Piracetam for Treatment Tardive Dyskinesia

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Brief Title

Piracetam for Treatment Tardive Dyskinesia

Official Title

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.

      References

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        2. Gouliaev AH, Senning A. Piracetam and other structurally related nootropics. Brain Res
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        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.

        4. Giurgea C, Salama M. Nootropic Drugs. Prog Neuropsychopharmacol 1977;1:235-247.

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       11. Obeso JA, Artieda J, Quinn N, et al. Piracetam in the treatment of different types of
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           akathisia: a case report. J Clin Psychopharmacol 2001;21(2):248-9.

       15. Chouinard G, Ross-Chouinard A, Annable L, Jones B. Extrapyramidal Symptom Rating Scale.
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Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Extrapyramidal Symptom Rating Scale


Condition

Tardive Dyskinesia

Intervention

piracetam


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

40

Start Date

August 2003



Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Vladimir Lerner, MD, PhD, , 

Location Countries

Israel

Location Countries

Israel

Administrative Informations


NCT ID

NCT00190008

Organization ID

BMHC-3529



Study Sponsor

Beersheva Mental Health Center

Collaborators

 Stanley Medical Research Institute

Study Sponsor

Vladimir Lerner, MD, PhD, Principal Investigator, Ben-Gurion University of the Negev


Verification Date

November 2009