DataPDF Available

Appendix: Traceable Extracted Data from Included Studies of Tardive Dyskinesia Reviews

Authors:

Abstract

This data set includes the extracted data from all the available randomized/controlled clinical trials on tardive dyskinesia at the time of project. The file is available here in both PDF and DOCX formats to download.
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Appendix: Traceable Extracted Data from Included
Studies of Tardive Dyskinesia Reviews
Citation to Appendix
Adams CE, Walker DM, Gray B, Soares-Weiser K, Bergman H, Zhao S, Asher R,
Ogawa Y, Shokraneh F. Appendix: Traceable Extracted Data from Included Studies
of Tardive Dyskinesia Reviews. [DOI: 10.13140/RG.2.2.28907.95529]. Available at:
http://dx.doi.org/10.13140/RG.2.2.28907.95529 [Date Accessed: 28 September
2016].
Citation to Project
Adams CE, Walker DM, Gray B, Soares-Weiser K. HTA - 14/27/02: A systematic
review and network meta-analysis of the safety and clinical effectiveness of
interventions for treating or preventing deterioration of symptoms of antipsychotic-
induced tardive dyskinesia (TD). Available at:
http://www.nets.nihr.ac.uk/projects/hta/142702 [Date Accessed: 28 September 2016].
Acknowledgments
Thanks to Hanna Bergman, Sai Zhao, Rosie Asher, Yusuke Ogawa, and Farhad
Shokraneh for extracting data from studies.
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Guide to track the data back into the PDFs
The location of data inside the each PDF has been presented in a column in the tables. Depending on
the location in which the data has been extracted, the location of data has been identified in one of the
following ways:
If data is in the Text:
Location Code Structure: PDF File Name*/PDF File Page Number/Text Column Number/Paragraph
Number/Line Number
Example: 23451PG1C2P3L5
Interpretation: Data is from the first page of pdf file, in column 2, paragraph 3, line 5
If data is in a Table:
Location Code Structure: PDF File Name*/PDF File Page Number/Table Number/Column Number/Row Number
Example: 23451PG4T3C4R4
Interpretation: Data is from the fourth page of pdf file, table 3 of paper, column 4 of table, row 4
If data is in a Figure:
Location Code Structure: PDF File Name*/PDF File Page Number/Figure Number
Example: 23451PG3F2
Interpretation: Data is from the third page of pdf file, figure 2
This structure is flexible for reporting the location of data in Boxes or Headlines or any other part of
the paper too.
* PDF File Name refers to the name of pdf file in Cochrane Schizophrenia Group's archives. Because
of Copyright issues it is not possible to share the PDF files publicly but if the readers have access to
the PDF files personally from any source, they can use the provided coordination for the location of
the data in these forms.
5
Table of Contents
6
Anticholinergic Medication for Neuroleptic-Induced Tardive Dyskinesia
Bucci 1971
Reference
Bucci L. The Dyskinesias: A New Therapeutic Approach. Dyskinesias 1971: 324-327.
Characteristics
Location in PDF
Study design Parallel RCT 4747PG325C1P1L1
Methods Allocation: random. Details not reported 4747PG325C1P3L1
Blindness: not reported
Duration: 10 months (40 weeks) 4747PG325C2P2L2
Design: parallel 4747PG325C1P1L1
Setting: outpatients 4747PG325C1P2L1
Raters: not reported
Participants Diagnosis: chronic schizophrenia treated with phenothiazine for
several years and demonstrating obvious dyskinetic
manifestations
4747PG325C1P2L1
Total number randomised, N=20 4747PG325C1P2L1
Sex: 16 female and 4 male 4747PG325C1P2L8
Age: range 45-62 years 4747PG325C1P2L6
History: chronic schizophrenia outpatients previously treated with
phenothiazine irregularly for several years and continuous
phenotjiazine-antiparkisonian treatment for at least 2 years;
dyskinetic manifestations for over two years
4747PG325C1P2L1
Inclusion criteria: schizophrenic patients treated with neuroleptics
and manifesting dyskinetic movements
4747PG325C1P2L1
Exclusion criteria: not reported
Interventions 1. Procyclidine, 5 mg B.I.D + chlorpromazine, 100mg T.I.D N=1-
2. Isocarboxazid, 10mg B.I.D+ chlorpromazine, 100mg T.I.D.
N=10
4747PG325C1P3L1
4747PG325C1P3L3
Outcomes TD symptoms (clinical evaluation, scale not reported)
Mental state “increasingly tense, apprehensive and sleepless”
(clinical evaluation, scale not reported)
Leaving the study early
Adverse effects (Only AE resulting in withdrawal reported. “All
others tolerated the drug regimen quite well”.)
4747PG325C1P1L1
4
4747PG325C2P3L1
4747PG325C2P4L1
4747PG325C1P1L1
7
4747PG325C2P4L1
4747PG325C2P3L1
4747PG325C2P2L2
4747PG325C2P2L2
Notes Sponsorship source: Not reported
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation
(selection bias)
Unc lear risk
“The patients were divided at random
into groups of 10 each...”
4747PG325C1P3
L1
Allocation
concealment
(selection bias)
Unc lear risk
Allocation concealment not reported
7
Blinding of
participants and
personnel
(performance bias)
Unc lear risk
Blinding of participants and personnel
not reported
Blinding of outcome
assessment
(detection bias)
Unc lear risk
Blinding of outcome assessment not
reported
Incomplete
outcome data
(attrition bias)
Low risk
“One male patient on chlorpromazine
and Isocarboxazid was discontinued
after 6 weeks as he became increasingly
tense, apprehensive and sleepless.”
4747PG325C2P2
L2
Selective reporting
(reporting bias)
Unc lear risk
Unclear if all outcomes have been
reported. A protocol is not available for
verification. Adverse effects reported
only as those related to treatment.
Mental state data not reported for group
2.
4747PG325C2P2
L2
Other bias
Unc lear risk
Insufficient information to make a
judgement
Outcome
Dichotomous data (add more lines for more dichotomous outcomes)
Outcome Subgrou
p
Procyclidine +
chlorpromazine
Isocarboxazid +
chlorpromazine
Location in PDF
Events Total Events Total
TD symptoms: not any
improvement 10 10 1 10 4747PG325C2P3L6
4747PG325C2P4L4
TD symptoms: not
significant improvement 10 10 2 10 4747PG325C2P3L6
4747PG325C2P4L4
Leaving the study early 0 10 1 10 4747PG325C2P2L2
Adverse effects 0 10 1 10 4747PG325C2P2L2
8
Greil 1984
Reference
[Ref ID 4977] Greil W, Haag H, Rossnagl G, Ruther E. Effect of anticholinergics on tardive dyskinesia.
A controlled discontinuation study. British Journal of Psychiatry 1984; 145: 304-10.
Characteristics
Location in PDF
Methods Allocation: "randomly assigned" no further details 4977PG306C1P3L
3
Blind: "double-blind" no further details 4977PG306C1P3L
1
Design: parallel group 4977PG306C1P3L
4
Setting: Not reported of inpatients or outpatients or both, Germany
Duration: 7 weeks 4977PG306C1P5L
1
Participants
Diagnosis: chronic schizophrenia (ICD-9 criteria). Significant TD (a
total severity score of at least 3, according to AIMS). Tardive
dyskinesia diagnosis based on the presence of a 'typical' bucco-
linguo-masticatory syndrome and the absence of other adequate
explanations for the movement disorder. Long term maintenance
treatment with neuroleptics and anticholinergic drugs for at least
two years, the dosage having remained unchanged during the last
five months
4977PG304C2P4L
2
4977PG304C2P5L
6
4977PG305C2P1L
1
4977PG304C2P5L
2
N=10 4977PG304C2P4L
1
Sex: 3 male and 7 female 4977PG304C2P4L
1
Age: mean 56.6 (SD 9.2) years; range 35-65 years 4977PG304C2P4L
4
Inclusion criteria: Long-term maintenance treatment with
neuroleptics and anticholinergic; diagnosis of tardive dyskinesia
based on the presence of a 'typical' bucco-linguo-masticatory
syndrome and the absence of other adequate explanations for the
movement disorder (e.g., Huntington's chorea, Wilson's disease or
other heredofamilial diseases; significant TD (a total severity score
of at least 3, according to AIMS); TD duration at least one year;
severity of the symptoms stable for at least one month before
admission to the study.
Exclusion criteria: Severe physical illness, neurological disease or
alcoholism/drug dependence.
4977PG305C1P2L
1
Interventions
1. Biperiden stopped after 4 weeks (followed by placebo): Group A:
dose: the same dosage as prior to the study. N=4
4977PG306C1P3L
5
4977PG306C1P3L
4
2. Biperiden stopped after 1 week (followed by placebo): group B:
the same dosage as prior to the study. N=6
4977PG306C1P3L
7
4977PG306C1P3L
4
Outcomes TD symptoms: AIMS; TD scale constructed on the lines laid down
by Gerlach, Simpson, and Heinrich. Adverse effect
(Pseudoparkinsonism): Simpson-Angus Scale.
4977PG306C1P7L
3
4977PG306C1P7L
9
Leaving the study early
4
4977PG306C1P7L
2
4977PG306C2P2L
1
Notes Sponsorship source: Sponsorship source not reported.
Knoll AG supplied placebo 4977PG309C2P3L
3
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection
bias)
Unclear risk
"Randomly assigned" Details not
reported.
4977PG306C1P3
L3
Allocation concealment
(selection bias)
Unclear risk
Allocation concealment not
reported.
Blinding of participants
and personnel
(performance bias)
Unclear risk
"double-blind" Details not reported.
4977PG306C1P3
L1
Blinding of outcome
assessment (detection
bias)
Unclear risk
"double-blind" Details not reported.
4977PG306C1P3
L1
4977PG306C1P5
L1
Incomplete outcome
data (attrition bias)
Low risk
"Nine patients completed the trial.
One patient (number 10, group B)
dropped out one week after
biperiden withdrawal because of
severe parkinsonism; in this patient,
only one rating could be carried out
while on the placebo."
4977PG306C2P2
L1
Selective reporting
(reporting bias)
Unclear risk
Unclear if all pre-defined outcomes
were reported. A protocol is not
available for verification.
