Multimodal Physical Exercise Program (Physical Exercise for Psychosis) for People With Psychosis Treated With Long-Acting Injectable Antipsychotics (PEP)

PEP - Physical Exercise for Psychosis: A Study Protocol

People with psychotic disorders, such as schizophrenia, often experience significant difficulties in daily functioning, physical health, and quality of life. Long-acting injectable antipsychotics are an important part of treatment, but they can be associated with metabolic side effects and reduced physical fitness. Physical exercise has shown potential benefits for mental and physical health in this population; however, structured exercise programs implemented in real-world psychiatric services are still limited.

The purpose of this study is to evaluate the feasibility and clinical impact of a structured, multimodal physical exercise program for adults with psychosis who are receiving long-acting injectable antipsychotic treatment. The study aims to determine whether participation in a supervised exercise program can improve physical functioning, psychological well-being, and selected biological markers related to brain health and metabolism.

This study will be conducted in an outpatient psychiatric setting in Portugal and will include adults diagnosed with psychosis who are currently treated with long-acting injectable antipsychotics. Participants will be allocated to either an exercise group or a control group receiving usual care. The exercise program will last 24 weeks and will include aerobic, strength, mobility, and flexibility exercises, with supervised sessions conducted by qualified professionals.

Participants will be assessed at baseline, during the intervention, after completion of the program, and at follow-up. Assessments will include measures of physical function, body composition, psychological well-being, quality of life, and blood-based biomarkers such as brain-derived neurotrophic factor, dopamine, serotonin, and metabolic indicators.

The main hypothesis of this study is that individuals who participate in the physical exercise program will show improvements in physical function, mood, and overall well-being compared with those receiving usual care alone. The results of this study are expected to provide practical evidence to support the integration of structured physical exercise as an adjunct to routine psychiatric care for people with psychosis.

Study Overview

• Status: Recruiting
• Conditions: Psychotic Disorders; Severe Mental Illness; Schizophrenia Spectrum Disorders (SSD)
• Intervention / Treatment: Other: Physical Exercise

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Vila Real, Portugal, 5000
    • Recruiting
    • Local Health Unit of Trás-os-Montes and Alto Douro
    • Contact: Dulce Amélia Maia, MD; Phone Number: 259300500; Email: dulcefm@chtmad.min-saude.pt
    • Contact: Email: dulcefm@chtmad.min-saude.pt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older;
• Clinical diagnosis of psychosis;
• Currently undergoing treatment with long-acting injectable antipsychotics (LAIs);
• Follow-up at the Antipsychotic Clinic of ULSTMAD;
• Certificate of autonomy issued by the treating psychiatrist, confirming the participant's capacity to engage in the study procedures;
• Ability to provide written informed consent, either personally or through a legal representative;
• (Experimental group only) Residence within a reasonable distance from the physical exercise intervention site to allow attendance at supervised sessions.

Exclusion Criteria:

• Attendance below 85% of the supervised exercise sessions (experimental group);
• Failure to complete the four main assessment time points;
• Withdrawal or lack of informed consent at any stage of the study;
• Not prescribed long-acting injectable antipsychotics (LAIs);
• Not affiliated with or followed at the Antipsychotic Clinic of ULSTMAD.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients diagnosed with psychosis who are receiving farmacological treatment and exercise program.; Patients aged 18 years or older, diagnosed with psychosis, undergoing treatment with LAIs, and holding a certificate of autonomy issued by their psychiatrist, with the additional requirement for the experimental group to reside near the location of the physical exercise sessions.	Other: Physical Exercise; The program will be multimodal, integrating various exercise components. The aerobic component will consist of activities like walking, cycling, and circuit training. The functional strength component will include 2 to 3 exercises for the lower limbs, 2 to 3 exercises for the upper limbs, 1 to 2 exercises for the trunk and abdominal muscles, as well as 1 to 2 multi-joint exercises like burpees, swing kettlebell, among others. Lastly, the program will also incorporate mobility, balance, and flexibility exercises, such as stretching, postures, and joint mobilization.; Other Names: Multimodal Physical Exercise
No Intervention: Patients diagnosed with psychosis who are receiving farmacological treatment.; Patients aged 18 years or older, diagnosed with psychosis, undergoing treatment with LAIs, and holding a certificate of autonomy issued by their psychiatrist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass/weight	Body mass/weight measured in kilograms using a calibrated scale.	Baseline, 12 weeks, 24 weeks, 8-week post-intervention follow-up
Body mass index (BMI)	BMI calculated as weight (kg) / height (m²)	Baseline, 12 weeks, 24 weeks, 8-week post-intervention follow-up
Body fat percentage	Body fat percentage assessed by electrical bioimpedance analysis	Baseline, 12 weeks, 24 weeks, 8-week post-intervention follow-up
Lean body mass	Lean body mass (kg) assessed by electrical bioimpedance analysis	Baseline, 12 weeks, 24 weeks, 8-week post-intervention follow-up
Sit-to-Stand Test _ 30s	Used to measure lower limb strength and endurance through the number of repetitions performed in a specific period.	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Handgrip Test	Used to assess upper limb muscle strength	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
European Health Interview Survey - Quality of Life 8-item Index (EUROHIS-QOL-8)	The European Health Interview Survey - Quality of Life 8-item Index (EUROHIS-QOL-8) is an 8-item self-report questionnaire assessing overall quality of life across physical, psychological, social, and environmental domains. Each item is rated on a 5-point Likert scale, resulting in a total score ranging from 8 to 40. Higher total scores indicate better perceived quality of life. The scale demonstrates good psychometric properties and is suitable for use in clinical and research settings.	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Patient Health Questionnaire-9 - PHQ-9	The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-administered questionnaire designed to assess the severity of depressive symptoms based on the diagnostic criteria for major depressive episodes. Each item is scored on a 4-point Likert scale (0-3), yielding a total score ranging from 0 to 27. Higher total scores indicate greater severity of depressive symptoms. The PHQ-9 is widely used in clinical and research settings and demonstrates good psychometric properties.	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Positive and Negative Affect Scale (PANAS)	The Positive and Negative Affect Schedule (PANAS) is a 20-item self-report questionnaire designed to assess affective states, comprising two independent 10-item subscales: Positive Affect (PANAS-PA) and Negative Affect (PANAS-NA). Each item is rated on a 5-point Likert scale (1-5), yielding subscale scores ranging from 10 to 50. Higher scores on the Positive Affect subscale indicate higher levels of positive affect, whereas higher scores on the Negative Affect subscale indicate higher levels of negative affect. The PANAS is widely used in clinical and research settings and demonstrates good psychometric properties.	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Serum Brain-Derived Neurotrophic Factor (BDNF) levels	Serum BDNF concentration quantified using standardized Human BDNF ELISA Kit (Abcam). BDNF is a key neurotrophic marker associated with neuroplasticity and treatment-related neurobiological adaptations. Units: ng/mL.	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Serum lipid profile	Assessment of serum lipid parameters including total cholesterol, HDL cholesterol, LDL cholesterol (direct or calculated), and triglycerides, according to hospital laboratory reference standards. Units: mg/dL. Hospital laboratory references: Total cholesterol: < 200 mg/dL; LDL cholesterol: < 130 mg/dL; HDL cholesterol: > 60 mg/dL; Triglycerides: < 150 mg/dL	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Glycemic and metabolic markers	Evaluation of fasting blood glucose and glycated hemoglobin (HbA1c) as indicators of glycemic control and metabolic health. Units: Glucose: mg/dL; HbA1c: % Hospital reference values: Glucose: 74-106 mg/dL; HbA1c: 4.0-6.0 %	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Serum Serotonin levels	Quantification of serotonin concentration in serum using standardized laboratory procedures. Higher or lower concentrations will be interpreted as neurochemical modulation potentially associated with the exercise intervention and antipsychotic treatment. Unit: ng/mL	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up
Serum Dopamine levels	Quantification of dopamine concentration in serum using standardized laboratory procedures. Changes in dopamine concentration across timepoints will be analyzed as a marker of neurochemical modulation potentially associated with the exercise intervention and antipsychotic treatment. Unit: ng/mL or pg/mL	Baseline, 12 weeks, 24 weeks, and 8-week post-intervention follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height	Height measured in meters using stadiometer (baseline only, if applicable)	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sociodemographic Characterization	The sociodemographic characterization of participants will be performed using a structured questionnaire designed to collect information on variables such as age, gender, marital status, education, employment status, and family context. This instrument provides a comprehensive description of the sample profile and enables the analysis of potential sociodemographic factors associated with the clinical and functional variables under study.	Baseline

Collaborators and Investigators

• Sponsor: University of Trás-os-Montes and Alto Douro
• Collaborators: Centro Hospitalar De Trás-Os-Montes E Alto Douro, E.P.E.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: December 17, 2025
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: 2024.04489.BDANA; CES REG. 1612 (Other Identifier: Ethics Committee, Local Health Unit of Trás-os-Montes and Alto Douro, Vila Real, Portugal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. The dataset includes sensitive clinical, functional, and health-related information collected in a hospital setting. Data will be used exclusively for the purposes defined in the approved study protocol and in accordance with institutional ethical approval and data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No