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Meta-Analysis
. 2007 Jul 18;2007(3):CD001944.
doi: 10.1002/14651858.CD001944.pub2.

Thioridazine for schizophrenia

M Fenton, J Rathbone, J Reilly, A Sultana
Meta-Analysis

Thioridazine for schizophrenia

M Fenton et al. Cochrane Database Syst Rev. .

Abstract

Background: Thioridazine is an antipsychotic that can still be used for schizophrenia although it is associated with the cardiac arrhythmia, torsades de pointe.

Objectives: To review the effects of thioridazine for people with schizophrenia.

Search strategy: For this 2006 update, we searched the Cochrane Schizophrenia Group's Register (June 2006).

Selection criteria: We included all randomised clinical trials comparing thioridazine with other treatments for people with schizophrenia or other psychoses.

Data collection and analysis: We reliably selected, quality rated and extracted data from relevant studies. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) on an intention-to-treat basis.

Main results: This review currently includes 42 RCTs with 3498 participants. When thioridazine was compared with placebo (total n=668, 14 RCTs) we found global state outcomes favoured thioridazine (n=105, 3 RCTs, RR 'no change or worse' by 6 months 0.33 CI 0.2 to 0.5, NNT of 2 CI 2 to 3). Thioridazine is sedating (n=324, 3 RCTs, RR 5.37 CI 3.2 to 9.1, NNH 4 CI 2 to 74). Generally, thioridazine did not cause more movement disorders than placebo.Twenty-seven studies (total n=2598) compared thioridazine with typical antipsychotics. We found no significant difference in global state (n=743, 11 RCTs, RR no short-term change or worse 0.98 CI 0.8 to 1.2) and medium-term assessments (n=142, 3 RCTs, RR 0.99, CI 0.6 to 1.6). We found no significant differences in the number of people leaving the study early 'for any reason' (short-term, n=1587, 19 RCTs, RR 1.07 CI 0.9 to 1.3). Extrapyramidal adverse events lower for those allocated to thioridazine (n=1082, 7 RCTs, RR use of antiparkinsonian drugs 0.45 CI 0.4 to 0.6). Thioridazine did seem associated with cardiac adverse effects (n=74, 1 RCT, RR 'any cardiovascular adverse event' 3.17 CI 1.4 to 7.0, NNH 3 CI 2 to 5). Electrocardiogram changes were significantly more frequent in the thioridazine group (n=254, 2 RCTs, RR 2.38, CI 1.6 to 3.6, NNH 4 CI 3 to 10). Six RCTs (total n=344) randomised thioridazine against atypical antipsychotics. Global state rating did not reveal any short-term difference between thioridazine and remoxipride and sulpiride (n=203, RR not improved or worse 1.00 CI 0.8 to 1.3). Limited data did not highlight differences in adverse event profiles.

Authors' conclusions: Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified.

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Conflict of interest statement

None.