Other bias
Unclear risk
Insufficient information to make a
judgement.
Outcome
3 Anticholinergic drugs vs other compounds
Outcome Subgroup
Biperiden stopped after
4week (followed by
placebo): Group A
Biperiden stopped after 1
week (followed by
placebo): group B
Location in PDF
Events Total Events Total
3.1 Leaving
the study
early
3.1.1 Biperiden
vs Amantadine 0 4 1 6
4977PG306C2P2
L1
10
Benzodiazepines for Neuroleptic-Induced Tardive Dyskinesia
Bobruff 1981
Reference
[Ref. ID 4737] Bobruff A, Gardos G, Tarsy D, Rapkin RM, Cole JO, Moore P. Clonazepam and
phenobarbital in tardive dyskinesia. American Journal of Psychiatry 1981; 138: 189-93.
Characteristics
Location in PDF
Methods Allocation: "randomly assigned" no details reported. 4737PG190C1P5L
1
Blindness: "double blind", no details. 4737PG191C2P2L
2
Design: parallel group. 4737PG190C1P5L
1
Duration: not reported (optimal dose+2 weeks + taper off)
Setting: Not reported, USA.
Participants
Diagnosis: Psychiatric patients (details not reported). Obvious TD
(at least three scores of mild or one score of moderate on AIMS)
4737PG191C1P4L
1
4737PG190C1P4L
3
N=21. 4737PG191C1P4L
1
Age: mean 51.6 years; range 36-63 years 4737PG191C1P4L
10
Sex: 16 male and 5 female 4737PG191C1P4L
11
Interventions 1. Clonazepam: dose: 3.9±2.6 mg daily; optimal dose + 2 weeks +
taper. N=10
4737PG190C2P3L
2
2. Phenobarbital (as active placebo): 88.6 ± 45.7 mg/d, optimal
dose + 2 weeks + taper. N=11
4737PG190C2P3L
2
Outcomes TD symptoms: no improvement (AIMS) 4737PG190C2P4L
2
TD symptoms: not improved more than 50% (AIMS) 4737PG190C2P5L
1
Adverse effects
4737PG192C1P3L
1;
4737PG192C1P4L
1
Leaving the study early. 4737PG190C2P4L
2
Unable to use -
Mental State: Profile of Mood States (POMS)
4737PG190C2P2L
1
Notes Sponsorship source: Supported in part by NIMH grant.
Declarations of interest: Not reported.
4737PG189FP4L1
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence generation
(selection bias)
"Patients were randomly
assigned...” Details not
reported
4737PG190C1P5
L1
Allocation concealment
(selection bias)
Allocation concealment not
reported
11
Blinding of participants and
personnel (performance bias)
"...double-blind...” Details not
reported
4737PG191C2P2
L2
Blinding of outcome assessment
(detection bias)
"...double-blind...” Details not
reported
4737PG191C2P2
L2
Incomplete outcome data
(attrition bias)
Although not clearly
reported, it seems that all
subjects completed the
double-blind phase (data
reported for all 21 subjects)
4737PG190C2P4
L2
Selective reporting (reporting
bias)
All outcomes seem to have
been reported but not as
mean (SD). Also, a protocol
is not available, it is not
possible to verify that all
predefined outcomes were
reported
Other bias Insufficient information to
make a judgement
Outcome
2 BENZODIAZEPINE vs OTHER COMPOUNDS
Outcome Subgroup
Benzodiazepin
e
Other
compound
Location in PDF
Events Total Events Total
2.1 TD symptoms: not
improved more than 50% -
less than 6 weeks
2.1.2 Clonazepam vs
phenobarbital (as active
placebo)
4 10 10 11
4737PG190C2P5
L1
Outcome Subgroup
Benzodiazepin
e
Other
compound
Location in PDF
Events Total Events Total
2.2 TD symptoms: not any
improvement - less than 6
weeks
2.2.2 Clonazepam vs
phenobarbital (as active
placebo)
0 10 1 11
4737PG190C2P4
L1
Outcome Subgroup
Benzodiazepin
e
Other
compound
Location in PDF
Events Total Events Total
2.4 Leaving the study
early - less than 6
weeks
2.4.3 clonazepam vs
phenobarbital (as active
placebo)
0 10 0 11
4737PG190C2P4
L1
Outcome Subgroup
Benzodiazepin
e
Other
compound
Location in PDF
Events Total Events Total
2.5 Adverse
events
2.5.3 Clonazepam vs phenobarbital
(as active placebo) 10 10 7 11 4737PG192C1P2
L1
12
Csernansky 1988
References
[Ref. ID 4915] Csernanksy JG, Riney SJ, Lombrozo L, Overall JE, Hollister LE. Double-blind
comparison of alprazolam, diazepam, and placebo for the treatment of negative symptoms of
schizophrenia. Archives of General Psychiatry 1988; 45: 655-9.
[Ref. ID 4915] * Csernansky JG, Tacke U, Rusen D, Hollister LE. The effect of benzodiazepines on
tardive dyskinesia symptoms. Journal of Clinical Psychopharmacology 1988; 8: 154-5.
Characteristics
Location in PDF
Methods Allocation: "randomly assigned", no details reported. 4915PG656C1P3L
1
Blindness: "double blind", described. 4915PG656C1P3L
2
Design: parallel group. 4915PG656C1P3L
1
Duration: 5-6 weeks 4916PG154C1P2L
10
Setting: Outpatients (most) and inpatients from Veterans
Administration Medical Center, USA.
4915PG656C1P2L
2
Participants Diagnosis: Schizophrenia (RDC criteria) 4915PG656C1P2L
N=17
Age: not reported
Sex: not reported
Interventions 1. Alprazolam: dose 7.2 ± 1.8 mg for 5-6 weeks. N=5 4916PG154C1P2L
7
2. Diazepam: dose 48.3 ± 19.4 mg daily for 5-6 weeks. N=6 4916PG154C1P2L
8
3. Placebo for 5-6 weeks. N=6 4916PG154C1P2L
9
Outcomes TD symptoms: not improved by 50% 4916PG154T1
TD symptoms: not any improvement 4916PG154T1
TD symptoms: deterioration 4916PG154T1
Leaving the study early. 4916PG154C1P3L
3
Unusable data
Mental State: BPRS, SANS (data not reported for TD subgroup)
Adverse effects (data not reported for TD subgroup)
Notes Sponsorship source: Supported by a Public Health Service grant
and a grant from the National Institute of Mental Health, a VA
Career Development Award to the first author, a grant from the
Upjohn Company, and the Research Service of the VA.
4915PG659C2P2L
1
Participants were extracted post-hoc from a larger study examining
benzodiazepines for the treatment of the negative symptoms of
schizophrenia. Data on age, gender, baseline medication doses,
side effects and drop-out rate for the initial cohort are provided in
the parent study (Csernansky 1988b).
Risk of bias
13
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection
bias)
Unc lear risk
"Patients were randomly assigned to
the treatment with either Alprazolam,
Diazepam, or placebo..." Further
details not reported
4915PG656C1P3
L1
Allocation concealment
(selection bias)
Unc lear risk
Allocation concealment not reported
Blinding of participants
and personnel
(performance bias)
Low risk
"Patients were randomly assigned to
the treatment with either alprazolam,
diazepam, or placebo under double-
blind conditions. Identical capsules
contained either 1 mg of alprazolam,
10mg of diazepam, or the drug
carrier as placebo"
4915PG656C1P3
L2
Blinding of outcome
assessment (detection
bias)
Low risk
“two independent raters"
4915PG656C1P3
L2
Incomplete outcome
data (attrition bias)
Unc lear risk
"Fifty-five RDC schizophrenic
outpatients were rated using the
Gerlach Dyskinesia Scale (GDS)
before, and at weekly intervals
during, treatment... 17 patients were
identified with rateable TD
symptoms at baseline..." All 17
subjects were entered to analysis.
Table 1. However, as 72 subjects
were enrolled in the original study, it
is unclear if relevant data for any of
the 17/72 subjects that dropped-out
is missing.
4916PG154C1P2
L1
4916PG154T1
4915PG656C1P2
L1
Selective reporting
(reporting bias)
Unc lear risk
All outcomes for the main study
seem to have been reported. A
Protocol is not available for
verification. Although mental state
and adverse effects have not
reported separately for subjects with
TD symptoms. TD was not an
inclusion criterion and thus does not
seem to affect bias. "Since TD was
not a criterion for inclusion into or
exclusion from the trial, it was only
by chance that we identified 17
patients with TD symptoms"
4916PG154C1P3
L3
Other bias High risk Participants with TD at baseline
were extracted post-hoc from a
larger study examining
benzodiazepines for the treatment of
the negative symptoms of
schizophrenia.
Outcome
1 BENZODIAZEPINE versus PLACEBO/NO TREATMENT (all medium term)
Outcome Subgroup
Benzodiazepin
es
Placebo/no
treatment
Location in PDF
Events Total Events Total
1.1 TD symptoms: not improved 1.1.4 Diazepam 4 11 3 6 4916PG154T1
14
more than 50% - less than 6 weeks vs Placebo
Outcome Subgroup Diazepam Tetrabenazine
Events Total Events Total
1.3 TD symptoms: deterioration -
less than 6 weeks
1.3.1 Diazepam
vs Placebo 1 11 1 6 4916PG154T1
Outcome Subgroup
Benzodiazepine
sPlacebo Location in PDF
Mean SD Total Mean SD Total
1.4 Tardive dyskinesia: 2.
Average change TD score
(greater = better)
1.4.2 GDS score -
Diazepam vs Standard
care (treatment as usual)
1.18 1.3 11 0.15 1.61 6
4916PG154T1
Outcome Subgroup
Benzodiazepine
sPlacebo
Mean SD Total Mean SD Total
1.5 Tardive dyskinesia: 3.
Average TD score at the
end of treatment
1.5.3 GDS scores (IPD,
greater = worse) 0.96 1.09 11 1.25 1.38 6
4916PG154T1
Outcome Subgroup
Benzodiazepin
es Placebo Location in PDF
Events Total Event
sTotal
1.6 Leaving the study early - less
than 6 weeks
1.6.2 Diazepam vs
Placebo 0 11 064916PG154T1
15
Thaker 1990
Reference
[Ref. ID 5279] Thaker GK, Nguyen JA, Strauss ME, Jacobson R, Kaup BA, Tamminga CA.
Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy. American Journal of
Psychiatry 1990; 147: 445-51.
Characteristics
Location in PDF
Methods Allocation: "randomized crossover trial", no details reported. 5279PG446C2P1L4
Blindness: "double blind", not described. 5279PG446C2P1L4
Design: crossover. 5279PG446C2P1L5
Duration: 12 weeks (1 week run-in placebo, 4 weeks followed by 2
weeks wash-out then crossed over to another 4 weeks, 1 week
placebo)
5279PG446C2P1L5
Setting: Outpatients, USA. 5279PG446C1P2L1
Participants Diagnosis: Chronically ill patients treated with neuroleptics.
Schizophrenia, schizoaffective disorder, bipolar disorder (DSM-III
criteria) Persistent TD (diagnostic research criteria)
5279PG446C1P1L13
5279PG446C1P3L5
5279PG446C1P3L1
N= 22
Age: mean 39.14(SD 10.1) years 5279PG446C2P2L13
Sex: not reported.
History: patients with dystonic movements and those with choreo-
athetoid movements
Interventions 1. Clonazepam: dose 1mg/d (0.5 mg b.i.d.) increased every 3-4
days to a maximum of 4.5 mg/d for 4 weeks. N=not reported*.
2. Placebo for 4 weeks. N=not reported*
Outcomes Unable to use - TD symptoms score*:
Mental State: BPRS*
Leaving the study early*
Notes Sponsorship source: Supported by NIMH grant
*Results not reported per intervention group
(clonazepam/placebo)
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection bias)
Unclear risk
"...randomised crossover trial...” Details
not reported
5279PG445C1P1L4
Allocation concealment
(selection bias)
Unclear risk
Allocation concealment not reported
Blinding of participants and
personnel (performance
bias)
Unclear risk
"The drug was formulated as 0.5 mg of
clonazepam or as an identical sucrose
placebo capsule. The treating physicians
were blind to the treatment." However,
blind may have been not effective as "The
dose increments were carried out to a
maximum of nine capsules/day or until the
patients developed unwanted side effects.
In the presence of any untoward effects,
the dose (number of capsules) was
reduced to the maximum tolerated dose.
The doses of clonazepam in 11 patients
were increased to 4-4.5 mg per day of
clonazepam; six patients received 3
5279PG446C2P1L1
1
5279PG446C2P1L1
6
16
mg/day, and two patients received 2
mg/day "
Blinding of outcome
assessment (detection bias)
Low risk
"Videotapes of a standard examination
were recorded each week and were rated
at a later date by two of us (G.K.T. and
J.A.N.) using the Maryland Psychiatric
Research Center Movement Disorder
Scale. The scores from these videotape
ratings were the ones used in the data
analysis. The videotape ratings provided a
sensitive measure of change in dyskinesia
and also helped maintain the study blind
for the scorer."
5279PG447C1P1L1
Incomplete outcome data
(attrition bias)
Low risk 14% drop out. "Twenty-two patients gave
their voluntary consent to participate in the
study... Three of these patients dropped
out of the study for reasons unrelated to
the drug effect (one had a psychotic
relapse, one withdrew consent to the
double-blind procedure, and one lacked
transportation). All dropouts occurred early
in the protocol, before active clonazepam
treatment began".
5279PG446C1P2L6
Selective reporting
(reporting bias)
High risk Data (TD symptoms, mental state)
reported per diagnosis group (patients with
dystonic movements and those with
choreo-atheroid movements during each
intervention period) but not all the TD
patients per intervention (clonazepam vs
placebo). Adverse events not reported per
group.
5279PG448T2
5279PG448T3
5279PG448F1
Other bias
Unclear risk
Insufficient information to make a
judgement
17
Weber 1983
Reference
[Ref. ID 5290] Weber SR, Dufresne RL, Becker RE, Mastrati P. Diazepam in tardive dyskinesia. Drug
Intelligence and Clinical Pharmacy 1983; 17: 523-7.
Characteristics
Location in PDF
Methods Allocation: randomised. 5290PG524C2P5L
1
Blindness: single. 5290PG523C1P3L
5
Design: cross-over. 5290PG523C1P3L
5
Duration: 24 weeks (10 weeks followed by 4 weeks wash-out then
crossed over to another 10 weeks)
5290PG524C2P5L
3
Setting: Inpatients in a long-term state psychiatric hospital, USA 5290PG524C2P3L
2
Participants Diagnosis: Schizophrenia (12), organic brain syndrome (1),
unknown (2).
History: TD history of 2-6 years. Baseline AIMS rating or two or
more on one item, and drug-induced parkinsonian movements of
six or less.
5290PG524C2P4L
17
5290PG524C2P4L
13
5290PG524C2P3L
3
N=15. 5290PG524C2P4L
1
Age: mean 57.4 years, 50-65 years. 5290PG524C2P4L
6
Sex: 10 male and 3 female 5290PG524C2P4L
5
Interventions 1. Standard care plus Diazepam: dose 6-25 mg/day, mean 12
mg/day. N=8.
5290PG525C2P3L
5
2. Standard care. N=5.
Outcomes Tardive dyskinesia: AIMS. 5290PG524C2P2L
2
Leaving the study early. 5290PG524C2P4L
1
Unable to use - Mental state: BPRS (no total scores reported). 5290PG524C2P2L
3
Notes Sponsorship source: Sponsorship Source not reported
Two participants also had their medication altered during the study. 5290PG525C2P4L
3
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation
(selection bias)
Unclear risk
"Each patient was assigned randomly..."
Further details not reported.
5290PG524C2P5
L1
Allocation
concealment
(selection bias)
Unclear risk
Allocation concealment not reported
Blinding of
participants and
personnel
(performance bias)
High risk
As one of the groups received an
intervention and the second standard
care, blinding of participants and
personnel could not have been possible
5290PG524C2P5
L1
18
Blinding of outcome
assessment
(detection bias)
Low risk "rater-blind" "The rating scales were
administered by trained observers who
did not know which patients received
diazepam"
5290PG523C1P3
L5
Incomplete
outcome data
(attrition bias)
Low risk
13% drop-out. "Fifteen patients began
the study. Two failed to complete the
entire protocol (one because she
continued to receive diazepam
throughout the study and the other
because she was discharged from the
hospital)"
5290PG524C2P4
L1
Selective reporting
(reporting bias)
Unclear risk
The outcomes seem to have been
reported. However, a Protocol is not
available for verification
Other bias Unclear risk Change in medication for two
participants may have had a confounding
effect, however, both substitutions
occurred four weeks into the second
phase of the study.
Outcome
1 BENZODIAZEPINE versus PLACEBO/NO TREATMENT (all medium term)
Outcome Subgroup
Benzodiazepin
es
Placebo/no
treatment
Location in PDF
Events Total Events Total
1.1 TD symptoms: not
improved more than 50%
1.1.2 Diazepam vs
TAU - 10 weeks 9 10 3 5 5290PG525T1
1.2 TD symptoms: not any
improvement
1.2.2 Diazepam vs
TAU - 10 weeks 5 10 1 5 5290PG525T1
Outcome Subgroup Diazepam Tetrabenazine
Events Total Events Total
1.3 TD symptoms:
deterioration
1.3.2 Diazepam vs
TAU - 10 weeks 3 8 0 5 5290PG525T1
Outcome Subgroup
Benzodiazepine
sPlacebo Location in PDF
Mean SD Total Mean SD Total
1.4 TD symptoms: Average
TD score at the end of
treatment
1.4.1 AIMS scores (IPD,
greater = worse) - 10
weeks
11.4 6.86 8 5.6 2.7 5
5290PG525T1
Outcome Subgroup Benzodiazepines Placebo Location in PDF
Mean SD Total Mean SD Total
1.5 Mental state: Average
score at the end of treatment
(BPRS, low = best)
1.5.1 Diazepam vs
TAU - medium term
(8-10 weeks)
42.5 15.11 6 43.0 6.4 5
5290PG525T1
Outcome Subgroup
Benzodiazepin
es Placebo Location in PDF
Events Total Event
sTotal
1.6 Leaving the study
early
1.6.1 Diazepam vs TAU - 10
weeks 2 10 0 5 5290PG524C2P4L1
19
Xiang 1997
Reference
Xiang H, Zhen C. Clonazepam therapy of tardive dyskinesia: a double-blind trial. West China Medical
Journal [华华华华] 1997; 12(1): 17-8.
Characteristics
Methods Allocation: Quote “randomized controlled trial” (p.17).
Blinding: Quote “double blind (p.17). “The two drugs were contained in capsules
with same appearance.” (p.17).
Duration: Quote “8 weeks” (p.17).
Location: Quote “inpatients” (p.17).
Length of follow up: 8 weeks (p.17).
Participants Diagnose: Antipsychotics-induced tardive dyskinesia
Total: N=24
Sex: male 15, female 9
Agemean~ 39.44 years old, sd~8.43 years old.
Length of illness (schizophrenia): not reported.
Length of illness (TD): mean~ 2.7years, sd~1.21 years (p.17).
Inclusion criteria: inpatients with antipsychotics-induced tardive dyskinesia.
Exclusion criteria: participants with a stable or aggravating symptoms of TD after
suspending antipsychotic drugs for 2 weeks. AIMS ≥5; participants with torsion-
spasm, stereotyped movement, habitual tic, Huntington disease, harelip syndrome,
month or tongue movement disorder, akathisia will be excluded. (p.17).
Interventions 1. Clonazepam Group: (n=12)
Management: initial dosage, three tablets per day; after two weeks of treatment, the
dosage were reduced to two tablets per day.
Treatment duration (weeks): 8 weeks.
2. Placebo Group: (n=12)
Management: initial dosage, three tablets per day; after two weeks of treatment, the
dosage were reduced to two tablets per day.
Treatment duration (weeks) 8 weeks.
All cases continued the use of antipsychotics and anticholinergic drugs.
Outcomes AIMS
Adverse events: drowsiness
Blood routine examination, urine routine test and liver function test,
electrocardiography, electroencephalogram (the author only stated results of these
tests were normal but did not report the data). (p.17)
Notes Funding sources: not reported.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence
generation (selection bias)
Uncl ear r i sk
Quote: “randomized controlled trial” (p.17)
Comments: The author did not state the method of
randomization.
