Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia

NCT00621634 | Withdrawn Phase 2 DMC

• 1 other identifier: HD06.067
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Tardive dyskinesia (TD) is a well-known complication of antipsychotic drug therapy in individuals treated for mental disorders such as schizophrenia. It typically consists of purposeless, involuntary movements involving the mouth area or the trunk and limb muscles, occurring within months or years of drug use. The annual incidence of TD in the population treated with antipsychotic drugs is between 1-5%, but the risk is 5-fold greater in older individuals. Once triggered, TD is often irreversible and untreatable. Its cause is unknown, but an imbalance between chaotic mechanisms triggered by the drugs and natural protective factors fighting against these may provide an explanation. One way to activate this protective response is to supplement the diet with high doses of essential fatty acids of the omega-3 class, which constitute a critical component of nerve cell membranes. Using this strategy, one research team showed a 50% reduction in the severity of TD-like movements in mice treated with docosahexaenoic acid (DHA). We hypothesize that DHA supplements can do the same in patients living with schizophrenia displaying TD movements. Forty (40) subjects between 30-75 years of age will be recruited. The participants will be randomized and equally distributed in two groups to take either DHA capsules (3 grams a day) or matching placebo for 12 weeks, after providing informed consent, and TD will be measured with a magnetic tracker system and clinical scales. The finding of a beneficial effect with DHA against TD would improve the quality of life for thousands of patients under long-term antipsychotic drug treatment.

Conditions

Tardive Dyskinesia

Keywords

Tardive dyskinesia; Schizophrenia; Essential fatty acids

Outcome Measures

Primary Outcomes (1)

• Clinical rating scales (AIMS, St.Hans)

  Baseline, Week 2, Week 14

Secondary Outcomes (3)

• Quantitative motor testing (kinematic parameters)

  Baseline, Week 14

• Monitoring of psychopathology (Neuro-Psychiatric Inventory, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia)

  Baseline, Week 2, Week 14

• Erythrocyte membrane phospholipid profile (gas chromatography)

  Baseline, Week 14

Study Arms (2)

1

EXPERIMENTAL

Active treatment with omega-3 fish oil capsules (1 g each capsule, 50% DHA): 2 capsules every meal (6 capsules each day) for 12 consecutive weeks

Dietary Supplement: Omega-3 fish oil capsules (including DHA)

2

PLACEBO COMPARATOR

Matching placebo treatment: 2 capsules every meal (6 capsules each day) for 12 consecutive weeks

Dietary Supplement: Placebo

Interventions

Omega-3 fish oil capsules (including DHA) DIETARY_SUPPLEMENT

Fish oil capsules of 1000 mg ea., including DHA 460-540 mg/capsule 2 capsules TID daily at mealtime for 12 consecutive weeks

Also known as: 0355EEPB1000CT (Ocean Nutrition Canada)

1

Placebo DIETARY_SUPPLEMENT

Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks

Also known as: Placebo1000 (Ocean Nutrition Canada)

2

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients under long-term antipsychotic drug treatment, stable for at least 3 months before study entry;
• presence of tardive dyskinesia following Schooler-Kane research criteria (mild intensity (2/4 points) in at least two body segments, or moderate intensity (3∕4 points) for at least one body segment);
• patients capable to understand the goals and procedures of the study, and to provide informed consent;
• women of childbearing age will be requested to use an effective contraceptive method throughout the study.

You may not qualify if:

• subjects with medical conditions susceptible to significantly increase the risk of adverse effects, or to interfere with the conduct of the study; in particular, those with coronary artery disease treated with clopidogrel, coagulation disorders, or hemorrhagic conditions;
• those regularly taking anticoagulants or certain triglyceride-lowering agents;
• those intolerant or allergic to fish, seafood, or any other substance contained in the study medication or matching placebo;
• those who have abused illegal street drugs during the past year;
• those unlikely to comply with the study requirements;
• those who consume natural health products of marine or vegetable source, containing omega-3 essential fatty acids;
• women who are pregnant or breastfeeding.

Sponsors & Collaborators

• National Alliance for Research on Schizophrenia and Depression: collaborator
• Université de Montréal: lead

Study Sites (2)

Notre-Dame Hospital/CHU Montreal

Montreal, Quebec, H2L 4M1, Canada

Location

Douglas Mental Health University Institute

Montreal, Quebec, H4H 1R3, Canada

Location

Related Publications (3)

• Ethier I, Kagechika H, Shudo K, Rouillard C, Levesque D. Docosahexaenoic acid reduces haloperidol-induced dyskinesias in mice: involvement of Nur77 and retinoid receptors. Biol Psychiatry. 2004 Oct 1;56(7):522-6. doi: 10.1016/j.biopsych.2004.06.036.

  PMID: 15450789 BACKGROUND

• Beaudry G, Langlois MC, Weppe I, Rouillard C, Levesque D. Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. J Neurochem. 2000 Oct;75(4):1694-702. doi: 10.1046/j.1471-4159.2000.0751694.x.

  PMID: 10987852 BACKGROUND

• Langlois MC, Beaudry G, Zekki H, Rouillard C, Levesque D. Impact of antipsychotic drug administration on the expression of nuclear receptors in the neocortex and striatum of the rat brain. Neuroscience. 2001;106(1):117-28. doi: 10.1016/s0306-4522(01)00248-2.

  PMID: 11564422 BACKGROUND

MeSH Terms

Conditions

Tardive Dyskinesia; Schizophrenia

Interventions

Fish Oils

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Oils; Lipids

Study Officials

• Pierre J. Blanchet, MD, PhD

  Faculty of Dental Medicine, University of Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2008
• First Posted: February 22, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CA (2)