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Background Mental disorders are a leading cause of global disability, driven primarily by depression and anxiety. Most of the disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Our research team has worked in western Kenya for nearly ten years. Primary care populations in Kenya have high prevalence of Major Depressive Disorder (MDD) and Posttraumatic Stress Disorder (PTSD). To address these treatment needs with a sustainable, scalable mental health care strategy, we are partnering with local and national mental health stakeholders in Kenya and Uganda to identify 1) evidence-based strategies for first-line and second-line treatment delivered by non-specialists integrated with primary care, 2) investigate presumed mediators of treatment outcome and 3) determine patient-level moderators of treatment effect to inform personalized, resource-efficient, non-specialist treatments and sequencing, with costing analyses. Our implementation approach is guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Methods/design We will use a Sequential, Multiple Assignment Randomized Trial (SMART) to randomize 2710 patients from the outpatient clinics at Kisumu County Hospital (KCH) who have MDD, PTSD or both to either 12 weekly sessions of non-specialist-delivered Interpersonal Psychotherapy (IPT) or to 6 months of fluoxetine prescribed by a nurse or clinical officer. Participants who are not in remission at the conclusion of treatment will be re-randomized to receive the other treatment (IPT receives fluoxetine and vice versa) or to combination treatment (IPT and fluoxetine). The SMART-DAPPER Implementation Resource Team, (IRT) will drive the application of the EPIS model and adaptations during the course of the study to optimize the relevance of the data for generalizability and scale –up. Discussion The results of this research will be significant in three ways: 1) they will determine the effectiveness of non-specialist delivered first- and second-line treatment for MDD and/or PTSD, 2) they will investigate key mechanisms of action for each treatment and 3) they will produce tailored adaptive treatment strategies essential for optimal sequencing of treatment for MDD and/or PTSD in low resource settings with associated cost information – a critical gap for addressing a leading global cause of disability. Trial registration ClinicalTrials.govNCT03466346, registered March 15, 2018.

Introduction This retrospective consecutive case series assessed 12-month effectiveness and safety of iStent® or iStent inject® trabecular micro-bypass implants with cataract surgery in patients with open-angle glaucoma (OAG) in a real-world clinical setting. Methods Effectiveness outcomes consisted of intraocular pressure (IOP) reduction; glaucoma medication reduction; proportions of eyes achieving IOP

Objective: Several studies have investigated whether in utero exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with increased risk of developing mental or behavioural disorders. The aim of this study was to perform a systematic review and meta-analysis based on this literature. Methods: A systematic search of eligible literature in PubMed, EMBASE, and PsycINFO and subsequent meta-analysis was conducted in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Results: A total of 20 studies were included in the review, and results from 18 of these were meta-analyzed. We found a statistically significant positive association between in utero exposure to SSRIs and mental or behavioural disorders such as autism spectrum disorder (hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.10–1.47), attention-deficit/hyperactivity disorder (HR = 1.33; 95% CI = 1.06–1.66) and mental retardation (HR = 1.41; 95% CI = 1.03–1.91). Confounding by indication was identified in five of seven studies investigating this aspect. Conclusion: Exposure to SSRIs in utero is associated with increased risk of developing mental or behavioural disorders. However, these associations do not necessarily reflect a causal relationship since the results included in this meta-analysis are likely affected by residual confounding by indication, which is likely to account for some (or all) of the positive association.

Aims/hypothesis Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. Methods People living in Sweden diagnosed with new-onset pharmacologically treated type 2 diabetes between 2006 and 2012 were identified through the Swedish Prescribed Drug Register. They were followed until 31 December 2016 for ACM and until 31 December 2012 for CSM. Analyses were adjusted for age at diagnosis, sex, socioeconomic status, education, treatment and region. Associations were assessed using Cox regression analysis. Results In total, 138,085 individuals were diagnosed with type 2 diabetes between 2006 and 2012 and fulfilled inclusion criteria. Of these, 102,163 (74.0%) were native Swedes, 28,819 (20.9%) were first-generation immigrants and 7103 (5.1%) were second-generation immigrants with either one or both parents born outside Sweden. First-generation immigrants had lower ACM rate (HR 0.80 [95% CI 0.76, 0.84]) compared with native Swedes. The mortality rates were particularly low in people born in non-Western regions (0.46 [0.42, 0.50]; the Middle East, 0.41 [0.36, 0.47]; Asia, 0.53 [0.43, 0.66]; Africa, 0.47 [0.38, 0.59]; and Latin America, 0.53 [0.42, 0.68]). ACM rates decreased with older age at migration and shorter stay in Sweden. Compared with native Swedes, first-generation immigrants with ≤ 24 years in Sweden (0.55 [0.51, 0.60]) displayed lower ACM rates than those spending >24 years in Sweden (0.92 [0.87, 0.97]). Second-generation immigrants did not have better survival rates than native Swedes but rather displayed higher ACM rates for people with both parents born abroad (1.28 [1.05, 1.56]). Conclusions/interpretation In people with type 2 diabetes, the lower mortality rate in first-generation non-Western immigrants compared with native Swedes was reduced over time and was equalised in second-generation immigrants. These findings suggest that acculturation to Western culture may impact ACM and CSM in immigrants with type 2 diabetes but further investigation is needed.

