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  • Efficacy and safety of first-generation and second- generation anti psychotic drugs for schizophrenia in adults. An overview of systematic reviews

Systematic review

Efficacy and safety of first-generation and second- generation anti psychotic drugs for schizophrenia in adults. An overview of systematic reviews

Published Updated

The Norwegian Medicines Agency asked the Norwegian Knowledge Centre for the Health Services to review the documentation for antipsychotic drugs in order to evaluate differences in efficacy and safety between the various drugs used for schizophrenia in adults.

The Norwegian Medicines Agency asked the Norwegian Knowledge Centre for the Health Services to review the documentation for antipsychotic drugs in order to evaluate differences in efficacy and safety between the various drugs used for schizophrenia in adults.


About this publication

  • Year: 2009
  • By: Norwegian Knowledge Centre for the Health Services
  • Authors Pike E, Leiknes KA, Wisløff T, Ringerike T, Klemp M.
  • ISSN (digital): 1890-1298
  • ISBN (digital): 978-82-8121-266-4

Key message

Background
The Norwegian Medicines Agency asked the Norwegian Knowledge Centre for the Health Services to review the documentation for antipsychotic drugs in order to evaluate differences in efficacy and safety between the various drugs used for schizophrenia in adults.

Methods
We searched systematically for literature in the Cochrane Library, Medline, Embase and PsychInfo. We evaluated all identified reviews according to predefined inclusion criteria and appraised the methodological quality of the included systematic reviews.

Results
We included six systematic reviews. We extracted and analyzed results on the efficacy or safety of first generation antipsychotics (typical antipsychotics) versus second generation antipsychotics (atypical antipsychotics) and among the various second generation antipsychotics. Of 99 possible comparisons, data were available on only 30. We found few differences in efficacy. However, haloperidole showed less efficacy than amisulpride and clozapine, and olanzapine led to greater improvement in functional capacity than quetiapine and ziprasidone. With respect to efficacy measured as symptom response among the second generation antipsychotics there were no differences. For adverse events, metabolic adverse events were most obvious for the second-generation antipsychotic drug olanzapine followed by clozapine and quetiapine, and extrapyramidal adverse events were most obvious for the first- generation antipsychotic drugs haloperidole and perfenazine. There were no differences in extrapyramidal symptoms among the second generation antipsychotics, except that quetiapin caused extrapyramidal symptoms in a greater proportion of patients than risperidon. There were no or few differences between the groups regarding cardiovascular, anticholinergic and hormonal adverse events as well as for discontinuation.

Conclusion
We found few differences in efficacy between first- and second- generation antipsychotic drugs, and among the second generation antipsychotics. For adverse events there were reported differences for at least one type of adverse event for the majority of the comparisons.

Summary

Background
The Norwegian Medicines Agency asked the Norwegian Knowledge Centre for the Health Services for a review of the documentation for antipsychotic drugs in order to evaluate differences in efficacy and safety between the various drugs used for schizophrenia in adults. Antipsychotic drugs consist of the first- generation (typical) and the second -generation (atypical) antipsychotics.

The incidence of schizophrenia in the adult population is 0,5-1 %. It is a chronic disease and the patient will often need lifetime treatment and care. The symptoms are serious and disabling. The treatment consists of a combination of psychosocial measures and drug treatment. This report includes results both from short term treatment and long term-treatment with first-and second -generation antipsychotic drugs.

Objective
The Norwegian Medicines Agency commissioned a review that would help answer the question of whether there were differences in efficacy and safety

1) between first- generation and second- generation antipsychotic drugs?

2) among the second-generation antipsychotic drugs?

Method
This report is an overview of systematic reviews. We searched systematically for reviews in the Cochrane Library, Medline, Embase and PsychInfo. In December 2007, and updated the search in December 2008. We evaluated all identified reviews according to predefined inclusion criteria and appraised the methodological quality of the included systematic reviews.  For systematic reviews with overlapping focus, we included the latest and the one with highest quality.

Results
We included six systematic reviews of high quality. We extracted and analyzed results that reported on the efficacy or safety of first- generation antipsychotics (typical antipsychotics) versus second- generation antipsychotics (atypical antipsychotics) and among the various second- generation antipsychotics. The evidence base was thin. Of 99 possible comparisons, data were available on only 30. Further, only a minority of the comparisons reported the same outcomes both for short- and longterm studies.

We found few differences in efficacy. When there were differences in efficacy between first- and second- generation antipsychotics, haloperidole showed less efficacy than amisulpride and clozapine. Second- generation antipsychotics compared with each other showed that olanzapine led to greater improvement in functional capacity than quetiapine and ziprasidone. However, there were no differences in efficacy among the second- generation antipsychotics when efficacy was measured as symptom response.

For adverse events there were reported differences for at least one type of those for the majority of the comparisons. When metabolic adverse events were reported, the majority of the comparisons reported differences between the groups. Metabolic adverse events were most obvious for olanzapine followed by clozapine and quetiapine.

When extrapyramidal adverse events were reported the first-generation antipsychotic drugs gave in the majority of the comparisons higher responses than the second-generation antipsychotics. Where this was not the case, there were no difference between the groups. Extrapyramidal adverse events were most obvious for haloperidol and perfenazin. There were no differences in extrapyramidal symptoms among the second- generation antipsychotics, except that quetiapin caused extrapyramidal symptoms in a greater proportion of patients compared to risperidon. When cardiovascular adverse events were reported there were no differences between the groups for the majority of the comparisons. The exceptions were that haloperidol caused less prolonged QTc interval than sertindole, and that a lower proportion of the patients in the olanzapine group had prolonged QTc-interval compared to patients in the quetiapine and risperidone groups. When anticholinergic adverse events were reported there were no differences between the first –generation- and the second- generation antipsychotic drugs. When the second- generation antipsychotics were compared among each other, there were no differences between the groups in the majority of the cases. The exceptions were that a higher proportion of the patients in the quetiapine group suffered dry mouth than patients in the risperidone group, and that a higher proportion of the patients in the quetiapine group suffered dry mouth, constipation and urinary hesitancy than in the ziprasidone group. A lower proportion of the patients in the clozapine group suffered dry mouth compared to patients in the olanzapine group. With respect to hormonal adverse events, with the exception of prolactin, there were no differences between the groups, with one exception. A lower proportion of the patients in the quetiapin group experienced adverse sexual events and menstrual irregularities compared to patients the risperidone group. Risperidone led to an increase in prolactin, while perfenazine, clozapine, olanzapine, quetiapine and ziprasidone led to a reduction in prolactin.  When discontinuation of treatment was reported there were for the most part no differences between the groups. The exceptions were that haloperidol caused higher discontinuation rates, due to any reason, than aripiprazole and clozapine, and discontinuation due to adverse events than aripirazole and quetiapine. Haloperidole led to lower discontinuation rates, due to adverse events, than sertindole. Olanzapine led to lower discontinuation rates, due to any reason, than quetiapine, and higher discontinuation rates, due to adverse events, than risperidone.

Discussion
Of 99 possible comparisons, data were available on only 30. However, the available comparisons were of moderate quality, such that we should trust the findings. Of seven possible first- generation antipsychotic drugs, only three haloperidol, perfenazine and flupentixole were compared with second- generation antipsychotics. We should therefore be careful not to draw general conclusions for comparisons between first- generation and second- generation antipsychotic drugs.

Conclusion
We found few differences in efficacy between first- generation and second- generation antipsychotic drugs, and among the second generation antipsychotics. For adverse events there were reported differences for at least one type of adverse event for the majority of the comparisons. Only a minority of the comparisons reported the same outcomes both in short- and longterm studies.