Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient. AREAS COVERED: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action. EXPERT OPINION: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

Marital Quality-A Neglected Player in the Prevention of Cardiovascular Diseases: A Systematic Review of Longitudinal Studies.

PURPOSE OF REVIEW: Marital quality (MQ) is a psychosocial factor that has been neglected in cardiovascular prevention guidelines, although its association with cardiovascular diseases has been identified in several studies. Therefore, we aim to investigate how MQ either in positive or negative dimensions affect different cardiovascular risk factors and diseases. RECENT FINDINGS: We systematically searched different databases in September 2023 for longitudinal studies conducted to assess the contribution of MQ to well-established cardiovascular risk factors and diseases. Two independent researchers screened studies and carried out data extraction and quality assessment of included ones. From 12,175 potential studies screened, 40 were included. The presence of significant heterogeneity in methodology, follow-up, and subsequent effect estimates made it unfeasible to do a meta-analysis. Despite the variation, most studies found a significant association of negative MQ measures with physical inactivity (2/2), high levels of smoking (4/5) and alcohol (3/3) use, increased metabolic syndrome risk (3/3), elevated type 2 diabetes mellitus (T2DM) risk and poor T2DM management (3/6), elevated cardiovascular disease risk and progression (9/11), increased body weight and obesity risk (2/3), elevated blood pressure and hypertension risk (7/8). Positive MQ measures were mainly associated with improvement in blood pressure control (2/2), reduced T2DM risk and its good management (1/1), reduced body weight and obesity risk (2/2), and increased survival in cardiovascular diseases (4/4). Based on current evidence, MQ seems to play a crucial role in developing established cardiovascular risk factors and diseases and is worth considering in preventive strategies.

Efficacy and safety of celecoxib for treatment of mild to moderate postpartum depression: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Evidence has demonstrated the roles of inflammatory processes in pathogenesis of depression. We aim to assess the effects of adjunctive celecoxib with cognitive behavioral therapy (CBT), an anti-inflammatory agent, in treatment of postpartum depression and on levels of Brain-derived neurotrophic factor (BDNF) and inflammatory cytokines. METHODS: This was a randomized, double-blind, placebo-controlled trial to investigate the effects of adjunctive celecoxib with CBT on postpartum depression. Fifty outpatient women with postpartum depression, participated in this study. Patients randomly received either a celecoxib capsule twice a day or a placebo capsule twice a day for 6 weeks. Patients were assessed using the Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and weeks 2, 4, and 6. RESULTS: Patients in the celecoxib group showed a greater decline in HDRS scores from baseline to all three study time points compared to the placebo group (p = 0.12 for week 2, p = 0.001 for week 4, p < 0.001 for week 6). Rate of response to treatment was significantly higher in the celecoxib group compared to the placebo group at week 4 (60 vs 24%, p = 0.010) and week 6 (96 vs 44%, p < 0.001). Rate of remission was significantly higher in the celecoxib group compared to the placebo group at week 4 (52 vs 20%, p = 0.018) and week 6 (96 vs 36%, p < 0.001). Levels of most inflammatory markers were significantly lower in the celecoxib group compared to the placebo group at week 6. Levels of BDNF were significantly higher in the celecoxib group compared to the placebo group at week 6 (p < 0.001). CONCLUSIONS: Findings suggest adjunctive celecoxib is an effective treatment for the improvement of postpartum depressive symptoms.

L-theanine combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial.

