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Study flow diagram ‐ update 2016.
Figures and Tables -
Figure 1

Study flow diagram ‐ update 2016.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figures and Tables -
Analysis 1.1

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.
Figures and Tables -
Analysis 1.2

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.
Figures and Tables -
Analysis 1.3

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.
Figures and Tables -
Analysis 1.4

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).
Figures and Tables -
Analysis 1.5

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.
Figures and Tables -
Analysis 1.6

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).
Figures and Tables -
Analysis 2.1

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.
Figures and Tables -
Analysis 2.2

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).
Figures and Tables -
Analysis 2.3

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).
Figures and Tables -
Analysis 2.4

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).
Figures and Tables -
Analysis 2.5

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.
Figures and Tables -
Analysis 2.6

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).
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Analysis 2.7

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).
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Analysis 2.8

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).
Figures and Tables -
Analysis 2.9

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).
Figures and Tables -
Analysis 2.10

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).
Figures and Tables -
Analysis 2.11

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.
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Analysis 2.12

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.
Figures and Tables -
Analysis 2.13

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.
Figures and Tables -
Analysis 2.14

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Study

Zuclopenthixol

Chlorpromazine

Kingstone 1970

n = 5, authors do not state which additional medication.

n = 2, authors do not state which additional medication.

Kordas 1968

Benzhexol and diazepam if necessary.

Benzhexol and diazepam if necessary.

Wang 1995a

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.

Figures and Tables -
Analysis 2.15

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use.

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).
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Analysis 3.1

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).
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Analysis 3.2

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figures and Tables -
Analysis 4.1

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Study

Zuclopenthixol (n = 36)

Clozapine (n = 38)

Fischer‐Cornelssen 1976

Drowsiness (12%); Stimulation (14%); Confusion (1%); GI (1%); anticholinergic (14%); dizziness (6%); Orthostatic reaction (1%); Headache (2%); Hypersalivation (2%); hypokinesia (4%); hyperkinesia (2%); dyskinesia (0.4%); rigor (5%); tremor (5%); akathisia (3%)

Drowsiness (12%); Stimulation (21%); Confusion (3%); GI (8%); anticholinergic (8%); dizziness (15%); Orthostatic reaction (6%); Headache (3%); Hypersalivation (4%); hypokinesia (2%); hyperkinesia (4%); dyskinesia (0%); rigor (1%); tremor (3%); akathisia (3%)

Figures and Tables -
Analysis 4.2

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).
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Analysis 5.1

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).
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Analysis 5.2

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).
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Analysis 5.3

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.
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Analysis 5.4

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.
Figures and Tables -
Analysis 5.5

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.
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Analysis 5.6

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.
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Analysis 5.7

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.
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Analysis 6.1

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.
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Analysis 6.2

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.
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Analysis 6.3

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.
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Analysis 6.4

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.
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Analysis 7.1

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.
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Analysis 7.2

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.
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Analysis 7.3

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.
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Analysis 7.4

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.
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Analysis 7.5

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.

Study

Zuclopenthixol

Risperidone

Fagerlund 2004

Benzodiazepines n = 7

Anticholinergics n = 11

Benzodiazepines n = 8

Anticholinergics n = 7

Glenthoj 2007

Anticholinergic n = 10, Benzodiazepines n = 11, Antidepressant n = 1

Authors do not differentiate the use of additional medication between the two groups, totals only given.

Figures and Tables -
Analysis 7.6

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.
Figures and Tables -
Analysis 7.7

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.
Figures and Tables -
Analysis 7.8

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.
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Analysis 7.9

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).
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Analysis 8.1

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).
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Analysis 8.2

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).
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Analysis 8.3

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).
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Analysis 8.4

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).

Study

Zuclopenthixol

Sulpiride

Mahadevan 1991

n = 4 Amitriptyline

n = 4 Amitryptyline

Figures and Tables -
Analysis 8.5

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.
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Analysis 8.6

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.
Figures and Tables -
Analysis 8.7

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).
Figures and Tables -
Analysis 9.1

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).
Figures and Tables -
Analysis 9.2

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figures and Tables -
Analysis 10.1

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).
Figures and Tables -
Analysis 11.1

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.
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Analysis 11.2

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.

Study

Zuclopenthixol

Depot

Arango 2006

n = 1 Propanolol

n = 1 venlafaxine

n = 1 Lithium

Figures and Tables -
Analysis 11.3

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use.

