The objective of this review was to evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in preventing relapse after an episode of major depressive disorder (MDD). An Ovid MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the following terms: selective serotonin reuptake inhibitors, antidepressants, depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria, two authors independently selected and reached consensus on the included studies. Sixteen articles met the criteria: 10 compared the relapse rate of selective SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included studies, the relapse risk in adults was lower when SSRIs were combined with psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St Johns Wort) had no significant difference in efficacy and remission rates compared with SSRIs. Escitalopram appeared to fare better in efficacy than other SSRIs, owing to a higher prophylactic efficacy and lower side effects; however, according to the current data, this difference was not significant. To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural therapy may effectively reduce relapse. Escitalopram appeared to yield better results and fewer side effects than did other SSRIs or SNRIs. The effectiveness in reducing relapse of SSRIs was similar to that of TCAs and atypical antidepressants.

Among patients with Parkinsons disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine. A comprehensive literature search was conducted using the PubMed database. We also searched the following databases up to March 1, 2018: Ovid MEDLINE, PsycINFO, CINAHL, Google Scholar, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The following keywords were used: NMDA antagonist and Parkinsons disease. Two authors independently reviewed the articles identified from the search using specific selection criteria, focusing on studies of mood, psychiatric condition, depression, cognition, and quality of life, and the consensus was reached on the 20 studies included. There is a preliminary evidence that NMDA antagonists may modulate psychiatric symptoms in PD. However, current evidence of psychiatric symptom-modifying effects is inconclusive and requires that further trials be conducted in PD. The repurposing of old NMDA antagonists, such as ketamine for depression and newer therapies, such as rapastinel, suggests that there is an emerging place for modulating the glutamatergic system for treating non-motor symptoms in PD.

Cryptococcal meningitis is a life-threatening condition most commonly observed in immunocompromised individuals. We describe a daily cannabis smoker without evidence of immunodeficiency presenting with confirmed Cryptococcus neoformans meningitis. An investigation of cannabis samples from the patients preferred dispensary demonstrated contamination with several varieties of Cryptococcus, including C. neoformans, and other opportunistic fungi. These findings raise concern regarding the safety of dispensary-grade cannabis, even in immunocompetent users.

BACKGROUND: The presence of Major Depressive Disorder (MDD) is often comorbid in patients with a variety of general medical conditions (GMCs) which could lead to less favorable outcomes. OBJECTIVE: The goal of this analysis is to examine functional outcomes of QOL and functioning before and after antidepressant treatment among patients with MDD with and without GMCs. METHODS: We performed a secondary analysis based on the STAR*D database. The analysis included two patient groups from the STAR*D trial: 1,198 patients comorbid with MDD and GMCs (MDD + GMC) and 1,082 patients with MDD and no GMCs (MDDnoGMC), as defined by the Cumulative Illness Rating Scale. We analyzed depressive symptom severity, functioning and quality of life (QOL) before and after level 1 treatment with citalopram. RESULTS: At baseline, the MDD + GMC group had significantly lower QOL (p < 0.001) and functioning (p = 0.001) than the MDDnoGMC group, although depressive symptom severity was not significantly different. Following antidepressant treatment, QOL, functioning and depressive symptom severity significantly improved for both MDD + GMC and MDDnoGMC groups. However, patients with MDD + GMC were more likely to experience severe impairments in QOL in (56.8% vs. 43.5% for MDDnoGMC, p < 0.001) and functioning (42.5% vs. 29.3% for MDDnoGMC, p < 0.001) following treatment. The remission rate was significantly lower for MDD + GMC (30.6% vs. 41.1% for MDDnoGMC, p < 0.001). CONCLUSIONS: Our findings suggest that antidepressant treatment had a positive impact on patients with and without GMCs. However, those with GMCs experienced not only a lower remission rate, but also continued to experience more significantly severe impairments in QOL and functioning.

OBJECTIVE: While trazodone is approved for the treatment of depression, the off-label use of this medication for insomnia has surpassed its usage as an antidepressant. In this systematic review, we examined the evidence for the efficacy and safety of trazodone for insomnia. METHODS: A literature search was conducted using MEDLINE/PubMed databases from the past 33 years (1983-2016) and the keywords insomnia, trazodone, sedative, treatment, and hypnotics. The results were restricted to English language and human subjects. All randomized clinical trials, meta-analyses, observational studies, and placebo-controlled trials regarding trazodone for the treatment of primary or secondary insomnia were reported, per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The study selection process yielded a total of 45 studies. RESULTS: Evidence for the efficacy of trazodone has been repeatedly demonstrated for primary insomnia, as well as secondary insomnia, including for symptoms that are a result of depression, dementia, and being a healthy man. Earlier studies (1980-2000) focused on utilizing trazodone at high doses (≥100mg/d) for the treatment of insomnia among the depressed population; however, since the 2000s, the utility of trazodone has been expanded to treat secondary insomnia among the non-depressed population as well. The side effects are dose-dependent, and the most common is drowsiness. CONCLUSION: A review of the literature suggests that there are adequate data supporting the efficacy and general safety of the low-dose use of trazodone for the treatment of insomnia.

BACKGROUND: Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. METHODS: We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. RESULTS: Hispanic participants had significantly worse QOL scores at entry and exit (p < 0.01). However, after controlling for baseline QOL, there was no difference between Hispanic and non-Hispanic patients QOL at exit (p = 0.21). There were no significant between-group differences at entry or at exit for depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values < 0.01). Patients with private insurance had lower depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. LIMITATIONS: This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. CONCLUSIONS: Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry.

We conducted a systematic review of the published literature relating to the assessment and measurement of wellness in order to answer the following questions: 1) What is the working definition of wellness? 2) What wellness assessment instruments have been evaluated or applied in medical settings? 3) How valid, reliable, and accessible are these wellness assessment tools? The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review. Studies published from1990 to 2016 on wellness assessment were identified through Medline and PsycINFO using the following keywords: assessment OR evaluation OR measurement AND wellness OR wellbeing. Two authors independently conducted a focused analysis then reached a consensus on 23 studies that met the specific selection criteria. This review revealed that there is a lack of uniform definition of wellness. The studies utilizing wellness assessment tools demonstrate strongest reliability values for the following instruments: Wellness Evaluation of Lifestyle, Five-factor Wellness Evaluation of Lifestyle, Perceived Wellness Survey, the Optimal Living Profile, and the Body-Mind-Spirit Wellness Behavior and Characteristic Inventory. However, there is insufficient evidence to support the clinical utility of a single particular wellness instrument. Properly defining wellness might help drive the development and validation of more precise assessment and measurement methods. This could reinforce interventions that promote wellness.

Objectives

Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months.

Methods

Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed.

Conclusions

The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings.

Registration

ClinicalTrials.Gov Identifier: NCT03688100.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Purpose

Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).

Methods

Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.

Results

Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.

Conclusions

A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.