AIM: The main aim of this study was to investigate the additional effects of L-theanine, an amino acid in tea and an analog of glutamate with neuroprotective and anti-depressant properties, on obsessive-compulsive disorder (OCD) symptoms in combination with fluvoxamine. METHODS: Patients from either sex aged between 18 and 60 years diagnosed with OCD, based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of more than 21 were enrolled in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either L-theanine (100 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 5) or placebo and fluvoxamine. The primary outcome of interest in this study was the Y-BOCS total score decrease from baseline. RESULTS: From a total of 95 evaluated patients, 50 completed our study; 30 were randomly assigned to each group. Multivariate analysis (ANOVA) showed a significant effect of time × $$ \times $$ treatment for L-theanine in obsession subscale (F = 5.51, P = 0.008) of the Y-BOCS score but not in the total and compulsion scores. Our results showed significantly more improvement in obsession subscale scores in L-theanine compared to placebo group (P = 0.007, Cohen's d = 0.82). Also, total Y-BOCS scores were lower in L-theanine compared to placebo group at week 5 (P = 0.039, Cohen's d = 0.60) and 10 (P = 0.008, Cohen's d = 0.80). However, there was no significant between-group differences in compulsion subscale scores. Complete response was also more frequent in the L-theanine group (P = 0.0001). CONCLUSION: Findings in this study suggest L-theanine as a relatively safe and effective adjuvant therapy for moderate to severe OCD.

Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double-blind, placebo-controlled trial.

AIM: Palmitoylethanolamide is an endogenous fatty acid amide with neuroprotective and anti-inflammatory actions. We performed a randomized, double-blind, placebo-controlled clinical trial to investigate the efficacy and safety of palmitoylethanolamide combination therapy in acute mania. METHODS: Patients in the acute phase of mania were assigned into two parallel groups given either lithium (blood level of 0.8-1.1 mEq/L) and risperidone 3 mg plus palmitoylethanolamide 600 mg or placebo twice per day for 6 weeks. All participants were assessed with the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, and 6. RESULTS: A total of 63 patients (32 in palmitoylethanolamide and 31 in placebo groups) completed the trial. We found a significant effect for time×treatment interaction on the YMRS score (F = 5.22, d.f. = 2.34, P= 0.004) from baseline to study end point. Results from independent t test showed a significantly greater decrease in YMRS scores in the palmitoylethanolamide group, compared with the placebo group, from baseline to weeks 4 and 6 (P= 0.018 and P= 0.002, respectively). There was no significant difference between palmitoylethanolamide and placebo groups based on ESRS scores or ESRS changes in scores (P>0.05). CONCLUSIONS: Our findings provide preliminary evidence that palmitoylethanolamide is an effective adjunctive medication that improves manic symptoms and overall clinical status in acute episodes of mania. However, larger sample sizes and more extended follow-up therapy are needed in future studies to confirm our findings.

Expectations of Health Researchers From Academic Social Network Sites: Qualitative Study.

BACKGROUND: Today, academic social network sites' role in improving the quality of education and how investigators conduct their research has become more critical. OBJECTIVE: This study aimed to investigate Iranian health researchers' requirements for academic social network sites from a low-income country perspective. METHODS: This qualitative study with a phenomenological approach was done in 2020. In this study, 23 researchers in the health system were selected by purposive sampling. Semistructured interviews were used to collect data. Data were analyzed by MaxQDA-10 software and the content analysis method. RESULTS: We identified 2 categories of functional and technical characteristics in the study participants' expectations. Functional characteristics included facilitating communication and team activities, managing scientific publications, enhancing the process of conducting research, being informative, and sharing and trading laboratory materials and equipment. Technical characteristics of an academic social network include user management capabilities, high security and privacy, being user-friendly, and other technical features. CONCLUSIONS: Health researchers emphasized 2 functional and technical characteristics required to meet academic social network sites' expectations.

Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Depression has been recognized as one of the disorders associated with cardiac interventions such as percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). In the present study, we evaluated the efficacy and safety of sulforaphane in treatment of depression induced by cardiac interventions. METHODS: After initial screening, 66 patients with previous history of at least one cardiac intervention and current mild to moderate depression were randomly assigned to two parallel groups receiving either sulforaphane (n = 33) or placebo (n = 33) for six successive weeks. Efficacy was assessed using the Hamilton Rating Scale for Depression (HAM-D) at baseline and week 2, 4, and 6. Safety of the treatments was checked during the trial period. RESULTS: Sixty participants completed the clinical trial (n = 30 in each group). Baseline demographic and clinical parameters were all similar among groups. Repeated measures analysis indicated that the sulforaphane group exhibited greater improvement in HAM-D scores throughout the trial (P < 0.001). Response to treatment (≥50% reduction in the HAM-D score) rate was higher in the sulforaphane group at trial endpoint (30% vs 6.67%, P = 0.042). Remission (HAM-D score ≤ 7) rate was also higher in the sulforaphane group; however, the difference was not significant (23.33% vs 3.33%, P = 0.052). Finally, no significant difference was observed between the two groups in terms of frequency of side effects. CONCLUSIONS: Sulforaphane could safely improve depressive symptoms induced by cardiac interventions. Further clinical trials with larger sample sizes and longer follow-up periods are warranted to confirm our results.

Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Tipepidine, a synthetic, non-opioid expectorant, has been shown to improve depressive-like behavior in animal models of depression. In this study, we assessed the efficacy and tolerability of tipepidine combination therapy with citalopram in treatment of major depressive disorder (MDD). METHODS: In a randomized, double-blinded, placebo-controlled clinical trial, 62 patients with MDD were assigned into two parallel groups to receive citalopram (up to 40 mg/day) plus placebo or citalopram plus tipepidine (30 mg twice daily) for 6 weeks. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D) at baseline and Weeks 2, 4, and 6. RESULTS: Fifty-six patients completed the trial. The tipepidine group showed greater improvement in HAM-D scores from baseline to all three study time points (P = 0.048 for all). The remission and response-to-treatment rates were significantly higher in the tipepidine group (53.6% and 100%) compared to the placebo group (25.0% and 75%) at the study end-point (P = 0.029 and 0.005, respectively). The remission and response times in patients in the tipepidine group were also shorter compared with the placebo group (log-rank P = 0.020 and 0.004). There was no significant difference between the two groups in baseline parameters or frequency of side-effects. CONCLUSION: Tipepidine combination therapy with citalopram can effectively improve symptoms of patients with MDD in a shorter period of treatment. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.

Resveratrol adjunct to methylphenidate improves symptoms of attention-deficit/hyperactivity disorder: a randomized, double-blinded, placebo-controlled clinical trial.

Current pharmacological approaches have failed to provide complete remission for patients with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to evaluate the efficacy and tolerability of resveratrol (that have been shown to have antioxidative, anti-inflammatory, and anti-apoptotic effects) as an adjunct to methylphenidate in pharmacologic treatment of ADHD. This 8-week, double-blinded, placebo-controlled trial randomized 66 participants to receive either 500 mg/day resveratrol or matched placebo in addition to methylphenidate. ADHD symptoms were evaluated in the patients using the Parent and Teacher versions of ADHD-Rating Scale (ADHD-RS) at three measurement points with time intervals of 4 weeks. Furthermore, the tolerability of the treatment strategies was systematically compared. Repeated measures analysis demonstrated a significant effect for time-treatment interaction on all three subscales of the Parent ADHD-RS during the trial period (total: p = 0.015; inattention: p = 0.032; hyperactivity/impulsivity: p = 0.036). Nevertheless, the effect for time-treatment interaction was not significant for the Teacher version of ADHD-RS (total: F = 0.81, df = 1.33, p = 0.401; inattention: F = 0.57, df = 1.37, p = 0.507; hyperactivity/impulsivity: F = 0.65, df = 1.34, p = 0.466). The frequencies of complications in the treatment groups were similar. Resveratrol administration for a duration of 8 weeks improved characteristic symptoms in patients with ADHD according to their parents. Further investigations containing larger sample sizes, longer supplementation periods, and dose-response evaluations are required to replicate these findings in ADHD children more confidently.

Impact of opioid agonist treatment on mental health in patients with opioid use disorder: a systematic review and network meta-analysis of randomized clinical trials.

Background: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.Objectives: We compared mental health outcomes between different opioid agonist treatments and placebo/waitlist, and between the different opioids themselves.Methods: This meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with placebo/waitlist in the treatment of patients with opioid use disorder and reported at least one mental health outcome after 1-month post-baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. The primary outcome was overall mental health symptomatology, e.g. Symptom Checklist 90 total score, between opioids and placebo/waitlist. Random effects models were used for all the meta-analyses.Results: Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on the network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%) = -0.61 (-1.20, -0.11)), DAM (-1.40 (-2.70, -0.23)), and methadone (-1.20 (-2.30, -0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (-0.23 (-0.34, -0.13)).Conclusions: Opioid agonist treatments used for the treatment of opioid use disorder improve mental health independent of psychosocial services.

Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial.

This is a double-blind, placebo-controlled randomized trial to investigate the potential therapeutic effects of folinic acid/placebo as an adjuvant to risperidone on inappropriate speech and other behavioral symptoms of autism spectrum disorder (ASD). Fifty-five ASD children (age (mean ± standard deviation) = 13.40 ± 2.00; male/female: 35/20) were evaluated for behavioral symptoms at baseline, week 5, and week 10 using the aberrant behavior checklist-community (ABC-C). Folinic acid dosage was 2 mg/kg up to 50 mg per day for the entire course of the study. The repeated measures analysis showed significant effect for time × treatment interaction on inappropriate speech (F = 3.51; df = 1.61; P = 0.044), stereotypic behavior (F = 4.02; df = 1.37; P = 0.036), and hyperactivity/noncompliance (F = 6.79; df = 1.66; P = 0.003) subscale scores. In contrast, no significant effect for time × treatment interaction was found on lethargy/social withdrawal (F = 1.06; df = 1.57; P = 0.336) and irritability (F = 2.86; df = 1.91; P = 0.064) subscale scores. Our study provided preliminary evidence suggesting that folinic acid could be recommended as a beneficial complementary supplement for alleviating speech and behavioral symptoms in children with ASD.Clinical trial registeration: This trial was registered in the Iranian Registry of Clinical Trials ( www.irct.ir ; No. IRCT20090117001556N114).

Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial.

BACKGROUND: Patients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia. METHODS: In a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms. RESULTS: A total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups. CONCLUSION: Adding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.

Is transcranial direct current stimulation an effective modality in reducing food craving? A systematic review and meta-analysis.

Non-invasive electrical stimulation of the brain has recently been extensively investigated to regulate food craving. However, the existing literature is controversial and there are some important questions which need to be addressed about clinical and technical factors contributing to efficacy of this method. A systematic search was performed in reliable scientific databases, and 15 eligible studies were identified. The pooled standardized mean differences for the effects of transcranial direct current stimulation (tDCS) on Visual Analogue Scale, energy intake and food craving questionnaire were -0.78 [-1.12, -0.44], -0.91 [-1.38, -0.44], -0.54 [-0.85, -0.24], respectively. Subgroup analysis showed that the most important factors associated with the impact of tDCS on food craving were the population under study, current intensity of stimulation, and number of stimulation sessions. The findings of this study support a significant impact of neuromodulation of dorsolateral prefrontal cortex (DLPFC) on energy intake and food craving using tDCS. It is recommended that multisession bilateral stimulation of the DLPFC with the current intensity of 2 mA be used to reduce food craving.

A comparative, single-blind, randomized study on quetiapine and aripiperazole augmentation in treatment of selective serotonin reuptake inhibitor refractory obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder, of unknown etiology, that affects 2.5% of the population. An appropriate therapeutic response to conventional treatment is seen. Some studies use augmentative treatment by antipsychotics, glutamatergic, lithium, buspirone, and others agents to improve the therapeutic response. In this study, we aimed to evaluate the efficacy and tolerability of aripiprazole and quetiapine as augmentative treatments in patients with selective serotonin reuptake inhibitor (SSRI) refractory OCD. The OCD patients were initially treated for 12 weeks with a SSRI. If after 12 weeks their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score was more than 16, they were randomly assigned to either the aripiprazole or the quetiapine augmentation group for an additional 12 weeks. There were no significant differences in age, sex, education, marital status, or score of Y-BOCS and Clinical Global Impression-Severity Scale (CGI-S) between groups (p > 0.05) at the outset of the study. Significant differences were noted after 1 month when compared with results at 2, 3, and 4 months in both groups (p < 0.001). Both quetiapine and aripiprazole may be effective and well-tolerated augmentative agents in the treatment of SSRI-refractory OCD. Because of positive results, aripiprazole may be considered more effective and may have a more rapid onset in terms of therapeutic response.