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.
Figures and Tables -
Analysis 11.4

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.
Figures and Tables -
Analysis 12.1

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.
Figures and Tables -
Analysis 12.2

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).
Figures and Tables -
Analysis 12.3

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.
Figures and Tables -
Analysis 12.4

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.

Study

Cis Z

Cis(Z)/Trans(E)

Gravem 1981

EPSEs most frequent.

Authors state no significant difference between two isomers.

EPSEs most frequent.

Heikkila 1981

Dry mouth, Disturbance of accommodation, Disturbance of urination, Constipation, Dizziness, Headache, Increased sweating, Drowsiness, Anxiety, Parkinsonism, Akathisia, Tardive dyskinesia and others

Dry mouth, Disturbance of urination, Constipation, Dizziness, Drowsiness, Parkinsonism, Akathisia, Tardive dyskinesia, others

Figures and Tables -
Analysis 12.5

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects.

Summary of findings for the main comparison. Zuclopenthixol dihydrochloride versus placebo

Patient or population: people with schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: PLACEBO (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with PLACEBO (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (extrapyramidal effects ‐ UKU side effect rating scale)

80 per 1000

486 per 1000
(69 to 1000)

RR 6.07
(0.86 to 43.04)

28
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2, 3,4, 5, 6

Risk assumed to be moderate and rounded from 7.69% to 8%.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: Duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

40 per 1000

12 per 1000
(0 to 264)

RR 0.29
(0.01 to 6.60)

100
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1, 6

Risk assumed to be moderate and rounded from 3.85% to 4%. Low number of events in both RCTs.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated 'very serious' ‐ possible selection bias, blinding may have been single, attrition bias and reporting bias.

2 Risk of bias: rated 'very serious' ‐ selection, attrition and reporting bias

3 Risk of inconsistency: rated 'not serious' ‐ suspected but not found.

4 Risk of publication bias: rated 'strongly suspected' ‐ multiple papers published with the same patient cohort.

5 Risk of large effect: rated 'very large' ‐ RR 6.07, small n number but result likely when versus placebo.

6 Risk of imprecision: rated 'very serious' ‐ low n numbers

Figures and Tables -
Summary of findings for the main comparison. Zuclopenthixol dihydrochloride versus placebo
Summary of findings 2. Zuclopenthixol dihydrochloride versus chlorpromazine

Patient or population: schizophrenia
Setting: Outpatient and inpatient (predominantly hospitalised)
Intervention: ZUCLOPENTHIXOL
Comparison: CHLORPROMAZINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CHLORPROMAZINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI‐SI, high score not reported, average score = 2.2)

The mean CGI‐SI endpoint score in the intervention group (MD) was 0 (‐0.49 lower to 0.49 higher)

64
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 5

Translated study.

Adverse effects: Clinically important general adverse effect (EPSEs)

300 per 1000

282 per 1000
(183 to 435)

RR 0.94
(0.61 to 1.45)

199
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 2 4 5 6

Risk control rounded to 30% and set to moderate. Mixture of inpatient and outpatient, though predominantly hospitalised patients.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (BPRS, high score = 34.2)

The mean mental state: average endpoint score (BPRS, high score = 34.2) in the intervention group was 0.4 more (2.43 fewer to 3.23 more)

221
(3 RCTs)

⊕⊕⊝⊝
LOW 2 6

Mixture of inpatient and outpatient, though predominantly hospitalised patients.

Leaving the study early (any reason)

70 per 1000

38 per 1000
(25 to 57)

RR 0.54
(0.36 to 0.81)

766
(6 RCTs)

⊕⊕⊝⊝
LOW 3 6

Mixture of inpatient and outpatient, though predominantly hospitalised patients. Risk control set to moderate and rounded to 7%; extreme values not likely.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated 'serious' ‐ Selection and attrition bias likely.

2 Risk of bias: rated 'serious' ‐ Selection attrition bias.

3 Risk of bias: rated 'serious' ‐ Selection, attrition and reporting bias.

4 Risk of bias: rated 'serious' ‐ Selection, attrition and reporting bias. Risk of inconsistency: rated as 'serious' ‐ All three papers reported on differing population sizes and obtained different levels of EPSEs in the experimental and control groups.

