Cochrane Database of Systematic Reviews

Benzodiazepines for catatonia in people with schizophrenia

and other serious mental illnesses (Review)

Gibson RC, Walcott G

Gibson RC, Walcott G.

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses.
Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006570.
DOI: 10.1002/14651858.CD006570.pub2.

www.cochranelibrary.com

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 16
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) i
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Benzodiazepines for catatonia in people with schizophrenia

and other serious mental illnesses

Roger Carl Gibson1 , Geoffery Walcott2

1 Department of Community Health & Psychiatry, University of the West Indies, Mona, Jamaica. 2 Department of Psychiatry, University

Hospital of the West Indies, Kingston, Jamaica

Contact address: Roger Carl Gibson, Department of Community Health & Psychiatry, University of the West Indies, Hospital Ring
Road, University Hospital of the West Indies, Mona, Kingston 7, Kgn 7, Jamaica. rcgib@hotmail.com.

Editorial group: Cochrane Schizophrenia Group.

Publication status and date: Edited (no change to conclusions), published in Issue 2, 2013.

Citation: Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses.
Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006570. DOI: 10.1002/14651858.CD006570.pub2.

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background

Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental disorders. People
in a catatonic state have increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of
treatment has been drug therapies and electroconvulsive therapy.

Objectives

To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for people with catatonia.

Search methods

We searched the Cochrane Schizophrenia Group Trials Register (March 2007) and manually searched reference lists from the selected
studies.

Selection criteria

All relevant randomised controlled clinical trials.

Data collection and analysis

We (RCG, GW) extracted data independently. For dichotomous data we would have calculated relative risks (RR) and their 95%
confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model.

Main results

No studies could be included. We did find studies reporting no usable data that we had to exclude or assign to those awaiting assessment.
These studies, although poorly reported, do illustrate that relevant studies have been undertaken, and are not impossible.

Authors’ conclusions

Studies have been justified and undertaken in the past. This justification remains as relevant as ever. Further studies with a high-quality
methodology and reporting are required and it may be for countries where catatonia is seen often to take a lead in this area.
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 1
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PLAIN LANGUAGE SUMMARY

Benzodiazepines for extreme movement problems (catatonia) in people with schizophrenia and other serious mental illnesses.

Some people who have schizophrenia or other serious mental illnesses develop catatonia, which consists of extreme lack of movement
or constant repetitive movement over which they seem to have very little control. Whilst in a catatonic state these people are unable to
interact with their environment and may go on to acquire secondary problems such as pneumonia, blood clotting problems (thrombosis),
malnutrition or dehydration. Current treatments for this are either drugs, which are given by injection, or electric shock treatment
(electroconvulsive therapy). The aim of this review is to look at how effective benzodiazepines are compared to placebo or other drug
treatments in treating this problem. However, while some clinical trials that seemed relevant were identified, no usable data could be
extracted from them. There is no good trial-derived data on this subject. However, there are five trials on which more information
needs to be collected. In the longer term, to make sure people with catatonia receive the most effective treatment, this is an area
that would benefit from good research and well planned and reported trials. Also, since the condition is rare, there should be good
communication between those involved in researching it.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)

BACKGROUND Much of the evidence-base for the use of benzodiazepines for cata-
tonia consists of case reports and small studies. This systematic re-
view will attempt to identify and summarise any relevant evidence
Description of the condition from trials.

Catatonia is a syndrome characterised by motor abnormalities such

as purposeless activity, immobility and posturing, together with
disturbances of consciousness and volition. In 1874 observers de-
scribed seventeen typical signs, although many more have since OBJECTIVES
been added (Kahlbaum 1973). Catatonia has been described in
the context of schizophrenia, organic illnesses and mood disorders To compare the effects of benzodiazepines compared with placebo,
(APA 2000; WHO 1992). Regardless of the cause, when catato- other pharmacological agents, or electroconvulsive therapy for
nia is not aggressively treated the patient is at increased risk for treatment of catatonia.
a number of negative outcomes. People with catatonia may de-
velop pneumonia and thromboembolic complications (Regestein
1977). Malnutrition and dehydration are also common (Penland METHODS
2006).

