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Cochrane Database of Systematic Reviews

Piridoxal 5 fosfato para la discinesia tardía inducida por neurolépticos

Information

DOI:
https://doi.org/10.1002/14651858.CD010501.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 13 April 2015see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Schizophrenia Group

Copyright:
  1. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Adegoke Oloruntoba Adelufosi

    Correspondence to: Community Mental Health Program, Northern Regional Health Authority, Manitoba, Canada

    [email protected]

  • Olukayode Abayomi

    Psychiatry, Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria

  • Tunde Massey‐Ferguson Ojo

    Clinicial Sciences (Resident Doctors Office), Neuropsychiatric Hospital, Ogun State, Nigeria

Contributions of authors

Adegoke Oloruntoba Adelufosi ‐ Data collection and interpretation, statistical analysis, writing the review.

Olukayode Abayomi ‐ Data collection and interpretation, assisted in writing the review.

Tunde Massey‐Ferguson Ojo ‐ Data collection, assisted in writing the review.

Sources of support

Internal sources

  • Reviews for Africa (Nigeria) Programme Fellowship, Nigeria.

External sources

  • UK Department for International Development (DFID) through the Effective Healthcare Research Consortium at the Liverpool School of tropical Medicine., UK.

Declarations of interest

The authors received no financial consideration from any parties for the preparation of this review.

Acknowledgements

The Cochrane Schizophrenia Group Editorial Base in Nottingham produces and maintains standard text for use in the Methods sections of their reviews. This text was used as the basis of the protocol, with modifications where necessary.

Adegoke Oloruntoba Adelufosi was awarded a Reviews for Africa (Nigeria) Programme Fellowship funded by a grant from the  UK Department for International Development (DFID) through the Effective Healthcare Research Consortium at the Liverpool School of tropical Medicine. This review was developed in part during the Reviews for Africa Programme protocol development course organised by the Nigerian Branch of South African Cochrane Centre, April 2013.

The search terms were developed by the Trials Search Co‐ordinator of the Cochrane Schizophrenia Group, Samantha Roberts.

We would like to thank Michael Wilson for peer reviewing this version of our review, his comments were most helpful.

We would also like to acknowledge and thank our copy editor, Heather Maxwell.

Version history

Published

Title

Stage

Authors

Version

2015 Apr 13

Pyridoxal 5 phosphate for neuroleptic‐induced tardive dyskinesia

Review

Adegoke Oloruntoba Adelufosi, Olukayode Abayomi, Tunde Massey‐Ferguson Ojo

https://doi.org/10.1002/14651858.CD010501.pub2

2013 Apr 30

Pyridoxal 5 phosphate for neuroleptic‐induced tardive dyskinesia

Protocol

Adegoke Oloruntoba Adelufosi, Olukayode Abayomi, Tunde Massey‐Ferguson Ojo

https://doi.org/10.1002/14651858.CD010501

Differences between protocol and review

There are two major differences between the protocol of this review and the final review viz;

1. Since the studies included in this review were generally of short duration, the classification of outcomes into short term, medium term and long term outcomes was eliminated. For the same reason, assessment of clinical improvement in tardive dyskinesia symptoms was changed from "at least six weeks of treatment" to "at least four weeks".

2. The definition of clinical efficacy for pyridoxal 5 phosphate was changed to > 40% improvement in tardive dyskinesia symptoms after at least four weeks of treatment. This was necessary for interpretation of results and to reflect the definitions of moderate to marked clinical improvement in tardive dyskinesia symptoms used in the included studies.

3. Due to the small sample sizes of studies included in this review and the possible bias that can be introduced by using a random‐effects model for data synthesis, we decided to use a fixed‐effect model for all our data analysis.

4. As at the time of writing this review, one pharmaceutical company was still recruiting participants for a trial on the safety and efficacy of pyridoxal 5 phosphate on treatment of tardive dyskinesia. Since the trial was still ongoing, we did not contact the pharmaceutical company as stated in the protocol of this review.

