Do antipsychotics differ in efficacy? This is an extremely hard question to answer as many antipsychotic drugs have not been compared head to head. Multiple metaanalysis is a methodology to synthesise data from different trials (by integrating direct and indirect comparisons) to create efficacy ladders or comparative efficacy tables.Antidepressant efficacy tables attracted significant interest ( Cipriani et al) few years ago. Stefan Leucht, Andrea Cipriani and team compared efficacy of the two prototypical first-generation (haloperidol and chlorpromazine) and 13 second-generation antipsychotic drugs used in patients with schizophrenia.
Studies that met the strict quality criteria were only included in the analysis.The primary outcome was the mean overall change in symptoms (PANSS or BPRS).Cumulative ranking probabilities expressed as a percentage of imaginary intervention that is always the best without uncertainty ( SUCRA) was used to create ranking of efficacy. Analysis included 212 studies with 43,049 participants with mean duration of illness being 12 years.68% of studies were done by pharma. 94% were double blinded.
Results: All drugs were superior to placebo (range of mean effect sizes –0·33 to –0·88). (Effect size of –0·2 is small, –0·5 medium, and –0·8 large).Clozapine was significantly more effective than all the other drugs.Amisulpride, olanzapine, and risperidone were significantly more effective than the other drugs apart from paliperidone and zotepine .
Efficacy table (effect size)
Clozapine –0·88 (–1·03 to –0·73) Amisulpride –0·66 (–0·78 to –0·53) Olanzapine –0·59 (–0·65 to –0·53) Risperidone –0·56 (–0·63 to –0·50) Paliperidone –0·50 (–0·60 to –0·39) Zotepine –0·49 (–0·66 to –0·31) Haloperidol –0·45 (–0·51 to –0·39) Quetiapine –0·44 (–0·52 to –0·35) Aripiprazole –0·43 (–0·52 to –0·34) Sertindole –0·39 (–0·52 to –0·26) Ziprasidone –0·39 (–0·49 to –0·30) Chlorpromazine –0·38 (–0·54 to –0·23) Asenapine –0·38 (–0·51 to –0·25) Lurasidone –0·33 (–0·45 to –0·21) Iloperidone –0·33 (–0·43 to –0·22)
The efficacy of all antipsychotic drugs is NOT the same .Even though the differences in efficacy between drugs were small the differences compared with placebo were of only medium size and hence the differences in efficacy between drugs are possibly substantial enough to be clinically important.
This analysis also show that clozapine is more effective in non-refractory patients as well.However this was mainly based on older comparisons of clozapine with first-generation drugs.
Old drugs such as perphenazine and sulpiride, which have had good results, are not included. Young people with schizophrenia, those with negative symptoms, refractory patients, or stable patients, were all excluded to enhance homogeneity as required by multiple-treatments meta-analysis and hence findings cannot be generalised to these groups.
Summary of the article:
Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM.Lancet. 2013 Jun 26. doi:pii: S0140-6736(13)60733-3. 10.1016/S0140-6736(13)60733-3. [Epub ahead of print]