There is a dearth of information on the risk of inadequate and excess gestational weight gain (GWG) among different generations of Hispanic women in the United States. Therefore, the objective of this study was to understand the relationship of GWG and immigration across three generations of Hispanic women. The study was conducted using data from National Longitudinal Survey of Youth 1979 (NLSY79). The study sample included 580 (unweighted count) women (148 first-generation, 117 second-generation, and 315 third-/higher-generation). Sociodemographic and immigration data were extracted from the main NLSY79 survey, and pregnancy data were extracted from the child/young adult survey following the biological children born to women in NLSY79. Covariate adjusted weighted logistic regression models were conducted to assess the risk of inadequate and excess GWG among the groups. Average total GWG was 14.98 kg, 23% had inadequate GWG, and 50% had excess GWG. After controlling for the covariates, there was no difference in the risk of inadequate GWG between the three generations. First-generation women (OR = 0.47, p = 0.039) and third-/higher-generation women (OR = 0.39, p = 0.004) had significantly lower risk of excess GWG compared to second-generation women. It is important to recognize the generational status of Hispanic women as a risk factor for excess GWG.

BackgroundFemale genital mutilation (FGM) is a deeply-rooted cultural practice mainly undertaken in Africa, the Middle East and Asian countries. Evidence to date suggests that although first-generation migrants to the West are abandoning FGM, the custom continues in some places, albeit in small numbers. This study examined how young people living in FGM affected communities in the United Kingdom (UK), interpreted and explained FGM.MethodsA community-based participatory research (CBPR) approach was used to recruit and train nine young people aged 15–18 as co-researchers. These comprised eight females and one male from second-generation FGM affected communities, living in Bristol. The co-researchers then undertook focus groups and semi-structured interviews with twenty participants aged 13–15 living in Bristol, Cardiff and Milton Keynes. The qualitative data from the training workshops, interviews and focus groups were collected and analysed using thematic analysis.ResultsThere were conflicting views among participants. Some perceived FGM as a historical tradition that was of very little, if any, relevance to them. In contrast, others perceived that the more archaic, cultural interpretation of FGM, more commonly shared by older generations, had been supplanted by a new form of FGM, which they believed to be a safe procedure, made so by the availability of highly-trained, qualified doctors and better equipment in the UK. Participants spoke of challenges encountered when attempting to raise the issue of FGM with parents. Nevertheless, they acknowledged that– being born and raised in the UK – enabled them to talk openly and to challenge others.ConclusionFuture strategies to address and prevent FGM in the UK will require a public health approach that is holistic, intersectional and empowering. Such measures should be relevant to young people born and raised in the UK who interpret FGM differently to previous first-generation migrant relatives and communities. Tackling FGM requires a shift away from a principal preoccupation with harm reduction and criminalisation towards collaboration and active dialogue with communities, in positive and productive ways that acknowledge and engage issues of identity, race, gender, and generation, enabling people affected by FGM to take control of their health and well-being.