Criteria for considering studies for this review

Description of the intervention
A number of different treatments have been advocated for catato-
nia. Attention to underlying causes is important, although, in some
Types of studies
instances, antipsychotics may worsen catatonia (Penland 2006).
Benzodiazepines, especially lorazepam, have been thought to be Randomised controlled trials. Where a trial was described as ’dou-
of some benefit (Rosebush 1990; Schmider 1999). Together with ble-blind’, but it was only implied that the study was randomised,
electroconvulsive therapy, benzodiazepines are perhaps the most these trials were included in a sensitivity analysis. If there was no
widely reported treatment. substantive difference within primary outcomes (see types of out-
come measures) when these ’implied randomisation’ studies were
added, then they were included in the final analysis. If there was
Why it is important to do this review a substantive difference, only clearly randomised trials were used
and the results of the sensitivity analysis were described in the text.
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Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Quasi-randomised studies, such as those allocating by using alter-
nate days of the week, were excluded. For studies with cross-over
designs, only data from the first cross-over phase were analysed.
Types of participants
We included all people with schizophrenia, other psychoses or af-
fective disorders who have catatonia, however defined, as a prin-
cipal feature of their clinical presentation.
Types of interventions
1. Benzodiazepines of any type, dose and means of administration.
2. Any other class of pharmacological agent at any dose or placebo.
3. Electroconvulsive therapy.
Types of outcome measures
*Primary outcomes: These primary outcomes will help focus the
discussion of the review. Sensitivity analyses will also be restricted
to these areas.
All outcomes were grouped according to time - short term (up to
12 weeks), medium term (13 to 26 weeks) and long term (over
26 weeks). Short-term studies were also distinguished according
to whether they were single injection, one day or longer studies.
Primary outcomes
1. Clinical response: Clinically significant reduction in severity of
catatonic symptoms (as defined by each study).
2. Hospital and service outcomes: Duration of stay in hospital.
3. Satisfaction with care: Informal care givers.
Secondary outcomes
1. Death.
2. Clinical response
2.1 Any reduction in severity of symptoms.
2.2 Any increase in severity of symptoms.
2.3 Degree of change in severity of symptoms.
2.4 Clinically significant improvement in self care.
3. Leaving the study early.
4. Adverse effects.
4.1 Incidence of adverse effects (general and specific).
4.2 Measured acceptability of treatment.
5. Hospital and service outcomes.
5.1 Changes in hospital status (e.g. level of observation).
6. Satisfaction with care.
6.1 Recipients of care.
6.2 Professional carers.
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Search methods for identification of studies
Electronic searches
1. The Cochrane Schizophrenia Group Trials Register (March
2007)
We searched using the phrase:
[((catatoni*) in title, abstract and index fields in REFERENCE)
OR ((benzodia* OR alprazo* OR chlordiaz* OR cloraze* OR
estazo* OR medazepam* OR midazol* OR triazolam* OR
clobazam* OR loprazol*) in interventions field in STUDY]
Searching other resources
1. Hand searches
We searched reference lists from the selected studies for reports of
additional trials.
2. Requests for additional data
Where necessary we contacted authors’ of relevant published and
unpublished material for additional data.
Data collection and analysis
[For definitions of terms used in this, and other sections, please
refer to The Cochrane Library Glossary]
Selection of studies
We (RCG, GW) independently inspected citations identified from
the search. We identified potentially relevant reports and ordered
full papers for reassessment. If doubts remained we acquired the
full article for further inspection. We obtained full reports and
independently reassessed these for inclusion.This process was re-
peated for the full papers. If it was impossible to resolve disagree-
ments these studies were added to those awaiting assessment and
the authors of the papers contacted for clarification.
Data extraction and management
1. Extraction
We (RCG, GW) independently extracted data from the selected
trials. Again, where disagreement occurred attempts were made to
resolve this by discussion, where doubt still remained we acquired
further information from authors. Data were extracted onto stan-
dard, simple forms.
2. Management
2.1 Continuous to binary
Where possible, efforts were made to convert outcome measures
to binary data. This can be done by identifying cut off points on
rating scales and dividing participants accordingly into ’clinically
improved’ or ’not clinically improved’. It was generally assumed
that if there had been a 50% reduction in a scale-derived score
3
such as the Brief Psychiatric Rating Scale (BPRS, Overall 1962)
or the Positive and Negative Syndrome Scale (PANSS, Kay 1986),
this could be considered as a clinically significant response (Leucht
2005a, Leucht 2005b). It was recognised that for many people,
especially those with chronic or severe illness, a less rigorous defi-
nition of important improvement (e.g. 25% on the BPRS) would
be equally valid. If individual patient data had been available, the
50% cut-off would have been used for the definition in the case of
non-chronically ill people and 25% for those with chronic illness.
If data based on these thresholds were not available, we would have
used the primary cut-off presented by the original authors.
2.2 Normal distribution
For continuous data we calculated the weighted mean difference
(WMD) between groups and its 95% confidence interval (CI)
using a fixed effects model. Continuous data on outcomes in trials
relevant to mental health issues are often not normally distributed.
To avoid the pitfall of applying parametric tests to non-parametric
data we applied the following standards to continuous final value
endpoint data before inclusion: (a) standard deviations and means
were reported in the paper or were obtainable from the authors;
(b) when a scale started from zero, the standard deviation, when
multiplied by two, should be less than the mean (otherwise the
mean is unlikely to be an appropriate measure of the centre of the
distribution - Altman 1996); in cases with data that are greater
than the mean they were entered into ’Other data’ table as skewed
data. If a scale starts from a positive value (such as PANSS, which
can have values from 30 to 210) the calculation described above in
(b) should be modified to take the scale starting point into account.
In these cases skewness is present if 2SD>(S-Smin), where S is the
mean score and Smin is the minimum score.
For change data (mean change from baseline on a rating scale)
it is impossible to tell whether data are non-normally distributed
(skewed) or not, unless individual patient data are available. Af-
ter consulting the ALLSTAT electronic statistics mailing list, we