Allocation concealment
(selection bias)
Uncl ear r i sk
Comments: not stated.
Blinding of participants and
personnel (performance
bias)
Low r i sk
Quote: “double blind” (p.17) “The two drugs were
contained in capsules with same appearance.” (p.17)
Comments: Blinding of participants and key study personnel
ensured.
Blinding of outcome
assessment (detection bias)
Uncl ear r i sk
Comments: not stated.
Incomplete outcome data
(attrition bias)
Low r i sk
Comments: all participants competed the study.
20
Selective reporting
(reporting bias)
Low r i sk
Comments: the author reported all measured outcomes.
Other bias
Low r i sk
Comments: none obvious.
Outcome
Dichotomous Outcomes
Name of outcomes: data extraction
Adverse events: drowsiness Event Total
Clonazepam group(at 8 weeks) 3 12
Placebo group(at 8 weeks) 0 12
Continuous Outcomes
华华Baseline 华华华华华华华华华华华华华华华华
Name of outcomes: data extraction
AIMS M SD N
Clonazepam group (at 8 weeks) 4.81 1.24 12
Placebo group (at 8 weeks) 8.03 2.16 12
21
Calcium Channel Blockers for Neuroleptic-Induced Tardive Dyskinesia
Loonen 1992
Reference
Loonen AJM, Verwey HA, Roels PR, van Bavel LP, Doorschot CH. Is diltiazem effective in treating the
symptoms of (tardive) dyskinesia in chronic psychiatric inpatients? A negative, double-blind, placebo-
controlled trial. Journal of Clinical Psychopharmacology 1992; 12: 39-42.
Characteristics
Methods Allocation: "random permuted block", allocation not described 5084PG40C1P3L3
Blindness: "double-blind to placebo tablets which looked identical" 5084PG40C1P3L6
Duration: 6 weeks (3 weeks then crossed over to another 3 weeks) 5084PG40C1P3L5
Design: crossover. 5084PG39C1P1L6
Setting: Psychiatric Hospital Reinier Van Arkel, Netherlands 5084PG39C2P3L2
Raters: not reported.
Participants Diagnosis: Axis I and Axis II diagnoses (DSM III-R criteria) Clinical
diagnosis of tardive dyskinesia based on a history of neuroleptic drug
treatment over a period of at least 4 months.
5084PG39C2P3L3
History: neuroleptic, anticholinergic, antihistaminic, or anxiolytic drugs,
stable for at least 3 weeks before entry until the end of the trial (long-
acting neuroleptic: the preceding 3 doses and dosage intervals
constant or the last administration at least 7 weeks before entry. The
concomitant medication comprised antipsychotics (n=17; short-acting,
n=10; long-acting, n=8), anticholinergics (n=9), benzodiazepines
(n=2), anticonvulsants (n=2), and diuretics (n=2), whereas single
patients received a variety of somatic drugs unlikely to affect trial
results.
5084PG40C2P4L16
N=18. 5084PG40C2P4L1
Sex: 6 male and 11 female (among completers) 5084PG40C2P4L10;
PG8T1
Age: mean (SD), 52.2(9.30) years; range 37-69 years 5084PG39C2P3L3;
PG8T1
Inclusion criteria: Clinical diagnosis of tardive dyskinesia based on a
history of neuroleptic drug treatment over a period of at least 4
months; either moderate or severe hyperkinesia according to the UKU
definition, present for at least 6 months preferably, a history of
aggravation due to dose reduction of the neuroleptic or addition of an
antiparkinson drug; clinical condition stable for at least 3 weeks;
neuroleptic, anticholinergic, antihistaminic, or anxiolytic drugs, en
stable for at least 3 weeks before entry until the end of the trial (long-
acting neuroleptic: the preceding 3 doses and dosage intervals
constant or the last administration at least 7 weeks before entry
5084PG40C1P1L1
Excluded: Pregnant or lactating women; women of child-bearing
potential; patients known to be incompliant or insufficiently
cooperative; patients suffering from or with a history of a medical
condition which would prevent them from entering a drug trial or
contraindicate the use of diltiazem; drugs, which might adversely
interact with diltiazem (adrenergic beta receptor blockaders, cardiac
glycosides, calcium channel blockers, lithium) discontinued for at least
3 weeks prior to entry.
PG4P2L1
Interventions 1. Diltiazem hydrochloride: dose 60mg q.i.d. N=9.
2. Placebo. N=9
5084PG40C1P3L4
5084PG40C2P4L1
5084PG40C1P3L7
Outcomes TD symptoms: AIMS 5084PG40C1P4L5
22
Mental state: severity of psychiatric symptoms (CGI) 5084PG40C1P4L13
Notes Sponsorship source: Not reported
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence
generation
(selection bias)
Low risk
Patients who entered the study were
randomly allocated to treatment group I or
II by random permuted block technique
with a block size of 2. Random number
generator method to select random
permuted blocks not reported, but likely
computer generated.
5084PG40C1P3
L1
Allocation
concealment
(selection bias)
Unclear risk
Allocation concealment was not reported
Blinding of
participants and
personnel
(performance bias)
Low risk
"Double-blind to placebo tablets which
looked identically" "The double-blind code
was not broken until the last patient had
terminated".
5084PG40C1P3
L6
PG4P4L9
Blinding of outcome
assessment
(detection bias)
Unclear risk
Details of blinding of assessors was not
reported
Incomplete
outcome data
(attrition bias)
Unclear risk
"Eighteen patients with TD entered the
study. During the study, three subjects
terminated prematurely. Two of them
showed an obvious lack of compliance
unrelated to trial medication; these
subjects were replaced. One patient
developed atrial fibrillation, which required
digitalization. When the double-blind code
of this patient was broken, it appeared
that the atrial fibrillation had started during
the placebo period. Thus, the number of
subjects who completed the study was
17". Unclear when the non-compliant
subjects were replaced (period 1 or 2)
and which group they were randomized
to.
5084PG40C2P4
L1
Selective reporting
(reporting bias)
Unclear risk
Other bias
Unclear risk
As baseline Characteristics were reported
for the total completed population, it is
unclear if there were confounding variable
that may have affected bias (results for
TS symptoms have been reported per
period)
5084PG40C2P4
L9
Outcome
Outcome Subgroup Diltiazem hydrochloride Placebo
Mean SD Total Mean SD Total
2.1 TD symptoms (short
term): AIMS 7.31 5.26 8 7.44 6.13 9
5084PG41T1C3L
4;
5084PG4T1C4L5
Outcome Subgrou Diltiazem hydrochloride Placebo
23
p Events Total Events Total
Mental state: deterioration 0 9 0 9 See comment
above
Schwartz 1997
References
Schwartz B, McCarthy MF, Kendrick K, Rosse R, Deutsch S. Effect of nifedipine on motor skill
learning in schizophrenia. Schizophrenia research 1997; 24(1-2): 125.
Schwartz BL, Fay McCarthy M, Kendrick K, Rosse RB, Deutsch SI. Effects of nifedipine, a calcium
channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia. Clinical
Neuropharmacology 1997; 20(4): 364-70.
Characteristics
Methods Allocation: "random assignment", allocation not described 5188PG368P3L
3
Blindness: not described
Duration: 8 weeks (4 weeks then crossed-over to another 4 weeks) 5188PG365P4L
4
Design: crossover. 5188PG365P4L
1
Setting: not described, USA
Raters: not described.
Participants Diagnosis: Schizophrenia or schizoaffective disorder according to
information obtained during the structured clinical interview for DSM-
lll-R.
5188PG365P3L
2
N=15. 5188PG365P3L
1
Sex: 14 male and 1 female 5188PG365P3L
1
Age: mean (SD not reported) 45.7 years; range 36-58 years 5188PG365P3L
2
Interventions
1. Nifedipine: dose 60mg/day for 4 weeks. N=9.
2. Placebo. N=5
5188PG365P4L
2;
5188PG366P2L
3
Outcomes Cognitive changes (DRS)
Unable to use, data were not fully reported (only correlations) -
BPRS, SANS, AIMS, SAS, BAS, Chouinard and Ross-Chouinard
Scale
5188PG366P2L
1
Notes Sponsorship source: Support from the National Institute of Mental
Health (to last author)
5188PG369P3L
1
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence
generation
(selection bias)
Unc lear risk
"Random assignment" Details were not
reported.
5188PG368P3
L3
Allocation
concealment
(selection bias)
Unc lear risk
Allocation concealment details not
reported.
Blinding of
participants and
Unc lear risk
"double-blind" Details were not reported. 5188P365P4L1
24
personnel
(performance bias)
Blinding of outcome
assessment
(detection bias)
Unclear risk
"double-blind" Details of blinding of
outcome assessment were not reported.
5188P365P4L1
Incomplete outcome
data (attrition bias)
Low risk
"The data for one patient from one test
phase was missing; therefore, there were
14 patients included in the analysis of
data".
5188PG366P2
L1
Selective reporting
(reporting bias)
High risk
Several outcomes were not fully reported.
Other bias
Low risk
"Statistical comparisons showed that
patients in the two drug orders did not
differ from each other in terms of age,
severity of initial psychiatric symptoms or
abnormal movements, dose of neuroleptic
medication, or duration of illness." The
study seems to be free of other sources of
bias.
5188PG368P3
L4
Outcome
Outcome Subgroup Nifedipine Placebo
Mean SD Total Mean SD Total
1.1 Cognitive changes -
Short term - 4 weeks 34.0 1.2 9 31.5 2.9069 5 5188P368F
2
25
Zeng 1994
Reference
Zeng ZX, Li ZC, Yu XW, Zhang YD, Cao ZC. A double-blind trial of flunarizine therapy for tardive
dyskinesia. Chinese Journal of Pharmaco Epidemiology [华华华华华华华华]. 1994; 3(4): 183-4.
Characteristics
Methods Allocation: Quote “cross over randomized trial” (p.183).
Blinding: Quote” double blind study, the interventions were coded as intervention A or
B by the researcher in pharmacy. “Participants and personnel did not know the
allocation result. The two drugs were contained in capsules with same appearance.”
(p.183).
