Diet and Exercise for Schizophrenia

Overseen By Kristina T Legget, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must be taking: Olanzapine, Risperidone, Clozapine, Haloperidol

Disqualifiers: Pregnancy, Substance abuse, Endocrine/metabolic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how diet and exercise affect weight gain and brain responses in people with schizophrenia. It examines how common medications might lead to weight gain and how changes in diet or exercise can influence food cravings and preferences. Participants will follow either a 10-week exercise plan or a diet plan to observe the impact on their brains and eating habits. Suitable candidates include those with schizophrenia or schizoaffective disorder who have maintained stable weight for six months and are either on specific medications or not on any. As an unphased trial, this study offers a unique opportunity to contribute to understanding lifestyle impacts on mental health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it includes participants who are either on specific medications (olanzapine, risperidone, clozapine, or haloperidol) or not on any neuroleptic medications, so it seems you can continue your current treatment if it fits these criteria.

What prior data suggests that diet and exercise interventions are safe for individuals with schizophrenia?

Research shows that exercise is safe and beneficial for people with schizophrenia. Studies have found that activities like aerobic exercise can reduce symptoms of psychosis without causing harm. Exercise, even when combined with strength training, is well-tolerated and enhances muscle strength.

Regarding diet, studies indicate that dietary changes are safe for people with schizophrenia. For instance, a ketogenic diet (low-carb, high-fat) has been found to be safe and well-tolerated, with participants experiencing improvements in mental health symptoms.

Overall, both exercise and dietary changes appear safe, with no major negative effects reported in these studies. Participants generally manage these lifestyle changes well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using diet and exercise for schizophrenia because these approaches could offer a more holistic and side-effect-free alternative to standard medications. Unlike traditional antipsychotic drugs, which can have significant side effects and often require long-term use, dietary changes and exercise focus on improving overall health and well-being. They aim to enhance brain function naturally, potentially leading to better symptom management and quality of life for individuals with schizophrenia. This trial could pave the way for new, integrative strategies that empower patients to take an active role in their treatment.

What evidence suggests that this trial's treatments could be effective for schizophrenia?

Research has shown that exercise, included in the exercise intervention arm of this trial, can greatly benefit people with schizophrenia. It improves thinking skills, reduces symptoms, and enhances mood and quality of life. One study found that exercise lowered symptoms measured by a specific scale for schizophrenia.

Regarding diet, studied in a separate arm of this trial, several studies suggest that dietary changes can also help those with schizophrenia. For example, a ketogenic diet led to a 32% improvement in psychiatric symptoms. Other research indicates that dietary changes can improve overall health, which is important for managing schizophrenia. Both exercise and dietary changes show promise for improving the well-being of people with this condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Jason R. Tregellas, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults aged 21-70 with schizophrenia or schizoaffective disorder, who are either on olanzapine, risperidone, clozapine, haloperidol or not on neuroleptic medications. They should have had a stable weight in the past 6 months. Pregnant individuals, those with substance abuse issues or significant metabolic diseases, and anyone unable to undergo MRI due to claustrophobia or metal implants cannot participate.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder.

I am taking olanzapine, risperidone, clozapine, or haloperidol, or I am not on any neuroleptic medications.

I am between 21 and 70 years old.

Exclusion Criteria

MRI-specific exclusion criteria (e.g., claustrophobia, metal in the body)

Pregnancy

Substance abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exercise Intervention

Participants undergo a moderate exercise intervention to evaluate changes in brain responses and food preferences

10 weeks

Diet Intervention

Participants follow a diet intervention to evaluate changes in brain responses and food preferences

10 weeks

Follow-up

Participants are monitored for changes in neuronal response and fasting hormone levels after interventions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diet
• Exercise

Trial Overview

The study examines how diet and exercise affect brain response to food images and preferences in people taking common schizophrenia drugs that may cause weight gain. Participants will be asked about their eating habits and symptoms and might do an exercise or diet program to see if it changes how their brain reacts to food.

How Is the Trial Designed?

Group I: Exercise intervention Experimental Treatment 1 Intervention

10 weeks of a moderate exercise intervention

Group II: Diet intervention Active Control 1 Intervention

10 weeks of a diet intervention

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Non-pharmacological interventions, including psychoeducation, diet, and physical activity, were effective in reducing metabolic syndrome risk factors in individuals with schizophrenia, as shown in a review of 11 studies from 1968 to 2017.

These interventions led to significant reductions in body weight, body mass index, waist circumference, and blood glucose levels, demonstrating that lifestyle changes are a safe and cost-effective approach to managing antipsychotic-induced weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review. Gurusamy, J., Gandhi, S., Damodharan, D., et al.[2019]

A 12-week resistance training program was found to be safe for schizophrenia patients and led to significant improvements in their level of functioning, as measured by the Global Assessment of Functioning Scale (GAF).

Although the resistance training did not show significant effects on health-related difficulties assessed by the WHO-DAS, the positive outcomes suggest that tailored resistance training could be beneficial for managing symptoms and improving quality of life in schizophrenia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance training in patients with schizophrenia: Concept and proof of principle trial. Maurus, I., Mantel, C., Keller-Varady, K., et al.[2021]

A systematic review of 17 studies found that incorporating physical activity into the treatment of schizophrenia positively impacts symptoms and overall well-being.

