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. 2003;2003(4):CD004410.
doi: 10.1002/14651858.CD004410.

New generation antipsychotics for first episode schizophrenia

C Rummel  1 , J Hamann, W Kissling, S Leucht
Affiliations

New generation antipsychotics for first episode schizophrenia

C Rummel et al. Cochrane Database Syst Rev. 2003.

Abstract

Background: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia.

Objectives: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses.

Search strategy: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials.

Selection criteria: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses.

Data collection and analysis: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD).

Main results: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information.

Reviewer's conclusions: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question.

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Conflict of interest statement

CR received lecture honoraria and/or travel grants to attend scientific meetings from Janssen‐Cilag, Eli Lilly and Pfizer. SL and WK received lecture honoraria and/or travel grants to attend scientific meetings from Janssen‐Cilag, Eli Lilly, Lundbeck, Pfizer, Sanofi‐Synthlabo and Zeneca. They also received financial support for a randomised trial from Eli Lilly, and for a meta‐analysis on amisulpride from Sanofi‐Synthelabo. WK received lecture honoraria form Novartis and BMS. JH received financial support to attend a scientific meeting from Janssen‐ Cilag.

Figures

1.1
1.1. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 1 Leaving the study early due to any reason.
1.2
1.2. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 2 Global state: 1. No clinically significant change (CGI < much improved).
1.3
1.3. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 3 Global state: 2. Need of additional medication (at least one dose of benzodiazepine).
1.4
1.4. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 4 Mental state: 1. General a. No clinically significant improvement ‐ as defined by each of the studies.
1.5
1.5. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 5 Mental state: 1. General b. Various measures of change.
1.6
1.6. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 6 Mental state: 1. General c. Average change (PANSS endpoint, low=poor).
1.7
1.7. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 7 Mental state: 1. General d. Average change (BPRS endpoint, low=poor).
1.8
1.8. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 8 Mental state: 2. Specific a. Positive symptoms ‐ average change (PANSS positive subscore endpoint, low=poor).
1.9
1.9. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 9 Mental state: 2. Specific b. Positive symptoms ‐ average change (BPRS positive subscore endpoint, low=poor).
1.10
1.10. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 10 Mental state: 2. Specific c. Negative symptoms ‐ average change (PANSS negative subscore endpoint, low=poor).
1.11
1.11. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 11 Mental state: 2. Specific d. Negative symptoms ‐ average change (BPRS negative subscore endpoint, low=poor).
1.12
1.12. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 12 Mental state: 2. Specific e. Depressive symptoms ‐ average change (MADRS endpoint, low=poor).
1.13
1.13. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 13 Adverse events: 1. General a. At least one adverse event.
1.14
1.14. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 14 Adverse events: 2. Extrapyramdial problems a. General i. Needing anticholinergic medication at least once.
1.15
1.15. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 15 Adverse events: 2. Extrapyramdial problems a. General ii. Not improved (SAS total >3).
1.16
1.16. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 16 Adverse events: 2. Extrapyramdial problems a. General iii. Average change (SAS, low=poor).
1.17
1.17. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 17 Adverse events: 2. Extrapyramdial problems b. Specific i. Akathisia.
1.18
1.18. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 18 Adverse events: 2. Extrapyramdial problems b. Specific ii. Akathisia ‐ average change (BAS, low=poor).
1.19
1.19. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 19 Adverse Events: 2. Extrapyramdial problems b. Specific iii. Others.
1.20
1.20. Analysis
Comparison 1 NEW GENERATION ANTIPSYCHOTICS versus CONVENTIONAL ANTIPSYCHOTICS (HALOPERIDOL), Outcome 20 Adverse events: 3. Others.
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Edwards 1999 {published data only}
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