Duration: Quote “4 weeks” (p.183).
Location: not stated.
Length of follow up: 10 weeks (p.4).
Participants Diagnose: Antipsychotics-induced tardive dyskinesia
Total: N= 14 (however the author stated that they used sequential test method, when
the 10th participants completed the trial, a significant difference was detected, so they
terminated enrolling participants)
Sex: male 11, female 3
Age: mean years 31 old, SD 9 years old.
Length of illness (schizophrenia): mean~ 8.7 years, SD~ 3.5years. Length of illness
(TD): mean~ 5.9 years, SD~ 3.4years.
Inclusion criteria: patients with antipsychotics-induced tardive dyskinesia; AIMS ≥5;
Normal physical and laboratory examinations.
Exclusion criteria: participants with stereotyped movement, habitual tic, Huntington
disease, harelip syndrome, month or tongue movement disorder, and akathisia were
excluded. (p.183).
Interventions 2. Flunarizine Group: (n=10)
Management: At first phrase of the trial, the participants received flunarizine, one
capsule each time, twice per day for 4 weeks. The second phrase was a two-week
washout period. At the third phrase of the trial, the participants received placebo for 4
weeks.
Treatment duration (weeks)
2. Placebo Group: (n=10)
Management: At first phrase of the trial, the participants received placebo, one
capsule each time, twice per day for 4 weeks. The second phrase was a two-week
washout period. At the third phrase of the trial, the participants received flunarizine for
4 weeks.
Treatment duration (weeks) 4 weeks.
Outcomes Tardive dyskinesia: AIMS (Abnormal Involuntary Movement Scale)
Adverse events: any adverse events (no adverse events were observed).
Notes Funding source: not reported.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence
generation (selection
bias)
Uncl ear r i sk
Quote: “cross over randomized trial”
Comments: The author did not state the method of
randomization.
Allocation concealment
(selection bias)
Low r i sk
Quote: “the interventions were coded as intervention A or B by
the researcher in pharmacy.
Comments: Central allocation, pharmacy-controlled
randomization.
Blinding of participants
and personnel
(performance bias)
Low r i sk
Blinding: Quote “double blind study, the interventions were
coded as intervention A or B by the researcher in pharmacy.
“Participants and personnel did not know the allocation result.
The two drugs were contained in capsules with same
appearance.
26
Comments: Blinding of participants and key study personnel
ensured.
Blinding of outcome
assessment (detection
bias)
Uncl ear r i sk
Comments: not stated.
Incomplete outcome
data (attrition bias)
Low r i sk
Comments: all participants competed the study.
Selective reporting
(reporting bias)
Low r i sk
Comments: the author reported all measured outcomes.
Other bias
Low r i sk
Comments: none obvious.
Outcome
Continuous Outcomes
华华Baseline 华华华华华华华华华华华华华华华华
Name of outcomes: data extraction
AIMS endpoint score M SD N
Flunarizine group(at 10 weeks) 5.7 2 10
Placebo group(at 10 weeks) 6.5 2.76 10
NOTE: data also available at ______weeks
Data is not available because ________ (simply described? Or in specific graph? Or not reported?
And Other reasons)
Name of outcomes: Data extraction
AIMS change score M SD N
Flunarizine group(at 10
weeks)
-3 0.94 1
0
Placebo group(at 10 weeks) -1.1 1.37 1
0
27
Cholinergic Medication for Neuroleptic-Induced Tardive Dyskinesia
Beckham 1981
Reference
[Ref.ID 4730] * Beckham BJ. Lecithin therapy for tardive dyskinesia [dissertation]. Denton, Texas:
North Texas State University, 1981.
Characteristics
Location in PDF
Methods Allocation: randomised, no details.
Blindness: double, described and adequate.
Duration: 11 days.
Design: parallel.
Raters: 1 blinded rater, frequency of dyskinesia count
rated from videotapes presented in random order.
4730PG39P4L1
4730PG35P2L3
4730PG42P1L2
4730PG39P4L1
4730PG53P2L1;
4730PG42P2L1
4730PG43P3L2
Participants Diagnosis: schizophrenia (21), affective disorder (3),
OBS (7), neurosis (2).
History: TD present and stable >6 months, antipsychotic
dose stable >4 months, mean duration psychiatric ill 17
years (range 1-45), CPE dose (mg/day) mean 420 (SD
430)
N=50.
Sex: all male.
Age: mean 55 yrs., range 23-77.
Setting: mostly inpatients, some outpatients.
4730PG40T2
4730PG36P2L14;
4730PG36P2L3;
4730PG39P2L3 ;
4730PG57T5
4730PG36P3L1
4730PG36P3L1
4730PG40T2;
4730PG39P2L2
4730PG36P3L1
Interventions 1. Lecithin: dose 60 g/day containing
phosphatidylcholine 33 g/day. N=25.
4730PG42P1L2;
4730PG38T1
2. Placebo. N=25. Effort made to keep antipsychotic
medication stable during study, 7 received
anticholinergic (-parkinsonian) medication.
4730PG38T1;
4730PG41P1L1;
4730PG41P1L1;
4730PG41P2L9
Outcomes TD symptoms: CGI. 4730PG43P2L3
Leaving the study early. 4730PG37P2L1;
4730PG38T1
Unable to use - Frequency of dyskinetic movement
count (frequency of one selected movement/minute in 4
body areas counted visually from videotapes)
(validation unsure, no SD).
Adverse effects (reporting unspecific).
Patient's subjective assessments (not reported).
4730PG53P3L1
4730PG49P1L1
Notes Intention-to-treat analysis not performed for continuous
outcomes (CGI), results reported only for N=31 who
completed study (lecithin group 15, control group 16).
4730PG49T4
Sample attrition well reported.
Author contacted 2002, awaiting further information.
Sponsorship source: Supported in part by a grant by the
Veterans Administration.
4730PGiiiP1L1
Risk of bias
Bias Authors' judgement Support for judgement Location in
PDF
Random sequence
generation (selection
bias)
Unclear risk
"Patients were randomly assigned"
Details not reported.
4730PG39P4L
1
28
Allocation concealment
Unclear risk
Allocation concealment not reported.
Blinding of participants
and personnel
(performance bias)
Low risk
"Double blind". "Only a member of the
hospital pharmacy staff was aware of
each patient's group assignment
during the study. The investigator,
patients, ward nurses, and physicians
were all blind to patient status." "The
control substance was a mixture of
crushed graham cracker and corn oil
which, when mixed with milk,
resembled the lecithin mixture in taste,
appearance, and viscosity. The
mixtures were further disguised and
made more palatable by the addition
of artificial sweetener and vanilla
extract."
4730PG35P2L
3
4730PG39P4L
3
4730PG41P2L
6
Blinding of outcome
assessment (detection
bias)
Low risk
“Double blind". "Only a member of the
hospital pharmacy staff was aware of
each patient's group assignment
during the study. The investigator,
patients, ward nurses, and physicians
were all blind to patient status.";
"Treatment effect was assessed by
blind evaluation of randomly
sequenced videotapes wade during
standard examinations before, during,
and after treatment."; "The sole rater
was blind to patient treatment
assignment".
4730PG35P2L
3
4730PG39P4L
3
4730PG42P2L
1
4730PG53P2L
1
Incomplete outcome data
(attrition bias)
High risk
High drop-out rate: 24%. 38/50
subjects completed the trial (reasons
reported per intervention group.
Moreover, only 31/50 (62%) were
included in the analysis (reasons
reported.
4730PG37P2L
1 4730PG38T1
Selective reporting
Low risk
Dissertation. All outcomes seem to
have been reported
Other bias
Unclear risk
The groups seem to have had
differences in their baseline dental
status.
4730PG40T2
Outcome
Outcome Subgroup Cholinergic drug Placebo Location in PDF
Events Total Events Total
Death for any
reason
Lecithin vs Placebo - less than 6
weeks 0 25 0 25 4730PG38T1
Outcome Subgroup
Cholinergic
drug Placebo Location in
PDF
Mean SD Total Mean SD Total
Tardive dyskinesia: Average
endpoint score on CGI (low score
= better)
Lecithin vs Placebo -
less than 6 weeks 3.2 1.42 15 3.63 1.2 16
Outcome Subgroup Experimental Placebo Location in
PDF
29
Events Total Event
sTotal
Mental state:
Deterioration
Lecithin vs Placebo - less than
6 weeks 0 25 1 25
Outcome Subgroup
Cholinergic
drug Placebo
Events Total Event
sTotal
Leaving the study early Lecithin vs Placebo - less than
6 weeks 4 25 8 25 4730PG38T1
Caroff 2007
References
[Ref. ID 4752] Caroff SN Waljer P Campbell C Lorry A Petro C Lynch K Gallop R. Treatment of tardive
dyskinesia with galantamine: a randomized controlled crossover trial. Journal of Clinical Psychiatry
2007;68(3): 410-15.
NCT00164242 2005. Treatment of tardive dyskinesia with galantamine
Characteristics
Location in PDF
Methods Allocation: randomised, no details. 4752PG411C1P2L
26
Blindness: double blind, no details. 4752PG411C1P2L
26
Duration: 30 weeks (2 weeks baseline, 12 weeks followed by 4
weeks wash-out then crossed over to another 12 weeks)
4752PG411C1P3L
1
Design: crossover 4752PG411C1P2L
27
Raters: no details
Participants
Diagnosis: tardive dyskinesia (research criteria), long-duration.
Schizophrenia (DSM-IV criteria)
4752PG411C1P3L
1
4752PG411C1P3L
13
Sex: all male. 4752PG411C1P3L
12
Age: mean 56, 4 (SD 9.9) years. 4752PG411C1P3L
14
N=38 4752PG411C1P3L
1
Setting: Patients treated in the Department of Veteran Affairs
Medical Center, USA.
4752PG411C1P3L
2
History: Clinical diagnosis of tardive dyskinesia lasting at least 3
months; treatment with antipsychotic drugs at least for 3 months.
