Influence of Simvastatin as Augmentative Therapy in the Treatment of Generalized Anxiety Disorder: A Pilot Randomized, Placebo-Controlled Study.

BACKGROUND: Preliminary evidence is promising regarding the anxiolytic effects of statins in animal models of anxiety. Hence, this study aimed to evaluate the efficacy of simvastatin augmentation versus placebo in the treatment of patients with generalized anxiety disorder (GAD) with residual symptoms despite treatment with selective serotonin reuptake inhibitors (SSRIs). METHODS: A double-blind, 8-week controlled trial was conducted from August 2018 to December 2019 in an outpatient psychiatry clinic in Hamadan, Iran. A total of 138 patients with a diagnosis of GAD were assessed for eligibility. Of them, 84 patients who met the study criteria were randomly assigned either to the adjuvant simvastatin (20 mg/day) or to the placebo group. Standard medication consisting of SSRIs was consistent 2 months prior to and during the study. The severity of anxiety symptoms for each patient was assessed based on the Hamilton Anxiety Rating Scale (HAM-A) score at baseline, week 4, and week 8 after treatment. Additionally, blood lipid values were assessed at baseline and on completion of the study. RESULTS: Thirty-three out of 42 patients in the intervention group and 35 out of 42 patients in the control group completed the 8 weeks of the study period. Compared to the placebo group, in the simvastatin group cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and high-density lipoprotein significantly increased over time. General linear model analysis demonstrated that although over time a higher decrease in mean HAM-A scores was observed in the intervention group compared to the control group, this difference was not statistically significant (p = 0.11). In addition, at the end of the study, the number of responders and remitters was comparable in the two groups. CONCLUSIONS: The results from this clinical study did not support the potential efficacy of adjunctive simvastatin in the treatment of patients with GAD. Thus, large-scale and long-term clinical trials are required to more accurately assess the potential efficacy of statins in the treatment of patients with anxiety disorders.

Evaluation of Efficacy of Mirtazapine on Pruritus and Serum Histamine and Serotonin Levels in Patients Undergoing Hemodialysis: A Before-After Pilot Clinical Trial.

BACKGROUND: Although chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and frustrating symptom in patients with advanced kidney diseases, its optimal treatments are not well defined. Based on its mechanism of action, as a histamine-1 (H1), 5-(hydroxytryptamine) HT2, and 5HT3-receptor blocker, mirtazapine may be effective in the treatment of CKD-aP. Hence, this study aimed to investigate the efficacy of mirtazapine for the treatment of pruritus in patients undergoing hemodialysis (HD). METHODS: A before-after clinical trial was conducted from September 2018 until March 2019, on 30 HD-patients that had been referred to the HD ward of a tertiary hospital, in Hamadan, Iran. After the 2-week washout period, mirtazapine was administered with a dosage of 15 mg/day for an additional 2 weeks. At baseline and at each dialysis session, the effects of the mirtazapine on the pruritus severity based on the visual analogue scale (VAS) and degree of sleep interference resulting from the pruritus were asked and recorded. Additionally, at the baseline and the end of 2 weeks of treatment, the serum histamine and serotonin levels, as the main chemical pruritogens evoking pruritus symptoms, were also determined. RESULTS: Twenty-seven patients completed the entire course of the study. Based on the general linear model analysis, a progressive decline in the mean VAS score was observed over time during the study. The mean VAS score decreased from 8.48 ± 1.01 at baseline to 1.04 ±0.79 at the end of treatment (P-value<0.001). Similarly, the mean sleep interference scores were also significantly improved throughout treatment (decreased from 8.07±1.43 to 2.81± 0.74; P-value<0.001). Further, at the end of the treatment, a noticeable decrement in the serum histamine level was also seen (P-value = 0.006). The drug was acceptably well-tolerated and a majority of the patients were satisfied with this treatment. CONCLUSION: This pilot study suggests that mirtazapine may be an effective treatment option for the management of CKD-aP. However, further studies would be needed to confirm these results.

Effect of mirtazapine on pruritus in patients on hemodialysis: a cross-over pilot study.

