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Simultaneous Comparison of Efficacy and Tolerability of Second-Generation Antipsychotics in Schizophrenia: Mixed-Treatment Comparison Analysis Based on Head-to-Head Trial Data.

Oh GH, Yu JC, Choi KS, Joo EJ, Jeong SH - Psychiatry Investig (2014)

Bottom Line: Second-generation antipsychotics have been repeatedly shown to be superior to placebo.Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability.Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Eulji University School of Medicine, Eulji University Hospital, Daejeon, Republic of Korea.

ABSTRACT

Objective: Second-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics.

Methods: Seven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons.

Results: All the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain.

Conclusion: Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

No MeSH data available.


Related in: MedlinePlus

The inconsistency between the results obtained from direct comparison data and those from indirect comparison data. The lines depict the distribution of the obtained log odds ratios from the two types of data. This illustrative example compared the "percentage of no clinically important result" between quetiapine and clozapine. In direct comparison, quetiapine seemed to have superior efficacy, but in indirect comparison, clozapine was found to be superior. However, the narrowness of the graph indicates that the indirect data is more reliable.
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Figure 1: The inconsistency between the results obtained from direct comparison data and those from indirect comparison data. The lines depict the distribution of the obtained log odds ratios from the two types of data. This illustrative example compared the "percentage of no clinically important result" between quetiapine and clozapine. In direct comparison, quetiapine seemed to have superior efficacy, but in indirect comparison, clozapine was found to be superior. However, the narrowness of the graph indicates that the indirect data is more reliable.

Mentions: In order to illustrate the possible inconsistency between direct and indirect comparisons, the consistency checking procedure was performed on the measured variable "no clinically important response". Although there were no significant differences between the logit values obtained from direct comparison and those obtained from indirect comparison (all of the 95% CIs with difference in the logit values between the two types of comparisons contained zero), several comparisons changed their signs. For example, clozapine was found to be inferior (logit value=0.51) to quetiapine in direct comparison, but superior in indirect comparison (logit value=-0.43). Careful inspection of this inconsistency revealed that the distribution of the sampled log odds ratio for direct comparison was so broad that it lacked sufficient accuracy (Figure 1). Overall, no obvious inconsistency was found between direct and indirect comparison results.


Simultaneous Comparison of Efficacy and Tolerability of Second-Generation Antipsychotics in Schizophrenia: Mixed-Treatment Comparison Analysis Based on Head-to-Head Trial Data.

Oh GH, Yu JC, Choi KS, Joo EJ, Jeong SH - Psychiatry Investig (2014)

The inconsistency between the results obtained from direct comparison data and those from indirect comparison data. The lines depict the distribution of the obtained log odds ratios from the two types of data. This illustrative example compared the "percentage of no clinically important result" between quetiapine and clozapine. In direct comparison, quetiapine seemed to have superior efficacy, but in indirect comparison, clozapine was found to be superior. However, the narrowness of the graph indicates that the indirect data is more reliable.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310920&req=5

Figure 1: The inconsistency between the results obtained from direct comparison data and those from indirect comparison data. The lines depict the distribution of the obtained log odds ratios from the two types of data. This illustrative example compared the "percentage of no clinically important result" between quetiapine and clozapine. In direct comparison, quetiapine seemed to have superior efficacy, but in indirect comparison, clozapine was found to be superior. However, the narrowness of the graph indicates that the indirect data is more reliable.
Mentions: In order to illustrate the possible inconsistency between direct and indirect comparisons, the consistency checking procedure was performed on the measured variable "no clinically important response". Although there were no significant differences between the logit values obtained from direct comparison and those obtained from indirect comparison (all of the 95% CIs with difference in the logit values between the two types of comparisons contained zero), several comparisons changed their signs. For example, clozapine was found to be inferior (logit value=0.51) to quetiapine in direct comparison, but superior in indirect comparison (logit value=-0.43). Careful inspection of this inconsistency revealed that the distribution of the sampled log odds ratio for direct comparison was so broad that it lacked sufficient accuracy (Figure 1). Overall, no obvious inconsistency was found between direct and indirect comparison results.

Bottom Line: Second-generation antipsychotics have been repeatedly shown to be superior to placebo.Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability.Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Eulji University School of Medicine, Eulji University Hospital, Daejeon, Republic of Korea.

ABSTRACT

Objective: Second-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics.

Methods: Seven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons.

Results: All the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain.

Conclusion: Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

No MeSH data available.


Related in: MedlinePlus