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Meta-Analysis
. 2010 Jan 20;2010(1):CD006624.
doi: 10.1002/14651858.CD006624.pub2.

Amisulpride versus other atypical antipsychotics for schizophrenia

Katja Komossa  1 , Christine Rummel-Kluge, Heike Hunger, Franziska Schmid, Sandra Schwarz, Joaquim I Silveira da Mota Neto, Werner Kissling, Stefan Leucht
Affiliations
Meta-Analysis

Amisulpride versus other atypical antipsychotics for schizophrenia

Katja Komossa et al. Cochrane Database Syst Rev. .

Abstract

Background: In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics.

Objectives: To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.

Search strategy: We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.

Selection criteria: We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.

Data collection and analysis: We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.

Main results: The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).

Authors' conclusions: There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

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Conflict of interest statement

Katja Komossa: none. Stefan Leucht: received speaker/consultancy honoria from Sanofi‐Aventis, BMS, Eli Lilly, Janssen, Lundbeck and Pfizer. He received research support from Sanofi‐Aventis and Eli Lilly. Werner Kissling: received speaker or consultancy honoraria from SanofiAventis, BMS, Lilly, Janssen, Lundbeck, Bayer and Pfizer. Christine Rummel: received lecture honoraria and travel grants to attend scientific meetings from AstraZeneca, Janssen‐Cilag, Eli Lilly and Pfizer. Heike Hunger: none. Franziska Schmid: none. Sandra Schwarz: none. Joaquim Silveira da Mota Neto: none.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 1 Global state: 1a. No clinically significant response (as defined by original studies).
1.2
1.2. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 2 Global State: 1b. No clinically important change (as defined by original studies).
1.3
1.3. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 3 Global State: 1c. Relapse ‐ medium term (as defined by the original studies).
1.4
1.4. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 4 Leaving the study early.
1.5
1.5. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 5 Mental state: 1a. General ‐ no clinically important change ‐ short term (less than 50% PANSS total score reduction).
1.6
1.6. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 6 Mental state: 1b. General ‐ average score at endpoint (PANSS total, high=poor).
1.7
1.7. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 7 Mental state: 1c. General ‐ no clinically important change ‐ medium term (less than 50% BPRS total score reduction).
1.8
1.8. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 8 Mental state: 1d. General ‐ average score at endpoint (BPRS total, high=poor).
1.9
1.9. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 9 Mental state: 2a. Positive symptoms ‐ no clinically important change ‐ short term (less than 50% PANSS positive subscore reduction).
1.10
1.10. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 10 Mental state: 2b. Positive symptoms ‐ average score at endpoint (PANSS positive subscore, high=poor).
1.11
1.11. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 11 Mental state: 3a. Negative symptoms ‐ no clinically important change ‐ medium term (less than 20% SANS total plus 10% PANSS total reduction).
1.12
1.12. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 12 Mental state: 3b. Negative symptoms ‐ average score at endpoint (PANSS negative subscore, high=poor).
1.13
1.13. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 13 Mental state: 3c. Negative symptoms ‐ average score at endpoint (SANS total score, high=poor).
1.14
1.14. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 14 General functioning: General ‐ average score at endpoint ‐ medium term (SOFAS total ‐ percent change,high=poor).
1.15
1.15. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 15 Quality of life: General ‐ average score at endpoint ‐ medium term (QLS total score, high=poor).
1.16
1.16. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 16 Cognitive functioning: 1a. No clinically important change ‐ short term (less than 50% Global Cognitive Index reduction).
1.17
1.17. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 17 Cognitive functioning: 1b. General ‐ average score at endpoint ‐ short term (Global Cognitive Index, high=poor).
1.18
1.18. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 18 Adverse effects: 1. General ‐ at least one adverse effect.
1.19
1.19. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 19 Adverse effects: 2. Death.
1.20
1.20. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 20 Adverse effects: 3a. Cardiac effects ‐ QTc prolongation.
1.21
1.21. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 21 Adverse effects: 3b. Cardiac effects ‐ QTc abnormalities ‐ change from baseline in ms.
1.22
1.22. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 22 Adverse effects: 4a. Central nervous system ‐ sedation.
1.23
1.23. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 23 Adverse effects: 4b. Central nervous system ‐ seizures.
1.24
1.24. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 24 Adverse effects: 5a. Extrapyramidal effects.
1.25
1.25. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 25 Adverse effects: 5b. Extrapyramidal effects ‐ scale measured.
1.26
1.26. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 26 Adverse effects: 6. Haematological ‐ white blood cell count ‐ leukopenia.
1.27
1.27. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 27 Adverse effects: 7. Prolactin associated side effects.
1.28
1.28. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 28 Adverse effects: 8a. Metabolic ‐ cholesterol ‐ change from baseline in mg/dl.
1.29
1.29. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 29 Adverse effects: 8b. Metabolic ‐ glucose ‐ diabetes mellitus.