Resveratrol as adjunctive therapy in treatment of irritability in children with autism: A double-blind and placebo-controlled randomized trial.

WHAT IS KNOWN AND OBJECTIVE: The underlying pathophysiology of autism spectrum disorder (ASD) has been linked to immune dysregulation, oxidative stress and excitation-inhibition imbalance. Among associated symptoms of ASD, management of irritability has gained considerable attention as it complicates adjustment of ASD patients and thus necessitates its pharmacological treatment. Resveratrol is a plant phytoalexin, which has been demonstrated to have neuroprotective effects through its anti-inflammatory and antioxidant properties. This double-blind, placebo-controlled randomized trial was designed to assess the potential therapeutic effects of resveratrol plus risperidone on irritability of ASD patients. METHODS: Sixty-two patients were assigned randomly into two groups of resveratrol and placebo. Both groups were treated with risperidone twice daily starting at a dose of 0.5 mg with a dose increase of 0.5 mg per week (for the first 3 weeks). Resveratrol dosage was 250 mg twice per day from the beginning of the study. Using the Aberrant Behavior Checklist-Community (ABC-C), patients were assessed for ASD-related behavioural symptoms at baseline, week 5 and week 10. The frequency of adverse events was recorded using a checklist containing 25 possible side effects, including general, gastrointestinal, neurological and cardiovascular complications. RESULTS AND DISCUSSION: Improvements in primary outcome measure (irritability) and three secondary outcome measures (lethargy/social withdrawal, stereotypic behaviour and inappropriate speech subscales) in the resveratrol group were statistically similar to those in the placebo group. The repeated measures analysis showed no time × treatment interaction on these subscale scores. In contrast, patients in the resveratrol group showed greater decline in hyperactivity/non-compliance score as a secondary outcome measure (mean difference [CI = 95%] = 4.51 [0.10-8.92], t = 2.04; P = .04), and repeated measures analysis showed significant effect for time × treatment effect on this subscale score (F = 3.81; df = 1.30; P = .043). There was no significant difference in number and severity of adverse events between the two groups. WHAT IS NEW AND CONCLUSION: This clinical trial demonstrated no significant effect for adjunctive treatment with resveratrol on irritability of patients with ASD. However, it provided preliminary evidence indicating that resveratrol could improve hyperactivity/non-compliance of ASD patients.

A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression.

WHAT IS KNOWN AND OBJECTIVE: Crocus sativus L., commonly known as saffron, has known anti-depressive properties. However, its effects on food craving and body weight in depressed patients are unknown. Hence, we aimed to evaluate the effects of saffron capsules on food craving, body weight and depression among overweight women with mild and moderate depression compared to the placebo. METHODS: Seventy-three women with BMI ≥ 25 comorbid with mild-to-moderate depression were recruited in this 12-week double-blind, placebo-controlled randomized clinical trial. Participants were randomly assigned into one of the two groups receiving daily either 30 mg of Crocus sativus capsules (15 mg twice/day) or placebo capsules (twice/day). We performed body composition assessments, and beck depression inventory-II at the baseline, and then 2, 4, 8 and 12 weeks later. One month after the participants stopped taking the capsules, weight differences were measured and compared between groups. RESULTS AND DISCUSSION: Fifty-two patients finished the study. The demographic and clinical variables at baseline were the same in two groups. Mean depression scores in the saffron group significantly decreased compared to placebo (mean ± SD: -8.4 score ± 5.9 vs -3.9 ± 5.5; t[50] = 2; P = .007; 95% CI: 1.3-7.7). There was not a significant effect of saffron on food craving using repeated-measures ANOVA, F(1, 29) = 0.38, P = .54. Patients in the saffron group showed fewer side effects. WHAT IS NEW AND CONCLUSION: Saffron capsules were not effective in reducing food craving, but as a safe over-the-counter supplement, it may help reduce the symptoms of depression in patients who experience mild or moderate depression and are overweight.

