Efficacy and Safety of Varenicline for Smoking Cessation in Schizophrenia: A Meta-Analysis

Objective: Smoking represents a major public health problem among patients with schizophrenia. To this end, some studies have investigated the efficacy of varenicline for facilitating smoking cessation in schizophrenia patients. The present review seeks to synthesize the results of these studies as well as document the reported side effects of using this medication. Methods: An electronic search was performed using five major databases: PubMed, Scopus, EMBASE, Web of Science, and Cochrane Library. Included in the current analysis were randomized clinical trials (RCTs) that have investigated the effect of varenicline in promoting smoking cessation in patients with schizophrenia. Risk of bias among included RCTs was assessed using the Cochrane Collaboration’s quality assessment tool. Results: Among the 828 screened articles, only four RCTs, which involved 239 participants, were eligible for meta-analysis. In patients with schizophrenia, varenicline treatment when compared to placebo significantly reduced the number of cigarettes consumed per day [SMD (95% CI) = 0.89(0.57–1.22)] and expired carbon monoxide levels [SMD (95% CI) = 0.50 (0.06–0.94)] respectively. Conclusion: Despite a limited number of studies included in the meta-analysis, our results suggest that varenicline is an effective and safe drug to assist smoking cessation in patients with schizophrenia. Future large-scale well-designed RCTs are required to validate these findings

Cognitive Behavioral Therapy versus Eye Movement Desensitization and Reprocessing in Patients with Posttraumatic Stress Disorder: Systematic Review and Meta-analysis of Randomized Clinical Trials

Background Post-traumatic stress disorder (PTSD) is prevalent in children, adolescents and adults. It can occur alone or in comorbidity with other disorders. A broad range of psychotherapies such as cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) have been developed for the treatment of PTSD. Aim Through quantitative meta-analysis, we aimed to compare the efficacy of CBT and EMDR: (i) relieving the post-traumatic symptoms, and (ii) alleviating anxiety and depression, in patients with PTSD. Methods We systematically searched EMBASE, Medline and Cochrane central register of controlled trials (CENTRAL) for articles published between 1999 and December 2017. Randomized clinical trials (RCTs) that compare CBT and EMDR in PTSD patients were included for quantitative meta-analysis using RevMan Version 5. Results Fourteen studies out of 714 were finally eligible. Meta-analysis of 11 studies (n = 547) showed that EMDR is better than CBT in reducing post-traumatic symptoms [SDM (95% CI) = -0.43 (-0.73 – -0.12), p = 0.006]. However, meta-analysis of four studies (n = 186) at three-month follow-up revealed no statistically significant difference [SDM (95% CI) = -0.21 (-0.50 – 0.08), p = 0.15]. The EMDR was also better than CBT in reducing anxiety [SDM (95% CI) = -0.71 (-1.21 – -0.21), p = 0.005]. Unfortunately, there was no difference between CBT and EMDR in reducing depression [SDM (95% CI) = -0.21 (-0.44 – 0.02), p = 0.08]. Conclusion The results of this meta-analysis suggested that EMDR is better than CBT in reducing post-traumatic symptoms and anxiety. However, there was no difference reported in reducing depression. Large population randomized trials with longer follow-up are recommended to build conclusive evidence

The role of metformin in treatment of weight gain associated with atypical antipsychotic treatment in children and adolescents: A systematic review and meta-analysis of randomized controlled trials

