International clinical psychopharmacology
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Int Clin Psychopharmacol · Sep 2018
Review Historical ArticleThe conundrum of depression clinical trials: one size does not fit all.
In this paper we review the history of antidepressant (AD) development, since the discovery of imipramine in 1957 to the present day. Through this exploration we will show that the increasing placebo response is likely a red herring and that a higher magnitude of placebo response is not an adequate explanation for AD trials' high failure rates. ⋯ In addition, we describe the lack of precision in the depression outcome measurements for the past 40 years and show how these measures contrast with those used in clinical trials of other chronic diseases, which use simpler outcome measures. Finally, we describe the role of regulatory agencies in influencing clinical trial design and how the assumption that 'one size fits all' for the past 60 years has led to flawed design of AD clinical trials.
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Int Clin Psychopharmacol · Sep 2018
ReviewA review and study of aspirin utilization for the primary prevention of cardiovascular events in a psychiatric population.
In April 2016, the US Preventive Service Task Force (USPSTF) updated the aspirin guidelines for the primary prevention of cardiovascular disease (CVD) and colorectal cancer. This review assesses the importance of appropriate use of aspirin for the primary prevention of CVD and, specifically, how individuals with psychiatric disorders may benefit from such use. This study examined how current prescribing practices of aspirin in a state psychiatric hospital align with these new guidelines and how inappropriate prescribing may jeopardize patient safety. ⋯ Overutilization did not pose a serious risk for those on aspirin therapy in this sample, as there were no major episodes of bleeding. However, future harm from aspirin still exists based on the significant number of major and moderate potential drug interactions with aspirin and the increased risk of decreased adherence to critical psychiatric medications due to increased pill burden and regimen complexity. Our findings demonstrate that there is an opportunity to educate prescribers on the updated 2016 USPSTF guidelines to improve preventive care and patient safety, which include harm reduction by initiating aspirin in those who are at a risk of cardiovascular events, continuing aspirin in those who are currently receiving aspirin appropriately, and discontinuing aspirin in those who are not considered to be at a high risk of CVD and who may also be at a risk of experiencing an increased risk of bleeding.
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Int Clin Psychopharmacol · Sep 2015
Review Comparative StudyLong-acting injectable versus daily oral antipsychotic treatment trials in schizophrenia: pragmatic versus explanatory study designs.
Trial design characteristics related to the explanatory : pragmatic spectrum may contribute toward the inconsistent results reported in studies comparing long-acting injectable (LAI) versus daily oral antipsychotic (AP) treatments in schizophrenia. A novel approach examined the hypothesis that a more pragmatic design is important to show the advantages of LAI versus oral APs. A literature search identified comparative studies assessing the clinical efficacy/effectiveness of LAI versus oral APs in more than 100 schizophrenia patients, with 6-month or more duration/follow-up, and published between January 1993 and December 2013 (n=11). ⋯ The rank order of this significance among domains was as follows: 'participant compliance assessment' (P=0.005), 'medical practice setting/practitioner expertise' (P=0.006), 'intervention flexibility' (P=0.007), 'follow-up intensity/duration' (P=0.009), 'primary trial outcomes' (P=0.012), and 'participant eligibility' (P=0.015). Findings support that more pragmatic, less explanatory design features are important to show advantages for LAI treatment. Explanatory studies may introduce features that obscure advantages related to adherence.
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Int Clin Psychopharmacol · Nov 2006
ReviewEfficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect?
The evidence that the effects of the antidepressant duloxetine on painful physical symptoms in depression and chronic pain disorders are a direct analgesic effect rather than an indirect antidepressant effect is reviewed. Data from placebo-controlled acute studies of duloxetine in major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia syndrome are included in this review. In placebo-controlled studies of duloxetine in patients with major depressive disorder, non-depressed diabetic peripheral neuropathic pain, and fibromyalgia syndrome, duloxetine has a statistically significantly greater effect on pain than placebo. ⋯ In fibromyalgia syndrome studies, duloxetine had similar and substantial effects on pain regardless of whether patients had comorbid major depressive disorder. Pain is a complex experience, involving both the physiological responses of the nociceptive system and the processing of that information in brain regions associated with emotion. While some effects of duloxetine on painful symptoms can be accounted for by its antidepressant action, the data strongly suggest that duloxetine also exerts a substantial direct analgesic effect over and above its antidepressant effects, in patients with major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia syndrome.
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Int Clin Psychopharmacol · May 1999
ReviewMetabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors.
Selective serotonin reuptake inhibitors (SSRIs) are prescribed alone and in combination with other psychotropic medications in the treatment of a variety of psychiatric disorders. Such combinations create the potential for pharmacokinetic interactions by affecting the activity of the cytochromes P450 (CYP450), drug metabolizing oxidative enzymes. SSRIs are not equivalent in their potential for interactions when combined with other central nervous system (CNS) medication. ⋯ Fluoxetine also inhibits CYP3A and CYP2C19, increasing serum concentrations of some benzodiazepines. Fluvoxamine is a potent inhibitor of CYP1A2, a moderate inhibitor of CYP3A and a mild inhibitor of CYP2D6. Therefore, interactions with clozapine and benzodiazepines are evident.