presented change data in RevMan graphs to summarise available
information. In doing this, we assumed either that data were not
skewed or that the analysis could cope with the unknown degree
of skew.
2.3 Final endpoint value versus change data
Where both final endpoint data and change data were available
for the same outcome category, only final endpoint data were pre-
sented. We acknowledge that by doing this much of the published
change data may be excluded, but argue that endpoint data is more
clinically relevant and that if change data were to be presented
along with endpoint data, it would be given undeserved equal
prominence. Authors of studies reporting only change data are
being contacted for endpoint figures. Again, where loss to follow
up is greater than 20%, we will not use data because we (RCG,
GW) consider that, for short-term studies such as those likely to
be included in this review, this degree of loss would be indicative
of poor study quality.
2.4 Scale-derived data
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A wide range of instruments are available to measure mental health
outcomes. These instruments vary in quality and many are not
valid, and are known to be subject to bias in trials of treatments for
schizophrenia (Marshall 2000). Therefore, continuous data from
rating scales were included only if the measuring instrument had
been described in a peer-reviewed journal. Scales which had been
rated by therapists, rather than an independent rater were reported
as ’prone to bias’.
Assessment of risk of bias in included studies
Again working independently, RCG and GW assessed risk of bias
using the tool described in the Cochrane Collaboration Hand-
book (Higgins 2005). This tool encourages consideration of how
the sequence was generated, how allocation was concealed, the in-
tegrity of blinding at outcome, the completeness of outcome data,
selective reporting and other biases. We would not have included
studies where sequence generation was at high risk of bias or where
allocation was clearly not concealed.
Measures of treatment effect
1. Binary data
For binary outcomes we would have calculated the relative risk
(RR) and its 95% confidence interval (CI) based on the fixed-effect
model. Relative Risk is more intuitive (Boissel 1999) than odds
ratios and odds ratios tend to be interpreted as RR by clinicians
(Deeks 2000). This misinterpretation then leads to an overestimate
of the impression of the effect. Should the overall results have been
significant we would have calculated the number needed to treat
(NNT) and the number-needed-to-harm (NNH).
2. Continuous data
For continuous outcomes we would have estimated a fixed-effect
weighted mean difference (WMD) between groups. We would
not have calculated effect size measures.
Unit of analysis issues
1. Cluster trials
Studies increasingly employ ’cluster randomisation’ (e.g. randomi-
sation by clinician or practice) but analysis and pooling of clus-
tered data poses problems. Firstly, authors often fail to account
for intraclass correlation in clustered studies, leading to a ’unit
of analysis’ error (Divine 1992) whereby p values are spuriously
low, confidence intervals unduly narrow and statistical significance
overestimated. This causes type 1 errors (Bland 1997, Gulliford
1999).
Should clustering not have been accounted for in primary stud-
ies, we would have presented the data in a table, with a (*) sym-
bol to indicate the presence of a probable unit of analysis error.
In subsequent versions of this review we will seek to contact first
authors of studies to obtain intraclass correlation co-efficients of
their clustered data and to adjust for this using accepted methods
4
(Gulliford 1999). Should clustering have been incorporated into
the analysis of primary studies, we would have also presented these
data as if from a non-cluster randomised study, but adjusted for
the clustering effect. We have sought statistical advice and have
been advised that the binary data as presented in a report should be
divided by a ’design effect’. This is calculated using the mean num-
ber of participants per cluster (m) and the intraclass correlation
co-efficient (ICC) [Design effect=1+(m-1)*ICC] (Donner 2002).
If the ICC had not been reported it would have been assumed
to be 0.1 (Ukoumunne 1999). Should cluster studies have been
appropriately analysed taking into account intraclass correlation
coefficients and relevant data documented in the report, synthe-
sis with other studies would have been possible using the generic
inverse variance technique.
2. Cross-over trials
A major concern of cross-over trials is the carryover effect. It occurs
if an effect (e.g. pharmacological, physiological or psychological) of
the treatment in the first phase is carried over to the second phase.
As a consequence on entry to the second phase the participants
can differ systematically from their initial state despite a wash-out
phase. For the same reason cross-over trials are not appropriate
if the condition of interest is unstable (Elbourne 2002). As both
effects are very likely in schizophrenia, we would have only used
data of the first phase of cross-over studies.
3. Studies with multiple treatment groups
Should a study have involved more than two treatment arms, if
relevant, the additional treatment arms would have been presented
in comparisons. Where the additional treatment arms were not
relevant, these data were not reproduced.
Dealing with missing data
1. Unreported data
We would have contacted the primary author of each included
study for any unreported data (e.g. standard deviations, details of
dropouts, details of interventions received by control group).
2. Overall loss of credibility
At some degree of loss of follow up, data must lose credibility. We
are forced to make a judgment where this is for the very short-term
trials likely to be included in this review. Should more than 20%
of data have been unaccounted for we would not have reproduced
these data or used them within analyses.
3. Binary
In the case where attrition for a binary outcome was between 0
and 20% and outcomes of these people had been described, we
would have included these data as reported. Where these data were
not clearly described, we would have assumed the worst primary
outcome, and rates of adverse effects similar to those who did
continue to have their data recorded.
4. Continuous
In the case where attrition for a continuous outcome had been
between 0 and 20% and completer-only data were reported, we
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
would have reproduced the findings.
Assessment of heterogeneity
1. Clinical heterogeneity
Firstly, consideration of all the included studies within any com-
parison would have been undertaken to judge clinical heterogene-
ity.
2. Statistical
2.1 Visual inspection
Then visual inspection of graphs would have been used to inves-
tigate the possibility of statistical heterogeneity.
2.2 Employing the I-squared statistic
Visual inspection would have been supplemented using, primarily,
the I-squared statistic. This provides an estimate of the percentage
of variability due to heterogeneity rather than chance alone. Should
