Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis.

OBJECTIVE: Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression. METHODS: We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects. RESULTS: A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18-0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose. LIMITATIONS: Overall quality of evidence was low and limited by small number of studies. Publication bias was high. CONCLUSIONS: This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.

Metabolomic biomarkers for (R, S)-ketamine and (S)-ketamine in treatment-resistant depression and healthy controls: A systematic review.

BACKGROUND: Ketamine is increasingly used for treatment-resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs). METHODS: A comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine. RESULTS: A total of 1859 abstracts were screened of which 11 were included for full-text review. Of these, a total of five articles were included (N = 147), including three RCTs (n = 129) and two open-label trials (n = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment-resistant bipolar depression (n = 22), unipolar depression (n = 91), and HCs (n = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post-infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients. CONCLUSIONS: This systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed.

The Association Between Thyroid Stimulating Hormone and Depression: A Historical Cohort Study.

OBJECTIVE: To investigate the association between thyroid-stimulating hormone (TSH) and clinically relevant depression (CRD) in a population-based study. PATIENTS AND METHODS: Adult patients (≥18 years of age) who received care at Mayo Clinic in Rochester, Minnesota, and completed a TSH and Patient Health Questionnaire - 9 (PHQ-9) within 6 months of each other, between July 8, 2017, and August 31, 2021, were included. Demographics, medical comorbidities, thyroid function laboratory data, psychotropic medications, presence of primary thyroid disorder, thyroid hormone replacement (T4 and/or T3), and mood disorder diagnoses (using International Classification of Diseases, 10th version, Clinical Modifications codes) were extracted electronically. The primary outcome, CRD, was defined as a PHQ-9 score greater than or equal to 10. Logistic regression analysis was conducted to assess the association between TSH categories (low ≤0.3 mIU/L; normal >0.3-4.2 mIU/L; high >4.2 mIU/L) and CRD. RESULTS: The cohort included 29,034 patients, mean age 51.4 years, 65% females, 89.9% White, and a mean body mass index of 29.9 kg/m2. The mean ± standard deviation for TSH was 3.0±8.5 mIU/L, and the mean PHQ-9 score was 6.3±6.2. After adjustment, the odds of CRD were significantly higher among the low TSH category (odds ratio, 1.37; 95% CI, 1.18-1.57; P<.001) compared with the normal TSH category, especially in people 70 years of age or younger compared with people older than 70 years of age. Subgroup analysis did not show an increase in odds of CRD among patients with subclinical/overt hypothyroidism/hyperthyroidism (after adjustment). CONCLUSION: In this large population-based cross-sectional study, we report that low TSH was associated with higher odds of depression. Future longitudinal cohort studies are needed to investigate the relationship between thyroid dysfunction and depression as well as sex differences.

Efficacy and Safety of Clonidine in the Treatment of Acute Mania in Bipolar Disorder: A Systematic Review.

Clonidine, an alpha-2 adrenergic agonist, has been proposed as an antimanic agent that acts by reducing noradrenergic transmission. We conducted a systematic review to examine the efficacy and safety of clonidine for acute mania/hypomania. A comprehensive literature search was performed to identify randomized controlled trials (RCT) and non-randomized studies investigating the efficacy and safety of monotherapy/adjuvant treatment with clonidine for acute mania/hypomania in patients with bipolar disorder (BD). Nine studies (n = 222) met our inclusion criteria, including five RCTs (n = 159) and four non-randomized studies (n = 63). Non-randomized studies showed clonidine to help reduce symptoms of mania. However, data from placebo controlled RCTs were inconsistent. One RCT showed adjuvant clonidine as superior to placebo, whereas another RCT reported that clonidine was not better than placebo. In individual RCTs, lithium and valproate offered better antimanic effects compared to clonidine. Studies reported hypotension, depression, and somnolence as common adverse effects. Significant differences in study design and sample size contributed to high heterogeneity. This systematic review suggests low-grade evidence for clonidine as an adjuvant treatment for acute mania with mood stabilizers and inconclusive efficacy as monotherapy, warranting further well-designed RCTs.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review.

Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review-conducted in accordance with the PRISMA guidelines-of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report significant thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.

Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents. METHODS: We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model. RESULTS: A total of 65 studies (N = 12,415) with 19 augmentation agents were included in the NMA. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine (fluoxetine), cariprazine, and lisdexamfetamine. For remission rates, compared to placebo, were significant for: thyroid hormone(T4), aripiprazole, brexpiprazole, risperidone, quetiapine, and olanzapine (fluoxetine). Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias (RoB), 63% had moderate RoB and 13% had high RoB. LIMITATIONS: Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons. CONCLUSIONS: This NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.

Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis.

Objective: To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD).Data Sources: Ovid MEDLINE, PsycInfo, and Embase databases were systematically searched for clinical studies of adult patients with MDD on long-term aripiprazole augmentation.Study Selection and Data Extraction: Long-term follow-up was defined as ≥ 6 months. Primary outcome was remission from depression. Secondary outcome was incidence of adverse effects.Results: Four open-label studies were included in this review. Random effects meta-analysis of 3 studies (n = 2,117) revealed a weighted average remission proportion of 0.33 (0.16-0.51), showing trend of improved response with duration of treatment. Three studies (n = 2,231) provided adverse effects data. Medically significant weight gain (25%-28% participants) was higher in studies with patients receiving doses ≥ 5 mg and lower (3.5%) in a study using doses < 5 mg. Akathisia (15%-16%), insomnia (12%-17%), somnolence (14%), and fatigue (18%) were common adverse effects. Tardive dyskinesia risk was low (< 1%) at 1-year follow-up. All included studies were open-label, noncontrolled studies, with longest follow-up of 52 weeks, limiting efficacy and safety conclusions.Conclusions: Aripiprazole augmentation may be an effective long-term strategy for treatment of refractory MDD. Lower maintenance doses (2-5 mg) of aripiprazole may be effective and have fewer side effects compared to larger doses (> 5 mg-10 mg).

Mindfulness-Based Cognitive Therapy, Acceptance and Commitment Therapy, and Positive Psychotherapy for Major Depression.

OBJECTIVE: In the past two decades, newer psychotherapy treatments have emerged for the treatment of major depression. This review aimed to comprehensively synthesize the evidence for mindfulness-based cognitive therapy (MBCT), acceptance and commitment therapy (ACT), and positive psychotherapy (PPT) in treating a current episode of major depression. METHODS: A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials of MBCT, ACT, and PPT for major depression. Standardized mean differences were calculated with Hedges' g to complete random-effects meta-analysis. Heterogeneity was assessed with the Cochran Q statistic and I2 statistic. Subgroup analysis was conducted to further investigate heterogeneity. RESULTS: A random-effects meta-analysis of 15 studies (MBCT, N=7; ACT, N=4; PPT, N=4) revealed that all three therapies showed efficacy in reducing symptoms of depression with a small favorable effect, compared with all control conditions (N=946; Hedges' g=0.34; 95% confidence interval=0.14, 0.54; p<0.001). Cochrane's Q statistic (Q=32, df=15, p=0.007) suggested significant heterogeneity (I2=53%). A mixed-effects model test for subgroup differences showed significant differences between active controls and treatment-as-usual controls (χ2=15.3, df=1, p<0.001). Overall quality of evidence and publication bias were low. CONCLUSIONS: Meta-analysis shows that MBCT and ACT may be superior to inactive or treatment-as-usual controls and that PPT may be comparable to active controls for reducing symptoms of major depression after an acute course of therapy. However, the quality of the evidence was low. High-quality studies are needed to confirm the efficacy of these interventions.

Artificial intelligence as an emerging technology in the current care of neurological disorders.

BACKGROUND: Artificial intelligence (AI) has influenced all aspects of human life and neurology is no exception to this growing trend. The aim of this paper is to guide medical practitioners on the relevant aspects of artificial intelligence, i.e., machine learning, and deep learning, to review the development of technological advancement equipped with AI, and to elucidate how machine learning can revolutionize the management of neurological diseases. This review focuses on unsupervised aspects of machine learning, and how these aspects could be applied to precision neurology to improve patient outcomes. We have mentioned various forms of available AI, prior research, outcomes, benefits and limitations of AI, effective accessibility and future of AI, keeping the current burden of neurological disorders in mind. DISCUSSION: The smart device system to monitor tremors and to recognize its phenotypes for better outcomes of deep brain stimulation, applications evaluating fine motor functions, AI integrated electroencephalogram learning to diagnose epilepsy and psychological non-epileptic seizure, predict outcome of seizure surgeries, recognize patterns of autonomic instability to prevent sudden unexpected death in epilepsy (SUDEP), identify the pattern of complex algorithm in neuroimaging classifying cognitive impairment, differentiating and classifying concussion phenotypes, smartwatches monitoring atrial fibrillation to prevent strokes, and prediction of prognosis in dementia are unique examples of experimental utilizations of AI in the field of neurology. Though there are obvious limitations of AI, the general consensus among several nationwide studies is that this new technology has the ability to improve the prognosis of neurological disorders and as a result should become a staple in the medical community. CONCLUSION: AI not only helps to analyze medical data in disease prevention, diagnosis, patient monitoring, and development of new protocols, but can also assist clinicians in dealing with voluminous data in a more accurate and efficient manner.