Objective Nonspecific factors, such as treatment outcome expectancy and working alliance, can influence treatment outcome. No studies to date have examined the role of expectancy and alliance on pharmacotherapy outcomes in individuals with complicated grief (CG). Method This secondary analysis of a larger randomized, control trial (RCT) examined the relationship between pharmacotherapy expectancy and alliance on treatment outcome in adults with CG who were participating in a multisite, double-blind, RCT examining the efficacy of citalopram and complicated grief treatment (CGT). Participants (n = 202) were randomized to one of four treatment conditions: citalopram (CIT), placebo (PBO), CGT + citalopram (CGT + CIT), or CGT + placebo (CGT + PBO). Results Pharmacotherapy outcome expectancy and working alliance were higher among individuals randomized to CGT + CIT and CGT + PBO compared with CIT or PBO without CGT. Pharmacotherapy outcome expectancy was higher at Week 2 among individuals who ultimately responded to treatment compared with those who did not and among those who remained in treatment compared with those who dropped out. In contrast, working alliance did not correlate with dropout or treatment outcomes in pharmacotherapy. Conclusions Expectancy for medication was higher among individuals randomized to receive CGT. Clinicians should assess symptoms and expectancies in the first weeks of treatment because these could be early markers of drop out and treatment response. (PsycINFO Database Record

Author(s): La, Alice L; Walsh, Christine M; Neylan, Thomas C; Vossel, Keith A; Yaffe, Kristine; Krystal, Andrew D; Miller, Bruce L; Karageorgiou, Elissaios | Abstract: BACKGROUND:Recent studies reveal an association between slow-wave sleep (SWS), amyloid-β aggregation, and cognition. OBJECTIVE:This retrospective study examines whether long-term use of trazodone, an SWS enhancer, is associated with delayed cognitive decline. METHODS:We identified 25 regular trazodone users (mean age 75.4±7.5; 9 women, 16 men) who carried a diagnosis of Alzheimer's dementia, mild cognitive impairment, or normal cognition, and 25 propensity-matched trazodone non-users (mean age 74.5±8.0; 13 women, 12 men), accounting for age, sex, education, type of sleep deficit (hypersomnia, insomnia, parasomnia), diagnosis, and baseline Mini-Mental State Examination (MMSE). Longitudinal group differences in cognitive testing were evaluated through repeated measures tests over an average inter-evaluation interval of four years. RESULTS:Trazodone non-users had 2.6-fold faster decline MMSE (primary outcome) compared to trazodone users, 0.27 (95% confidence interval [CI]: 0.07-0.48) versus 0.70 (95% CI: 0.50-0.90) points per year (p = 0.023). The observed effects were especially associated with subjective improvement of sleep complaints in post-hoc analyses (p = 0.0006). Secondary outcomes of other cognitive and functional scores had variable worsening in non-users and varied in significance when accounting for co-administered medications and multiple comparisons. Trazodone effects on MMSE remained significant within participants with AD-predicted pathology, with 2.4-fold faster decline in non-users (p = 0.038). CONCLUSIONS:These results suggest an association between trazodone use and delayed cognitive decline, adding support for a potentially attractive and cost-effective intervention in dementia. Whether the observed relationship of trazodone to cognitive function is causal or an indirect marker of other effects, such as treated sleep disruption, and if such effects are mediated through SWS enhancement requires confirmation through prospective studies.

Gestational diabetes (GD) has a negative impact on neurodevelopment, resulting in cognitive and neurological deficiencies. Oxidative stress (OS) has been reported in the brain of the first-generation offspring of GD rats. OS has been strongly associated with neurodegenerative diseases. In this work, we determined the effect of GD on the cognitive behavior, oxidative stress and metabolism of second-generation offspring. GD was induced with streptozotocin (STZ) in pregnant rats to obtain first-generation offspring (F1), next female F1 rats were mated with control males to obtain second-generation offspring (F2). Two and six-month-old F2 males and females were employed. Anxious-type behavior, spatial learning and spatial working memory were evaluated. In cerebral cortex and hippocampus, the oxidative stress and serum biochemical parameters were measured. Male F2 GD offspring presented the highest level of anxiety-type behavior, whilst females had the lowest level of anxiety-type behavior at juvenile age. In short-term memory, adult females presented deficiencies. The offspring F2 GD females presented modifications in oxidative stress biomarkers in the cerebral cortex as lipid-peroxidation, oxidized glutathione and catalase activity. We also observed metabolic disturbances, particularly in the lipid and insulin levels of male and female F2 GD offspring. Our results suggest a transgenerational effect of GD on metabolism, anxiety-like behavior, and spatial working memory.