Interventions 1. Galantamine: dose 4 mg b.i.d for 4 weeks followed by 8 mg b.i.d.
for 4 weeks, and 12 mg b.i.d for an additional 4 weeks (followed by
4 weeks washout ad 12 weeks placebo). N=19
4752PG411C2P3L
6
4752PG411C1P3L
10 4752PG411T2
2. Placebo: 12 weeks placebo (followed by 4 weeks "washout" and
12 weeks galantamine). N=19
4752PG411C1P3L
10 4752PG411T2
Outcomes TD symptoms: total AIMS 4752PG411C2P3L
16
Leaving the study early 4752PD411C1P3L
10
Unable to use - no report from first phase separately: Simpson-
Angus Scale, Barnes Akathisia Scale, BPRS, Mini-Mental State
30
Examination.
Notes Sponsorship source: Supported by a grant from Ortho-McNeil
Neurologics, Inc.
4752PG410C2P2L
1
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection bias)
Unclear risk
"randomized controlled trial,"
Details not reported
4752PG411C1P2L
26
Allocation concealment
(selection bias)
Unclear risk
Allocation concealment not
reported
Blinding of participants and
personnel (performance
bias)
Unclear risk
"double-blind," Details not
reported
4752PG411C1P2L
26
Blinding of outcome
assessment (detection
bias)
Unclear risk
"Double blind". Details not
reported
4752PG411C1P2L
26
Incomplete outcome data
(attrition bias)
Unclear risk
"Overall, 10 (31.3%) of 32
patients receiving galantamine
dropped out, and 6 (23.1%) of
26 patients receiving placebo
dropped out. Twelve patients
dropped out during phase 1
(galantamine, N=9; placebo,
N=3), and 4 dropped out during
phase 2 (galantamine, N = 1;
placebo, N=3). Differences in
the dropout rate between
treatments were not significant.
4752PG413C1P2L
1
Selective reporting
(reporting bias)
High risk
Although the protocol specified
that Simpson Angus Scale and
BAS should have been reported
at the end of three months
(phase I), data not reported per
phase. Also data for BPRS not
reported per period
4752PG412T1
Other bias
Unclear risk
Insufficient information to make
a judgement
Outcome
Outcome Subgroup Cholinergic drug Placebo
Mean SD Total Mean SD Total
1.7 Tardive dyskinesia: 4a.
Average endpoint score on
AIMS (low score = better)
1.7.5 Galantamine vs
Placebo - more than
6 weeks
9.1 2.969
818 7.6 2.886
217
4752PG412T
2
Outcome Subgroup
Cholinergic
drug Placebo
Events Total Event
sTotal
1.12 Leaving the
study early
1.12.9 Galantamine vs Placebo -
more than 6 weeks 9 19 3 19 4752PG412C1P2
L4
31
de Montigny 1979
Reference
[Ref. ID 4921]de Montigny C, Chouinard G, Annable L. Ineffectiveness of deanol in tardive dyskinesia:
a placebo controlled study. Psychopharmacology 1979; 65: 219-23.
Characteristics
Location in PDF
Methods Allocation: randomised, no details. 4921PG230C1P2
L1
Blindness: double, no details. 4921PG230C1P2
L3
Duration: 3 weeks. 4921PG230C1P2
L2
Design: parallel. 4921PG230C1P2
L1
Raters: ESRS rated independently by 2 psychiatrists. 4921PG220C1P2
L10
Participant
s Diagnosis: chronic schizophrenia. TD: significant (Clinical Global
Impression Scale TD)
4921PG220C1P1
L1
4921PG220C1P1
L6
History: TD moderate to severe, maintenance antipsychotic
treatment >6 yrs., CPE dose range 0-1850 mg/day.
4921PG220C1P1
L3
N=20. 4921PG220C1P1
L1
Sex: 10 female, 10 male. 4921PG220T1
Age: Median 61 years, range 34-73 years. 4921PG220T1
Setting: from long-term wards. 4921PG220C1P1
L2
Interventio
ns 1. Deanol: dose increased from 600 to 1500 mg/day during first
week, constant thereafter. N=10, for three weeks.
4921PG220C1P2
L3
4921PG220T1
2. Placebo. N=10. Antipsychotic dose stable during study, no
other psychotropics permitted.
4921PG220T1
4921PG220C1P2
L5
Outcomes Adverse effects. 4921PG221C1P2
L1
Leaving the study early. 4921PG220C1P1
L11
Death 4921PG220C1P1
L11
Unable to use - TD symptom scores: ESRS (no SD).
Mental state scores: BPRS (no SD).
4921PG220C1P2
L8
4921PG220C1P2
L12
Notes Sponsorship source: Sponsorship source not reported
Analysis of ESRS scores in publication did not detect significant
treatment effect.
No difference between treatments regarding parkinsonism. There
was significant increase in mean schizophrenic subscore of
BPRS in deanol treated group.
Authors contacted - no reply.
4921PG220C2P1
L3
4921PG220C2P1
L12
4921PG221C1P1
L2
Risk of bias
32
Bias Authors'
judgement Support for judgement Location in PDF
Random sequence
generation (selection bias)
Unclear risk
"Patients were randomly
assigned"
Details not reported
4921PG230C1P
2L1
Allocation concealment
(selection bias)
Unclear risk
Allocation concealment not
reported.
Blinding of participants
and personnel
(performance bias)
Unclear risk
"double-blind" Details not
reported
4921PG230C1P
2L3
Blinding of outcome
assessment (detection
bias)
Unclear risk
"The ESRS was completed
independently by two
psychiatrists during the
same interview and a final
rating was made by
consensus."
"Double-blind". Details of
blinding not reported
4921PG220C1P
2L10
4921PG230C1P
2L3
Incomplete outcome data
(attrition bias)
Low risk
"All subjects completed the
3-week trial"
4921PG220C1P
1L11
Selective reporting
(reporting bias)
High risk
TD symptoms (ESRS) and
Mental State (BPRS) not
reported neither
continuously as mean (SD)
nor dichotomously; reported
as means only
4921PG220T2
4921PG221C1P
2L1
Other bias
Low risk
The study seems to have
been free of other sources
of data.
Outcome
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Tot
al
Eve
nts
Tot
al
1.1 Death for any
reason
1.1.2 Deanol vs Placebo -
less than 6 weeks 0 10 0 10 4921PG220C1P
1L11
Outcome Subgroup
Cholinergic
drug Placebo
Events Tot
al
Eve
nts
Tot
al
1.12 Leaving the
study early
1.12.2 Deanol vs Placebo -
less than 6 weeks 0 10 0 10 4921PG220C1P
1L11
Outcome Subgroup
Cholinergic
drug Control Location in PDF
Events Tota
l
Eve
nts
Tot
al
1.12 Adverse
effects: Various
1.12.3 deanol - gastric
adverse effects 4 10 0 10 4921PG221C1P
2L1
1.12 Adverse
effects: Various
1.12.4 deanol - sedation,
peripheral cholinergic
effects, undesirable body
odour
5 10 0 10
4921PG221C1P
2L1
33
Gelenberg 1990
Reference
[Ref. ID 4955] * Gelenberg AJ, Dorer DJ, Wojcik JD, Falk WE, Brotman AW, Leahy L. A crossover
study of lecithin treatment of tardive dyskinesia. Journal of Clinical Psychiatry 1990;51(4):149-53.
Characteristics
Location in PDF
Methods Allocation: randomised, procedure conducted independently by trial
statistician, stratified by maintenance antipsychotic drug therapy.
4955PG149P1L1
4955PG149C2P2L
5
Blindness: double. 1 blind rater assessed TD and psychopathology.
1 open rater assessed side-effects and distributed medication.
4955PG149C1P2L
4
Duration: 18-20 weeks (4 weeks baseline, 8 weeks followed by 2-4
weeks washout and then crossed to another 8 weeks)
4955PG149C2P2L
3
Design: Crossover. 4955PG149C1P2L
4
Participants Diagnosis: schizophrenia (9), bipolar (6), major depression (3),
generalized anxiety disorder (1), brief reactive psychosis (1), no
psychiatric diagnosis (1). TD diagnosed by psychiatrist and
neurologist on the basis of abnormal involuntary movements of a
choreoathetotic type that involved the mouth, face, and/or
extremities and that occurred in patients treated with an
antipsychotic drug for at least 6 months; AIMS global rating of mild
or greater
4955PG151C1P2L
3
4955PG149C2P1L
3
4955PG150C1P3L
4
History: TD present 6 months - 17 yrs. (median 1.5 yrs.). 4955PG151C1P2L
13
N=21. 4955PG151C1P2L
1
Sex: 11 female, 10 male. 4955PG151C1P2L
1
Age: median 47 years, range 19-70. 4955PG151C1P2L
2
Setting: Outpatients: patients recruited from mental health centers
and private physicians.
4955PG149C2P1L
1
Interventions
1. Lecithin: containing PC 20 g/day. N=5 of completers of trial.
4955PG150C1P2L
8
4955PG151C1P3L
5
2. Placebo. N=9 of completers. 4955PG151C1P3L
5
No information given on how many were originally allocated to each
group. 14 of 21 completed trial. Antipsychotics stable during trial. No
anticholinergics permitted. Patients took the following concomitant
medications during the trial: antipsychotic agents alone (N=7),
antipsychotic drugs plus lithium (N=3), antipsychotic drugs plus
trazodone (N=1), antipsychotic drugs plus an antianxiety agent (N1),
antianxiety drugs alone (N1), antianxiety drugs plus lithium (N=3),
and lithium alone (N=1). Two patients took no other medications,
and 2 took non psychoactive drugs
4955PG151C1P3L
1
4955PG149C2P3L
3;
4955PG151C2P1L
1
Outcomes TD symptoms: AIMS. 4955PG150C1P3L
4
Unable to use - Global impression: CGI-Improvement (not reported).
Movement disorders: TAKE (reported only final summary scores
from both segments, after cross-over).
Mental state: BPRS, HAM-D (reported only final summary scores
from both segments, after cross-over).CGI data not reported
4955PG150C1P3L
7
4955PG150C1P3L
9
4955PG151C2P3L
34
Adverse effects (reported only final summary scores from both
segments, after cross-over).
Leaving study early (reported only final summary scores from both
segments, after cross-over).
1
4955PG150C1P3L
12
4955PG151C2P3L
6
4955PG150C1P3L
14
4955PG151C2P2L
1
4955PG151C1P3L
1
Notes Sponsorship source: Funded by National Institute of Mental Health
grant, the Arbour Research Foundation, and the Center for Brain
Sciences.
