Ignite Creation Date:
2024-05-05 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00190008
Status:
COMPLETED
Last Update Posted:
2009-11-25
First Post:
2005-09-11
Brief Title:
Piracetam for Treatment Tardive Dyskinesia
Sponsor:
Beersheva Mental Health Center
Organization:
Beersheva Mental Health Center
Study Overview
Official Title:
Therapeutic Use of Piracetam for Treatment of Patients Suffering From Tardive Dyskinesia a Double Blind Placebo-Controlled Crossover Study
Status:
COMPLETED
Status Verified Date:
2009-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 mgday to 24000 mgday 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
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 mgday to 24000 mgday 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 Huntingtons 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 mgday 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
1 Lohr JB Oxygen radicals and neuropsychiatric illness Some speculations Arch Gen Psychiatry 199148121097-1106
2 Gouliaev AH Senning A Piracetam and other structurally related nootropics Brain Res Brain Res Rev 1994192180-222
3 Kabes J Sikora J Pisvejc J et al Effect of piracetam on extrapyramidal side effects induced by neuroleptic drugs Int Pharmacopsychiatry 1982173185-92
4 Giurgea C Salama M Nootropic Drugs Prog Neuropsychopharmacol 19771235-247
5 Pepeu G Spignoli G Nootropic drugs and brain cholinergic mechanisms Prog Neuropsychopharmacol Biol Psychiatry 198913SupplS77-88
6 Pilch H Muller WE Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice Psychopharmacology 198894174-8
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 authors transl Cesk Psychiatr 1981772137-42
9 Kabes J Sikora J Stary O et al Effectiveness of piracetam in tardive dyskinesia - double-blind cross-over controlled trial with a placebo Cesk Psychiatr 1983795339-45
10 Chaturvedi SK Piracetam for drug-induced dyskinesia J Clin Psychiatry 1987486255
11 Obeso JA Artieda J Quinn N et al Piracetam in the treatment of different types of myoclonus Clin Neuropharmacol 1988116529-36
12 Piperidou C Maltezos E Kafalis G et al Piracetam for choreoathetosis Lancet 198828616906
13 Fleischhacker WW Roth SD Kane JM The pharmacologic treatment of neuroleptic-induced akathisia J Clin Psychopharmacol 199010112-21
14 Fehr C Dahmen N Klawe C et al Piracetam in the treatment of tardive dyskinesia and akathisia a case report J Clin Psychopharmacol 2001212248-9
15 Chouinard G Ross-Chouinard A Annable L Jones B Extrapyramidal Symptom Rating Scale Can J Neurol Sci abstract 19807233
Exclusion criteria will be a evidence of family history of Huntingtons 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 mgday 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
1 Lohr JB Oxygen radicals and neuropsychiatric illness Some speculations Arch Gen Psychiatry 199148121097-1106
2 Gouliaev AH Senning A Piracetam and other structurally related nootropics Brain Res Brain Res Rev 1994192180-222
3 Kabes J Sikora J Pisvejc J et al Effect of piracetam on extrapyramidal side effects induced by neuroleptic drugs Int Pharmacopsychiatry 1982173185-92
4 Giurgea C Salama M Nootropic Drugs Prog Neuropsychopharmacol 19771235-247
5 Pepeu G Spignoli G Nootropic drugs and brain cholinergic mechanisms Prog Neuropsychopharmacol Biol Psychiatry 198913SupplS77-88
6 Pilch H Muller WE Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice Psychopharmacology 198894174-8
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 authors transl Cesk Psychiatr 1981772137-42
9 Kabes J Sikora J Stary O et al Effectiveness of piracetam in tardive dyskinesia - double-blind cross-over controlled trial with a placebo Cesk Psychiatr 1983795339-45
10 Chaturvedi SK Piracetam for drug-induced dyskinesia J Clin Psychiatry 1987486255
11 Obeso JA Artieda J Quinn N et al Piracetam in the treatment of different types of myoclonus Clin Neuropharmacol 1988116529-36
12 Piperidou C Maltezos E Kafalis G et al Piracetam for choreoathetosis Lancet 198828616906
13 Fleischhacker WW Roth SD Kane JM The pharmacologic treatment of neuroleptic-induced akathisia J Clin Psychopharmacol 199010112-21
14 Fehr C Dahmen N Klawe C et al Piracetam in the treatment of tardive dyskinesia and akathisia a case report J Clin Psychopharmacol 2001212248-9
15 Chouinard G Ross-Chouinard A Annable L Jones B Extrapyramidal Symptom Rating Scale Can J Neurol Sci abstract 19807233
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None