STUDY OBJECTIVES: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions’ effects relative to control in women with comparably severe insomnia symptoms and VMS. METHODS: We analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) ≥ 12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included the following: escitalopram 10–20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8–12 weeks of treatment. RESULTS: CBT-I produced the greatest reduction in ISI from baseline relative to control at −5.2 points (95% CI −7.0 to −3.4). Effects on ISI were similar for exercise at −2.1 and venlafaxine at −2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at −2.7 points (−3.9 to −1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol, and venlafaxine. Omega-3 supplements did not improve insomnia symptoms. CONCLUSIONS: This study’s findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS.

Borderline personality disorder (BPD) is characterized by affective instability, impulsive behaviors, and disturbed interpersonal relationships. A previous study of our group found that combined therapy with interpersonal psychotherapy adapted to BPD (IPT-BPD) and fluoxetine was superior to single pharmacotherapy in BPD patients. The aim of the present study was to examine what clinical factors predicted response to combined therapy in patients evaluated in the previous efficacy study. The subgroup of 27 patients allocated to combined therapy was analyzed. Patients were treated for 32 weeks with fluoxetine 20-40 mg/day plus IPT-BPD. Patients were assessed at baseline and week 32 with an interview for demographic and clinical variables, CGI-S, HDRS, HARS, SOFAS, BPDSI, and SAT-P. Statistical analysis was performed with multiple regression. The difference of CGI-S score between baseline and week 32 (∆CGI-S) was the dependent variable. Factors significantly and independently related to ∆CGI-S were the BPDSI total score and the items abandonment, affective instability, and identity. Patients with more severe BPD psychopathology and with a higher degree of core symptoms such as fear of abandonment, affective instability, and identity disturbance have a better chance to improve with combined therapy with fluoxetine and IPT-BPD.

Background: Guidance of patients treated with antidepressants is paramount for successful therapy. The aim was to assess patients' needs and suggestions for improvement of guidance by physicians and pharmacists during second generation antidepressant (SGA) therapy.Methods: Five focus group discussions were held with a total of 34 patients using an SGA. The discussions were conducted flexibly and responsively using a semi-structured topic list. All focus group discussions were video-recorded and transcripts were analyzed using ATLAS.ti for coding, thematic and open analysis.Results: Participants stated they were in need of better guidance. They suggested improving content of information during decisional moments, patient-health care professional communication and communication between health care professionals, and finally, organization of guidance. Barriers to achieving improved guidance were cited.Conclusions: Content, communication and organization of guidance are pivotal for achieving optimal guidance. Participants mentioned their current experienced guidance had limitations and brought up solutions for improvement. A next step would be to discuss the suggested solutions with health care professionals to assess their views and to discuss the possibility for implementation. After implementation, future studies could be aimed at determination of its impact on patients' treatment efficacy, quality of life, treatment satisfaction and healthcare costs.

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.

Study objective To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design A blinded, randomized split-plot experimental study. Setting Two urban academic clinical centers. Participants 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and results Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH's sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I.

Introduction: Prevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care. Methods: We narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second- generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors. Results: LAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a ‘‘naturalistic’’ study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years. Conclusion: Results across the ‘‘full spectrum’’ of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.

BackgroundWhether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses.MethodCortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined.ResultsThe effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p ConclusionsOur results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.

PurposeRe-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs.MethodsIn the Kaiser Permanente Medical Care Program in Northern California, 906 men with testicular cancer diagnosed August 1996-December 2010 were compared with 38,253 matched controls with race/ethnicity recorded regarding receipt of antidepressant drugs at least 2 years before diagnosis or control index date. Analyses emphasized duration of use and histological subgroups.ResultsWith control for race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95 % confidence intervals (CI) for associations with testicular cancer were as follows: fluoxetine 1.22 (0.88-1.71), paroxetine 1.19 (0.78-1.83), and 1.21 (0.92-1.58) for all serotonin reuptake inhibitors. There was no statistically significant association with risk of all testicular cancers or their histological subtypes for any individual drug or for tricyclics or all antidepressants combined except for citalopram with all testicular cancers 2.55 (1.43-4.52) and those of mixed histology 4.36 (1.50-12.68) and nefazodone with embryonal cancers 9.79 (1.85-51.81). These could readily be chance findings in the context of the many analyses that were performed. Duration of use was not associated with risk of the drugs and drug groups with sufficient numbers of exposed cases for analysis.ConclusionsWe found little evidence to support a testicular carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs, but a weakly positive association is not ruled out. The signals in prior screening may have been due to chance and/or uncontrolled confounding.