BACKGROUND: Uremic pruritus (UP) is a highly prevalent and disturbing problem in patients with advanced chronic kidney disease (CKD); however, treatment of UP is largely unsatisfactory. The present study was designed to investigate the effectiveness of mirtazapine, an atypical antidepressant agent with potent antagonistic activity against serotonin (5HT2, 5HT3) and histamine (H1) receptors, in the treatment of pruritus in hemodialysis (HD) patients. METHODS: An 8-week long, prospective, open-label, and cross-over randomized clinical trial study was conducted on 77 HD patients with chronic pruritus. After a 2-week washout period, eligible patients were randomly assigned either to the mirtazapine (15 mg per day) or gabapentin (100 per day) for 2 weeks. Following 2 weeks washout period, subjects crossed over to the other treatment arm for 2 more weeks. The severity of pruritus was measured seven times during each treatment period using the visual analogue scale (VAS). Furthermore, at the end of the study, patients also were blindly asked which treatment (first or last in the sequential course of the study) they preferred. RESULTS: Sixty-one patients completed two treatment periods of the study. Although, compared to baseline, both gabapentin and mirtazapine treatment resulting in significant improvement in VAS scores, decreasing in pruritus severity was significantly greater in the mirtazapine treatment period compared with the gabapentin treatment period (P < 0.001). Furthermore, although side effects such as drowsiness and dry mouth more reported in the mirtazapine treatment period, overall higher percentage of the study patients preferred mirtazapine over gabapentin for the treatment of their pruritus symptoms. CONCLUSIONS: Although preliminary, our study provides evidence that mirtazapine can be an effective therapy for UP in patients who are on maintenance HD. However, further studies would be necessary to confirm effectiveness as well as the safety of mirtazapine in the long-term management of chronic pruritus.

Influence of adjuvant Coenzyme Q10 on inflammatory and oxidative stress biomarkers in patients with bipolar disorders during the depressive episode.

Bipolar disorder (BPD) is a severe and chronic mental disease with high rates of social and functional disability. To explain the emergence and maintenance of BPD, increasing attention has been focused on dimensions of inflammation and oxidative stress (OTS). Coenzyme Q10 (CoQ10) is known for its anti-oxidant and anti-inflammatory effects; accordingly, the aim of the present study was to investigate, if compared to placebo, adjuvant CoQ10 might favorably impact on serum levels of inflammatory and OTS biomarkers in patients with BPD during their depressive phase. A total of 89 BPD patients, currently in a depressive episode were allocated by block randomization either to the adjuvant CoQ10 (200 mg/day) condition or to the placebo condition. At baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interlukin-6 (IL-6), and IL-10 were assessed. 69 patients completed the 8-week lasting study. Compared to baseline and to the placebo condition, serum levels of TTG and TAC significantly increased, and TNF-α, IL-10, and NO statistically decreased over time in the adjuvant CoQ10 condition. No statistically significant changes were observed for CAT, MDA, and IL-6. The pattern of results suggests that compared to placebo and over a time lapse of 8 weeks, adjuvant CoQ10 favorably impacted on OTS and inflammatory biomarkers in patients with BPD during the depressive episode. Thus, CoQ10 might be considered a safe and effective strategy for treatment of patients with BPD during their depressive phase.

Comparison of Sertraline with Rifampin in the treatment of Cholestatic Pruritus: A Randomized Clinical Trial.

BACKGROUND: Pruritus is one of the most common and disabling symptoms of liver disease such as Primary Sclerosing Cholangitis and Primary Biliary Cholangitis. Cholestyramine, rifampin, opioid antagonists, antihistaminic agents and SSRIs are used for the management of pruritus. Due to rifampin drug interactions as well as its serious side effects such as hepatotoxicity, clinicians are endeavoruing to find a safer and a more effective substitution. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of sertraline with rifampin in the management of cholestatic pruritus. METHODS: In a single-blinded randomized clinical trial a total of 36 patients of PSC and PBC were divided into two equal groups, one group received 100 mg/day sertraline and the other group received rifampin 300 mg/day for 4 weeks. Visual analog scale was used to record pruritus severity at baseline and 4 weeks after drug intervention, also, ALT, AST, ALP and total bilirubin of all patients were measured at three different time points. RESULTS: Over the follow-up period, pruritus had relieved in both groups, but there was no significant differences between sertraline and rifampin in pruritus management (pvalue=0.740), also there was no significant difference between the two intervention strategies (A versus B) in total bilirubin level (pvalue=0.106). Moreover, the ALT, AST and ALP levels were found to be significantly different between the two groups (Pvalue˂0.01). CONCLUSION: There is no difference between sertraline and rifampin in pruritus improvement, but sertraline has less adverse effects on hepatobiliary enzyme levels, so it seems to be safer than rifampin.

Evaluating the Effect of Coenzyme Q10 Augmentation on Treatment of Bipolar Depression: A Double-Blind Controlled Clinical Trial.

