CATIE and CUtLASS: can we handle the truth?
ABSTRACT Two large, non-commercial clinical trials comparing first- and second-generation antipsychotic drugs for people with chronic schizophrenia in the US and UK have shown unexpected results. in general, the newer drugs were no more effective or better tolerated than the older drugs. Clozapine outperformed other second-gene ration drugs. The implications are considered. Declaration of interest S.L. is the Chief investigator of the CUtLASS study and J.L. is the Chief Investigator of the CATIE study, S.L. has received honoraria from several pharmaceutical companies. J.L. has received research funding from several pharmaceutical companies.
- SourceAvailable from: Dorota Frydecka
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- "Perazine is a phenothiazine derivative widely used in some European countries, including Germany and Poland, and it is thought to exert potent antipsychotic and sedative effects, as well as a relatively low risk of extrapyramidal side effects (Leucht et al., 2014; Adamowski and Kiejna, 2012). Interestingly, recent naturalistic studies have demonstrated that the effectiveness of some typical and atypical antipsychotics did not differ in clinical settings (Lieberman, 2006; Lewis and Lieberman, 2008; Stahl, 2008; Leucht et al., 2009; Naber and Lambert, 2009). At the time of study conception, perazine and olanzapine were the two most widely used antipsychotic drugs at both recruiting centers and ziprasidone had just been introduced to the Polish market. "
ABSTRACT: The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.Psychiatry Research 06/2014; 219(2). DOI:10.1016/j.psychres.2014.05.039 · 2.47 Impact Factor
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- "Clozapine, an atypical antipsychotic drug, is used to treat the symptoms of schizophrenia patient who do not respond to other medications [42,43]. After searching the database using "clozapine" in the "Drug Name" option, a summary table and several data extraction options mentioned previously appeared in the search output page. "
ABSTRACT: Understanding drug bioactivities is crucial for early-stage drug discovery, toxicology studies and clinical trials. Network pharmacology is a promising approach to better understand the molecular mechanisms of drug bioactivities. With a dramatic increase of rich data sources that document drugs' structural, chemical, and biological activities, it is necessary to develop an automated tool to construct a drug-target network for candidate drugs, thus facilitating the drug discovery process. We designed a computational workflow to construct drug-target networks from different knowledge bases including DrugBank, PharmGKB, and the PINA database. To automatically implement the workflow, we created a web-based tool called DTome (Drug-Target interactome tool), which is comprised of a database schema and a user-friendly web interface. The DTome tool utilizes web-based queries to search candidate drugs and then construct a DTome network by extracting and integrating four types of interactions. The four types are adverse drug interactions, drug-target interactions, drug-gene associations, and target-/gene-protein interactions. Additionally, we provided a detailed network analysis and visualization process to illustrate how to analyze and interpret the DTome network. The DTome tool is publicly available at http://bioinfo.mc.vanderbilt.edu/DTome. As demonstrated with the antipsychotic drug clozapine, the DTome tool was effective and promising for the investigation of relationships among drugs, adverse interaction drugs, drug primary targets, drug-associated genes, and proteins directly interacting with targets or genes. The resultant DTome network provides researchers with direct insights into their interest drug(s), such as the molecular mechanisms of drug actions. We believe such a tool can facilitate identification of drug targets and drug adverse interactions.BMC Bioinformatics 06/2012; 13 Suppl 9(Suppl 9):S7. DOI:10.1186/1471-2105-13-S9-S7 · 2.58 Impact Factor
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- "For example, little is known about the cost/benefit efficacy of the standard 15-minute medication check used in the community for managing psychiatric patients on drug therapy. Comparative effectiveness studies by disorder type are only beginning to be performed and the early results show that aggregate differential benefits by one drug over another are small (Lewis & Lieberman 2008, Warden et al 2007). A major barrier to mental health outcome has been identified as access to care, which involves current, standard treatments, not innovative ones – according to major reports from the US government (Satcher 1999, President's New Freedom Commission on Mental Health, 2002). "
ABSTRACT: A recent literature review of commentaries and 'state of the art' articles from researchers in psychiatric genetics (PMG) offers a consensus about progress in the science of genetics, disappointments in the discovery of new and effective treatments, and a general optimism about the future of the field. I argue that optimism for the field of psychiatric molecular genetics (PMG) is overwrought, and consider progress in the field in reference to a sample estimate of US National Institute of Mental Health funding for this paradigm for the years 2008 and 2009. I conclude that the amounts of financial investment in PMG is questionable from an ethical perspective, given other research and clinical needs in the USA.Journal of Bioethical Inquiry 03/2011; 8(1):27-34. DOI:10.1007/s11673-010-9273-z · 0.75 Impact Factor