Depressed mood has been associated with HIV transmission risk behavior. To determine whether effective depression treatment could reduce the frequency of sexual risk behavior, we analyzed secondary outcome data from a 36-week, two-arm, parallel-design, randomized controlled trial, in which homeless and marginally housed, HIV-infected persons with comorbid depressive disorders were randomized to receive either: (a) directly observed treatment with the antidepressant medication fluoxetine, or (b) referral to a local public mental health clinic. Self-reported sexual risk outcomes, which were measured at 3, 6, and 9 months, included: total number of sexual partners, unprotected sexual intercourse, unprotected sexual intercourse with an HIV-uninfected partner or a partner of unknown serostatus, and transactional sex. Estimates from generalized estimating equations regression models did not suggest consistent reductions in sexual risk behaviors resulting from treatment. Mental health interventions may need to combine depression treatment with specific skills training in order to achieve durable impacts on HIV prevention outcomes. © 2013 Springer Science+Business Media New York.

Objective Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial ( N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting substance use disorder criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded. Results Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among the subjects who progressed to high substance-related impairment (≥75th percentile) versus those whose substance-related impairment remained low ( Conclusions Substance use is common among adolescents with treatment-resistant MDD. The subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain.

Objective To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies. Method Youths who had not improved during an adequate SSRI trial ( N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response. Results Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy. Conclusions Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.

Background: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery Score II (SS-II) can well predict 4-year mortality in patients with complex coronary artery disease (CAD), and guide decision-making between coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). However, there is lack of data regarding the utility of the SS-II in patients with three-vessel CAD undergoing PCI treated with second-generation drug-eluting stents (DES). The purpose of the present study was to evaluate the ability of the SS-II to predict long-term mortality in patients with three-vessel CAD undergoing PCI with second-generation DES. Methods: Totally, 573 consecutive patients with de novo three-vessel CAD who underwent PCI with second-generation DES were retrospectively studied. According to the tertiles of the SS-II, the patients were divided into three groups: The lowest SS-II tertile (SS-II ≤20), intermediate SS-II tertile (SS-II of 21–31), and the highest SS-II tertile (SS-II ≥32). The survival curves of the different groups were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relationship between the SS-II and 5-year mortality. The performance of the SS-II with respect to predicting the rate of mortality was studied by calculating the area under the receiver operator characteristic (ROC) curve. The predictive ability of the SS-II for 5-year mortality was evaluated and compared with the SS alone. Results: The overall SS-II was 27.6 ± 9.0. Among patients in the lowest, intermediate and the highest SS-II tertiles, the 5-year rates of mortality were 1.6%, 3.2%, and 8.6%, respectively ( P = 0.003); the cardiac mortality rates were 0.5%, 1.9%, and 5.2%, respectively ( P = 0.014). By multivariable analysis, adjusting for the potential confounders, the SS-II was an independent predictor of 5-year mortality (hazard ratio: 2.45, 95% confidence interval: 1.38–4.36; P = 0.002). The SS-II demonstrated a higher predictive accuracy for 5-year mortality compared with the SS alone (the area under the ROC curve was 0.705 and 0.598, respectively). Conclusion: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.

While the important roles of post-quit affect and withdrawal symptoms in the process of smoking cessation have been well established, little is known about the relations between pre-quit affective trajectories and cessation outcome on the target quit date (TQD). This study examined whether a 16-week course of fluoxetine initiated 8 weeks pre-quit (“sequential” fluoxetine) improved TQD abstinence relative to placebo through its effects on pre-quit depressive symptoms, affect (withdrawal-relevant negative affect, general negative affect, and positive affect), and craving to smoke among 206 smokers with elevated depressed symptoms. The moderating effects of gender were also examined. A total of 83 smokers (40%) failed to achieve abstinence on TQD, with no difference between treatment conditions or gender. Overall structural equation models showed that fluoxetine had significant indirect effects on TQD abstinence through changes in pre-quit withdrawal-relevant negative affect and craving, but not depressive symptoms. However, multigroup analyses revealed gender differences. Sequential fluoxetine reduced pre-quit depressive symptoms, withdrawal-relevant negative affect, and craving only among women. Reduction in pre-quit depressive symptoms and craving among women, and withdrawal-relevant negative affect among men was associated with TQD abstinence. Moreover, exploratory analysis showed negative trend-level indirect effects of fluoxetine on TQD abstinence via increased side effects, regardless of gender. This study demonstrated the importance of considering gender when examining treatment efficacy. Identifying ways to further reduce pre-quit depressive symptoms and craving for women and withdrawal-relevant negative affect for men while alleviating side effects may help smokers with elevated depressed symptoms achieve the first smoking cessation milestone.