5. We did not conduct a sensitivity analyses as stated in the protocol due to the similarities in inclusion criteria, characteristics of intervention/comparator and study design among the included studies.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 1 Global: Clinical efficacy ‐ significant reduction in ESRS scores from baseline.
Figures and Tables -
Analysis 1.1

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 1 Global: Clinical efficacy ‐ significant reduction in ESRS scores from baseline.

Study

Lerner 2001

400 mg daily

Lerner 2007

1200 mg daily

Miodownik 2003

400 mg daily

Figures and Tables -
Analysis 1.2

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 2 Global 1. Average endpoint dose of pyridoxal 5 phosphate.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 3 Global: 2. Other adverse effects than tardive dyskinesia.
Figures and Tables -
Analysis 1.3

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 3 Global: 2. Other adverse effects than tardive dyskinesia.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 4 Global: 3. Discontinuation of Vitamin B6.
Figures and Tables -
Analysis 1.4

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 4 Global: 3. Discontinuation of Vitamin B6.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 5 Tardive dyskinesia: 1. Deterioration in tardive dyskinesia symptoms.
Figures and Tables -
Analysis 1.5

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 5 Tardive dyskinesia: 1. Deterioration in tardive dyskinesia symptoms.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 6 Tardive dyskinesia: 2. Average endpoint ESRS tardive dyskinesia scores.
Figures and Tables -
Analysis 1.6

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 6 Tardive dyskinesia: 2. Average endpoint ESRS tardive dyskinesia scores.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 7 General Mental State: Average endpoint positive psychiatric symptoms score.
Figures and Tables -
Analysis 1.7

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 7 General Mental State: Average endpoint positive psychiatric symptoms score.

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 8 General mental state: Average endpoint negative psychiatric symptoms score.
Figures and Tables -
Analysis 1.8

Comparison 1 Pyridoxal 5 phosphate (Vitamin B6) versus placebo, Outcome 8 General mental state: Average endpoint negative psychiatric symptoms score.

Table 1. Possible design for a future study

Method

Allocation: randomised ‐ clearly described generation of sequence and concealment of allocation.
Blinding: double ‐ described and tested.
Duration: long term.
Setting: Inpatients and outpatients

Design: Single phase, longer study duration.

Participants

People with schizophrenia or schizophrenia‐like disorder.
N = Sample size obtained through power calculation.
Age: any
Sex: both

History: History of tardive dyskinesia, fulfilling diagnostic criteria for tardive dyskinesia, stable on antipsychotic medication for at least 3 months.

Intervention

1.Pyridoxal Phosphate (vitamin B6), any dose

2. Placebo

Outcomes

Tardive dyskinesia scores measured using AIMS (primary outcome)

Deterioration of tardive dyskinesia symptoms

Any other adverse effects

Discontinuation of pyridoxal phosphate (with reasons)

Psychiatric symptoms score using a standardised rating scale (PANSS, BPRS)

Pyridoxal phosphate dose

Plasma pyridoxal phosphate level

Quality of life

Satisfaction with care

AIMS: Abnormal Involuntary Movement Scale
BPRS: Brief Psychiatric Rating Scale
PANSS: Positve and Negative Scale of Schizophrenia

Figures and Tables -
Table 1. Possible design for a future study
Summary of findings for the main comparison. Pyridoxal 5 phosphate (vitamin B6) compared with Placebo for neuroleptic‐induced tardive dyskinesia

Pyridoxal 5 phosphate (vitamin B6) compared with Placebo for neuroleptic‐induced tardive dyskinesia

Patient or population: patients with neuroleptic‐induced tardive dyskinesia
Settings: Inpatients
Intervention: Pyridoxal 5 phosphate (vitamin B6)
Comparison: Placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Pyridoxal 5 phosphate (vitamin B6)

Clinical efficacy ‐ improvement (> 40%) in ESRS scores from baseline
ESRS1
Follow‐up: mean 17.5 weeks2

Study population

RR 19.97
(2.87 to 139.19)

65
(2 studies)

⊕⊕⊝⊝
low3,4

0 per 1000

0 per 1000
(0 to 0)

Moderate

0 per 1000

0 per 1000
(0 to 0)

Global: Other adverse effects than tardive dyskinesia
Self‐report by participants
Follow‐up: mean 17.5 weeks2

Study population

RR 3.97
(0.2 to 78.59)

65
(2 studies)

⊕⊕⊝⊝
low3,4

0 per 1000

0 per 1000
(0 to 0)

Moderate

0 per 1000

0 per 1000
(0 to 0)

Global: Discontinuation of Vitamin B6
Follow‐up: mean 17.5 weeks2

Study population

RR 8.72
(0.51 to 149.75)

65
(2 studies)

⊕⊕⊝⊝
low3,4

0 per 1000

0 per 1000
(0 to 0)

Moderate

0 per 1000

0 per 1000
(0 to 0)

Tardive dyskinesia: Deterioration in tardive dyskinesia symptoms
ESRS1
Follow‐up: mean 17.5 weeks2

Study population

RR 0.16
(0.01 to 3.14)

65
(2 studies)

⊕⊕⊝⊝
low3,4

69 per 1000

11 per 1000
(1 to 217)

Moderate

46 per 1000

7 per 1000
(0 to 144)

General mental state: Positive psychiatric symptom score
PANSS5. Scale from: 7 to 49.
Follow‐up: 9 weeks

The mean general mental state: positive psychiatric symptom score in the control groups was
15.6

The mean general mental state: positive psychiatric symptom score in the intervention groups was
1.50 lower
(4.80 lower to 1.80 higher)

15
(1 study)

⊕⊕⊝⊝
low3,6

General mental state: Negative psychiatric symptoms
PANSS5. Scale from: 7 to 49.
Follow‐up: 9 weeks

The mean general mental state: negative psychiatric symptoms in the control groups was
14.6

The mean general mental state: negative psychiatric symptoms in the intervention groups was
1.10 lower
(5.92 lower to 3.72 higher)

15
(1 study)

⊕⊕⊝⊝
low3,6

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Extrapyramidal Symptom Rating Scale (high scores = worse)
2 Study duration: 9 weeks and 26 weeks respectively for the two included studies
3 Adequate description of randomisation methods was not provided. Methods for allocation concealment and blinding were not described.
4 The included studies have small sample sizes
5 Positive and Negative Symptoms Scale (high scores = worse)
6 Study has a small sample size

Figures and Tables -
Summary of findings for the main comparison. Pyridoxal 5 phosphate (vitamin B6) compared with Placebo for neuroleptic‐induced tardive dyskinesia
Comparison 1. Pyridoxal 5 phosphate (Vitamin B6) versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global: Clinical efficacy ‐ significant reduction in ESRS scores from baseline Show forest plot

2

65

Risk Ratio (M‐H, Fixed, 95% CI)

19.97 [2.87, 139.19]

2 Global 1. Average endpoint dose of pyridoxal 5 phosphate Show forest plot

Other data

No numeric data

3 Global: 2. Other adverse effects than tardive dyskinesia Show forest plot

2

65

Risk Ratio (M‐H, Fixed, 95% CI)

3.97 [0.20, 78.59]

4 Global: 3. Discontinuation of Vitamin B6 Show forest plot

2

65

Risk Ratio (M‐H, Fixed, 95% CI)

8.72 [0.51, 149.75]

5 Tardive dyskinesia: 1. Deterioration in tardive dyskinesia symptoms Show forest plot

2

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 3.14]

6 Tardive dyskinesia: 2. Average endpoint ESRS tardive dyskinesia scores Show forest plot

2

60

Mean Difference (IV, Fixed, 95% CI)

‐4.07 [‐6.36, ‐1.79]

7 General Mental State: Average endpoint positive psychiatric symptoms score Show forest plot

1

15

Mean Difference (IV, Fixed, 95% CI)

‐1.50 [‐4.80, 1.80]

8 General mental state: Average endpoint negative psychiatric symptoms score Show forest plot

1

15

Mean Difference (IV, Fixed, 95% CI)

‐1.10 [‐5.92, 3.72]

Figures and Tables -
Comparison 1. Pyridoxal 5 phosphate (Vitamin B6) versus placebo