Vortioxetine effects on quality of life of irritable bowel syndrome patients: A randomized, double-blind, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease causing a substantial productivity loss with no definite treatment. Our study investigates the effects of vortioxetine vs placebo in enhancing the IBS patients' quality of life. METHODS: In a double-blinded, placebo-controlled, randomized trial, adults with IBS, according to the ROME IV criteria, were randomized to placebo and vortioxetine for 6 weeks. Participants were visited every two weeks to fill IBS quality of life, hospital anxiety and depression scale, and adverse effect questionnaires. RESULTS: Eighty patients were randomized, and seventy-two finished the trial. Baseline characteristics of groups were similar. Both placebo and vortioxetine significantly increased the quality of life during course of the study (both P-values < .001), whereas vortioxetine demonstrated a greater increase (P-value < .001). According to the analysis of covariances, this enhancement was irrespective of depression or anxiety score changes (P-value = .002). Adverse effect profile was similar between the groups and can increase IBS patients' quality of life superior to placebo. Vortioxetine effects in our study were observed irrespective of the depression and anxiety levels.

Comparison of vortioxetine and sertraline for treatment of major depressive disorder in elderly patients: A double-blind randomized trial.

WHAT IS KNOWN AND OBJECTIVE: Major depressive disorder (MDD) is a complex disease and one of the leading contributors to disease burden throughout the world. In the current study, we explored the efficacy and tolerability of vortioxetine versus sertraline on symptoms of depression in elderly patients with MDD. METHODS: Sixty patients diagnosed with MDD (based on DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were entered into a randomized double-blind study and were randomized to receive either vortioxetine (15 mg daily) or sertraline (75 mg daily) for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 3 and 6. Changes in HAM-D score, response rates, remission rate and time to response or remission were also compared between the two study groups. RESULTS AND DISCUSSION: Fifty patients completed the trial after six weeks. General linear model repeated measures demonstrated no difference in trend of the two treatment groups (P = .897). There was no significantly different improvement in the HDRS scores from baseline to weeks 3 and 6, as well. Differences in response rate, remission rate, time to response and time to remission periods were not statistically significant. Finally, there was not any significantly difference between the two study groups in the frequency of adverse events. WHAT IS NEW AND CONCLUSION: This study showed no significant differences in the efficacy and safety of vortioxetine in comparison with sertraline in order for it to be used safely for treatment of major depressive disorder in elderly patients.

Sulforaphane as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Irritability related to autism spectrum disorder (ASD) complicates the management of ASD patients at home and in clinical settings. In this randomized, double-blind, placebo-controlled clinical trial, we aimed to investigate the beneficial effects of adjuvant treatment with risperidone and sulforaphane in alleviating the irritability of children with ASD. METHODS: Sixty drug-free patients aged 4-12 years were randomly assigned to one of two groups receiving risperidone plus sulforaphane or placebo. Risperidone was started with a daily dose of 0.25 mg in patients weighing <20 kg and 0.5 mg in those weighing ≥20 kg and increased stepwise to reach a maximum of 1 mg (<20 kg), 2.5 mg (20-45 kg), and 3.5 mg (>45 kg). Sulforaphane was administered at a daily dose of 50 µmol (≤45 kg) or 100 µmol (>45 kg). The participants were assessed with the Aberrant Behavior Checklist - Community Edition at baseline and at Weeks 5 and 10. RESULTS: Compared to the placebo group, ASD patients in the sulforaphane group showed greater improvements in Irritability score (primary outcome measure; P = 0.001) and Hyperactivity/Noncompliance score (secondary outcome measure; P = 0.015), and significant Time × Treatment effect for Irritability (P = 0.007) and Hyperactivity/Noncompliance (P = 0.008). However, no difference was seen in improvements in the other secondary measures: Lethargy/Social Interaction score, Stereotypic Behavior score, Inappropriate Speech score, and frequency of adverse events. CONCLUSION: Our results support the safety and efficacy of sulforaphane as an adjuvant to risperidone for improvement of irritability and hyperactivity symptoms in children with ASD.