19 research outputs found

    Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

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    <p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

    Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

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    BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

    Surface roughness of packable composite resins polished with various systems

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    Purpose: The aim of this study was to evaluate the surface roughness of four packable composite resins, SureFil™ (Dentsply, Petrópolis, Rio de Janeiro, Brazil), Prodigy Condensable™ (Kerr Co., Orange, CA, USA), Filtek P60™ (3M do Brasil, São Paulo, Brazil), and ALERT® (Jeneric/Pentron, Inc., Wallingford, CT, USA) and one microhybrid composite resin (Filtek Z250™, 3M do Brasil) after polishing with four finishing systems. Materials and Methods: Twenty specimens were made of each material (5 mm in diameter and 4 mm high) and were analyzed with a profilometer (Perthometer® S8P, Perthen, Mahr, Germany) to measure the mean surface roughness (Ra). The specimens were then divided into four groups according to the polishing system: group 1 - Sof-Lex™ (3M do Brasil), group 2 - Enhance™ (Dentsply), group 3 - Composite Finishing Kit (KG Sorensen, Barueri, São Paulo, Brazil), and group 4 - Jiffy Polisher Cups® (Ultradent Products, Inc., South Jordan, UT, USA). The specimens were polished and then evaluated for Ra, and the data were subjected to analysis of variance, analysis of covariance, and Tukey's test (p = .05). Results: The mean Ra of SureFil polished with Sof-Lex was significantly lower than that of KG points. Prodigy Condensable polished with Enhance showed a significantly less rough surface than when polished with Sof-Lex. Filtek P60 did not exhibit a significant difference with the various polishing systems. For ALERT the lowest mean Ra was obtained with Sof-Lex and the highest mean Ra with KG points. Regarding Filtek Z250, polishing with KG and Jiffy points resulted in a significantly lower mean Ra than when polished with Enhance. Conclusions: Packable composite resins display variable roughness depending on the polishing system used; the Sof-Lex disks and Jiffy points resulted in the best Ra values for the majority of the materials tested
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