5 Risk of imprecision: rated 'very serious' ‐ low n numbers

6 Risk of indirectness: rated 'very serious' ‐ mixed samples

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 2. Zuclopenthixol dihydrochloride versus chlorpromazine
Summary of findings 3. Zuclopenthixol dihydrochloride versus chlorprothixene

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: CHLORPROTHIXENE (medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CHLORPROTHIXENE (medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

400 per 1000

400 per 1000
(136 to 1000)

RR 1.00
(0.34 to 2.93)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, reporting bias likely.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same cohort of patients.

3 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 3. Zuclopenthixol dihydrochloride versus chlorprothixene
Summary of findings 4. Zuclopenthixol dihydrochloride versus clozapine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: CLOZAPINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CLOZAPINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

0 per 1000

0 per 1000
(0 to 0)

not estimable

407
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

Multi‐centre, multi‐drug trial with disproportionate numbers of people in different arms of the study. The authors did not report that anybody left the study in the Zuclopenthixol and clozapine arms.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, attrition, reporting and performance bias likely.

2 Risk of indirectness: rated 'serious' ‐ Multiple study arms

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 4. Zuclopenthixol dihydrochloride versus clozapine
Summary of findings 5. Zuclopenthixol dihydrochloride versus haloperidol

Patient or population: schizophrenia
Setting: Hospital only.
Intervention: ZUCLOPENTHIXOL
Comparison: HALOPERIDOL (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with HALOPERIDOL (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI, mean score = 1.25)

The mean CGI endpoint score in the intervention group (MD) was 0.13 more (‐0.3 fewer to 0.55 more)

49
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 3 4

Small study, multiple scales used (NOSIE30, BPRS, CGI). Paper only reported outcomes of some of these scales.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

300 per 1000

297 per 1000
(216 to 405)

RR 0.99
(0.72 to 1.35)

141
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 3 4

Risk control rounded to 30% from 29.25% and, as extreme values unlikely, it was set to moderate.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ likely selection, attrition, reporting and diagnostic purity bias.

2 Risk of bias: rated as 'serious' ‐ likely selection, attrition, reporting and diagnostic purity bias. Risk of inconsistency: rated as 'serious' ‐ both papers generated differing values for people leaving the study and do not appear consistent (face validity).

3 Risk of imprecision: rated 'serious' ‐ low n numbers

4 Risk of indirectness: rated 'serious' ‐ not all scales reported

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 5. Zuclopenthixol dihydrochloride versus haloperidol
Summary of findings 6. Zuclopenthixol dihydrochloride versus perphenazine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: PERPHENAZINE (short and medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with PERPHENAZINE (short and medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (EPSEs requiring medication ‐ medium term)

400 per 1000

760 per 1000
(448 to 1000)

RR 1.90
(1.12 to 3.22)

50
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason, short and medium term)

207 per 1000

130 per 1000
(56 to 304)

RR 0.63
(0.27 to 1.47)

104
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ likely selection and reporting bias.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 6. Zuclopenthixol dihydrochloride versus perphenazine
Summary of findings 7. Zuclopenthixol dihydrochloride versus risperidone

Patient or population: schizophrenia
Setting: Mostly hospital. Huttunen group did not state
Intervention: ZUCLOPENTHIXOL
Comparison: RISPERIDONE (short and medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with RISPERIDONE (short and medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect ‐ short term (EPSEs requiring medication)

271 per 1000

520 per 1000
(303 to 888)

RR 1.92
(1.12 to 3.28)

98
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2 5 6

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (PANSS, average score = 20.5) ‐ medium term

The mean PANNS endpoint score in the intervention group (MD) was 3.2 fewer (‐7.71 fewer to 1.31 more)

25
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Small study. Standard deviations may be standard errors. Open label trial.

Leaving the study early (any reason, short and medium term)

310 per 1000

403 per 1000
(260 to 626)

RR 1.30
(0.84 to 2.02)

154
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 3 4

Risk control taken as mean of extremes: high + low / 2 (changed from 21.43% to 31%)

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ open label trial, likely selection bias.

2 Risk of imprecision: rated as 'very serious' ‐ strongly suspect reported standard deviations are standard errors, low n numbers

3 Risk of publication bias: rated as 'strongly suspected' ‐ all studies published findings across several consecutive years in different journals and at conferences.

4 Risk of bias: rated as 'very serious' ‐ study 1 (selection, reporting, diagnostic purity and attrition bias likely ‐ author emailed); study 2 (open label); study 3 (reporting and attrition bias).