Background The European literature on mental health of the children of immigrants is limited. Therefore this study aims to investigate gender-specific mental health reported by teachers, parents and the children themselves in 12-year old children of immigrants and non-immigrants and also to study the level of agreement between the different informants. Methods This cross-sectional study is a part of the longitudinal South East Sweden Birth Cohort-study (the SESBiC-study) on children’s health. All children born in town in the south of Sweden 1995-1996 were invited to take part. The mothers of 1723 children (88%) consented. In this part 87 Swedish-born 12-year old children of immigrants and 687 12-year old children of non-immigrants were investigated regarding gender-specific differences in mental health as reported by teachers (Teacher-report form), parents (Child behavior checklist), and children (Strengths and Difficulties Questionnaire) and the agreement reached between the informants. Results Parental immigrant status was not associated with mental health in any of the groups, but living arrangements and parental educational level were mainly found to have an effect on the health status of boys (TRF-Internalizing β = .77 95% CI = .02-1.52; TRF-Externalizing.β = 2.31 95% CI = .63-3.99; TRF-Total β = 6.22 95% CI = 2.27-10.18) The agreement between different informants was generally low, except for externalizing problems among boys (Boys of immigrant parents: Parent and teacher correlation ρ = .422 and Child teacher correlation ρ = .524, p-value Total = .400, ρ Internalizing = .240 and ρ Externalizing = .524, p-value Conclusion This study confirms previous findings that the mental health of children of immigrants is similar to that of children of non-immigrants. We found that family factors have a greater impact on the reported mental health than immigrant status does. This might be of clinical importance for healthcare workers to recognize when investigating and treating children from other cultures.

Objectives. We assessed whether directly observed fluoxetine treatment reduced depression symptom severity and improved HIV outcomes among homeless and marginally housed HIV-positive adults in San Francisco, California, from 2002 to 2008. Methods. We conducted a nonblinded, randomized controlled trial of once-weekly fluoxetine, directly observed for 24 weeks, then self-administered for 12 weeks (n = 137 persons with major or minor depressive disorder or dysthymia). Hamilton Depression Rating Scale score was the primary outcome. Response was a 50% reduction from baseline and remission a score below 8. Secondary measures were Beck Depression Inventory-II (BDI-II) score, antiretroviral uptake, antiretroviral adherence (measured by unannounced pill count), and HIV-1 RNA viral suppression ( Results. The intervention reduced depression symptom severity (b = −1.97; 95% confidence interval [CI] = −0.85, −3.08; P Conclusions. Directly observed fluoxetine may be an effective depression treatment strategy for HIV-positive homeless and marginally housed adults, a vulnerable population with multiple barriers to adherence.

The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy.Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively.Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores.In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.

We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery.By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P.03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P.001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment.clinicaltrials.gov Identifier: NCT00018902.

Lung cancer is the leading cause of cancer death in the US. About 50% of lung cancer patients are current smokers at the time of diagnosis and up to 83% continue to smoke after diagnosis. A recent study suggests that people who continue to smoke after a diagnosis of early-stage lung cancer almost double their risk of dying. Despite a growing body of evidence that continued smoking by patients after a lung cancer diagnosis is linked with less effective treatment and a poorer prognosis, the belief prevails that treating tobacco dependence is useless. With improved cancer treatments and survival rates, smoking cessation among lung cancer patients has become increasingly important. There is a pressing need to clarify the role of smoking cessation in the care of lung cancer patients. Objective: This paper will report on the benefits of smoking cessation for lung cancer patients and the elements of smoking cessation treatment, with consideration of tailoring to the needs of lung cancer patients. Results: Given the significant benefits of smoking cessation and that tobacco dependence remains a challenge for many lung cancer patients, cancer care providers need to offer full support and intensive treatment with a smoking cessation program that is tailored to lung cancer patients’ specific needs. Conclusion: A tobacco dependence treatment plan for lung cancer patients is provided.

The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator.Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3%) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24.Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among nonresponders could be important.