Xenazine in Late Dyskinetic Syndrome With Neuroleptics

• Status: Completed
• Trial end date: 2017-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Late dyskinetic syndrome with neuroleptics, or tardive dyskinesia, is the appearance of abnormal involuntary movements (AIM) in patients treated with antipsychotics for at least three months. This important public health issue arises for 15-20% of patients treated with neuroleptics, the most prescribed psychotropic drugs in mental disorders in France, and seriously impacts the patients' quality of life. In over 50% of cases, it is irreversible-that is to say that he will persist despite discontinuation of the offending drug.

Risk factors have been described: the age and female gender are established, a higher dosage of antipsychotic, a long-term treatment, a psychiatric condition other than schizophrenia are likely risk factors, intermittent treatment, previous acute dyskinesia, neuroleptics or powerful, longer term use of corrective treatments including anticholinergics are still discussed.

Apart from preventive treatment, which consists in using antipsychotics as being coerced, support is disappointing: the etiological treatment, which is to stop the offending antipsychotic, is effective only in less than 50% of cases, the syndrome is most often late irreversible. Must still have the possibility to interrupt the treatment, which is usually impossible in the risk of decompensation of the mental illness for which the neuroleptic was prescribed. Remains symptomatic treatment: functional neurosurgery is only for extreme cases, because it is not without risk, in terms of morbidity and mortality. So it's the medication that is most often offered: many drugs have been proposed, a direct result of the multiplicity of neurotransmitter systems implicated.

However, in the vast majority of cases, this approach is disappointing not to say ineffective. The only exception is the tetrabenazine, marketed under the name of Xenazine®. Empirically, neurologists specializing in pathology of the movement are almost unanimous: its efficiency is very good, with good tolerance. Some preliminary studies have reinforced this impression. However, their level of evidence remains low and that is why the investigators propose to implement a prospective multicenter clinical trial, double-blind with placebo which will include two groups of 27 patients.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier Universitaire, Amiens
• Treatments: Antipsychotic Agents; Tetrabenazine

Criteria

Inclusion Criteria:

1. Adult (age over 18) or adult under judicial protection (tutor or curator).

2. Patient with late dyskinetic syndrome with neuroleptics yielding functional disability and/or impact in every day's life, according to the investigator, and/or the patient and/or the patient's family.

3. Patient with persistent late dyskinetic syndrome, even if the neuroleptic has been stopped for more than 6 months or patient with late dyskinetic syndrome under neuroleptic treatment unchanged for at least 3 months and which would a priori not need any dose variation during the study time.

4. MADRS < 18

5. QTc < 450 ms for men and < 470 for women.

Exclusion Criteria:

1. Lack of social insurance

2. Neuroleptic treatment less than 3 months

3. Insanity according to the DSM IV and MMS < 24

4. Predominant akathisia

5. Psychiatric disease not stabilized for more than 6 months and/or which could require a neuroleptic treatment adaptation during study time.

6. Pregnancy and lactating

7. Women in genital activity without efficient contraception method (IUD or estrogen-progestin pill)

8. Hypersensitivity to tetrabenazine

9. Renal failure

10. Drugs: Non-selective MAOIs, dopaminergic (or other antiparkinsonian)

11. Other severe pathology

12. Patient non compliant to protocol, at the investigator's appreciation

13. Simultaneous participation to other clinical trial

14. Congenital galactosemia, glucose malabsorption or lactase deficiency