Figures

Analysis 1.1
Analysis 1.1
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 1 Global state: 1. No change or worse (LOCF).
Analysis 1.2
Analysis 1.2
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 2 Global state: 2. Moderate or severely ill (CGI >=4, LOCF).
Analysis 1.3
Analysis 1.3
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 3 Global state: 3. Average endpoint change score by 6 months (CGI, high=poor, LOCF).
Analysis 1.4
Analysis 1.4
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 4 Global state: 4. Average endpoint change score by 4 weeks (GAS, low=poor, LOCF).
Analysis 1.5
Analysis 1.5
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 5 Mental state: 1. Relapse.
Analysis 1.6
Analysis 1.6
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 6 Mental state: 2. No improved or worse (LOCF).
Analysis 1.7
Analysis 1.7
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 7 Mental state: 3. Moderately or severely ill by 4 weeks (LOCF).
Analysis 1.9
Analysis 1.9
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 9 Mental state: 5. Depression.
Analysis 1.10
Analysis 1.10
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 10 Leaving the study early: 1a. Any reason.
Analysis 1.11
Analysis 1.11
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 11 Leaving the study early: 1b. Due to adverse events ‐ by 3 months.
Analysis 1.12
Analysis 1.12
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 12 Leaving the study early: 1c. Due to refusal of treatment.
Analysis 1.13
Analysis 1.13
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 13 Leaving the study early: 1d. Due to relapse / worsening or no improvement.
Analysis 1.14
Analysis 1.14
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 14 Adverse events: 1. Anticholinergic.
Analysis 1.15
Analysis 1.15
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 15 Adverse events: 2. Arousal.
Analysis 1.16
Analysis 1.16
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 16 Adverse events: 3. Cardiovascular.
Analysis 1.17
Analysis 1.17
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 17 Adverse events: 4. Central nervous system ‐ other.
Analysis 1.18
Analysis 1.18
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 18 Adverse events: 5. Endocrine.
Analysis 1.19
Analysis 1.19
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 19 Adverse events: 6. Movement disorders.
Analysis 1.20
Analysis 1.20
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 20 Adverse events: 7. Gastrointestinal.
Analysis 1.21
Analysis 1.21
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 21 Adverse events: 8. Genitourinary.
Analysis 1.22
Analysis 1.22
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 22 Adverse events: 9. Haematology ‐ abnormal laboratory results ‐ >3 months to 1 year.
Analysis 1.23
Analysis 1.23
Comparison 1 THIORIDAZINE versus PLACEBO, Outcome 23 Adverse events: 10. Other.
Analysis 2.1
Analysis 2.1
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 1 Death.
Analysis 2.2
Analysis 2.2
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 2 Global state: 1. No change or worse (LOCF).
Analysis 2.3
Analysis 2.3
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 3 Global state: 2. Moderately or severely ill (CGI >=4 (LOCF).
Analysis 2.4
Analysis 2.4
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 4 Global state: 3. Average endpoint change score by 6 months (CGI, high=poor, LOCF).
Analysis 2.5
Analysis 2.5
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 5 Mental state: 4. Relapse.
Analysis 2.6
Analysis 2.6
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 6 Mental state: 5. No change or worse (LOCF).
Analysis 2.7
Analysis 2.7
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 7 Mental state: 8. Average endpoint score at 6 weeks (BPRS, high=poor, LOCF).
Analysis 2.8
Analysis 2.8
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 8 Mental state: 7. Moderately or severely ill by 3 months (LOCF).
Analysis 2.10
Analysis 2.10
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 10 Mental state: 11. Depression (clinical diagnosis).
Analysis 2.11
Analysis 2.11
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 11 Behaviour: 1. Not improved or worse by 5 weeks (NOSIE, LOCF).
Analysis 2.12
Analysis 2.12
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 12 Leaving the study early: 1a. Any reason.
Analysis 2.13
Analysis 2.13
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 13 Leaving the study early: 1b. Due to absence without leave or refusing to continue.
Analysis 2.14
Analysis 2.14
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 14 Leaving the study early: 1c. Due to adverse events.
Analysis 2.15
Analysis 2.15
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 15 Leaving the study early: 1d. Due to refusal of medication/poor compliance.
Analysis 2.16
Analysis 2.16
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 16 Leaving the study early: 1e. Due to relapse, worsening or no improvement.