Introduction: Second-generation antipsychotics are associated with significant weight gain. The aim of this systematic review and meta-analysis was to determine the efficacy and safety of metformin for the treatment of weight gain in children and young adults treated with second-generation antipsychotics. Methods: We followed PRISMA guidelines to evaluated studies published before March 2020 in Medline, Google Scholar, PubMed, Cochrane library database, annual scientific sessions of the American Psychiatric Association, American Academy of Child and Adolescent, Psychiatry, and American Society of Clinical Psychopharmacology. Studies included compared metformin with the placebo for management of weight gain in children and adolescents taking atypical antipsychotics. Non-randomized studies, animal experiment studies, editorials, and review studies were excluded. Multiple parameters, including change in anthropometric-biochemical parameters, drug discontinuation rate, and side effects among the groups were assessed. The random-effects method was used for meta-analysis. Results: Four studies with were included in the final analysis (213 patients; metformin: 106; control: 107). After pooled analysis, 12–16 weeks of metformin therapy was associated with a significant reduction in weight [(mean difference (MD): −4.53 lbs, confidence interval (CI): −6.19 to −2.87, p-value \u3c 0.001)], and BMI z score [MD, −0.09, CI: −0.16, −0.03, p-value: 0.004] compared to control. Metformin was also associated with a significant reduction in insulin resistance [MD: −1.38, CI: −2.26 to −0.51, p-value: 0.002]. There were higher odds of nausea-vomiting [OR: 4.07, CI: 1.32–12.54, p-value: 0.02] and diarrhea [OR: 2.93, CI: 1.50–5.71, p-value: 0.002] in the metformin group. However, there was no difference in drug discontinuation rate [OR: 1.45, CI: 0.41–5.06, p-value: 0.56]. Conclusion: Metformin may prove beneficial in the treatment of weight gain in children treated with second-generation antipsychotics. The pooled treatment effect showed a significant reduction in BMI Z-score and weight in just 12–16 weeks. The limitations include small sample size, variation in metformin dose, and duration of treatment. This meta-analysis should be interpreted as promising, and further larger studies are warranted before drawing a conclusion

Risk of Suicide in Patients With Major Depressive Disorder and Comorbid Chronic Pain Disorder: An Insight From National Inpatient Sample Data

Background: Approximately 17.3 million adults in the United States have had a minimum of one major depressive episode. Comorbidity of depression and pain can affect individuals of any age, but is more prevalent in the elderly affecting up to 13% of people in the elderly population. Given that depression and suicidal ideation (SI) pose a considerable burden resulting in enormous suffering, there is a need to understand the factors of the relationship between chronic pain (CP), depression, and SI. Objectives: Our primary objective in this study was to compare suicidality (SI/attempt [SA]) between patients with major depressive disorder (MDD) and CP and a matched control group. The secondary objective was to compare length of stay, total hospital costs, and discharge disposition in these populations. Study design: The National Inpatient Sample (NIS) dataset developed by the Healthcare Cost and Utilization Project was used for this study. The NIS is a database of hospital inpatient stays derived from billing data submitted by hospitals to statewide data organizations across the United States. We obtained patient records from the NIS dataset for the years 2006 to 2017. All data were de-identified so Institutional Review Board approval was waived. Methods: We used mean and standard error to describe continuous data and counts (percentage) to describe categorical data. Categorical data were compared using Rao-Scott adjusted chi-square tests and continuous data were compared using Student\u27s t tests. Matching was performed using propensity scores in random order with a caliper size of 0.001. To assess predictors associated with suicidality, logistic regression analysis was performed. Results: A total of 393,481 patients having MDD with CP (MDD+CP) were included in the analysis. The mean age was 49.4 years, and 54.9% of patients were women. Overall, rate of composite outcome of SI/SA was more prevalent in MDD+CP group (51% vs 41%, P \u3c 0.001). Rate of SI was 48% vs 39% (P \u3c 0.001) in the MDD+CP and MDD without CP (MDD-CP) groups, respectively. MDD+CP was one of the strongest predictors of suicidality, responsible for 48% more risk of SI/SA compared to MDD-CP group. In comparison to non-Whites, the rate of suicidality was 7.5% less in White population. Alcohol abuse and substance abuse were associated with 17% and 8% greater risk of SI/SA, respectively. For women, the odds of having SI/SA was 1.20 greater compared to men. Limitations: No information was available on the causal relationship between MDD+CP disorder and SI/SA. Retrospective studies are susceptible to recognition, reporting, and coding bias. There is no information available on medications use or the duration and severity of CP and bipolar disorder, which can all be confounding factors. Conclusions: Psychiatrists and other physicians must be cognizant of the presence of CP and the risk of suicide, especially when patients present with depressive symptoms. The treatment plan for this patient population should include routine screening for pain symptoms and risk assessment for SI

Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act as a scavenger by effectively increasing the levels of NAGS, ultimately enhancing the conversion of ammonia to urea. In our case report, we have mentioned a patient with treatment-resistant bipolar disorder, who presented with elevated ammonia levels secondary to valproic acid treatment. Valproic acid was the only drug that was effective in his case, so we initiated therapy to reduce his elevated ammonia levels. After a thorough evaluation, we found the patient had a genetic NAGS deficiency. Carglumic acid was initiated and proved efficacious in our patient

