International clinical psychopharmacology
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Int Clin Psychopharmacol · Jul 2016
Randomized Controlled TrialA thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.
Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. ⋯ The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.
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Int Clin Psychopharmacol · Mar 2016
Randomized Controlled Trial Multicenter StudyCariprazine in the treatment of schizophrenia: a proof-of-concept trial.
This 6-week, double-blind, placebo-controlled, proof-of-concept study evaluated the efficacy, safety, and tolerability of low-dose (1.5-4.5 mg/day) and high-dose (6-12 mg/day) cariprazine in patients with acute exacerbation of schizophrenia (NCT00404573). The primary efficacy measure was change in the Positive and Negative Syndrome Scale (PANSS) total score, analyzed using a last observation carried forward approach. Other efficacy measures included the Clinical Global Impression-Severity (secondary) and PANSS subscales (additional). ⋯ In this study, the overall cariprazine treatment effect was not statistically significant, but patients treated with low-dose cariprazine showed significantly greater improvement in schizophrenia symptoms relative to placebo-treated patients. Cariprazine was generally well tolerated. Results of this study suggest that cariprazine may be effective in treating schizophrenia and future research is warranted.
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Int Clin Psychopharmacol · Mar 2016
Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study.
Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. ⋯ A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56-4.22±3.09 kg, P<0.001) and leptin (3.88±2.87-2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex).
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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 · Sep 2015
Multicenter Study Observational StudyPregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.
To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. ⋯ The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms.