METHODS: The decision aid prototype was developed following a literature review and six focus groups. Alpha testing assessed its comprehensibility, acceptability, usability and desirability through user-centered cognitive interviews. Beta-testing evaluated preliminary evidence on its efficacy using the SDM Scale and PDMS. Feasibility was assessed by timing the consultation.
RESULTS: The alpha testing demonstrated that the decision aid was patient-oriented, comprehensible, comprehensive, concise and objective with an appealing design. Beta-testing indicated that PtDA significantly increased patients satisfaction with SDM from patients' [83.32 (13.92) vs 85.76 (13.80); p
METHODS: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score.
RESULTS: Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total score. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo.
CONCLUSIONS: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older.
TRIAL REGISTRATION: EudraCT identifier: 2012-005612-26.
PURPOSE: The purpose of this comprehensive review is to compile and analyze the information related to the pharmacokinetic, pharmacological, and toxicological studies reported on α- and β-asarone using preclinical in vitro and in vivo models. Besides, the molecular targets and mechanism(s) involved in the biological activities of α- and β-asarone were discussed.
METHODS: Databases including PubMed, ScienceDirect and Google scholar were searched and the literature from the year 1960 to January 2017 was retrieved using keywords such as α-asarone, β-asarone, pharmacokinetics, toxicology, pharmacological activities (e.g. depression, anxiety).
RESULTS: Based on the data obtained from the literature search, the pharmacokinetic studies of α- and β-asarone revealed that their oral bioavailability in rodents is poor with a short plasma half-life. Moreover, the metabolism of α- and β-asarone occurs mainly through cytochrome-P450 pathways. Besides, both α- and/or β-asarone possess a wide range of pharmacological activities such as antidepressant, antianxiety, anti-Alzheimer's, anti-Parkinson's, antiepileptic, anticancer, antihyperlipidemic, antithrombotic, anticholestatic and radioprotective activities through its interaction with multiple molecular targets. Importantly, the toxicological studies revealed that both α- and β-asarone can cause hepatomas and might possess mutagenicity, genotoxicity, and teratogenicity.
CONCLUSIONS: Taken together, further preclinical studies are required to confirm the pharmacological properties of α-asarone against depression, anxiety, Parkinson's disease, psychosis, drug dependence, pain, inflammation, cholestasis and thrombosis. Besides, the anticancer effect of β-asarone should be further studied in different types of cancers using in vivo models. Moreover, further dose-dependent in vivo studies are required to confirm the toxicity of α- and β-asarone. Overall, this extensive review provides a detailed information on the preclinical pharmacological and toxicological activities of α-and β-asarone and this could be very useful for researchers who wish to conduct further preclinical studies using α- and β-asarone.