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Cochrane Database of Systematic Reviews

Aumento de la dosis del antipsicótico versus cambio de antipsicótico para la falta de respuesta en la esquizofrenia

Información

DOI:
https://doi.org/10.1002/14651858.CD011884.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 11 mayo 2018see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Esquizofrenia

Copyright:
  1. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Myrto T Samara

    Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany

  • Elisabeth Klupp

    Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, München, Germany

  • Bartosz Helfer

    Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany

  • Philipp H Rothe

    Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany

  • Johannes Schneider‐Thoma

    Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany

  • Stefan Leucht

    Correspondencia a: Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany

    [email protected]

Contributions of authors

Myrto Samara: protocol development, study selection, data extraction, writing the report.

Elisabeth Klupp: study selection, data extraction.

Bartosz Helfer: protocol development.

Philipp Rothe: protocol development.

Johannes Schneider‐Thoma: writing of a summary report for the review.

Stefan Leucht: protocol development, study selection, data extraction, writing the report.

Sources of support

Internal sources

  • Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, München, Germany.

    Employs review authors Myrto T Samara, Bartosz Helfer, Philipp H Rothe, Johannes Schneider‐Thoma and Stefan Leucht.

External sources

  • Bundesministerium für Bildung und Forschung (BMBF), Germany.

    Grant number: FKZ 01KG1407

Declarations of interest

Myrto Samara: none known.

Elisabeth Klupp: none known.

Bartosz Helfer: none known.

Philipp Rothe: none known.

Johannes Schneider‐Thoma: none known.

Stefan Leucht ‐ has received honoraria for consulting from LB Pharma, Lundbeck, Otsuka, TEVA, Geodon Richter, Recordati, LTS Lohmann, and Boehringer Ingelheim; and for lectures from Janssen, Lilly, Lundbeck, Otsuka, SanofiAventis, and Servier.

Acknowledgements

The Cochrane Schizophrenia Group Editorial Base in Nottingham produces and maintains standard text for use in the Methods section of their reviews. We have used this text as the basis of what appears here and adapted it as required.

The search term was developed by the Trial Search Co‐ordinator of the Cochrane Schizophrenia Group and the contact author of this review.

We would like to thank Dr Georgios Mikellides for peer reviewing the protocol and Joey Kwong for copy editing. We also thank Wing Chung Chang, Yuen‐Shan Ho and Brittany Dutton for peer reviewing the full review version.

Version history

Published

Title

Stage

Authors

Version

2018 May 11

Increasing antipsychotic dose versus switching antipsychotic for non response in schizophrenia

Review

Myrto T Samara, Elisabeth Klupp, Bartosz Helfer, Philipp H Rothe, Johannes Schneider‐Thoma, Stefan Leucht

https://doi.org/10.1002/14651858.CD011884.pub2

2015 Oct 21

Increasing antipsychotic dose versus switching antipsychotic for non response in schizophrenia

Protocol

Myrto T Samara, Bartosz Helfer, Philipp H Rothe, Stefan Leucht

https://doi.org/10.1002/14651858.CD011884

Differences between protocol and review

We have removed the second sentence from Objectives ("We will include any antipsychotic drug studies in any people with schizophrenia, however diagnosed") as this is also described in Types of participants.

We have renamed outcomes from 'Clinically significant response' to 'Clinically important change'.

We have now specified 'Summary of findings' table outcomes should be 'Clinically important change' but if data were not available for these pre‐specified outcomes but were available for ones that are similar, we presented the closest outcome to the pre‐specified one in the table but took this into account when grading the finding.

We have updated the methods template to the latest version provided by Cochrane Schizophrenia. This does not involve a change to the methods but updating of references and rewording of some sections.

We have reworded some of the background to harmonise this review with its 'sibling review' Helfer 2015

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram for trial selection up to March 2017
Figuras y tablas -
Figure 1

Study flow diagram for trial selection up to March 2017

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
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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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

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

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Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 1 Global state: clinically relevant response – as defined by trial.
Figuras y tablas -
Analysis 1.1

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 1 Global state: clinically relevant response – as defined by trial.

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Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor).
Figuras y tablas -
Analysis 1.2

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor).