the I-squared estimate have been greater than or equal to 50%,
this would have been interpreted as indicating the presence of high
levels of heterogeneity (Higgins 2003). If inconsistency had been
high, data would not have been summated, but would have been
presented separately and reasons for heterogeneity investigated.
Assessment of reporting biases
Reporting biases arise when the dissemination of research find-
ings is influenced by the nature and direction of results. These are
described in section 10.1 of the Cochrane Handbook (Higgins
2005). We are aware that funnel plots may be useful in investigat-
ing reporting biases but are of limited power to detect small-study
effects. We would not have used funnel plots for outcomes where
there were ten or fewer studies, or where all studies were of similar
sizes. In other cases, should funnel plots have been possible, we
would have sought statistical advice in their interpretation.
Data synthesis
Should it have been possible we would have employed a fixed-
effect model for analyses. We understand that there is no closed
argument for preference for use of fixed or random-effect models.
The random-effect method incorporates an assumption that the
different studies are estimating different, yet related, intervention
effects. This does seem true to us, however, random-effect does
put added weight onto the smaller of the studies - those trials that
are most vulnerable to bias. For this reason we favour using fixed-
effect models and would have employed only random-effect when
investigating heterogeneity.
Subgroup analysis and investigation of heterogeneity
If data had been clearly heterogeneous we would have checked
that data were correctly extracted and entered and that we had
made no unit-of-analysis errors. If the high levels of heterogene-
ity had remained we would not have undertake a meta-analysis
5
at this point for if there is considerable variation in results, and
particularly if there is inconsistency in the direction of effect, it
may be misleading to quote an average value for the intervention
effect. We would have wanted to explore heterogeneity. We pre-
specify no characteristics of studies that may be associated with
heterogeneity except quality of trial method. If no clear association
could have been shown by sorting studies by quality of methods a
random-effect meta-analysis would have been preformed. Should
other characteristics of the studies have been highlighted by the
investigation of heterogeneity, perhaps some plausible but unpre-
dicted clinical heterogeneity, these post-hoc reasons would have
been discussed, data analysed and presented. However, should the
heterogeneity have been substantially unaffected by use of ran-
dom-effect meta-analysis and no other reasons for heterogeneity
be clear, the final data would have been presented without a meta-
analysis.
Sensitivity analysis
Should data have been permitting, sensitivity analyses would have
been undertaken in order to see if sub-grouping data resulted in
important changes in the results. The following sub-groupings
were pre-specified:
1. Published (in a journal/chapter) versus unpublished trials.
2. High quality (well-described sequence generation and conceal-
ment of allocation) studies versus others.
3. Use of specific benzodiazepines versus use of all other benzodi-
azepines.
RESULTS
Description of studies
See: Characteristics of excluded studies; Characteristics of studies
awaiting classification.
For substantive descriptions of the studies please see Included and
Excluded Studies tables.
Results of the search
We found 130 citations using the search strategies and some studies
were multiply reported in different media. Of the 130 citations,
22 relevant studies were selected for detailed inspection.
Included studies
We could not include any studies.
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Excluded studies
We excluded seventeen studies from the review. Only ten of these
were randomised. Many of both the randomised and the non-
randomised excluded studies did not focus specifically on treat-
ment outcomes in people with catatonia. Of the ten randomised
studies, only three included more than one person with catatonia
(Fischer 1974, Kunigiri 2002, Ungvari 1997), and of these, none
employed benzodiazepines as a therapeutic intervention.
1. Studies awaiting assessment
Five studies currently await assessment. We were able to obtain
only abstracts for two (Patra 1998, Wetzel 1997) and these did
not contain any usable data. For a third study (Merlis 1962), we
found a full journal article. However, the method of allocation of
participants to the different therapeutic interventions was unclear.
Additionally, in that study, only twelve out of a total of eighty par-
ticipants suffered from catatonia and no independent data were
presented about these specific people. Two studies (Schmider 1999
and Ungvari 1999) were described as double-blind and had cross-
over designs; the latter with persons with chronic catatonia. How-
ever, in both cases, data were not reported separately for the first
cross-over phase and therefore could not be included for analy-
sis. Schmider 1999 presented findings graphically and as statistics
with accompanying p values, making them impossible to use in
this review. Where possible, relevant sources will be contacted for
further information.
2. Ongoing studies
We did not identify any ongoing studies.
Risk of bias in included studies
No studies were identified for inclusion.
Effects of interventions
We identified no usable trial-derived data as to the effects of ben-
zodiazepines for people with catatonia.
DISCUSSION
Summary of main results
We found some small relevant trials from which we could extract
no data. There are, to our knowledge, no good trial-derived data
as to the effects of benzodiazepines for people with catatonia.
6
Overall completeness and applicability of
evidence
In some excluded studies relevant data had been collected, but
these were not reported in a way that we could reproduce. In any
event, these data would have been few and would not have been
conclusive, but they would have helped generate hypotheses for
future work.
Quality of the evidence
Five studies require clarification of issues related to their methods
and findings. This small sample does not have high methodological
quality and comprehensive reporting of findings.
Potential biases in the review process
1. The search
It is feasible that we have failed to identify relevant studies by
using a search that was biased. Every effort is made to ensure that
searches are as comprehensive as possible, but there is evidence
that studies from low and middle-income countries are not well
represented in some of the databases we employ, and it is from
these countries that relevant trials may be more likely to come.
We, however, do not think that we would have missed any large
study as, we think, such a trial would have been widely reported.
2. Cross-over studies
Schmider 1999 and Ungvari 1999 were cross-over designs and
Ungvari 1999 specifically randomised people with chronic cata-
tonia. We had pre-stated in our protocol that such studies would
only have data extracted from the first period (pre-cross-over) be-