4955PG149FP3L1
Intention-to-treat analysis not performed for AIMS scores (results
reported only for completers).
4955PG151T3
Authors contacted, awaiting further information. Details of allocation
procedure from authors.
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection
bias)
Unclear risk
"random-order,"
"patients were stratified by whether
they were on maintenance
antipsychotic drug therapy."
Details of sequence generation not
reported
4955PG149P1L1
4955PG149C2P2L
5
Allocation
concealment
(selection bias)
Low risk
Allocation concealment not reported
Blinding of
participants and
personnel
(performance bias)
Unclear risk
"double-blind". Several lecithin
preparations were used during the
study. We started with frappes
prepared with chunks of 55% PC.
That preparation was succeeded by
chunks, chicken soup, and granola
bars that contained 80% to 100%
PC. Placebo included corn oil in
frappes, ground corn flakes, and
matching chicken noodle soup and
granola bars.". Unclear if the lecithin
and placebo preparations were
identical (color, taste, smell...)."The
14 completers were asked to fill out a
questionnaire in which they specified
(l) which of the two medications they
thought was most helpful, (2) what
effects (if any) they noted on their
mood, and (3) whether they could
guess which of the two medications
was lecithin and which was placebo.
Seven of the 14 patients felt that one
treatment was definitely more helpful
than the other; of those, 6 indicated
that lecithin was the more helpful
treatment."
4955PG149C1P2L
4
4955PG150C1P2L
1
4955PG151C2P4L
1
35
Blinding of outcome
assessment
(detection bias)
Unclear risk
"We used two clinical raters, one
blind rater who assessed TD and
psychopathology and one open rater
who rated side effects and
distributed medication." "Both the
blind rater and the patient completed
Clinical Global Impressions and
Improvement ratings at each visit
and the blind rater assessed
extrapyramidal effects with the
Target Abnormal Kinetic Effects
(TAKE) scale."
4955PG150C1P3L
1
4955PG150C1P3L
6
Incomplete outcome
data (attrition bias)
High risk
"Fourteen patients-7 men and 7
women-completed at least 3 visits on
the second leg of the trial. Data from
these 14 completers were used in
the efficacy analyses." Number
completed the first period and
number completed the trial not
reported. 14/21 subjects were
entered to the analyses
(approximately 33% drop out)
4955PG151C1P3L
1
Selective reporting
(reporting bias)
High risk
Clinical Global Impressions and
Improvement not reported,
TargetAbnormal Kinetic Effects
(TAKE) scale, Mental State (BPRS
abd HAM-D), Adverse Effects, and
Leaving the study early not fully
reported.
4955PG151C2P3L
1
4955PG150C1P3L
12
4955PG151C2P3L
6
4955PG150C1P3L
14
4955PG151C2P2L
1
4955PG151C1P3L
1
Other bias Low risk The study seems to be free from
other sources of bias.
Outcome
Outcome Subgroup
Cholinergic
drug Placebo Location in
PDF
Mean SD Total Mean SD Total
1.7 Tardive dyskinesia: 4a.
Average endpoint score on
AIMS (low score = better)
1.7.4 Lecithin vs
Placebo - more than
6 weeks
2.3 0.82 5 2.4 0.92 9
4955PG151T
3
36
George 1981
Reference
[Ref. ID 4956] * George J, Pridmore S, Aldous D. Double blind controlled trial of deanol in tardive
dyskinesia. Australian and New Zealand Journal of Psychiatry 1981; 15: 68-71.
Characteristics
Location in PDF
Methods Allocation: randomised, no details, stratified by severity of TD. 4956PG60C1P7
L7
Blindness: double. 4956PG60C1P3
L1
Duration: 4 weeks. 4956PG68P2L1
Design: parallel. 4956PG60C1P7
L6
Raters: Videotapes presented in random order and rated
independently by 2 raters.
4956PG60C1P5
L1
Participants Diagnosis: chronic psychiatric inpatients with oral TD. 4956PG62P1L1
History: All received neuroleptics, 7 on neuroleptics during trial, CPE
range 50-800 mg/day.
4956PG69C2P1
L5
4956PG69C2P2
L1
N=33. 4956PG60C1P3
L1
Sex: female 25, male 8. 4956PG60C1P3
L2
Age: range 49 - 89 yrs., mean ~ 70. 4956PG69C2P1
L1
Setting: chronic psychiatric hospital residents. 4956PG62P1L1
Interventions
1. Deanol: dose 2000 mg/day for four weeks. N=11.
4956PG60C2P3
L3
4956PG69C1P1
L2
2. Deanol: dose 1000 mg/day for four weeks. N=11.
4956PG60C2P3
L3
4956PG69C1P1
L2
3. Placebo four weeks. N=11.
4956PG60C2P3
L3
4956PG69C1P1
L1
Outcomes TD symptoms. 4956PG69C1P5
L1
Adverse effects. 4956PG69C2P7
L1
Leaving study early. 4956PG69C2P7
L6
Unable to use -
TD symptom scores: local scale (not validated).
Notes Sponsorship source: The drug used in this trial was supplied by Riker
Laboratories Pty. Ltd. who in addition, provided a grant for expenses
involved in this project.
4956PG70C2P7
L1
No information about medication status and dose prior to study, or
duration of TD.
In review the two deanol groups are analysed as one group.
Authors contacted - no reply.
37
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection bias)
Unclear risk
"Randomly assigned", further
details not reported.
4956PG60C1P7L
7
Allocation concealment
(selection bias)
Unclear risk
Allocation concealment not
reported.
Blinding of participants
and personnel
(performance bias)
Unclear risk
"Double-blind". Details not
reported.
4956PG60C1P3L
1
Blinding of outcome
assessment (detection
bias)
Unclear risk
"The baseline rating of filming 1
and the ratings of filmings 2, 3
and 4 were carried out by
randomizing. All film segments
and showing them unidentified to
the raters on the 30th day of the
study."
4956PG69C2P5L
4
Incomplete outcome data
(attrition bias)
Low risk "All patients completed the trial." 4956PG69C2P7L
6
Selective reporting
(reporting bias)
High risk
TD symptoms reported only as
means, Adverse events not fully
reported.
4956PG70T1
4956PG69C2P7L
1
Other bias
High risk
"One subject in Group A showed
'substantial improvement',
however, on preliminary and
baseline rating that patient was
one of the less severely afflicted.
In Group B one patient also
showed 'substantial improvement'
and this patient was receiving
thioridazine 200mg three times a
day in addition to deanol."
Possible confounding variables.
4956PG70C2P3L
1
Outcome
1 CHOLINERGIC DRUGS versus PLACEBO
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Total Event
sTotal
1.1 Death for any reason
1.1.5 Deanol 1g vs
Placebo - less
than 6 weeks
0 11 0 11
4956PG69C2P7
L6
1.1 Death for any reason
1.1.6 Deanol 2g vs
Placebo - less
than 6 weeks
0 11 0 11
4956PG69C2P7
L6
Outcome Subgroup
Cholinergic
drug Placebo
Events Total Event
sTotal
1.2 Tardive dyskinesia: 1. No clinically
important improvement (50% or more
change on any validated TD scale)
1.2.3 Deanol 1g vs
Placebo - less
than 6 weeks
10 11 10 11
4956PG70C2P3
L1
1.2 Tardive dyskinesia: 1. No clinically
important improvement (50% or more
1.2.4 Deanol 2g vs
Placebo - less
5 11 10 11 4956PG70C2P3
L7
38
change on any validated TD scale) than 6 weeks
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Total Event
sTotal
1.3 Tardive dyskinesia:
2a. Not any improvement
(as assessed by rater)
1.3.6 Deanol vs Placebo - less
than 6 weeks 10 22 10 11
4856PG70C2P3
L1
Outcome Subgroup
Cholinergic
drug Placebo
Events Total Event
sTotal
1.11 Adverse effects:
Various
1.11.2 Deanol vs Placebo - less
than 6 weeks - sedation,
periferal cholinergic effects,
undesirable body odour
3 22 0 11
4956PG69C2P7
L1
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Total Event
sTotal
1.12 Leaving the
study early
1.12.2 Deanol vs Placebo - less
than 6 weeks 0 22 0 11 4956PG69C2P7
L6
1.12 Leaving the
study early
1.12.6 Deanol 1g vs Placebo -
less than 6 weeks 0 11 0 11 4956PG69C2P7
L6
1.12 Leaving the
study early
1.12.7 Deanol 2g vs Placebo -
less than 6 weeks 0 11 0 11 4956PG69C2P7
L6
2 CHOLINERGIC DRUGS versus OTHER CHOLINERGIC DRUGS
Outcome Subgroup
Cholinergic
drug Control Location in PDF
Events Total Event
sTotal
2.1 Death for any reason
2.1.1 Deanol 1g vs
Deanol 2g - less
than 6 weeks
0 11 0 11
4956PG69C2P7
L6
Outcome Subgroup
Cholinergic
drug Control
Events Total Event
sTotal
2.2 Tardive dyskinesia: 1. No clinically
important improvement (50% or more
change on any validated TD scale)
2.2.1 Deanol 1g vs
Deanol 2g - less
than 6 weeks
10 11 5 11
4956PG70C2P3
L4
Outcome Subgroup
Cholinergic
drug Control Location in PDF
Events Total Event
sTotal
2.3 Tardive dyskinesia: 2a. Not
any improvement (as assessed
by rater)
2.3.1 Deanol 1g vs
Deanol 2g - less than 6
weeks
10 11 0 11
4956PG70C2P3
L4
Outcome Subgroup
Cholinergic
drug Control
Events Total Event
sTotal
39
2.4 Leaving the study early
2.4.1 Deanol 1g vs
Deanol 2g - less than 6
weeks
0 11 0 11
4956PG69C2P7
L6
40
Jackson 1978
Reference
[Ref. ID 5007] * Jackson IV. Cholinergic enhancement in tardive dyskinesia. Current Therapeutic
Research 1978;24(6):725-33.
Characteristics
Location in PDF
Methods Allocation: randomised, no details. 5007PG727P6L
1
Blindness: double. 5005PG726P7L
1
Duration: 32 weeks (withdrawal of neuroleptics/single neuroleptic in
constant dose followed by 4 weeks baseline, 12 weeks then crossed
over to another 12 weeks)
5007PG727P4L
1
Design: crossover. 5007PG731P4L
3
Setting: long-term inpatients Missuri Institute of Psychiatry research
ward, USA.
