aripiprazole 5 mg daily. 

Parkinsonism: dose reduction or switch to a weaker D2 antagonist or D2 partial agonist. Also review and minimise anticholinergic burden, particularly from clozapine, olanzapine, and quetiapine.

Target audience

This resource is intended for psychiatrists, psychiatric trainees, nurse practitioners, and general practitioners involved in the pharmacological management of adults with schizophrenia in New Zealand and Australian clinical settings, including inpatient, community mental health, and forensic services. It is particularly relevant to clinicians managing first-episode psychosis, treatment-resistant schizophrenia, and patients with significant cardiometabolic risk.

Implementation considerations

Medication availability

In Australia, most first-line oral antipsychotics (aripiprazole, brexpiprazole, cariprazine) are PBS-listed. In New Zealand, PHARMAC funds aripiprazole oral and long-acting injectable clozapine is publicly funded in both countries. VMAT2 inhibitors (e.g., valbenazine, deutetrabenazine) are not currently available through the PBS in Australia nor through PHARMAC in New Zealand. 

GLP-1 receptor agonists

In Australia, GLP-1 agonists may be PBS-accessible for patients meeting type 2 diabetes or established cardiovascular disease with obesity criteria. In New Zealand, semaglutide is available through Pharmac for people with type 2 diabetes with specific clinical and risk criteria. Liaison with primary care or endocrinology is recommended in both settings. 

Plasma level monitoring

Trough antipsychotic and clozapine plasma level testing is available at most Australian and New Zealand tertiary centres and is recommended when non-response or adherence concerns arise. 

Digital tools

The INTEGRATE digital tool (https://www.psymatik.com/about/) enables individualised algorithm outputs based on patient symptoms, medications, and side-effects. 

Implementation in services

Realising these recommendations may require service-level protocols for systematic metabolic monitoring, pathways for primary care co-management of cardiometabolic risk factors, and team training in shared decision-making.

Additional resources

The following resources provide additional guidance relevant to the INTEGRATE guidelines and their implementation in Australian clinical practice.

• McCutcheon RA, Pillinger T et al. “INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia.” Lancet Psychiatry 2025. https://doi.org/10.1016/S2215-0366(25)00031-8
• INTEGRATE digital decision-support tool. www.psymatik.com/guidelines/scz (Accessible via desktop and mobile; enter symptoms, medications, and side-effects to receive personalised guideline recommendations.)
• Suetani S, Dark F et al. Australian and New Zealand Journal of Psychiatry Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines for the management of schizophrenia. Aust N Z J Psychiatry. 2026;60:367-404.
• Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry (14th ed). Wiley-Blackwell, 2021.
• Wagner E, Siskind D et al. “Clozapine optimization: a Delphi consensus guideline from the Treatment Response and Resistance in Psychosis working group.” Schizophr Bull 2023; 49: 962–972.
• Pillinger T, Howes OD, Correll CU et al. “Antidepressant and antipsychotic side-effects and personalised prescribing.” Lancet Psychiatry 2023; 10: 860–876. (Side-effect comparison tool available at: www.psymatik.com)