5 Risk of publication bias: rated as 'strongly suspected' ‐ multiple papers over consecutive years published with the same data.

6 Risk of bias: rated as 'serious' ‐ diagnostic purity and attrition bias; likely selection and reporting bias (authors contacted)

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 7. Zuclopenthixol dihydrochloride versus risperidone
Summary of findings 8. Zuclopenthixol dihydrochloride versus sulpiride

Patient or population: schizophrenia
Setting: Not specified in study.
Intervention: ZUCLOPENTHIXOL
Comparison: SULPIRIDE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with SULPIRIDE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI ‐ unchanged/worse)

226 per 1000

266 per 1000
(111 to 644)

RR 1.18
(0.49 to 2.85)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

The study did not report clinical improvement so unchanged/worse is reported for this outcome. Usually we report clinical improvement.

Adverse effects: Clinically important general adverse effect ‐ requiring hypnotics/sedatives

419 per 1000

252 per 1000
(113 to 554)

RR 0.60
(0.27 to 1.32)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (BPRS)

The mean BPRS endpoint score in the intervention group (MD) was 1.3 fewer (‐5.08 fewer to 2.48 more)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Leaving the study early (any reason)

230 per 1000

476 per 1000
(223 to 1000)

RR 2.07
(0.97 to 4.40)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Control of risk rounded up from 22.58% to 23%.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ diagnostic purity, attrition bias. Per‐Protocol analysis suspected.

2 Risk of imprecision: rated as ' very serious' ‐ percentages used to describe data and comparisons are made against an assumption of baseline measurements. Low n numbers.

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 8. Zuclopenthixol dihydrochloride versus sulpiride
Summary of findings 9. Zuclopenthixol dihydrochloride versus thiothixene

Patient or population: schizophrenia
Setting: hospital
Intervention: ZUCLOPENTHIXOL
Comparison: THIOTHIXENE (medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with THIOTHIXENE (medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (unchanged/worse ‐ CGI)

600 per 1000

300 per 1000
(102 to 876)

RR 0.50
(0.17 to 1.46)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

The study did not report clinical improvement so unchanged/worse is reported for this outcome. Usually we report clinical improvement.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Leaving the study early (any reason)

700 per 1000

399 per 1000
(168 to 945)

RR 0.57
(0.24 to 1.35)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ likely selection and reporting bias.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same cohort.

3 Risk of imprecision: rated as 'serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 9. Zuclopenthixol dihydrochloride versus thiothixene
Summary of findings 10. Zuclopenthixol dihydrochloride versus trifluoperazine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: TRIFLUOPERAZINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with TRIFLUOPERAZINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

0 per 1000

0 per 1000
(0 to 0)

not estimable

72
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Multi‐centre and multi‐drug trial with low numbers in each arm.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, attrition, reporting and performance bias likely.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

3 Risk of indirectness: rated 'very serious' ‐ multiple arms, some missing

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 10. Zuclopenthixol dihydrochloride versus trifluoperazine
Summary of findings 11. Zuclopenthixol dihydrochloride versus zuclopenthixol depot

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: ZUCLOPENTHIXOL DEPOT (long term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with ZUCLOPENTHIXOL DEPOT (long term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

80 per 1000

156 per 1000
(29 to 846)

RR 1.95
(0.36 to 10.58)

46
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Control of risk rounded from 7.69% to 8%.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ single researcher did randomisation, selection bias likely, open label trial and incomplete outcome data.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same data and cohort.

3 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 11. Zuclopenthixol dihydrochloride versus zuclopenthixol depot
Summary of findings 12. Zuclopenthixol dihydrochloride (Cis Z isomer) versus Zuclopenthixol (Cis Z/Trans E isomer)

Patient or population: schizophrenia
Setting: Mostly inpatient. 4 Studies included of which two did not state but implied inpatient.
Intervention: CIS‐(Z) ZUCLOPENTHIXOL
Comparison: CIS(Z)/TRANS(E) ZUCLOPENTHIXOL (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CIS(Z)/TRANS(E) ZUCLOPENTHIXOL (short term)

Risk with CIS‐(Z) ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect

470 per 1000

630 per 1000
(385 to 1000)

RR 1.34
(0.82 to 2.18)

57
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Control of risk set at moderate and rounded up from 46.4% to 47%.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early: Any reason