The Effectiveness of Selective Serotonin Reuptake Inhibitors for Treatment of Obsessive-Compulsive Disorder in Adolescents and Children: A Systematic Review and Meta-Analysis

Background: Obsessive-compulsive disorder (OCD) is a common behavioral disorder among adolescents and children. The selective serotonin reuptake inhibitors (SSRIs) are the first pharmacological choice for this condition due to mild adverse effect profile. Objective: This systematic review was performed to evaluate the efficacy of SSRI for OCD in adolescents and children. Methods: Search terms were entered into PubMed, PsycINFO, Scopus, CINAHL, and Google Scholar. The included studies were randomized, placebo-controlled trials of SSRIs conducted in populations of children and adolescents younger than 18 years. Change from baseline Children\u27s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), end-treatment CY-BOCS with respective SD, and response and remission rates were collected for continuous and dichotomous outcome assessment, respectively. Cochrane Rev Man software was used for meta-analyses, providing Forest plots where applicable. Results: SSRIs were superior to placebo with a small effect size. There was no additional benefit of combination treatment over cognitive behavioral therapy (CBT) alone, but CBT added substantial benefit to SSRI monotherapy. Fluoxetine and sertraline appear to be superior to fluvoxamine. Conclusion: The results of current systematic review and meta-analysis support the existing National Institute for Health and Care Excellence (NICE) guidelines for choosing CBT as first line of treatment and substituting it with SSRI, depending on patient preference. Adding CBT to current SSRI treatment is effective for non-responders and partial responders, but adding SSRI to ongoing CBT does not prove beneficial. The SSRIs have different effectiveness, and their relative efficacy remains to be investigated

A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression

The biochemical processes involved in depression go beyond serotonin, norepinephrine, and dopamine. The N-methyl-D-aspartate (NMDA) receptor has a major role in the neurophysiology of depression. Ketamine, one of the prototypical NMDA antagonists, works rapidly in controlling depressive symptoms, including acutely suicidal behavior, by just a single injection. Ketamine may rapidly increase the glutamate levels and lead to structural neuronal changes. Increased neuronal dendritic growth may contribute to synaptogenesis and an increase in brain-derived neurotrophic factor (BDNF). Activation of the mechanistic target of rapamycin (mTOR), as well as increased levels of BDNF, may increase long-term potentiation and result in an improvement in the symptoms of depression. The mechanisms of ketamine’s proposed effect as an off-label treatment for resistant depression are outlined in this paper

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach

The synthesis of new 6-Bromoquinolin-4-ol derivatives (3a–3h) by Chan–Lam coupling utilizing different types of solvents (protic, aprotic, and mixed solvents) and bases was studied in the present manuscript. Furthermore, their potential against ESBL producing Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Commercially available 6-bromoquinolin-4-ol (3a) was reacted with different types of aryl boronic acids along with Cu(OAc)2 via Chan–Lam coupling methodology utilizing the protic and aprotic and mixed solvents. The molecules (3a–3h) exhibited very good yields with methanol, moderate yields with DMF, and low yields with ethanol solvents, while the mixed solvent CH3OH/H2O (8:1) gave more excellent results as compared to the other solvents. The in vitro antiseptic values against ESBL E. coli and MRSA were calculated at five different deliberations (10, 20, 30, 40, 50 mg/well) by agar well diffusion method. The molecule 3e depicted highest antibacterial activity while compounds 3b and 3d showed low antibacterial activity. Additionally, MIC and MBC standards were calculated against the established bacteria by broth dilution method. Furthermore, a molecular docking investigation of the derivatives (3a–3h) were performed. Compound (3e) was highly active and depicted the least binding energy of −5.4. Moreover, to investigate the essential structural and physical properties, the density functional theory (DFT) findings of the synthesized molecules were accomplished by using the basic set PBE0-D3BJ/def2-TZVP/SMD water level of the theory. The synthesized compounds showed an energy gap from 4.93 to 5.07 eV

Use of Gabapentin in the Treatment of Substance Use and Psychiatric Disorders: A Systematic Review