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Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor).
Figuras y tablas -
Analysis 1.3

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor).

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Table 1. Suggested design for future study

Methods

Randomisation: random
Allocation: concealed
Blinding: double blind
Duration: at least 2 weeks run‐in phase to confirm non response to initial treatment and at least 4 weeks' randomised double‐blind phase.
Setting: in‐ or out‐patients

Participants

Diagnosis: people with schizophrenia, schizoaffective disorder or schizophreniform disorder

N > 450
Gender: male and female
Age: mean 30 years (SD = 7.0), range 18 to 65 years

Interventions

All participants firstly receive treatment with one antipsychotic drug for at least 2 weeks. Those participants who do not at least minimally improve after 2 weeks, are considered non‐responders and are randomised to:

1. increasing the dose of the initial antipsychotic drug above the officially recommended dose range; or

2. switching the initial antipsychotic drug to another one with a different receptor profile; or

3. continuing treatment with the initial antipsychotic drug and at the same, initial dose (within the officially recommended dose range).

Outcomes

Response (defined as PANSS or BPRS decrease ≥ 50%)*

Relapse

Leaving the study early due to any reason

Leaving the study early due to side effects

General mental state: average change in general mental state scores

Adverse effects: at least one adverse effect; clinically important general adverse effects; sudden and unexpected death

Service use: time in hospital

Quality of life

All outcomes by time ‒ short term (up to 12 weeks), medium term (13 to 26 weeks) and long term (over 26 weeks)

Notes

*Primary outcome of interest
Figuras y tablas -
Table 1. Suggested design for future study
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Summary of findings for the main comparison. Increasing the antipsychotic dose compared to switching the antipsychotic drug for non response in schizophrenia

Increasing the antipsychotic dose compared to switching the antipsychotic drug for non responsein schizophrenia

Patient or population: patients with non response in schizophrenia
Settings: inpatients
Intervention: increasing the antipsychotic dose
Comparison: switching the antipsychotic drug

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Switching the atipsychotic drug

Increasing the antipsychotic dose

Global state: Clinically relevant response – as defined by trial
Risk ratio
Follow‐up: mean 4 weeks

77 per 1000

125 per 1000
(13 to 1000)

RR 1.63
(0.17 to 15.99)

29
(1 study)

⊕⊝⊝⊝
very low1,2

Leaving the study early: Tolerability ‒leaving the study early due to side effects

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Leaving the study early: Acceptability ‒leaving the study early due to any reason

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome,

General mental state ‒BPRS total score at endpoint*
Weighted mean difference
Follow‐up: mean 4 weeks

The mean general mental state ‒ BPRS total score at endpoint in the control groups was
38.2 points in BPRS

The mean general mental state ‐ BPRS total score at endpoint in the intervention groups was
2 higher
(4.2 lower to 8.2 higher)

29
(1 study)

⊕⊝⊝⊝
very low1,2

Data for prespecified outcome: Clinically important change were not reported.

Adverse effects ‒at least one adverse effect

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Service use ‒time in hospital

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Quality of life ‒average change in quality of life

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

*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 Imprecision: total (cumulative) sample size was just 29 participants and 95% confidence interval around the estimate of effect included no effect and appreciable benefit and appreciable harm; thus, very serious imprecision was present.
2 Publication bias: strongly suspected as there is only one study.

Figuras y tablas -
Summary of findings for the main comparison. Increasing the antipsychotic dose compared to switching the antipsychotic drug for non response in schizophrenia
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Comparison 1. Increasing the antipsychotic dose versus switching the atipsychotic drug

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: clinically relevant response – as defined by trial Show forest plot

1

29

Risk Ratio (M‐H, Random, 95% CI)

1.63 [0.17, 15.99]

2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor) Show forest plot

1

29

Mean Difference (IV, Random, 95% CI)

2.0 [‐4.20, 8.20]

3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor) Show forest plot

1

29

Mean Difference (IV, Random, 95% CI)

3.40 [‐12.56, 19.36]
Figuras y tablas -
Comparison 1. Increasing the antipsychotic dose versus switching the atipsychotic drug
Ir a la tabla de la revisión