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Piracetam for Treatment Tardive Dyskinesia

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ClinicalTrials.gov Identifier: NCT00190008
Recruitment Status : Completed
First Posted : September 19, 2005
Last Update Posted : November 25, 2009
Stanley Medical Research Institute
Information provided by:
Beersheva Mental Health Center

Tracking Information
First Submitted Date  ICMJE September 11, 2005
First Posted Date  ICMJE September 19, 2005
Last Update Posted Date November 25, 2009
Study Start Date  ICMJE August 2003
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2005)
Extrapyramidal Symptom Rating Scale
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Piracetam for Treatment Tardive Dyskinesia
Official Title  ICMJE Therapeutic Use of Piracetam for Treatment of Patients Suffering From Tardive Dyskinesia: a Double Blind, Placebo-Controlled Crossover Study
Brief Summary

The mechanism involved in the development of tardive dyskinesia (TD) is complicated. It now seems that several neurotransmitter systems may be affected, including dopaminergic, noradrenergic, gamma-amino-butyric acid (GABA) ergic, cholinergic and peptidergic pathways.

Piracetam (2-oxo-pyrrolidone) is a nootropic drug structurally related to GABA. It has been used clinically to treat a wide range of diseases and conditions, mainly in treatment of organic brain syndrome, myoclonus, memory impairment, post-concussional syndrome, vertigo, alcohol withdrawal, cerebrovascular insufficiency, hypoxia, intoxications of different origins or mechanic brain injures. Piracetam is cerebral homeostatic normalizer, neuroprotectant, cerebral metabolic enhancer and brain integrative agent. It enhances brain energy, especially under deficit condition: hypoxia, chemical toxicity or impaired cerebral microcirculation; preserve, protect and enhance synaptic membrane and receptor structure and plasticity. It has various effects on glutamate neurotransmission on micromolar levels piracetam potentiates potassium-induced release of glutamate from hippocampal nerves. It is an oxidant agent and may be useful for treatment TD. Piracetam is among the toxicologically safest drugs ever developed even in mega doses.

Data derived from some clinical reports have suggested that piracetam can improve symptoms and is effective agent for treatment of different movement disorders including acute neuroleptic induced extrapyramidal symptoms and TD. The doses that used for TD treatment varied from 800 mg/day to 24000 mg/day. According to these findings the symptoms of TD disappeared in the period of 3-7 days.

To date there was only one double-blind crossover study regarding use of piracetam for treatment TD that was conducted almost 20 years ago. The findings of this study were impressive, but to our knowledge nobody reproduced these results.

Detailed Description

We intend to examine 40 inpatients, aged 18-75 years old, suffering from TD and its variants. Criteria for inclusion into the study will be: a) DSM-IV diagnosis of tardive dyskinesia; b) stable psychotropic regimen of a month prior to entry into the study; c) duration of TD of at least 1 year; d) all patients had to be hospitalized.

Exclusion criteria will be: a) evidence of family history of Huntington's disease; b) evidence of substance or alcohol abuse; c) patients who received any form of vitamin medication; d) patients with concurrent medical illness or neurological disorders that may have influenced up the diagnosis of tardive dyskinesia.

The study design will be a double blind, randomized crossover group study and will be last for 8 weeks. This period provided an opportunity to exclude the influence of spontaneous fluctuations in the severity of TD. Full physical and laboratory examinations were performed on all inpatients in the beginning and at the end of the trial. Psychotropic medication will be maintained at fixed doses throughout the duration of study. The capsules preparations will be made by a professional pharmacist in the same size and color capsules in individual number-coded packages. The capsules will be added to the patients' usual medications and will be given by nurses.

Assessments for tardive dyskinesia and its variants will be done using Extrapyramidal Symptom Rating Scale (ESRS) at baseline and repeated every week, prior crossover, and then every week. This scale was developed by G. Chouinard and A. Ross-Chouinard (15) and was designed to rate three types of extrapyramidal symptoms: parkinsonian, dystonic and dyskinetic. Although the scale may be applied to non-drug-induced extrapyramidal symptoms, its sensitivity has been most often assessed in the evaluation of drug-induced extrapyramidal symptoms. The dose of piracetam or placebo will be increased every week on 2000 mg up to 8000 mg/day in dependence on the changes of movement disorders. The doses of their neuroleptic medications not will be change a month before and during the research. The patients will take piracetam or placebo as addition to their constant medication.

It should be emphasized again that improvement of TD symptoms after piracetam addition was appeared through very short period (3-7 days) in comparison to other medications used for treatment of TD. Moreover, if efficacy of piracetam will be proved in our study, clinicians obtain a new, effective, safe drug for TD treatment with rapid onset of the action.


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  2. Gouliaev AH, Senning A. Piracetam and other structurally related nootropics. Brain Res Brain Res Rev 1994;19(2):180-222.
  3. Kabes J, Sikora J, Pisvejc J, et al. Effect of piracetam on extrapyramidal side effects induced by neuroleptic drugs. Int Pharmacopsychiatry 1982;17(3):185-92.
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  6. Pilch H, Muller WE. Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice. Psychopharmacology 1988;94(1):74-8.
  7. Tacconi M, Wurtman R. Piracetam: physiological disposition amd mechanism of action. In: Fahn S, editor. Advances in Neurology. NY: Raven Press; 1986.
  8. Sikora J, Kabes J, Pisvejc J. [Management of neuroleptic side-effects with piracetam (author's transl)]. Cesk Psychiatr 1981;77(2):137-42.
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  15. Chouinard G, Ross-Chouinard A, Annable L, Jones B. Extrapyramidal Symptom Rating Scale. Can J Neurol Sci (abstract) 1980;7:233.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Tardive Dyskinesia
Intervention  ICMJE Drug: piracetam
Study Arms  ICMJE Not Provided
Publications * Libov I, Miodownik C, Bersudsky Y, Dwolatzky T, Lerner V. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2007 Jul;68(7):1031-7. doi: 10.4088/jcp.v68n0709.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: September 11, 2005)
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age 18-75
  • DSM-IV diagnosis of tardive dyskinesia
  • stable psychotropic regimen of a month prior to entry
  • duration of TD for at least one year
  • hospitalization at our Center

Exclusion Criteria:

  • family history of Huntington's disease
  • drug or alcohol abuse
  • concurrent medial illness or neurological disorder that may have contributed to the diagnosis of TD
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00190008
Other Study ID Numbers  ICMJE BMHC-3529
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Beersheva Mental Health Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Stanley Medical Research Institute
Investigators  ICMJE
Principal Investigator: Vladimir Lerner, MD, PhD Ben-Gurion University of the Negev
Principal Investigator: Igor Libov, MD Beersheva Mental Health Center
PRS Account Beersheva Mental Health Center
Verification Date November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP