Pyridoxal 5 phosphate for neuroleptic‐induced tardive dyskinesia

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

doi:10.1002/14651858.CD010501.pub2

Cochrane Database of Systematic Reviews

Pyridoxal 5 phosphate for neuroleptic‐induced tardive dyskinesia

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DOI:

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

Database:

Cochrane Database of Systematic Reviews

Version published:

13 April 2015see what's new

Type:

Intervention

Stage:

Review

Cochrane Editorial Group:

Cochrane Schizophrenia Group

Copyright:

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

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; Aged; Female; Humans; Male; Middle Aged;

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.

Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

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

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Analysis 1.1

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

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Study
Lerner 2001	400 mg daily
Lerner 2007	1200 mg daily
Miodownik 2003	400 mg daily

Analysis 1.2

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

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Analysis 1.3

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

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Analysis 1.4

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

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Analysis 1.5

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

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Analysis 1.6

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

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Analysis 1.7

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

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Analysis 1.8

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

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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

Table 1. Possible design for a future study

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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)	⊕⊕⊝⊝ low^3,4
	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)	⊕⊕⊝⊝ low^3,4
	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)	⊕⊕⊝⊝ low^3,4
	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)	⊕⊕⊝⊝ low^3,4
	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)	⊕⊕⊝⊝ low^3,6
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)	⊕⊕⊝⊝ low^3,6
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

Summary of findings for the main comparison. Pyridoxal 5 phosphate (vitamin B6) compared with Placebo for neuroleptic‐induced tardive dyskinesia

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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]

Comparison 1. Pyridoxal 5 phosphate (Vitamin B6) versus placebo

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Pyridoxal 5 phosphate for neuroleptic‐induced tardive dyskinesia

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