cause of a possible carry-over effect, and it is possible that we are
mistaken. We, however, feel justified in our decision as not only
could the effects of the drugs carry over (even beyond their period
of physiological effect) but also, we would suggest that the symp-
toms of even ’chronic’ catatonia would be unstable. It is, however,
of importance that such studies were possible.
Agreements and disagreements with other
studies or reviews
Because our review did not yield any usable data for analysis, we
are unable to comment on agreement or disagreement with other
studies or reviews. There still is insufficient trial-derived evidence
about the usefulness of benzodiazepines in the treatment of peo-
ple with catatonia. At this time, clinicians, patients and carers can
base decisions about using benzodiazepines to treat people with
catatonia only on anecdotal cases or small studies with some defi-
ciencies in methodology and/or reporting of findings. Such cases
and studies have tended to support the use of benzodiazepines in
the treatment of people with catatonia (Rosebush 1990).
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
AUTHORS’ CONCLUSIONS
Implications for practice
1. For people with catatonia and carers
We are unable to give any clear statements on the benefits or
risks associated with the use of benzodiazepines in the treatment
of people with catatonia. As far as we can see, treatment of this
distressing and serious condition will continue to be based on
evidence other than that derived from high-grade trials. Perhaps
carers and recipients of care could highlight the need for good
studies and their willingness to take part.
2. For clinicians
We are unable to give any clear statements on the benefits or risks
associated with the use of benzodiazepines in the treatment of
persons with catatonia. Clinicians will have to continue to make
judgements on how to treat people that are probably more based
on consensus than hard evidence. Again, should clinicians show
a willingness to take part in clinically relevant evaluative studies,
this would make this type of work much more possible.
3. For managers/policy makers
Policy will have to be based on non-trial evidence and consensus
until better data are available.
Implications for research
1. General
Trialists undertaking research in this area should ensure that both
methods and data reporting are of the highest quality. Some spe-
cific issues include the need for descriptions of both randomisation
and the process and testing of blinding. Reporting outcomes us-
ing only graphs, summary statistics or p values should be avoided.
Instead, authors should present means, standard deviations, confi-
dence intervals, measures of association between intervention and
outcome, e.g. relative risks and odds-ratios, as well as the raw num-
bers, if possible. Finally, trialists should report on all findings re-
lated to the method they describe. Where cross-over designs are
used, findings from each cross-over phase should be reported sep-
arately.
2. Specific
The use of specific treatments for people with catatonia is not
supported by any evidence from randomised trials. The excluded
studies and those awaiting assessment demonstrate that such stud-
ies are not impossible (Fischer 1974, Kunigiri 2002, Merlis 1962,
Patra 1998, Schmider 1999, Ungvari 1997, Ungvari 1999, Wetzel
1997). We suggest that there is an urgent need to test the ef-
fects of benzodiazepines for this condition, as, anecdotally, these
drugs would appear to be a promising pharmacological approach
(Rosebush 1990; Schmider 1999). We suggest a design for such a
study in Table 1.
7
ACKNOWLEDGEMENTS
We wish to thank the editorial base of the Cochrane Schizophrenia
Group and the Department of Community Health and Psychiatry,
University of the West Indies (Mona) for their support. Thanks
also to Peter Strate, Calvin Ng, Andrea Cipriani and Stefan Leucht
who provided help with translating information from some papers.
REFERENCES
References to studies excluded from this review
Arioni 1971 {published data only}
Arioni FBM, Gaston A, Pancheri P. Clinical experimentation
with the new drug LM-2717 [Sperimentazione clinica di un
nuovo farmaco LM 2717]. Rivista di Psichiatria 1971;6(6):
409–94. [: PsycINFO 1973–23370–001]
Barbee 1992 {published data only}
Barbee JG, Mancuso DM, Freed CR, Todorov AA.
Alprazolam as a neuroleptic adjunct in the emergency
treatment of schizophrenia. American Journal of Psychiatry
1992;149:506–10. MEDLINE: 1348161
Fischer 1974 {published data only}
Fischer Cornelssen K, Ferner U, Steiner H. Multifocal
psychopharmaceutic testing (“Multihospital trial”)
[Multifokale Psychopharmakaprufung (“Multihospital
Trial”)]. Arzneimittel Forschung 1974;24(10):1706–24.
MEDLINE: 75054421
Hekimian 1967 {published data only}
Hekimian LJ, Friedhoff AJ. A controlled study of placebo,
chlordiazepoxide and chlorpromazine with thirty male
schizophrenic patients. Diseases of the Nervous System 1967;
28(10):675–8. MEDLINE: 4860896
Holden 1968 {published data only}
Holden JM, Itil TM, Keskiner A, Fink M. Thioridazine and
chlordiazepoxide, alone and combined, in the treatment of
chronic schizophrenia. Comprehensive Psychiatry 1968;9(6):
633–43. MEDLINE: 4883430
Hu 2004 {published data only}
Hu W. Investigation of administering BZD medicament in
outpatients with psychosis. Heath Psychology Journal 2004;
12(1):43, 67. [: 116287]
Kunigiri 2002 {published data only}
Girish K, Gill NS. Electroconvulsive therapy in lorazepam
non-responsive catatonia. Indian Journal of Psychiatry 2003;
45:21–5.
Kunigiri G, Gill NS, B GN, Naimmagadda J.
Electroconvulsive therapy in lorazepam non-responsive
catatonia. 12th World Congress of Psychiatry; 2002 Aug
24-29; Yokohama, Japan. 2002. MEDLINE: 5458933
Kurland 1966 {published data only}
Kurland AA, Bethon GD, Michaux MH, Agallianos DD.
Chlorpromazine-chlordiazepoxide and chlorpromazine-
imipramine treatment: side effects and clinical laboratory
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
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findings. Journal of New Drugs 1966;6:80–95. MEDLINE:
67014950
Smith 1960 {published data only}
Smith ME. A comparative controlled study with
chlordiazepoxide. American Journal of Psychiatry 1960;117:
362–3. MEDLINE: 4556217
Smith 1961 {published data only}
Smith ME. A clinical study of chlorpromazine and
chlordiazepoxide. Connecticut State Medical Journal 1961;
25:153–7.
Ungvari 1997 {published data only}
Ungvari GS, Chow LY, Chiu HFK, Lau B. Diiferent
treatment response of distinct schizophrenia subtypes: the
group of systematic catatonias. 6th world Congress of
Biological Psychiatry; 1997 Jun 22-27; Nice, France. 1997.
Vasquez-Gomez 2001 {published data only}
Vasquez-Gomez F. The use of midazolam for control of
acutely agitated outpatients in psychiatry emergency. 7th
World Congress of Biological Psychiatry; 2001 Jul 1-6;
Berlin, Germany. 2001; Vol. 2, issue Suppl 1. [: 7th World
Congress of Biological Psychiatry [CD–ROM]: Conifer,
Excerpta Medica Medical Communications BV, 2001
P034–02]
Weckowicz 1960 {published data only}
Weckowicz TE, Ward T. Clinical trial of RO 5-0690
and chlorpromazine on disturbed chronic schizophrenic