Physical activity not only helps alleviate symptoms of schizophrenia but also supports patients in reintegrating into society, highlighting its importance in comprehensive treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity as a therapeutic method for non-pharmacological treatment of schizophrenia: A systematic literature review. Cempa, K., Jurys, T., Kluczyński, S., et al.[2023]

An umbrella review of nine systematic reviews found that physical activity, particularly yoga, can effectively improve both positive and negative symptoms of schizophrenia, as well as enhance overall well-being.

Supplementation with polyunsaturated fatty acids and trace elements was also shown to reduce negative symptoms of schizophrenia, suggesting that these interventions could be beneficial and cost-effective strategies for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of physical activity and nutrient supplementation on symptoms and well-being of schizophrenia patients: An umbrella review. El Kirat, H., Khattabi, A., Khalis, M., et al.[2023]

Physical exercise (PE) has a medium significant effect on reducing negative symptoms in schizophrenia patients, based on a meta-analysis of 22 studies involving 1249 participants.

Mind-body exercise (MBE) showed a stronger effect (medium significance) compared to aerobic exercise (AE), which had a smaller but still significant effect, indicating that different types of exercise may have varying levels of efficacy in managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mind-body and aerobic exercise on negative symptoms in schizophrenia: A meta-analysis. Vogel, JS., van der Gaag, M., Slofstra, C., et al.[2020]

Only 20.1% of patients with stable schizophrenia were physically active, compared to 35.9% of healthy individuals, indicating a significant gap in physical activity levels.

Only 29.5% of patients received physical activity counseling, suggesting a need for improved counseling strategies to encourage physical activity among this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Levels and evaluations of physical activity using 5-A counseling model in patients with stable schizophrenia]. Wang, J., Wei, Q., Li, G., et al.[2019]

A study involving 59 hospitalized patients with schizophrenia showed that a behavioral intervention, including nutritional education and physical exercise, led to significant reductions in BMI and weight after 3 months, which were maintained for a year.

The results suggest that with proper support and information, individuals with persistent schizophrenia can effectively manage their weight and improve their health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-modal weight control intervention for people with persistent mental disorders. Melamed, Y., Stein-Reisner, O., Gelkopf, M., et al.[2008]

An eight-month exercise program involving Greek traditional dancing significantly improved functional capacity in patients with schizophrenia, as evidenced by increased walking distance, better balance, and greater lower limb strength compared to a sedentary control group.

Participants in the dancing group also reported enhanced quality of life and improved mental health outcomes, indicating that engaging in physical activity can have positive effects on both physical and psychological well-being for individuals with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training with traditional dancing on functional capacity and quality of life in patients with schizophrenia: a randomized controlled study. Kaltsatou, A., Kouidi, E., Fountoulakis, K., et al.[2022]

Over 50% of adults with serious mental illness, such as schizophrenia, are obese, highlighting a significant health concern in this population.

Individuals with schizophrenia tend to consume more calories and saturated fats and have low levels of physical activity, indicating a need for lifestyle modification programs focused on diet and fitness in community mental health centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making evidence-based lifestyle modification programs available in community mental health centers: why so slow? Chwastiak, L.[2018]

A systematic review of two high-quality studies involving 48 patients with schizophrenia found conflicting evidence regarding the effects of physical exercise on hippocampal volume, although some increases were linked to better aerobic fitness and short-term memory.

The current evidence is insufficient to conclude that physical exercise positively influences brain health in individuals with schizophrenia, highlighting the need for further research into the neurobiological mechanisms and functional outcomes of exercise in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurobiological effects of physical exercise in schizophrenia: a systematic review. Vancampfort, D., Probst, M., De Hert, M., et al.[2018]

Aerobic exercise training significantly reduces negative symptoms of schizophrenia, as indicated by improvements in the Positive and Negative Syndrome Scale (PANSS) scores, while resistance training did not show significant effects on these symptoms.

Overall, participation in any form of exercise (aerobic, resistance, or combined) leads to improvements in health-related physical fitness indicators, including body mass index and oxygen consumption, highlighting the benefits of exercise for individuals living with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Aerobic, Resistance, and Combined Exercise Training on Psychiatric Symptom Severity and Related Health Measures in Adults Living With Schizophrenia: A Systematic Review and Meta-Analysis. Bredin, SSD., Kaufman, KL., Chow, MI., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7439299/

Dietary modification in the treatment of schizophrenia ...

This systematic review identified and analysed the findings of 25 clinical trials which modified participant diet and measured a mental health outcome.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0920996424003062

Dietary interventions to improve metabolic health in ...

Five reviews, with 79 unique trials concluded that such interventions that address diet along with other lifestyle factors were effective or relevant for ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11673491/

Relevance of diet in schizophrenia: a review focusing on ...

Emerging research suggests that diet may affect schizophrenia through different biological mechanisms beyond oxidative stress and inflammation.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178124001513

Ketogenic Diet Intervention on Metabolic and Psychiatric ...

Participants with schizophrenia showed an average of 32 % improvement according to the brief psychiatric rating scale.

5.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1591937/full

Case Report: Remission of schizophrenia using a ...

(15) reported that 10 patients with a primary diagnosis of schizophrenia who followed a ketogenic diet for two weeks exhibited improvement in ...

6.

stanmed.stanford.edu

stanmed.stanford.edu/power-diet-prevent-treat-disease/

Diet has outsized role in preventing and treating illness

Life satisfaction also jumped by 17%, and sleep quality improved by 19%. “This was the first clinical trial done since 1965 with a ketogenic ...

7.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.951376/full

The Ketogenic Diet for Refractory Mental Illness

This iteration of a KD was safe, feasible to administer in an inpatient setting, well tolerated by most patients, and associated with ...