1.30
1.30. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 30 Adverse effects: 8c. Metabolic ‐ glucose ‐ change from baseline in mg/dl.
1.31
1.31. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 31 Adverse effects: 8d. Metabolic ‐ weight ‐ gain.
1.32
1.32. Analysis
Comparison 1 AMISULPRIDE versus OLANZAPINE, Outcome 32 Adverse effects: 8e. Metabolic ‐ weight ‐ change from baseline in kg.
2.1
2.1. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 1 Global state: 1a. No clinically significant response (as def. by the original studies).
2.2
2.2. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 2 Global State: 1b. No clinically important change (as defined by the original studies).
2.3
2.3. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 3 Global State: 1c. Relapse ‐ medium term (as defined by the original studies).
2.4
2.4. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 4 Leaving the study early.
2.5
2.5. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 5 Mental state: 1a. General ‐ no clinically important change ‐medium term (less than 50% PANSS total score reduction).
2.6
2.6. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 6 Mental state: 1b. General ‐ no clinically important change ‐ short term (less than 20% PANSS total score reduction).
2.7
2.7. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 7 Mental state: 1c. General ‐ average score at endpoint (PANSS total, high=poor).
2.8
2.8. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 8 Mental state: 1d. General ‐ no clinically important change ‐ medium term (less than 50% BPRS total score reduction).
2.9
2.9. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 9 Mental state: 1e. General ‐ no clinically important change ‐ short term (less than 40% BPRS total score reduction).
2.10
2.10. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 10 Mental state: 1f. General ‐ average score at endpoint (BPRS total, high=poor).
2.11
2.11. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 11 Mental state: 2a. Positive symptoms ‐ average score at endpoint (PANSS positive subscore, high=poor).
2.12
2.12. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 12 Mental state: 2b. Positive symptoms ‐ average score at endpoint ‐ short term (BPRS positive subscore, high=poor).
2.13
2.13. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 13 Mental state: 3a. Negative symptoms ‐ average score at endpoint (PANSS negative subscore, high=poor).
2.14
2.14. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 14 Mental state: 3b. Negative symptoms ‐ average score at endpoint ‐ medium term (SANS total score, high=poor).
2.15
2.15. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 15 General functioning: 1a. No clinically important change ‐ medium term (less than 50% SOFAS total score reduction).
2.16
2.16. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 16 General functioning: 1b. General ‐ average score at endpoint (SOFAS total score, high=poor).
2.17
2.17. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 17 Adverse effects: 1. General ‐ at least one adverse effect.
2.18
2.18. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 18 Adverse effects: 2. Death.
2.19
2.19. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 19 Adverse effects: 3. Cardiac effects ‐ QTc prolongation.
2.20
2.20. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 20 Adverse effects: 4a. Central nervous system ‐ sedation.
2.21
2.21. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 21 Adverse effects: 4b. Central nervous system ‐ seizures.
2.22
2.22. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 22 Adverse effects: 5a. Extrapyramidal effects.
2.23
2.23. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 23 Adverse effects: 5b. Extrapyramidal effects ‐ scale measured.
2.24
2.24. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 24 Adverse effects: 6. Prolactin associated side effects.
2.25
2.25. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 25 Adverse effects: 7a. Metabolic ‐ weight ‐ gain.
2.26
2.26. Analysis
Comparison 2 AMISULPRIDE versus RISPERIDONE, Outcome 26 Adverse effects: 7b. Metabolic ‐ weight ‐ change from baseline in kg.
3.1
3.1. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 1 Global state: 1a. No clinically significant response (as defined by the original studies).
3.2
3.2. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 2 Global State: 1b. No clinically important change (as defined by the original studies).
3.3
3.3. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 3 Leaving the study early.
3.4
3.4. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 4 Mental state: 1a. General ‐ average score at endpoint (PANSS total, high=poor).
3.5
3.5. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 5 Mental state: 1b. General ‐ average score at endpoint (BPRS total, high=poor).
3.6
3.6. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 6 Mental state: 2a. Negative symptoms ‐ no clinically important change (less than 50% PANSS negative subscore reduction).
3.7
3.7. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 7 Mental state: 2b. Negative symptoms ‐ average score at endpoint (PANSS negative subscore, high=poor).
3.8
3.8. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 8 Adverse effects: 1. General ‐ at least one adverse effect.
3.9
3.9. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 9 Adverse effects: 2. Cardiac effects ‐ QTc prolongation.
3.10
3.10. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 10 Adverse effects: 3. Central nervous system ‐ sedation.
3.11
3.11. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 11 Adverse effects: 4. Extrapyramidal effects.
3.12
3.12. Analysis
Comparison 3 AMISULPRIDE versus ZIPRASIDONE ‐ all data short term, Outcome 12 Adverse effects: 5. Metabolic ‐ weight ‐ gain of 7% or more of total body weight.
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References

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