patients. Diseases of the Nervous System 1960;21:527–8.
MEDLINE: 13783681
Wolkowitz 1988 {published data only}
Wolkowitz OM, Breier A, Doran A, Kelsoe J, Lucas P,
Paul SM, Pickar D. Alprazolam augmentation of the
antipsychotic effects of fluphenazine in schizophrenic
patients - preliminary results. Archives of General Psychiatry
1988;45(7):664–71. MEDLINE: 88251245; : PsycINFO
76–02568
WolkowitzOM, Pickar D, Doran AR, Breier A, Tarell J,
Paul SM. Combination alprazolam-neuroleptic treatment
of the positive and negative symptoms of schizophrenia.
American Journal of Psychiatry 1986;143(1):85–7.
Wolkowitz 1992 {published data only}
Wolkowitz OM, Turetsky N, Reus VI, Hargreaves WA.
Benzodiazepine augmentation of neuroleptics in treatment
resistant schizophrenia. Psychopharmacology Bulletin
1992;28(3):291–5. MEDLINE: 1362277; : PsycINFO
80–18793
8
Wolkowitz 1993 {published data only}
Wolkowitz OM, Harris D, Turetsky NG, Reus VI, Johnson
R, Gustafson M, Espinoza S, Petty F, Cooper TB, Sheline
Y, Hargreaves WA. Alprazolam-neuroleptic treatment of
schizophrenia. 146th Annual Meeting of the American
Psychiatric Association; 1993 May 22-27; San Francisco,
California, USA. 1993:119.
Wyant 1990 {published data only}
Wyant M, Diamond BI, O’Neal E, Sloan A, Borison
RL. The use of midazolam in acutely agitated psychiatric
patients. Psychopharmacology Bulletin 1990;26(1):126–9.
MEDLINE: 2371367; : PsycINFO 79–28483
References to studies awaiting assessment
Merlis 1962 {published data only}
Merlis S, Turner WJ, Krumholz W. A double-
blind comparison of diazepam, chlordiazepoxide and
chlorpromazine in psychotic patients. Journal of
Neuropsychiatry 1962;3(Suppl 1):S133–8. [: PsycINFO
1977–03995–001]
Patra 1998 {published data only}
Patra A, Sarkar A, Kumar R. Outcome of lorazepam in
catatonia oral vs parenteral administration. Indian Journal
of Psychiatry 1998:91. MEDLINE: 8442962
Schmider 1999 {published data only}
Schmider J, Standhart H, Deuschle M, Drancoli J, Heuser
I. A double blind comparison of lorazepam and oxazepam
in psychogenic catatonia. 10th European College of
Neuropsychopharmacology Congress; 1997 Sep 13-17;
Vienna, Austria. 1997.
Schmider J, Standhart H, Deuschle M, Drancoli J, Heuser
I. A double blind comparison of lorazepam and oxazepam in
psychomotor retardation and mutism. Biological Psychiatry
1999;46(3):437–41. MEDLINE: 99364070; : EMBASE
1999252184
Ungvari 1999 {published data only}
Pang AHT, Ungvari G, Ng FS, Chiu H. Treatment response
of systematic catatonia (leonhard) to lorazepam. 21st
Collegium Internationale neuro-Psychopharmacologicum
Congress; 1998 Jul 12-16; Glasgow, UK. 1998.
Ungvari G, Pang A, Ng F, Chiu H, Wong C. Treatment
response studies in systematic catatonia (leonhard). i.
lorazepam challenge. 8th Congress of the Association of
European Psychiatrists; 1996 Jul 7-12; London, UK. 1996.
Ungvari GS, Chiu HF, Chow LY, Lau BS, Tang WK.
Lorazepam for chronic catatonia: a randomized,
double blind, placebo controlled cross over study.
Psychopharmacology Berlin 1999;142(4):393–8.
MEDLINE: 10229064
Wetzel 1997 {published data only}
Wetzel H, Klawe CJ, Muller MJ, Wiesner J, Benkert O.
Lorazepam for stupor and mutism: a double-blind placebo-
controlled cross-over study. 10th European College of
Neuropsychopharmacology Congress; 1997 Sep 13-17;
Vienna, Austria. 1997. MEDLINE: 79123210
Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review)
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Additional references
Altman 1996
Altman DG, Bland JM. Detecing skewness from summary
information. BMJ 1996;313:1200. [: OLZ020600]
APA 2000
American Psychiatric Association. Diagnostic and statistical
manual of mental disorders (DSM-IV TR). 4th Edition.
Washington: American Psychiatric Association, 2000.
Bland 1997
Bland JM. Statistics notes. Trials randomised in clusters.
BMJ 1997;315:600.
Boissel 1999
Boissel JP, Cucherat M, Li W, Chatellier G, Gueyffier F,
Buyse M, Boutitie F, Nony P, Haugh M, Mignot G. The
problem of therapeutic efficacy indices. 3. Comparison of
the indices and their use. Therapie 1999;54(4):405–11.
Deeks 2000
Deeks J. Issues in the selection for meta-analyses of binary
data. Abstracts of 8th International Cochrane Colloquium;
2000 Oct 25-28th; Cape Town, South Africa. 2000.
Divine 1992
Divine GW, Brown JT, Frazier LM. The unit of analysis
error in studies about physicians’ patient care behavior.
Journal of General Internal Medicine 1992;7(6):623–9.
Donner 2002
Donner A, Klar N. Issues in the meta-analysis of cluster
randomized trials. Statistics in Medicine 2002;21:2971–80.
Elbourne 2002
Elbourne DR, Altman DG, Higgins JP, Curtin F,
Worthington HV, Vail A. Meta-analyses involving cross-
over trials: methodological issues.. Int J Epidemiol 2002;31
(1):140–9.
Gulliford 1999
Gulliford MC. Components of variance and intraclass
correlations for the design of community-based surveys
and intervention studies: data from the Health Survey for
England 1994. American Journal of Epidemiology 1999;149:
876–83.
Higgins 2003
Higgins JP, Thompson SG, Deeks JJ, Altman DG.
Measuring inconsistency in meta-analyses. British Medical
Journal 2003;327:557–60.
Higgins 2005
Higgins JPT, Green S, editors. Cochrane Handbook for
Systematic Reviews of Interventions 4.2.5 [updated May
2005]. www.cochrane.org/resources/handbook/hbook.htm
(accessed 04 February 2006).
Kahlbaum 1973
Kahlbaum KL. Catatonia [Die Katatonie oder das
spannungirresein]. Catatonia. Baltimore: Johns Hopkins
University Press, 1973.
9
Kay 1986
Kay SR, Opler LA, Fiszbein A. Positive and negative syndrome
scale (PANSS) manual. North Tonawanda (NY): Multi-
Health Systems, 1986.
Leucht 2005a
Leucht S, Kane JM, Kissling W, Hamann J, Etschel E,
Engel R. Clinical implications of Brief Psychiatric Rating
Scale Scores. British Journal of Psychiatry 2005;187:366–71.
Leucht 2005b
Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel
R. What does the PANSS mean?. Schizophrenia Research
2005;79:231–8.
Marshall 2000
Marshall M, Lockwood A, Bradley C, Adams C, Joy C,
Fenton M. Unpublished rating scales: a major source
of bias in randomised controlled trials of treatments for
schizophrenia. British Journal of Psychiatry 2000;176:
249–52.
Overall 1962
Overall JE, Gorham DR. The Brief Psychiatric Rating Scale.
Psychological Reports 1962;10:799–812.
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Penland 2006
Penland HR, Weder N, Tampi RR. The catatonic dilemma
expanded. Annals of General Psychiatry 2006;5:14.
Regestein 1977
Regestein QR, Alpert JS, Reich P. Sudden catatonic stupor
with disastrous outcome. Journal of the American Medical
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Rosebush 1990
Rosebush PI, Hildebrand AM, Furlong BG, Mazurek MF.
Catatonic syndrome in a general psychiatric inpatient
population: frequency, clinical presentation, and response to
lorazepam. Journal of Clinical Psychiatry 1990;51:357–62.
Ukoumunne 1999
Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC,
Burney PGJ. Methods for evaluating area-wide and
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1–75.
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∗
Indicates the major publication for the study
10
CHARACTERISTICS OF STUDIES

