Tardive DyskinesiaPhase 2NCT00621634
Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia
A Phase 2 study testing Omega-3 fish oil capsules (including DHA) in people with Tardive Dyskinesia, run by Université de Montréal at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Tardive Dyskinesia
- What is being tested?
- Omega-3 fish oil capsules (including DHA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2008to 1 Feb 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Notre-Dame Hospital/CHU Montreal
Montreal, Quebec, H2L 4M1
Douglas Mental Health University Institute
Montreal, Quebec, H4H 1R3
About this study
Official title: Randomized, Double-blind, Placebo-controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia
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.
Read the detailed description
Background
Tardive dyskinesia (TD) is a well-known complication of antipsychotic drug (APD) therapy in individuals treated for mental disorders such as schizophrenia. It typically consists of purposeless, involuntary movements involving the oro-facial area, trunk, and/or limb muscles, occurring within months or years of APD use. Twisting and protruding movements of the tongue, lip smacking and puckering, and chewing movements, are often observed. Oral dyskinesia may cause pain, traumatic lesions, tooth wear, impaired retention of prosthetic devices, chewing difficulty, dysphagia, speech impairment, as well as social embarrassment. The annual incidence of TD in the population treated with these drugs is between 1-5%, but the risk in older individuals is 5-fold greater. The second-generation ("atypical") APDs have substantially reduced the short-term risk of TD, but the annual incidence of TD in older individuals taking these drugs remains comparable to that of younger adults treated with first-generation APDs. The cause of TD is unknown. Since all APDs are blockers of dopamine D2 receptors in the brain, researchers hypothesized that these receptors (or their signaling pathways) become supersensitive in such a way to promote TD. APDs also modulate the expression of a number of brain factors belonging to the nuclear receptor family, including Retinoid X Receptors (RXR) and Nur77, which are overexpressed following chronic APD treatment. These factors, seemingly mounting an adaptive response to fend off adverse drug reactions such as TD, may become incompetent or insufficient over time in those individuals developing TD. One way to activate this 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 and modulate a variety of brain receptors. Once triggered, TD is often irreversible and untreatable. However, one team recently showed a 50% reduction in the severity of TD-like movements in mice treated with docosahexaenoic acid (DHA).
Hypothesis
Since there is an apparent close relationship between retinoid receptors and dopamine systems in the human brain and DHA is a RXR agonist, our working hypothesis is that DHA will reduce TD intensity in patients living with schizophrenia by increasing the transcriptional activity along these pathways.
Objective
To evaluate the clinical impact of DHA on the intensity of TD in humans.
Study design
Forty (40) subjects between 30-75 years of age will be recruited. The participants will be randomized and equally distributed in parallel groups to take either DHA (3 grams a day) or matching placebo capsules for 12 weeks, after providing informed consent. The study will use questionnaires, venous blood sampling, as well as clinical scales, to monitor the psychiatric condition, the lipid profile, and TD intensity at the beginning and end of the study. Brief and simple tasks will also be completed with a motion analysis system using magnetic sensors in order to measure body movements and TD with accuracy.
Outcome
The finding of a beneficial effect with DHA against TD would improve the quality of life for thousands of patients under long-term APD treatment.
- Conditions
- Tardive Dyskinesia
- Being tested
- Omega-3 fish oil capsules (including DHA), Placebo
- Keywords
- Tardive dyskinesia, Schizophrenia, Essential fatty acids
- Medical subject headings
- Tardive Dyskinesia, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omega-3 fish oil capsules (including DHA)Dietary supplement
Also called 0355EEPB1000CT (Ocean Nutrition Canada)
Fish oil capsules of 1000 mg ea., including DHA 460-540 mg/capsule 2 capsules TID daily at mealtime for 12 consecutive weeks
PlaceboDietary supplement
Also called Placebo1000 (Ocean Nutrition Canada)
Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical rating scales (AIMS, St.Hans)
Measured: Baseline, Week 2, Week 14
Secondary outcomes (3)
Quantitative motor testing (kinematic parameters)
Measured: Baseline, Week 14
Monitoring of psychopathology (Neuro-Psychiatric Inventory, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia)
Measured: Baseline, Week 2, Week 14
Erythrocyte membrane phospholipid profile (gas chromatography)
Measured: Baseline, Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startFeb 2008 (estimated)
- Primary completion1 Feb 2010
- Study completion1 Feb 2010
Why it stopped: Study products withdrawn from market.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Tardive DyskinesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Montréal
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Sponsor
- Investigators
- Pierre J. Blanchet, MD, PhD, Principal investigator, Faculty of Dental Medicine, University of Montreal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621634
- Sponsor's protocol ID
- HD06.067
- Status last verified
- Apr 2026
- First submitted
- 12 Feb 2008
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15450789Beaudry 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.
