Waterpipe and cigarette smoking and drug and alcohol consumption, and the risk of primary progressive multiple sclerosis: A population-based case-control study.

Background: Multiple sclerosis (MS) is a chronic central nervous system disease, and primary progressive multiple sclerosis (PPMS) is one the main types of MS, which has unknown environmental risk factors. The present study was conducted with the aim to identify the association of waterpipe and cigarette smoking, substance abuse, and alcohol consumption with the risk of PPMS development. Methods: A population-based, case-control study was conducted in Tehran, Iran, on 146 PPMS cases and 294 controls. PPMS cases were diagnosed and confirmed by neurologists. Standard random digit dialing was used to select sex-matched healthy control participants from the same source population as the cases. Logistic regression analysis was used to estimate unadjusted and adjusted odds ratios (OR). Results: In total, 440 subjects participated in the study. PPMS was associated with ever smoking cigarettes [OR = 2.48; confidence interval (CI) = 1.44-4.27], and passive smoking (OR = 2.20; CI = 1.34-3.62). However, having ever smoked waterpipe was not significantly associated with PPMS risk (OR = 1.19; CI = 0.62-2.26). Those who had all 3 types of smoking had an accumulative OR that was 10.45 times higher than that in individuals without any type of smoking (OR: 10.45; 95% CI = 3.5-31.2). We did not find any significant association between PPMS risk and substance abuse and alcohol consumption. Conclusion: Cigarette smoking and being exposed to passive smoking are important risk factors for developing PPMS; in addition, the use of 3 types of smoking, showed an OR higher than that in those without any smoking. Considering the global increase in tobacco smoking, this finding emphasizes the importance of interventional programs for the prevention of tobacco smoking.

Ketamine and Other Glutamate Receptor Modulating Agents for Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials.

Objective: Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. Method : The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Results: Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. Conclusion: The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.

Environmental risk factors of multiple sclerosis in the Middle East and North Africa region: A systematic review.

Background: The environmental factors play a major role as risk factors of multiple sclerosis (MS). This study aimed at gathering environmental risk factors of MS in the Middle East and North Africa (MENA). Methods: We used MEDLINE and EMBASE databases by a systematic review method. Out of a total of 123 studies, 16 studies met the eligibility criteria. Results: Totally, 47 risk factors were assessed as follows: six studies found sunlight exposure as a protective factor with the odds ratio (OR) ranging from 0.06 to 0.57. Six studies evaluated smoking as a risk factor with the OR ranging from 1.69 in all patients to 6.48 in female patients. Four studies supported measles infection as a risk factor with the OR ranging from 1.60 to 3.77, and in 3 studies, stressful events had a significant association with the OR of 1.80, 1.90, and 32.57. Conclusion: Among 47 assessed risk factors, sunlight exposure, cigarette smoking, measles infection, Epstein-Barr virus (EBV) infection, and stressful events had a significant association with MS.

5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control.

On the basis of numerous previous studies, the serotonergic system plays a role in the pathogenesis of obsessive-compulsive disorder (OCD) and effective agents in this pathway, such as 5-hydroxytryptophan, can potentially contribute to treatment of patients with this disorder. Evaluating the efficacy of 5-hydroxytryptophan in treating OCD was the aim of the present randomized, double-blind, placebo-controlled 12-week trial. In a 12-week, randomized double-blind study, 60 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of moderate to severe OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of >21 were randomly assigned to receive either fluoxetine plus placebo or fluoxetine plus 5-hydroxytryptophan (100 mg twice daily). All patients, regardless of their treatment group, received fluoxetine at 20 mg/day for the initial 4 weeks of the study followed by 60 mg/day of fluoxetine for the rest of the trial course. Symptoms were assessed using the Y-BOCS at baseline and weeks 4, 8 and 12. General linear model repeated measure showed significant effects for time × treatment interaction on total Y-BOCS (F = 12.07, df = 2.29, P-value <0.001), obsession (F = 8.25, df = 1.91, P-value = 0.001) and compulsion subscale scores (F = 6.64, df = 2.01, P-value = 0.002). 5-Hydroxytryptophan augmentation therapy demonstrated higher partial and complete treatment response rate (P = 0.032 and P = 0.001, respectively) according to the Y-BOCS total scores. The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.

L-Carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD). METHODS: Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. RESULTS: Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects. LIMITATIONS: Short follow-up period and small population size were two important limitations of this study. CONCLUSIONS: L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.

Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescence. About 30% of patients do not respond to stimulants or cannot tolerate their side effects. Thus, alternative medication, like herbal medicine, should be considered. The aim of this trial is to compare the safety and efficacy of Crocus sativus (saffron) versus methylphenidate in improving symptoms of children with ADHD. METHODS: In a 6-week randomized double-blind study, 54 patients (children 6-17 years old) with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomly assigned to receive either 20-30 mg/d (20 mg/d for <30 kg and 30 mg/d for >30 kg) methylphenidate (MPH) or 20-30 mg/d saffron capsules depending on weight (20 mg/d for <30 kg and 30 mg/d for >30 kg). Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6. RESULTS: Fifty patients completed the trial. General linear model repeated measures showed no significant difference between the two groups on Parent and Teacher Rating Scale scores (F = 0.749, df = 1.317, p = 0.425, and F = 0.249, df = 1.410, p = 0.701, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the saffron group and the MPH group (p = 0.731 and p = 0.883, respectively). The frequency of adverse effects was similar between saffron and MPH groups. CONCLUSION: Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate. Nevertheless, larger controlled studies with longer treatment periods are necessary for future studies.

Amantadine as adjuvant therapy in the treatment of moderate to severe obsessive-compulsive disorder: A double-blind randomized trial with placebo control.

AIM: The role of the glutamatergic system in the pathogenesis of obsessive-compulsive disorder (OCD) has been shown by numerous studies. The aim of the present randomized, double-blind, placebo-controlled, 12-week trial was to assess the efficacy and tolerability of amantadine as an adjuvant to fluvoxamine in the treatment of patients with moderate to severe OCD. METHODS: One hundred patients diagnosed with moderate to severe OCD were randomized into two parallel groups to receive fluvoxamine (100 mg twice a day) plus placebo or fluvoxamine (100 mg twice a day) plus amantadine (100 mg daily) for 12 weeks. All patients received 100 mg/day fluvoxamine for 28 days followed by 200 mg/day for the rest of the trial, regardless of their treatment groups. Patients were evaluated for response to treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and at Weeks 4, 10, and 12. The main outcome measure was to assess the efficacy of amantadine in improving the OCD symptoms. RESULTS: Repeated-measure analysis of variance showed a significant effect for Time × Treatment interaction (Greenhouse-Geisser corrected: F = 3.84, d.f. = 1.50, P = 0.03) in the Y-BOCS total score and a significant effect for Time × Treatment interaction (Greenhouse-Geisser corrected: F = 5.67, d.f. = 1.48, P < 0.01) in the Y-BOCS Obsession subscale score between the two groups. CONCLUSION: The results of this study suggest that amantadine may be effective as an augmentative agent in the treatment of moderate-to-severe OCD.