Efficacy and Tolerability of Lamotrigine in Borderline Personality Disorder: A Systematic Review and Meta-Analysis.

Background: Patients with Borderline Personality Disorder (BPD) have a high prevalence of mood disorders. Lamotrigine (LAM) is often used as an off-label therapeutic option for BPD. We aimed to conduct a systematic review and meta-analysis to assess the efficacy and tolerability of LAM for the treatment of BPD. Methods: We comprehensively searched electronic databases for eligible studies from the inception of databases to September 2019. Outcomes investigated were BPD dimensions, tolerability, and adverse events. Quality assessments were completed for the included studies. Data were summarized using random-effects model. Results: Of the 619 records, five studies, including three randomized controlled trials (RCT; N = 330) were included for the qualitative analysis. A meta-analysis conducted on two RCTs measuring LAM efficacy at 12 weeks, showed no statistically significant difference at 12 weeks (SMD: -0.04; 95% CI: -0.49, 0.41; p = 0.87; I2 = 38%) and at study endpoints (SMD: 0.18, 95%CI: -0.89, 1.26; p = 0.74; I2 = 86%) as compared to placebo. Sensitivity analysis on three RCTs measuring impulsivity/aggression showed no statistically significant difference between LAM and placebo (SMD: -1.84, 95% CI: -3.94, 0.23; p = 0.08; I2 = 95%). LAM was well tolerated, and quality assessment of the included trials was good. Conclusions: Our results suggest there is limited data regarding efficacy of lamotrigine in BPD. There was no consistent evidence of lamotrigine's efficacy for the core symptom domains of BPD. Future studies should focus on examining targeted domains of BPD to clarify sub-phenotypes and individualized treatment for patients with BPD.

An Update on the Efficacy and Tolerability of Oral Ketamine for Major Depression: A Systematic Review and Meta-Analysis.

Background: Intravenous Ketamine has shown robust antidepressant efficacy although other routes of administration are currently needed. We conducted a systematic review and meta-analysis of studies evaluating the efficacy and tolerability of oral ketamine for depression. Methods: A comprehensive search of major electronic databases from inception to April 2020 was performed. Studies of oral ketamine for depression, from case series to randomized clinical trials, were eligible. Randomized controlled trials were included in a meta-analysis, focusing on response, remission, time to effect, and side effects. Results: A total of 917 articles were identified with 890 studies screened, yielding a total of 10 studies included in our systematic review.Three randomized controlled trials (RCTs) (N = 161, mean age 37.9 ± 9.5 years, 58.6% females) were included in the meta-analysis. Pooled analysis suggested a significant antidepressant effect of oral ketamine (SMD: -0.75; 95% CI: -1.08, -0.43; p<0.0001; I2 = 0%) although remission rates (RR:2.77; 95% CI:0.96, 8.00; p = 0.06) and response rates (RR:2.58; 95% CI:0.94,7.08; p = 0.07) were marginal compared to placebo at the endpoint. Oral ketamine antidepressant effects seemed to take effect at the 2nd week (SMD: -0.71; 95% CI: -1.08, -0.35; p = 0.001; I2 = 0%). There were no significant differences in the overall side-effects between oral ketamine and the placebo group (RR 1.28, 95% CI: 0.89-1.83; p = 0.19). Conclusion: This focused meta-analysis of oral ketamine suggests a marginal efficacy for major depressive disorder without increased risk of adverse events. Further larger sample studies are needed to confirm these preliminary findings, analyzing differential response/remission rates by affective disorder, optimal dosing strategies, and its long-term effects.

Initial and subsequent 3-year cost after hospitalization for first acute ischemic stroke and intracerebral hemorrhage.

