Efficacy and Safety of Anti-CGRP Monoclonal Antibodies in Prevention of Chronic Migraine: A Bayesian Network Meta-analysis

Due to the unmet needs in the management of migraine, a primary headache, and disabling disorder, the past decade has focused on developing monoclonal antibodies (mAbs) against the calcitonin-gene-related peptide (CGRP) as migraine prophylactic agents. The objective of the study was to evaluate the efficacy and safety of various anti-CGRP mAbs in the prevention of chronic migraine. Network meta-analysis (NMA) was performed using the Bayesian framework to estimate the efficacy and safety of mAbs after performing a literature search in PubMed, MEDLINE, Cochrane database, and International Clinical Trial Registry Platform (ICTRP). The outcomes calculated were in terms of mean difference (MD) or odds ratio (OR) with a 95% credible interval (95%CrI). Network graphs were constructed and node-split analysis was done to analyze the inconsistency. The NMA included a total of 10 clinical trials.Galacanezumab (120 mg) (MD: −2.7; 95%CrI: −4.8 to −0.83) was found to be better than other mAbs in terms of the difference in mean migraine days (MMD). Fremanezumab quarterly dose administration showed the best response (OR: 2.9; 95%CrI: 1.9 to 4.6) in terms of responder rate. Eptinezumab was found to be safer (OR: 0.88; 95%CrI: 0.61− 1.3) as compared to other mAbs in terms of the rate of adverse events. Fremanezumab (quarterly) ranked better in terms of response rate, and eptinezumab was found to be the safest in the prophylactic management of migraine.Galacenequmab was better at reducing MMD. Further studies are needed to evaluate the long-term safety, efficacy, and use of mAbs in migraine patients.

Augmentation Strategies for Partial or Non-responders to Clozapine in Patients with Schizophrenia: A Bayesian Network Meta-analysis of Randomized Controlled Trials

Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partialon-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine (−5.2 [95%CrI: −7.7, −2.7]) and memantine (−2.1 [95%CrI: −4.0, −0.19]) were more efficacious than placebo for augmentation of clozapine in partialon-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.

Can platelet-rich plasma injections provide better pain relief and functional outcomes in persons with common shoulder diseases: a meta-analysis of randomized controlled trials

To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases. Methods: The PubMed, Medline, and Central databases and trial registries were searched from their inception to October 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). Results: A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8–12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01–14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provided better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6–7 months. Conclusions: PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.

Effect of Haloperidol and Risperidone on Serum Melatonin and GAP-43 in Patients with Schizophrenia: A Prospective Cohort Study

Objective@#Serum melatonin, a biomarker of circadian rhythm, can upregulate Growth-associated protein 43 (GAP-43) which is involved in neural regeneration and plasticity. The present study was conducted to investigate the adequacy of the first-line antipsychotic drugs to improve sleep and circadian rhythm disruptions by assessing the effect of haloperidol and risperidone on serum melatonin and GAP-43 in schizophrenia. @*Methods@#In this cohort study, 100 schizophrenic patients were recruited, and clinical evaluations were done using the Positive and Negative Syndrome Scale (PANSS) and the Pittsburgh sleep quality index (PSQI). The patients with predominantly positive symptoms taking haloperidol (Group I) and patients with predominantly negative symptoms taking risperidone (Group II) were admitted and serum melatonin, arylalkylamine N-acetyltransferase, GAP-43 and urinary melatonin were estimated. After 8 weeks, all clinical and biochemical parameters were repeated. @*Results@#Serum melatonin (2:00 hours) was significantly decreased in both haloperidol (2.42; 95% confidence interval [95% CI]: 0.67−4.17; p = 0.008) and risperidone group (3.40; 95% CI: 0.54−6.25; p = 0.021). Urinary melatonin was significantly decreased in both haloperidol (p = 0.005) and risperidone group (p = 0.014). PSQI score was significantly increased in both haloperidol (p = 0.001) and risperidone group (p = 0.003). Serum GAP-43 was significantly decreased in both haloperidol and risperidone group (p ＜ 0.001). PANSS decreased significantly in both the groups and there was a significant negative correlation between serum melatonin at 2:00 hours and PANSS (r = −0.5) at baseline. @*Conclusion@#Monotherapy with haloperidol and risperidone can achieve symptomatic improvement but cannot improve sleep and circadian rhythm disturbances in schizophrenia.

Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis

BACKGROUND@#AND PURPOSE: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE.@*METHODS@#A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size.@*RESULTS@#The random-effects model analysis revealed a pooled effect size of −5.96 (95% CI= −8.98 to −2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p < 0.0001), with an overall effect size of −9.36 (95% CI=−13.24 to −5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect.@*CONCLUSIONS@#This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

Donepezil for Compulsive Behavior in Degenerative Dementia: Case Series

Diagnosing and managing dementia, presenting with compulsions is challenging. Presented are three cases, a possible representative subset of the Donepezil responders. Selective degeneration of dorsolateral prefrontal cortex networking striatum leading to compulsions would be amenable to cholinergic modulation.

Effect of Oxcarbazepine on Serum Brain Derived Neurotrophic Factor in Bipolar Mania: An Exploratory Study

OBJECTIVE: In bipolar disorder, serum brain-derived neurotrophic factor (BDNF) level decreases leading to dysfunctions of critical neurotrophic, cellular plasticity and neuroprotective processes. The present study was conducted to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar mania. METHODS: The present study is a prospective, interventional, open label clinical study conducted on 25 patients of bipolar mania and 25 healthy controls. Detailed history, clinical evaluation including Young Mania Rating Scale (YMRS) scoring and serum BDNF were assessed at baseline for all 50 subjects. The bipolar patients were prescribed tablet oxcarbazepine and followed up after 4 weeks for clinical evaluation and re-estimation of serum BDNF and YMRS scoring. RESULTS: The serum BDNF level in bipolar manic patients were compared with healthy controls at baseline and results revealed that there is a significant reduction (p=0.002) in serum BDNF level in bipolar patients. At follow-up after 4 weeks, the mean change in serum BDNF in bipolar group who were on oxcarbazepine monotherapy was found statistically significant (p=0.02) in comparison to healthy controls. In bipolar group, the YMRS score and serum BDNF at baseline have an inverse relation(r=−0.59) whereas change of the YMRS score had a positive correlation (r=0.67) with the change of serum BDNF over 4 weeks. CONCLUSION: In bipolar mania serum BDNF level is low and it is found to be increased with short term monotherapy with oxcarbazepine.

Prophylactic add on antiplatelet therapy in chronic kidney disease with type 2 diabetes mellitus: comparison between clopidogrel and low dose aspirin

Chronic kidney disease [CKD] coexisting with type 2 diabetes mellitus [DM] leads to coronary artery disease. The present study compares clopidogrel and low dose aspirin as prophylactic therapy against coronary events in patients with CKD with diabetes. Total 80 patients of CKD with type 2 DM were randomized and allocated to clopidogrel and aspirin groups to receive the drug at a dose of 75 mg and 150 mg once daily respectively for 8 weeks as add on therapy. Main outcome was change in blood pressure, metabolic parameters, renal function, inflammatory biomarkers, platelet aggregability and [UKPDS] United Kingdom Prospective Diabetes Study risk scoring. Significant decrease in blood pressure [P < 0.01], total cholesterol [P = 0.02], LDL [P < 0.01], triglyceride [P < 0.01] and a better glycemic control [P < 0.01] was found in clopidogrel group. Renal markers and electrolytes have been improved in clopidogrel group but in aspirin group there was deterioration [2.5%] of creatinine clearance. Clopidogrel group has shown a significant decrease in hsCRP [P < 0.01], UKPDS risk scoring [P < 0.01] and better anti aggregatory effect. Clopidogrel has prophylactic role in CKD with type 2 DM due to better control of metabolic parameters, renal function and inflammatory burden in comparison to aspirin