Objective: Gabapentin (GBP) is an anticonvulsant medication that is also used to treat restless legs syndrome (RLS) and posttherapeutic neuralgia. GBP is commonly prescribed off-label for psychiatric disorders despite the lack of strong evidence. However, there is growing evidence that GBP may be effective and clinically beneficial in both psychiatric disorders and substance use disorders. This review aimed to perform a systematic analysis of peer-reviewed published literature on the efficacy of GBP in the treatment of psychiatric disorders and substance use disorders. Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed and Ovid MEDLINE literature databases were screened and filtered by using specific search terms and inclusion/exclusion criteria. The full texts of selected studies were subsequently retrieved and reviewed. The search terms generated 2,604 results from the databases. After excluding all duplicates, 1,088 citations were left. Thereafter, we applied inclusion and exclusion criteria; a total of 54 papers were retained for detailed review. Results: This literature review concludes that GBP appears to be effective in the treatment of various forms of anxiety disorders. It shows some effectiveness in bipolar disorder as an adjunctive therapeutic agent, while the evidence for monotherapy is inconclusive. In substance use disorders, GBP is effective for acute alcohol withdrawal syndrome (AWS) with mild to moderate severity; it reduces cravings, improves the rate of abstinence, and delays return to heavy drinking. GBP may have some therapeutic potential in the treatment of opioid addiction and cannabis dependence, but there is limited evidence to support its use. No significant benefit of GBP has been conclusively observed in the treatment of OCD, PTSD, depression, or cocaine and amphetamine abuse. Conclusion: GBP appears to be effective in some forms of anxiety disorders such as preoperative anxiety, anxiety in breast cancer survivors, and social phobia. GBP has shown to be safe and effective in the treatment of alcohol dependence. However, the literature suggests that GBP is effective as an adjunctive medication rather than a monotherapy. More clinical trials with larger patient populations are needed to support gabapentin\u27s off-label use in psychiatric disorders and substance use disorders. It is worth noting that numerous clinical studies that are discussed in this review are open-label trials, which are inherently less rigorously analyzed. Therefore, more extensive investigations are required to examine not only the efficacy of GBP, but also its safety and tolerance

Use of Gabapentin in the Treatment of Substance Use and Psychiatric Disorders: A Systematic Review

Objective: Gabapentin (GBP) is an anticonvulsant medication that is also used to treat restless legs syndrome (RLS) and posttherapeutic neuralgia. GBP is commonly prescribed off-label for psychiatric disorders despite the lack of strong evidence. However, there is growing evidence that GBP may be effective and clinically beneficial in both psychiatric disorders and substance use disorders. This review aimed to perform a systematic analysis of peer-reviewed published literature on the efficacy of GBP in the treatment of psychiatric disorders and substance use disorders.Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed and Ovid MEDLINE literature databases were screened and filtered by using specific search terms and inclusion/exclusion criteria. The full texts of selected studies were subsequently retrieved and reviewed. The search terms generated 2,604 results from the databases. After excluding all duplicates, 1,088 citations were left. Thereafter, we applied inclusion and exclusion criteria; a total of 54 papers were retained for detailed review.Results: This literature review concludes that GBP appears to be effective in the treatment of various forms of anxiety disorders. It shows some effectiveness in bipolar disorder as an adjunctive therapeutic agent, while the evidence for monotherapy is inconclusive. In substance use disorders, GBP is effective for acute alcohol withdrawal syndrome (AWS) with mild to moderate severity; it reduces cravings, improves the rate of abstinence, and delays return to heavy drinking. GBP may have some therapeutic potential in the treatment of opioid addiction and cannabis dependence, but there is limited evidence to support its use. No significant benefit of GBP has been conclusively observed in the treatment of OCD, PTSD, depression, or cocaine and amphetamine abuse.Conclusion: GBP appears to be effective in some forms of anxiety disorders such as preoperative anxiety, anxiety in breast cancer survivors, and social phobia. GBP has shown to be safe and effective in the treatment of alcohol dependence. However, the literature suggests that GBP is effective as an adjunctive medication rather than a monotherapy. More clinical trials with larger patient populations are needed to support gabapentin’s off-label use in psychiatric disorders and substance use disorders. It is worth noting that numerous clinical studies that are discussed in this review are open-label trials, which are inherently less rigorously analyzed. Therefore, more extensive investigations are required to examine not only the efficacy of GBP, but also its safety and tolerance