AIMS: To examine 1) the major drivers of index hospitalization and 3-year post-acute follow-up care, 2) cost for rehabilitation and homecare, and 3) indirect cost from lost productivity after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Retrospective study of adults hospitalized with AIS (n = 811) and ICH (N = 145) between 2003 and 2014. Direct costs standardized to Medicare reimbursement rates were captured for hospitalization and 3-year follow-up or death. Adjusted cost estimates were assessed using generalized linear modeling with gamma distribution. Costs for rehabilitation, home healthcare, and lost productivity were assessed using sets of cost captured through literature review. RESULTS: Calculated as mean cost per person: hospitalization $18,154 for AIS and $24,077 for ICH; monthly 3-year aggregate $5138 for AIS and $8172 for ICH; 3-year inpatient rehabilitation $4185 for AIS and $4196 for ICH; homecare $19,728 for AIS and $14,487 for ICH; indirect cost from lost productivity $77,078 for AIS and $56,601 for ICH. Age < 55 years, being non-white, and stroke severity were strongly associated with greater hospitalization cost for AIS and ICH. Hyperlipidemia incurred lower while cancer, coronary artery disease, asthma/chronic obstructive pulmonary disease, heart failure, and anemia incurred higher 3-year aggregate cost for AIS. Cancer and diabetes mellitus incurred higher 3-year aggregate cost for ICH. CONCLUSIONS: We provide estimates of direct and indirect costs incurred for acute and continuing post-acute care through a 3-year follow-up period after first-ever AIS and ICH with important comparisons for predictors between index hospitalization and 3-year post-stroke costs.

Feasibility Study of Stress Management and Resiliency Training (SMART) in Patients With Major Depressive Disorder.

OBJECTIVE: Stress is associated with the onset, maintenance, and recurrence of depression. This study investigated the feasibility of stress management and resiliency training (SMART) for enhancing resiliency in a group of patients with major depressive disorder. METHODS: In an open-label study, patients with major depressive disorder were invited to participate in an adjunctive 8-week group therapy of SMART (from June 2017 to June 2018) that encompassed attention training and practice of gratitude, compassion, higher meaning, acceptance, and forgiveness. The primary outcome measure was baseline-to-endpoint change in resilience as measured by the Connor Davidson Resilience Scale (CD-RISC). Secondary outcome measures included baseline-to-endpoint change in stress using the Perceived Stress Scale (PSS) and in depression using the 17-item Hamilton Depression Rating Scale (HDRS-17) and 9-item Patient Health Questionnaire (PHQ-9). RESULTS: Twenty-three participants enrolled in the study (mean ± SD age = 46 ± 13 years, female = 91%). Baseline ratings of mood were of mild-to-moderate symptom severity (mean HDRS-17 score = 14.5 and PHQ-9 score = 12), resilience (mean CD-RISC score = 53.8), and perceived stress (mean PSS score = 23.5). Of the participants, 74% were study completers (attended ≥ 6 sessions). In an intention-to-treat analysis, at study endpoint there was a significant improvement in resilience (mean CD-RISC score = 61.1, P = .03), reduction in perceived stress (mean PSS score = 19.4, P = .002), and improvement in depression (mean HDRS-17 score = 9.1 and PHQ-9 score = 7.6, both P < .001). CONCLUSIONS: A resilience training program focused on wellness is feasible for patients who are currently symptomatic with major depressive disorder. A larger randomized controlled trial is needed to establish efficacy of this intervention and explore the long-term impact of stress management and resilience training in depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03275961.

Exercise, Yoga, and Tai Chi for Treatment of Major Depressive Disorder in Outpatient Settings: A Systematic Review and Meta-Analysis.

OBJECTIVE: Exercise, yoga, and tai chi are commonly used complementary approaches for health and wellness. This review aims to synthesize the evidence for exercise, yoga, and tai chi in the outpatient treatment of major depressive disorder. STUDY SELECTION: A systematic search of the Ovid MEDLINE, EMBASE, PsycINFO, and Cochrane databases was conducted for randomized controlled trials of exercise, yoga, and tai chi for major depressive disorder. DATA EXTRACTION: Standardized mean differences were calculated and meta-analyzed using a random effects multilevel modeling framework. Heterogeneity and subgroup analysis was conducted. RESULTS: Twenty-five studies were included for final analysis (exercise: 15, yoga: 7, tai chi: 3). Overall, meta-analysis showed a moderate significant clinical effect. However, when only studies (6 studies) with the lowest risk of bias were included, the overall effect size was reduced to low to moderate efficacy. Overall quality of evidence was low. Heterogeneity and publication bias were high. CONCLUSIONS: The current meta-analysis of outpatient exercise, yoga, and tai chi for treatment of major depressive disorder suggests that adjunctive exercise and yoga may have small additive clinical effects in comparison to control for reducing depressive symptoms. The evidence for tai chi is insufficient to draw conclusions. The concerns with quality of studies, high heterogeneity, and evidence of publication bias preclude making firm conclusions.

Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.

OBJECTIVE: To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature. DESIGN: Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis. SETTING: Large academic centre, 1996-2015. PARTICIPANTS: Hospitalised patients with AMI or ADHF. MAIN OUTCOMES AND MEASURES: All-cause mortality and meta-analysis of relative risks (RR). RESULTS: Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81). CONCLUSIONS: Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis.

Personality Disorders in Primary Care: Impact on Depression Outcomes Within Collaborative Care.

BACKGROUND: Individuals with personality disorders (PDs) are high utilizers of primary care and mental health services; however, they struggle to utilize the care effectively and studies have shown a strong association between having a PD and higher impairment in social role functioning. This is especially important because PDs are highly comorbid with a wide range of other mental health disorders. The collaborative care model (CCM) for depression was developed with an emphasis on patient engagement and aimed to reduce health care utilization, while improving treatment outcomes in primary care. We hypothesized that the diagnosis of a personality disorder in primary care patients will negatively affect 6-month depression outcomes after enrollment into a CCM. METHODS: This retrospective chart review study was conducted on patients enrolled into CCM over a period of 7 years with collection of 6-month follow-up data. A total of 2826 patients were enrolled into CCM with a clinical diagnosis of depression and a baseline Patient Health Questionnaire-9 (PHQ-9) ≥10 were included in the study cohort. Using the depression database, baseline and 6-month follow-up data were obtained. Adjusted odds ratios (AORs) were determined for both remission and persistent depressive symptoms using logistic regression modeling for the 6-month PHQ-9 outcome; while retaining all the study variables. RESULTS: Of the 2826 CCM patients with depression in our study, 216 (7.6%) were found to have a PD. Patients with PD were younger (37.7 vs 42.5 years, P < .001) and more likely to be unmarried (36.1% vs 55.6%, P < .001) than patients without a PD. While age, marital status, clinical diagnosis, and Mood Disorders Questionnaire (MDQ) score were significant predictors of remission; anxiety symptoms, gender, and race were not. The presence of a PD diagnosis was associated with a 60% lower likelihood of remission at 6 months (AOR = 0.39; 95% CI 0.28-0.54). Conversely, patients without a PD were 2.5 times as likely to experience remission at 6-month remission compared to patients with PD (AOR =2.57; 95% CI 1.85-3.56). CONCLUSION: Patients with a personality disorder were more likely to have a recurrent depressive disorder diagnosis, an abnormal MDQ score, increased anxiety symptoms, and higher baseline PHQ-9 score. Patients with PD had worse CCM outcomes at 6 months with only 25.0% able to achieve remission versus 54.3% ( P < .001) without a PD. The presence of a PD with depression was associated with poor outcomes (reduced remission rates and increased persistent depressive symptoms rates) in comparison to patients without a diagnosis of PD, while treated within CCM.

Psychogenic Non-epileptic Seizures: An Updated Primer.

BACKGROUND: Psychogenic non-epileptic seizures are the most common paroxysmal event misdiagnosed as epilepsy. They significantly affect quality of life, functional status, and use of medical resources. OBJECTIVE: The goal of this review is to provide guidance to psychiatrists and other mental health professionals in the understanding and practical management of this condition. RESULTS: An abundance of new reports on the pathogenesis and effective treatments have become available over the last decade, yet specific barriers impede the fluid transition to treatment and remain an important challenge in the management of patients with psychogenic non-epileptic seizures. In the context of these difficulties, we initially present background information on psychogenic non-epileptic seizures covering their historic context, epidemiology, etiologic factors (including psychiatric, neuromedical, and neuropsychological factors), and current neurobiological models. Updated evidence-based treatments are discussed along with data on long-term outcomes. We also provide practical tools to help clinicians navigate differential diagnoses, establish their interdisciplinary roles, communicate the diagnosis, deliver treatment, and sort out commonly encountered challenges in the management of this condition.