5007PG727P3L
1
Raters: videotapes presented in random temporal sequence and rated
independently by 4 psychiatrists using AIMS.
5007PG727P7L
6
Participants
Diagnosis: schizophrenia + TD (Global AIMS rating of moderate to
severe).
5007PG728P1L
1
5007PG727P3L
2
History: mean duration ill ~22 yrs. (range 18-30), high dose
antipsychotic drugs over extended periods of time.
5007PG728P1L
2
N=6. 5007PG731P3L
3
Sex: all female. 5007PG728P1L
1
Age: mean 48 years, range 34-59.
Interventions 1. Deanol: dose gradually increased to 1500 mg/day over 4 weeks.
N=4.
5007PG727P6L
3 5007PG730T2
2. Placebo. N=2. Maintained on single, stable antipsychotic dose
during study. No other psychotropics or anticholinergics permitted.
5007PG730T2
Outcomes TD symptoms: AIMS. 5005PG727P7L
4
Mental state: MIBS 5005PG727P7L
12
Adverse effects: Parkinsonism (Simpson Angus Scale; general
5005PG727P7L
10
5007PG730P1L
1
Leaving study early. 5007PG729T1
Unable to use - Mental state scores: MIBS (not reported).
Parkinsonism scores: Simpson and Angus scale (not reported).
Notes No participants developed clinical parkinsonism.
People leaving the study early may not have been reported. 5007PG729T1
Sponsorship source: Sponsorship source not reported
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
41
Random sequence
generation (selection
bias)
Unclear risk
"subjects were randomly assigned"
Details not reported.
5007PG727P6L
1
Allocation
concealment
(selection bias)
Unclear risk
Allocation concealment not reported.
Blinding of
participants and
personnel
(performance bias)
Unclear risk
"double-blind" Details not reported
5007PG726P7L
1
Blinding of outcome
assessment
(detection bias)
Low risk
"A 20-minute videotape of the patient
sitting alone and then of an examination
following the schema for the AIMS, by
the same psychiatrist known to the
patient. At the end of the study, the three
videotapes for each patient were
presented in random temporal sequence
and rated "blind" by 4 psychiatrists using
the AlMS."
"Additional AIMS ratings were made by
the same psychiatrist every 4 weeks on
the ward without the disturbance of the
videotape equipment. A weekly Global
AIMS and Missouri In-Patient Behavior
Seale (MlBS) was per formed by a ward
nurse"
5007PG727P7L
3
Incomplete outcome
data (attrition bias)
Low risk
All subjects completed the trial 5007PG729T1
Selective reporting
(reporting bias)
High risk AIMS scores reported as means only. -.
Data for Simpson Angus Scale not
reported: "there was no significant
change in the Simpson and Angus
ratings". “There was no significant or
sustained change in the Missouri In-
Patient Behavior Scale ratings. “Data for
MIBS not reported
5007PG730T2
5007PG730P1L
3
5007PG730P1L
4
Other bias Unclear risk "During the 32 weeks of the study,
interrater variability, day-to-day changes
in patient condition, and non-drug
related trends across time reduced the
power of the single crossover design to
the point where it would be unlikely to
detect any but the most clear-cut
changes in a single patient."
5007PG730P5L
1
Outcome
1 CHOLINERGIC DRUGS versus PLACEBO
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Total Event
sTotal
1.1 Death for any reason
1.1.3 Deanol vs
Placebo - more
than 6 weeks
0 6 0 6
Outcome Subgroup Cholinergic
drug Placebo
Events Total Event Total
42
s
1.2 Tardive dyskinesia: 1. No clinically
important improvement (50% or more
change on any validated TD scale)
1.2.1 Deanol vs
Placebo - more
than 6 weeks
3 4 2 2 5007PG729T1
Outcome Subgroup
Cholinergic
drug Placebo Location in PDF
Events Total Event
sTotal
1.3 Tardive dyskinesia: 2a. Not any
improvement (as assessed by rater)
1.3.7 Deanol vs
Placebo - more than 6
weeks
1 4 2 2
5007PG729T1
Outcome Subgroup
Cholinergic
drug Placebo
Events Total Event
sTotal
1.5 Tardive dyskinesia: 3a.
Deterioration (as assessed by rater)
1.5.3 Deanol vs
Placebo - more than 6
weeks
1 4 2 2
5007PG729T1
Outcome Subgroup
Cholinergic
drug Placebo Location in
PDF
Events Total Event
sTotal
1.11 Adverse
effects: Various
1.11.1 Deanol vs Placebo - less than 6
weeks - gastric adverse effects 0 4 025007PG730P1
L1
1.11 Adverse
effects: Various
1.11.2 Deanol vs Placebo - less than 6
weeks - sedation, periferal cholinergic
effects, undesirable body odour
0 4
0
2
5007PG730P1
L1
Outcome Subgroup
Cholinergic
drug Placebo Location in
PDF
Events Total Event
sTotal
1.12 Leaving
the study early
1.12.3 Deanol vs Placebo - more than 6
weeks 0 4 025007PG729T1
43
Jackson 1979
References
[Ref. ID 5008] Jackson IV, Davis LG, Cohen RK, Nuttall EA. Lecithin administration in tardive
dyskinesia: clinical and biomedical correlates. Biological Psychiatry 1981; 16(1): 85-90.
[Ref. ID 5009] * Jackson IV, Nuttall EA, Ibe IO, Perez-Cruet J. Treatment of tardive dyskinesia with
lecithin. American Journal of Psychiatry 1979; 136(11): 1458-60.
Characteristics
Location in PDF
Methods Allocation: randomised, no details. 5008PG1458C2P5L5
Blindness: double, described and adequate. 5008PG1458C1P1L2
Duration: 2 weeks (preceded by 2-4 weeks pre-entry). 5008PG1458C2P4L1
Design: crossover. 5009PG86P2L7
Setting: long-term inpatients, USA. 5008PG1458C2P2L1
Raters: videotapes presented in random temporal sequence
and rated blind and independently by 2 psychiatrists using
AIMS.
5008PG1459C1P2L9
Participants Diagnosis: long-term schizophrenia + TD (moderate or severe
on AIMS global rating).
5009PG86P2L4
5008PG1458C2P2L2
History: antipsychotics continuously >4 years (range 4-23). 5009PG86P2L2
N=6. 5008PG1458C2P2L1
Sex: 5 female, 1 male. 5009PG86P2L1
Age: mean 57 years, range 49-60. 5008PG1458C2P4L7
Interventions 1. Lecithin: dose 50 g/day. N=3. 5008PG1459C1P1L3
2. Placebo. N=3. Antipsychotics stable during study. No other
psychotropics or anticholinergics permitted.
Outcomes TD symptoms: AIMS. 5008PG1459C1P2L3
Adverse effects. 5008PG1459C1P5L6
Leaving study early. 5008PG1439C2P1L3
Unable to use -
Mental state scores: BPRS, MIBS (not reported).
5008PG1459C1P2L14
5008PG1459C1P2L18
Notes Sponsorship source: Sponsorship source not reported
One person withdrawn early due to nausea and vomiting on a
lecithin/water/orange flavour mix. Protocol changed to
lecithin/ice cream/chocolate mix - well tolerated!
Physiology (blood pressure, serum choline) monitored. Serum
choline increased substantially during lecithin.
Physiological assessment showed no evidence of adverse
effects.
5008PG1439C2P1L5
5008PG1439C1P2L18
5009PG87P2L1
5009PG88P1L1
Risk of bias
Bias Authors' judgement Support for judgement Location in PDF
Random sequence
generation (selection
bias)
Unclear risk
"Randomly assigned" Details not
reported.
5008PG1458C2P5L
5
Allocation
concealment
(selection bias)
Unclear risk
Allocation concealment not
reported
Blinding of
participants and
personnel
(performance bias)
Low risk
"double-blind"; “Each dose of
lecithin or placebo was prepared in
a coded bottle independent of the
patient clinical staff, and raters".
"No attempt was made to
5008PG1458C1P1L
2
5008PG1459C1P1L
8
44
systematically and objectively rate
body odour, but no significant
change, and particularly no "fishy
odour," was noted by the subjects,
ward staff, or raters.
5008PG1459C2P1L
10
Blinding of outcome
assessment
(detection bias)
Low risk
"Each dose of lecithin or placebo
was prepared in a coded bottle
independent of the patient clinical
staff, and raters". "At the end of the
study the 12 videotapes for each
patient were presented in random
temporal sequence and rated blind
and independently by 2
psychiatrists using the AIMS...two
raters' total AIMS scores, rated
blind and independently from
videotapes.” Mental state: The Brief
Psychiatric Rating Scale (BPRS)
was administered independently by
2 psychiatrists...” Although blinding
of the raters is not mentioned, for
these outcomes, it is assumed that
they, as all other staff were blinded.
5008PG1458C1P1L
2
5008PG1459C1P1L
8
5008PG1459C1P2L
8
5008PG1459P2L14
Incomplete outcome
data (attrition bias)
Unclear risk
Figure 1 reports data from all 6
subjects. ITT is not mentioned. One
subject was withdrawn from the
study; reason reported.
5008PG1459F1
5008PG1459C2P1L
5
Selective reporting
(reporting bias)
High risk
BPRS and MIBS data not reported.
Other bias
Unclear risk
Insufficient information to make a
judgement. 1/6 subjects was
neuroleptic free throughout the
study
5008PG1458C2P4L
2
45
Jahanian 2014
Reference
[Ref. ID 19855] Jahanian AA, Rezaei O, Fadai F, Yaraghchi A. The Effectiveness of Rivastigminein
Reducing Tardive Dyskinesia Symptoms in Patients with Schizophrenia. Iranian Journal of Psychiatry
and Clinical Psychology 2014; 20(1): 29-34.
Characteristics
Location in PDF
Methods Allocation: "randomly assigned" no details reported. 19855PG30C1P3L7
Blindness: "double blind" no details reported. 19855PG30C1P3L3
Design: not reported.
Duration: "eight weeks". 19855PG31C1P2L4