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Arioni 1971 Allocation: randomised.

Participants: did not include people with catatonia.

Barbee 1992 Allocation: randomised.

Participants: people with schizophrenia in general; no mention of people with catatonia

Fischer 1974 Allocation: randomised.

participants: people with schizophrenia including catatonic subtype.
Interventions: clozapine, chlorpromazine, no benzodiazepines

Hekimian 1967 Allocation: not randomised.

Holden 1968 Allocation: randomised.

Participants: people with schizophrenia of various subtypes, only one participant with catatonia

Hu 2004 Allocation: randomised.

Participants: people with psychosis, none with catatonia.

Kunigiri 2002 Allocation: randomised.

Participants: people with catatonia and non-responsiveness to lorazepam.
Interventions: electroconvulsive therapy and placebo versus electroconvulsive therapy and risperidone

Kurland 1966 Allocation: randomised.

Participants: people with schizophrenia, no subtypes given.

Smith 1960 Allocation: not randomised.

Smith 1961 Allocation: not randomised.

Ungvari 1997 Allocation: randomised.

Participants: people with catatonia.
Interventions: Citalopram and placebo.

Vasquez-Gomez 2001 Allocation: randomised.

Participants: people with agitation, no mention of catatonia specifically

Weckowicz 1960 Allocation: not randomised.

Wolkowitz 1988 Allocation: not randomised.

Wolkowitz 1992 Allocation not randomised, review article.

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 11
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Wolkowitz 1993 Allocation: randomised.

Participants: people with schizophrenia, no mention of catatonia

Wyant 1990 Allocation: randomised.

Participants: people with schizophrenia of the paranoid and undifferentiated types, none with catatonia

Characteristics of studies awaiting assessment [ordered by study ID]

Merlis 1962

Methods Allocation: unclear.

Blindness: not explicitly stated.
Duration: 4 weeks.
Design: controlled trial (no cross-over).
Setting: hospital, USA.
Consent: not stated.
Loss: described.

Participants Diagnosis: schizophrenia, psychosis with mental deficiency, psychosis with psychopathic personality (diagnostic
classification system not reported).
N=80.
Age: 14-62 years.
M 40, F 40.
History: chronic mental illness with at least two years of continued hospitalisation; catatonic features described in
12 participants.
Exclusions: not described.

Interventions 1. Chlorpromazine 50 mg three times daily N=20.