Analysis 2.17
Analysis 2.17
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 17 Adverse events: 1. Anticholinergic.
Analysis 2.18
Analysis 2.18
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 18 Adverse events: 2. Arousal.
Analysis 2.19
Analysis 2.19
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 19 Adverse events: 3. Cardiovascular.
Analysis 2.20
Analysis 2.20
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 20 Adverse events: 4. Central nervous system ‐ other.
Analysis 2.21
Analysis 2.21
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 21 Adverse events: 5. Endocrine.
Analysis 2.22
Analysis 2.22
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 22 Adverse events: 6. Movement disorders.
Analysis 2.23
Analysis 2.23
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 23 Adverse events: 7. Gastrointestinal.
Analysis 2.24
Analysis 2.24
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 24 Adverse events: 8. Genitourinary.
Analysis 2.25
Analysis 2.25
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 25 Adverse events: 9. Laboratory tests ‐ abnormal results.
Analysis 2.26
Analysis 2.26
Comparison 2 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC, Outcome 26 Adverse events: 10. Other.
Analysis 3.1
Analysis 3.1
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 1 Death.
Analysis 3.2
Analysis 3.2
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 2 Global state: 1. Not improved or worse (short term).
Analysis 3.3
Analysis 3.3
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 3 Global state: 2. Average endpoint change score by 6 weeks (CGI, high=poor, LOCF).
Analysis 3.4
Analysis 3.4
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 4 Mental state: 1. No important change (50% drop) by 6 weeks (BPRS, LOCF).
Analysis 3.5
Analysis 3.5
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 5 Mental state: 2. Average endpoint change score at 6 weeks (BPRS, high=poor, LOCF).
Analysis 3.9
Analysis 3.9
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 9 Mental state: 6. Use of benzodiazepines.
Analysis 3.10
Analysis 3.10
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 10 Leaving the study early: 1a. Any reason ‐ by 3 months.
Analysis 3.11
Analysis 3.11
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 11 Leaving the study early: 1b. Due to adverse events.
Analysis 3.12
Analysis 3.12
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 12 Leaving the study early: 1c. Due to refusal of medication/poor compliance.
Analysis 3.13
Analysis 3.13
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 13 Leaving the study early: 1d. Due to relapse, worsening or no improvement.
Analysis 3.14
Analysis 3.14
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 14 Adverse effects: 1. Anticholinergic.
Analysis 3.15
Analysis 3.15
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 15 Adverse events: 2. Arousal.
Analysis 3.16
Analysis 3.16
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 16 Adverse events: 3. Cardiovascular.
Analysis 3.17
Analysis 3.17
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 17 Adverse events: 4. Central nervous system ‐ other.
Analysis 3.18
Analysis 3.18
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 18 Adverse effects: 5. Movement disorders.
Analysis 3.19
Analysis 3.19
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 19 Adverse events: 6. Gastrointestinal.
Analysis 3.20
Analysis 3.20
Comparison 3 THIORIDAZINE versus ATYPICAL ANTIPSYCHOTIC, Outcome 20 Adverse effects: 7. Hepatic abnormality ‐ 12 weeks.
Analysis 4.1
Analysis 4.1
Comparison 4 THIORIDAZINE versus PLACEBO ‐ Intention to treat analysis for leaving the study, Outcome 1 Leaving the study early: 1a. Due to adverse events ‐ by 6 weeks.
Analysis 4.2
Analysis 4.2
Comparison 4 THIORIDAZINE versus PLACEBO ‐ Intention to treat analysis for leaving the study, Outcome 2 Leaving the study early: 1b. Due to refusal of treatment ‐ by 1 month.
Analysis 4.3
Analysis 4.3
Comparison 4 THIORIDAZINE versus PLACEBO ‐ Intention to treat analysis for leaving the study, Outcome 3 Leaving the study early: 1c. Due to relapse ‐ by 6 months.
Analysis 4.4
Analysis 4.4
Comparison 4 THIORIDAZINE versus PLACEBO ‐ Intention to treat analysis for leaving the study, Outcome 4 Leaving the study early: 1d. Due to worsening or no improvement ‐ by 3 months.
Analysis 5.1
Analysis 5.1
Comparison 5 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC ‐ Intention to treat analysis for leaving the study, Outcome 1 Leaving the study early: 1a. Due to any adverse event ‐ by 3 months.
Analysis 5.2
Analysis 5.2
Comparison 5 THIORIDAZINE versus TYPICAL ANTIPSYCHOTIC ‐ Intention to treat analysis for leaving the study, Outcome 2 Leaving the study early: 1b. Due to no improvement or worsening.
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References

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