Search

Background: Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission. Methods: Post hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined. Results: The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up. Conclusion: Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality. Trial registration: ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017). [ABSTRACT FROM AUTHOR]

Background: Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. Methods: A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. Results: Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. Conclusions: Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased. [ABSTRACT FROM AUTHOR]

Background: Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective. Methods: We present a systematic review of clinical trials comparing the serum levels of new-generation antidepressants in smokers and nonsmokers. Data were obtained from MEDLINE/PubMed, Embase, and other sources. Risk of bias was assessed for selection, performance, detection, attrition, and reporting of individual studies. Results: Twenty-one studies met inclusion criteria; seven involved fluvoxamine, two evaluated fluoxetine, sertraline, venlafaxine, duloxetine or mirtazapine, and escitalopram, citalopram, trazodone and bupropion were the subject of a single study. No trials were found involving other common antidepressants such as paroxetine or agomelatine. Serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone were significantly higher in nonsmokers compared with smokers. Conclusions: There is evidence showing a reduction in the concentration of serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone in smoking patients as compared to nonsmokers. The evidence regarding other commonly used antidepressants is scarce. Nonetheless, smoking status should be considered when choosing an antidepressant treatment, given the risk of pharmacokinetic interactions. [ABSTRACT FROM AUTHOR]

Background: Poor mental health is a major problem in most western societies, especially predominant among young adults. However, associations of self-reported poor mental health with subsequent psychiatric or medical treatment are unknown. We examined the relation between self-reported mental health and redeeming prescriptions of antidepressants among three age groups. Methods: We analyzed data from 16,233 individuals aged 16 years and over randomly selected to participate in the 2010 North Denmark Region Health Survey completed in February 2010. Mental health was defined according to the Short-Form 12 instrument (SF-12) and dichotomized into poor and good. Outcome data were retrieved from administrative information on redeemed prescriptions of antidepressants between February 2010 and December 2012. Crude cumulative incidence curves were produced to illustrate the probability of redeeming new prescriptions of antidepressants over time. Cox regression analysis was used to estimate risk of redeeming prescriptions of antidepressants when having poor mental health, adjusted for preselected explanatory covariates. Results: Among the young (16-29 years-old), 620 (23 %) participants suffered from poor mental health. Among the adults (30-59 years-old) and elderly (60 years-old or over), 1592 (18 %) participants and 723 (15 %) reported poor mental health, respectively. Overall, women were more likely than men to rate their mental health as poor. For all age groups, there was an increased probability for redeeming prescriptions of antidepressants when having poor mental health. The hazard ratio [HR] for redeeming prescriptions of antidepressants for those reporting poor versus good mental health, adjusted for sex, ethnicity, marital status, education level, occupational status, smoking and physical activity was 3.1 (95 % confidence interval [CI] 2.20-4.29) for young participants. For adults, the HR was 2.3 (95 % CI 1.86-2.78) and for elderly, it was 3.5 (95 % CI 2.66-4.57). Conclusion: Self-reported poor mental health was more frequent among younger than older participants. Overall, antidepressants were the most often used treatment. An increased probability of redeeming antidepressant prescriptions when having self-reported poor mental health was observed in all age groups. These findings suggest that frequent reporting of poor mental health is a common issue for all age groups that needs more attention. [ABSTRACT FROM AUTHOR]

Background: Poor mental health is a major problem in most western societies, especially predominant among young adults. However, associations of self-reported poor mental health with subsequent psychiatric or medical treatment are unknown. We examined the relation between self-reported mental health and redeeming prescriptions of antidepressants among three age groups., Methods: We analyzed data from 16,233 individuals aged 16 years and over randomly selected to participate in the 2010 North Denmark Region Health Survey completed in February 2010. Mental health was defined according to the Short-Form 12 instrument (SF-12) and dichotomized into poor and good. Outcome data were retrieved from administrative information on redeemed prescriptions of antidepressants between February 2010 and December 2012. Crude cumulative incidence curves were produced to illustrate the probability of redeeming new prescriptions of antidepressants over time. Cox regression analysis was used to estimate risk of redeeming prescriptions of antidepressants when having poor mental health, adjusted for preselected explanatory covariates., Results: Among the young (16-29 years-old), 620 (23 %) participants suffered from poor mental health. Among the adults (30-59 years-old) and elderly (60 years-old or over), 1592 (18 %) participants and 723 (15 %) reported poor mental health, respectively. Overall, women were more likely than men to rate their mental health as poor. For all age groups, there was an increased probability for redeeming prescriptions of antidepressants when having poor mental health. The hazard ratio [HR] for redeeming prescriptions of antidepressants for those reporting poor versus good mental health, adjusted for sex, ethnicity, marital status, education level, occupational status, smoking and physical activity was 3.1 (95 % confidence interval [CI] 2.20-4.29) for young participants. For adults, the HR was 2.3 (95 % CI 1.86-2.78) and for elderly, it was 3.5 (95 % CI 2.66-4.57)., Conclusion: Self-reported poor mental health was more frequent among younger than older participants. Overall, antidepressants were the most often used treatment. An increased probability of redeeming antidepressant prescriptions when having self-reported poor mental health was observed in all age groups. These findings suggest that frequent reporting of poor mental health is a common issue for all age groups that needs more attention.