BACKGROUND: Bipolar disorder (BPD) is a chronic and recurrent mood disorder characterized by episodes of mania, hypomania, and major depression. Based on available evidence, mitochondrial dysfunction, oxidative stress, and inflammation have important roles in the pathophysiology of bipolar depression. More specifically, it seems that coenzyme Q10 (CoQ10), a mitochondrial modulator, as well as an antioxidant and anti-inflammatory agent, might be effective in modulating these pathophysiological pathways. Accordingly, the aim of this study was to investigate whether and to what extent, compared with placebo, adjuvant CoQ10 might improve symptoms of depression in patients with BPD. METHODS: A total of 69 patients with BPD with a current depressive episode were randomly assigned either to the adjuvant CoQ10 (200 mg/d) or to the placebo group. Standard medication consisting of mood stabilizers and antidepressants was consistent 2 months prior and during the study. Depression severity for each patient was assessed based on the Montgomery-Asberg Depression Rating Scale scores at baseline, fourth week, and eighth week of the study. RESULTS: Symptoms of depression decreased over time in both groups. Compared with the placebo group, adjuvant CoQ10 to a standard medication improved symptoms of depression after 8 weeks of treatment. In addition, at the end of the study, it turned out that more responders were observed in the CoQ10 group, compared with the placebo group. CoQ10 had minimal adverse effects and was well tolerated. CONCLUSIONS: The present pattern of results suggests that among patients with BPD, compared with placebo, adjuvant CoQ10 probably because of its antioxidant and anti-inflammatory properties can improve symptoms of depression over a period of 8 weeks.

Evaluating the Effects of Oral and Topical Simvastatin in the Treatment of Acne Vulgaris: A Double-blind, Randomized, Placebo-controlled Clinical Trial.

BACKGROUND: Acne vulgaris is a common dermatologic disorder which results in psychological consequences. Inflammatory responses play an important role in the development of inflammatory acne lesions. Recently, many studies have demonstrated anti-inflammatory effects of statins; thus, the aim of this study was to evaluate the efficacy of oral and topical Simvastatin as adjunct therapy in the treatment of acne vulgaris. METHODS: A total of 76 patients with moderate to very severe acne vulgaris, all receiving oral azithromycin (250 mg, 3 times a week, orally) and topical benzoyl peroxide gel (5%, once daily) were assigned to three groups: 1) Oral group received 20mg/day of oral simvastatin and blank solution, 2) Topical group received simvastatin 1% topical solution and oral placebo, 3) Placebo group received oral placebo and blank solution. The severity of acne was determined by global acne grading system (GAGS) at baseline and after 8 weeks of treatment. RESULTS: Comparing the three groups showed that topical simvastatin was associated with greater decrease in acne severity as compared with those of oral and placebo groups. Moreover, the oral simvastatin appeared to be more efficacious as compared with placebo group (P value<0.001). Oral and topical simvastatin were well tolerated in almost all patients. CONCLUSION: Although preliminary, the results of this study showed that oral and topical statins, drugs with anti-inflammatory properties, can be considered as effective treatment for acne vulgaris as an adjunct to standard treatment. However, further studies with larger sample size, using improved formulations of topical simvastatin are needed to confirm these results.

Evaluating the Effect of Oral N-acetylcysteine as an Adjuvant Treatment on Clinical Outcomes of Patients with Rheumatoid Arthritis: A Randomized, Double Blind Clinical Trial.

OBJECTIVE: Oxidative stress and Overproduction of pro-inflammatory cytokines are contributed in Rheumatoid Arthritis (RA) pathogenesis. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent which demonstrated analgesic effects in some studies. This study is designed to assess the effects of oral NAC as an adjuvant therapy on the clinical outcomes of patients with active RA. METHODS: In this randomized clinical trial, 51 RA patients with active RA were studied in 2 groups: NAC group (27 patients) received standard treatment of RA and 600 mg NAC twice a day for 12 weeks, and placebo group (24 patients) received the standard treatment of RA and placebo. Disease activity score (DAS28) was used to assess the activity of RA, Visual Analog Scale (VAS) for the severity of pain, Health Assessment Questionnaire (HAQ) for the patients' physical performance, and Global Health (GH) parameter for the patients' assessment of their disease activity. The number of tender and swollen joints and Erythrocyte Sedimentation Rate (ESR) were also determined for each patient. Data were analyzed using SPSS version 16.0 (Chicago, IL, USA). RESULTS: After 12 weeks of intervention, there were no significant differences between two groups in DAS28 score and ESR (P values were 0.4 and 0.6, respectively). However, GH, VAS, and HAQ scores were improved significantly in the NAC group compared to the placebo group. CONCLUSION: Our findings indicate that oral administration of NAC may be associated with improving health status in RA patients and considered as an adjuvant therapy in these patients. Further studies with larger sample size, longer study duration and higher doses of NAC are needed to confirm the effects of oral NAC in RA patients.