28 per 1000

61 per 1000
(14 to 265)

RR 2.15
(0.49 to 9.41)

140
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection bias throughout. Very difficult to ascertain from published materials if selection bias has been minimised.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figures and Tables -
Summary of findings 12. Zuclopenthixol dihydrochloride (Cis Z isomer) versus Zuclopenthixol (Cis Z/Trans E isomer)
Comparison 1. ZUCLOPENTHIXOL versus PLACEBO ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

2

100

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 excitation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.62 [0.12, 59.40]

3.2 sleepiness / sedation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.89 [1.01, 8.30]

4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started Show forest plot

1

36

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 126.48]

5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores) Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

6.07 [0.86, 43.04]

6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 parkinsonism

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

6.2 oculogyric crisis

1

36

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.09]

6.3 tremor

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

Figures and Tables -
Comparison 1. ZUCLOPENTHIXOL versus PLACEBO ‐ all short term
Comparison 2. ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported) Show forest plot

2

135

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.75, 1.13]

2 Global state: 2. Average endpoint global state score ‐ No Recovery Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.89, 1.16]

3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐8.12, 6.92]

4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.49, 0.49]

5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported) Show forest plot

1

120

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.81, 1.18]

6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.25, 2.42]

7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2) Show forest plot

3

221

Mean Difference (IV, Random, 95% CI)

0.40 [‐2.43, 3.23]

8 Leaving the study early (any reason) Show forest plot

6

766

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.36, 0.81]

9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported) Show forest plot

1

94

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.77, 0.97]

10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

4.48 [‐2.38, 11.34]

11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope) Show forest plot

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.73]

12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

12.1 excitation

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.07, 5.47]

12.2 sedation

2

163

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.73, 1.70]

13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds Show forest plot

1

29

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.22, 1.75]

14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

3

199

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.61, 1.45]

15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 2. ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term
Comparison 3. ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.34, 2.93]

Figures and Tables -
Comparison 3. ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term
Comparison 4. ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

407

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 4. ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term
Comparison 5. ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25) Show forest plot

1

49

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.30, 0.55]

3 Leaving the study early (any reason) Show forest plot

2

141

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.72, 1.35]

4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figures and Tables -
Comparison 5. ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term
Comparison 6. ZUCLOPENTHIXOL versus PERPHENAZINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) ‐ short/medium term Show forest plot

2

104

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.27, 1.47]

3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figures and Tables -
Comparison 6. ZUCLOPENTHIXOL versus PERPHENAZINE
Comparison 7. ZUCLOPENTHIXOL versus RISPERIDONE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐3.20 [‐7.71, 1.31]

2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Short term

1

19

Mean Difference (IV, Random, 95% CI)

‐2.40 [‐4.52, ‐0.28]

2.2 Medium term

1

25

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐2.72, 2.12]

3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐2.69, 0.69]

4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.5 [‐4.05, 1.05]

5 Leaving the study early (any reason) ‐ short/medium term Show forest plot

3

154

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.84, 2.02]

6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term Show forest plot

Other data

No numeric data

7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term Show forest plot

1

19

Mean Difference (IV, Random, 95% CI)

4.5 [0.67, 8.33]

9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 UKU ‐ asthenia/lassitude/increased fatiguability

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.67, 1.01]

Figures and Tables -
Comparison 7. ZUCLOPENTHIXOL versus RISPERIDONE
Comparison 8. ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.75, 1.30]

3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7) Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.30 [‐5.08, 2.48]

4 Leaving the study early (any reason) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

2.07 [0.97, 4.40]

5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.60 [‐8.35, 5.15]

7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figures and Tables -
Comparison 8. ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term
Comparison 9. ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.24, 1.35]

Figures and Tables -
Comparison 9. ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term
Comparison 10. ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

72

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 10. ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term
Comparison 11. ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.95 [0.36, 10.58]

2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.44, 1.71]

3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.3 [0.59, 2.86]

Figures and Tables -
Comparison 11. ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term
Comparison 12. CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unwell Show forest plot

3

131

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.80, 1.17]

2 Mental state: Average endpoint general mental state score ‐ Not improved Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.45, 2.07]

3 Leaving the study early (any reason) Show forest plot

4

140

Risk Ratio (M‐H, Random, 95% CI)

2.15 [0.49, 9.41]

4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.82, 2.18]

5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 12. CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term