2. Diazepam 10 mg three times daily N=20.
3. Chlordiazepoxide 25 mg three times daily N=20.
4. Placebo three times daily N = 20. (All treatments with scope for increases in dosage at discretion of ward physician)

Outcomes Unable to use- Mental state: BPRS, MMS (no independent data specific for people with catatonic symptoms)

Notes

Patra 1998

Methods Allocation: unclear.

Blindness: not stated.
Duration: 1 hour.
Design: controlled trial (no cross-over).
Setting: psychiatric hospital outpatient department.
Loss: not described.

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 12
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Patra 1998 (Continued)

Participants Diagnosis: catatonic syndrome (Bush Francis Catatonia Rating Scale).

N: not reported.
Age: not reported.
M:F not reported.
History: features of catatonia.
Exclusions: not described.

Interventions 1. oral lorazepam.

2. parenteral lorazepam.
(Dosages not described).

Outcomes Unable to use- Catatonic symptoms: BFCRS (no figures presented in abstract)

Notes

Schmider 1999

Methods Allocation: unclear.

Blindness: double.
Duration: 3 days.
Design: cross-over.
Setting: hospital, Germany.
Consent: informed consent obtained from relative and patient.
Loss: described

Participants Diagnosis: major depressive disorder with/ without psychotic features, Bipolar disorder, schizoaffective disorder,
schizophrenia, or schizophreniform disorder (all DSM-III-R).
N=17.
Age: over 18, average 50.8 years.
M 4, F 13 (for patients included in analyses presented).
History: psychomotor retardation and mutism.
Exclusions: not described.

Interventions 1. Lorazepam/ Oxazepam: dose 2mg/60mg per day N=7.

2. Oxazepam/ Lorazepam: dose 60mg/2mg per day N=10.

Outcomes Unable to use -Catatonic symptoms: VAS (no means or SDs; no independent data specific for first cross-over arm)

Notes

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 13
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Ungvari 1999

Methods Allocation: randomised.

Blindness: double.
Duration: 12 weeks.
Design: cross-over.
Setting: long stay rehabilitation centre.
Consent: informed consent obtained from relative and patient.
Loss: not fully described.

Participants Diagnosis: schizophrenia, catatonic subtype (DSM-IV).

N=20.
Age: over 18, average 50.8 years.
M 13, F 5 (for patients included in analyses presented).
History: chronic schizophrenic illness.
Exclusions: head Injury, epileptic seizures, neurological condition

Interventions 1. Lorazepam/ Placebo: dose 6mg per day N=9.

2. Placebo/ Lorazepam: dose 6mg per day N = 8.

Outcomes Unable to use- Mental state: BPRS, HDRS, SANS. Catatonic symptoms: BFCRS, MRS, Global state: CGI, GAS,
NOSIE. Adverse effects: AIMS, SAS, BARS, VPAS (no independent data specific for first cross-over arm)

Notes

Wetzel 1997

Methods Allocation: randomised.

Blindness: double.
Duration: 2 days.
Design: cross-over.
Setting: not described.
Consent: not described.
Loss: not described.

Participants Diagnosis: not fully described.

N=10.
Age: not described.
M:F not described.
History: catatonic syndrome with stupor and mutism.
Exclusions: not described.

Interventions 1. Lorazepam 2mg intravenously over two hours N- not reported.

2. Placebo n- not reported.

Outcomes Unable to use- Global state: CGI. Catatonic symptoms: BFCRS (no means or SDs; no independent data specific for
first cross-over arm)

Notes

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 14
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DATA AND ANALYSES
This review has no analyses.

ADDITIONAL TABLES
Table 1. Suggested design of study

Methods Participants Interventions Outcomes Notes

Allocation: randomised, Diagnosis:catatonia. 1. Lorazepam 4 mg/ day. General: relapse, gen- * powered to be able
block, well described. N=300.* N=150. eral impression of clini- to identify a difference
Blinding: double, well Age: adults. 2. Placebo. N=150. cian (CGI), carer/ other of ~20% between groups
described and tested. Sex: both. (CGI), compliance with for primary outcome
Duration: 12-24 weeks. History: clearly treatment, healthy days, with adequate degree of
reported. time in hospital, satisfac- certainty
tion with care.
Mental state: CGI.
Catatonic symptoms:
BFCRS
Quality of life: CGI.
Family burden: CGI.
Social functioning: re-
turn to everyday living
for 80% of time.*
Adverse events: any ad-
verse event recorded.
Economic outcomes.

WHAT’S NEW
Last assessed as up-to-date: 22 June 2008.

Date Event Description

31 January 2013 Amended Contact details updated.

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 15
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
HISTORY
Protocol first published: Issue 2, 2007
Review first published: Issue 4, 2008

Date Event Description

29 July 2008 Amended Converted to new review format.

22 June 2008 New citation required and conclusions have changed Substantive amendment

CONTRIBUTIONS OF AUTHORS
Roger Gibson - protocol development, selection of trials, data extraction, data analysis, write-up of review.
Geoffery Walcott - protocol development, selection of trials, data extraction, write-up of review.

DECLARATIONS OF INTEREST
None known.

SOURCES OF SUPPORT

Internal sources
• Department of Community Health and Psychiatry, University of the West Indies (Mona), Jamaica.

External sources
• No sources of support supplied

DIFFERENCES BETWEEN PROTOCOL AND REVIEW

The protocol has been extensively re-written for the new version of RevMan (v5, 2008) but contains no substantive changes from the
original, other than form.

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 16
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
INDEX TERMS

Medical Subject Headings (MeSH)

Benzodiazepines [∗ therapeutic use]; Catatonia [∗ drug therapy]; Mental Disorders [∗ complications]; Schizophrenia, Catatonic [∗ drug
therapy]

MeSH check words

Humans

Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses (Review) 17
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.