Adjunctive aripiprazole, olanzapine, or quetiapine for major depressive disorder: an analysis of number needed to treat, number needed to harm, and likelihood to be helped or harmed.
ABSTRACT To describe the efficacy and safety of adjunctive aripiprazole, olanzapine, and quetiapine for major depressive disorder.
Published registration study reports, supplemented by clinical trial synopses as disclosed by manufacturers and product labeling.
All available reports of studies were identified.
Descriptions of the principal results and calculation of number needed to treat (NNT) for response and remission and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.
Three registration studies of adjunctive aripiprazole, 5 for olanzapine-fluoxetine combination, and 2 for quetiapine extended-release reveal NNT for response and remission to range from 7 to 14 and 7 to 13, respectively, for adjunctive antipsychotic versus antidepressant monotherapy, depending on the antipsychotic and/or dose. Adverse event profiles for the 3 different adjunctive antipsychotics are more diverse, with adjunctive aripiprazole more strongly associated with akathisia (NNH, 6), adjunctive olanzapine with weight gain (NNH, 3), and adjunctive quetiapine with somnolence (NNH, 5 for 300 mg/d and NNH, 6 for 150 mg/d).
Number needed to treat and NNH can be used to quantify efficacy and tolerability outcomes and help place various therapeutic options into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and the patient the trade-offs between obtaining potential benefits versus harms. In the case of the adjunctive second-generation antipsychotics approved for treating major depressive disorder, these trade-offs vary greatly among the choices available and require careful, individualized, patient-centered clinical decision making.
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ABSTRACT: ZET: P değeri zorbalığı: Etki büyüklüğü sorunu İstatistiksel önemlilik mutlaka klinik önemlilik anlamına gelmez. P-değerinin 0.05'ten az olması sonucun önemli ola-cağını garanti etmez. Kliniksel ilişkinin değerlendirebilmesi için etki büyüklüğü (effect size) hesaplanması gerekmekte-dir. Number needed to treat (NNT) klinik çalışma sonuçları-nı anlamaya yardımcı olan ve bir klinisyenin rakip girişimler arasındaki potansiyel farkları değerlendirmesine izin veren örnek bir etki büyüklüğü ölçüsüdür. Anahtar sözcükler: Klinik önemlilik, tedavi edilmesi gere-ken sayı, P-değeri, istatistiksel önemlilik Kli nik Psikofarmakoloji Bülteni 2011;21(2):91-2 ABS TRACT: The tyranny of the P-value: effect size matters Statistical significance does not necessarily imply clinical significance. A P-value of less than 0.05 does not guarantee that the result will be important. Effect size needs to be calculated in order to appraise clinical relevance. Number needed to treat (NNT) is an example of an effect size measure that helps translate clinical trial results and allows a clinician to evaluate potential differences between competing interventions.Bulletin of Clinical Psychopharmacology 01/2011; · 0.37 Impact Factor
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ABSTRACT: Objectives The purpose of this study was to investigate the central activity of the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic 5HT1A receptor agonists and postsynaptic 5HT1A, 5HT2A and D2 receptors antagonists. The compounds were examined using animal tests towards antipsychotic, antidepressant- and anxiolytic-like properties and then compared with effects evoked by an atypical antipsychotic drug ziprasidone.MethodsD-amphetamine-induced hyperactivity test was used to determine antipsychotic-like activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test were conducted to investigate antidepressant- and antianxiety-like activity, respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone were administered intraperitoneally 60 min before the tests. Diazepam and imipramine were used as standard anxiolytic and antidepressant drugs, respectively.Key findingsThe obtained results demonstrate that new synthesized compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties in behavioural tests in mice.Conclusions The present preclinical results indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine-2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an antipsychotic drug with additional antidepressant and anxiolytic properties.Journal of Pharmacy and Pharmacology. 09/2014;
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ABSTRACT: We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 06/2014; · 1.08 Impact Factor