PubMed 10987852Langlois 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.
PubMed 11564422
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia
- ClinicalTrials.gov ID
- NCT00621634
- Acronym / sponsor ID
- HD06.067
- Conditions
- Tardive Dyskinesia
- Keywords
- Tardive dyskinesia, Schizophrenia, Essential fatty acids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study products withdrawn from market.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Université de MontréalUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Feb 2008 (estimated)
- Primary completion
- 1 Feb 2010 (actual)
- Study completion
- 1 Feb 2010 (actual)
- First posted
- 22 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background
Tardive dyskinesia (TD) is a well-known complication of antipsychotic drug (APD) therapy in individuals treated for mental disorders such as schizophrenia. It typically consists of purposeless, involuntary movements involving the oro-facial area, trunk, and/or limb muscles, occurring within months or years of APD use. Twisting and protruding movements of the tongue, lip smacking and puckering, and chewing movements, are often observed. Oral dyskinesia may cause pain, traumatic lesions, tooth wear, impaired retention of prosthetic devices, chewing difficulty, dysphagia, speech impairment, as well as social embarrassment. The annual incidence of TD in the population treated with these drugs is between 1-5%, but the risk in older individuals is 5-fold greater. The second-generation ("atypical") APDs have substantially reduced the short-term risk of TD, but the annual incidence of TD in older individuals taking these drugs remains comparable to that of younger adults treated with first-generation APDs. The cause of TD is unknown. Since all APDs are blockers of dopamine D2 receptors in the brain, researchers hypothesized that these receptors (or their signaling pathways) become supersensitive in such a way to promote TD. APDs also modulate the expression of a number of brain factors belonging to the nuclear receptor family, including Retinoid X Receptors (RXR) and Nur77, which are overexpressed following chronic APD treatment. These factors, seemingly mounting an adaptive response to fend off adverse drug reactions such as TD, may become incompetent or insufficient over time in those individuals developing TD. One way to activate this 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 and modulate a variety of brain receptors. Once triggered, TD is often irreversible and untreatable. However, one team recently showed a 50% reduction in the severity of TD-like movements in mice treated with docosahexaenoic acid (DHA).
Hypothesis
Since there is an apparent close relationship between retinoid receptors and dopamine systems in the human brain and DHA is a RXR agonist, our working hypothesis is that DHA will reduce TD intensity in patients living with schizophrenia by increasing the transcriptional activity along these pathways.
Objective
To evaluate the clinical impact of DHA on the intensity of TD in humans.
Study design
Forty (40) subjects between 30-75 years of age will be recruited. The participants will be randomized and equally distributed in parallel groups to take either DHA (3 grams a day) or matching placebo capsules for 12 weeks, after providing informed consent. The study will use questionnaires, venous blood sampling, as well as clinical scales, to monitor the psychiatric condition, the lipid profile, and TD intensity at the beginning and end of the study. Brief and simple tasks will also be completed with a motion analysis system using magnetic sensors in order to measure body movements and TD with accuracy.
Outcome
The finding of a beneficial effect with DHA against TD would improve the quality of life for thousands of patients under long-term APD treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Dietary Supplement: Omega-3 fish oil capsules (including DHA)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 |
| 2 | Placebo comparator | Dietary Supplement: PlaceboMatching placebo treatment: 2 capsules every meal (6 capsules each day) for 12 consecutive weeks |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omega-3 fish oil capsules (including DHA)Also: 0355EEPB1000CT (Ocean Nutrition Canada)Fish oil capsules of 1000 mg ea., including DHA 460-540 mg/capsule 2 capsules TID daily at mealtime for 12 consecutive weeks | Dietary supplement | 1 |
| PlaceboAlso: Placebo1000 (Ocean Nutrition Canada)Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks | Dietary supplement | 2 |
Primary outcome
Clinical rating scales (AIMS, St.Hans)
Time frame: Baseline, Week 2, Week 14
3 secondary outcomes
Quantitative motor testing (kinematic parameters)
Time frame: Baseline, Week 14
Monitoring of psychopathology (Neuro-Psychiatric Inventory, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia)
Time frame: Baseline, Week 2, Week 14
Erythrocyte membrane phospholipid profile (gas chromatography)
Time frame: Baseline, Week 14
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Background: PubMed 15450789Ethier 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.
- Background: PubMed 10987852Beaudry 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.
- Background: PubMed 11564422Langlois 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre J. Blanchet, MD, PhD principal investigator
Faculty of Dental Medicine, University of Montreal
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omega-3 fish oil capsules (including DHA) in people with Tardive Dyskinesia, run by Université de Montréal at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical rating scales (AIMS, St.Hans) (time frame: Baseline, Week 2, Week 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00621634, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.