Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes. METHODS: Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study. RESULTS: Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly different between the two groups. CONCLUSIONS: Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.

Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The antidepressive effect of pioglitazone has been noted in patients with major depressive disorder in absence of metabolic syndrome. This study was conducted to evaluate the safety and efficacy of pioglitazone in patients with bipolar depression without concomitant metabolic syndrome or diabetes. METHOD: Forty-eight outpatients with the diagnosis of bipolar I disorder and a major depressive episode participated in a parallel, randomized, double-blind, placebo-controlled trial, and 44 patients underwent 6-week treatment with either pioglitazone (30 mg/day) or placebo as an adjunctive treatment to lithium. Therapeutic serum lithium levels of 0.6-0.8 mEq/L were required for two or more consecutive weeks immediately before starting pioglitazone and during the 6-week study. Patients were evaluated using Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) at baseline and weeks 1, 2, 4, and 6. The primary outcome was to evaluate the efficacy of pioglitazone in improving the depressive symptoms. RESULT: General linear model repeated measures showed significant effect for time × treatment interaction on the HDRS scores [F(2.78, 116.65) = 4.77, P = .005]. Significantly greater reduction was observed in HDRS scores in the pioglitazone group than the placebo group from baseline HDRS score at weeks 2, 4, and 6, P = .003, .006, and .006, respectively. No serious adverse event was observed. CONCLUSION: This study showed that pioglitazone could be a tolerable and effective adjunctive therapy for improving depressive symptoms in bipolar disorder without type 2 diabetes or metabolic syndrome.

Association between School Achievement and Tobacco Susceptibility among US Adolescents: Ethnic Differences.

BACKGROUND: Although risky behaviors such as educational problems and tobacco use tend to co-occur, these associations may vary across diverse ethnic groups, in part because ethnic minorities tend to reside in worse neighborhoods and tend to attend worse schools than Non-Latino White adolescents. AIM: To compare the association between baseline school achievement (student grades) and subsequent tobacco use susceptibility (openness to smoke in future) by ethnicity, we compared African American, Latino, and Non-Latino White adolescents in the US over a four-year period. METHODS: This longitudinal study followed 3636 adolescents who were never smokers at baseline for a period of four years. Baseline and four-year data of the Population Assessment of Tobacco and Health (PATH) study were used for this analysis. All participants were 12 to 17 years old at baseline and were either Non-Latino White (Majority), African American (Minority), or Latino (Minority). The outcome was a tobacco use susceptibility score at wave 4 which was defined as openness to use tobacco in the future, measured at year four. The predictor was school achievement at wave 1, measured as grades from F to A+. The moderator was ethnicity (African American, Latino, Non-Latino White), and covariates were age, gender, parental education, and family structure. RESULTS: Our linear regressions in the pooled sample showed an inverse association between baseline school achievement and subsequent tobacco use susceptibility four years later. However, this inverse association was weaker for ethnic minorities than for Non-Latino White adolescents, as documented by interaction effects between ethnic minority status and baseline school grades. CONCLUSION: Higher educational success better correlates with lower tobacco use susceptibility of non-Latino White than African American and Latino adolescents, which may reflect some tobacco use susceptibility of Latino and African American adolescents with highly educated parents. Future research should investigate how social context such as high-risk school environment, neighborhood risk, peer risk, and other mechanisms increase behavioral risk of educationally successful African American and Latino adolescents.

Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. METHOD: A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. RESULTS: Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). CONCLUSIONS: Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study.

Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion flower standardized extract on reaction time in patients with generalized anxiety disorder. Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was measured at baseline and after one month of treatment using computerized software. Correct responses, omission and substitution errors and the mean time of correct responses (reaction time) in both visual and auditory tests were collected. The analysis was performed between the two groups and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was considered statistically significant. Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference in any of the test items between assortments while a significant decline was observed in auditory omission errors in passion flower group after on month of treatment using intra-group analysis. Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized anxiety disorder with low side effects. Further studies with longer duration are recommended to confirm the results of this study. .

Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial.

Statins have been shown to decrease depressive symptoms in certain groups of patients, an effect that is mostly attributed to their anti-inflammatory and neurotransmitter modulatory potentials. We aimed to investigate the antidepressant effects of simvastatin as an adjuvant therapy in patients with moderate to severe depression. In this double-blind placebo-controlled clinical trial, 48 patients were randomly allocated to receive simvastatin or placebo as an adjunct to fluoxetine for six weeks. Patients were evaluated with the Hamilton Depression Rating Scale (HDRS) at baseline and weeks 2, 4 and 6. Probable clinical and laboratory adverse events were also monitored and compared between the two groups. Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36). No serious adverse event was reported during this trial. In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder. However, more confirmatory studies are warranted.

Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Several small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. STUDY DESIGN: This was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. STUDY SETTING: The study setting was outpatient clinics of two large referral centres. PATIENTS: Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21. INTERVENTIONS: Participants were randomly assigned to granisetron (Kytril(®); SmithKline Beecham, Philadelphia, PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks. MAIN OUTCOME MEASURE: Patients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups. RESULTS: Of the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and compulsion (F [2.050, 77.899] = 4.674, p = 0.012) subscales. By week 8, complete response and remission were achieved by 20 (100%) and 18 (90%) patients in the granisetron group and by 7 (35%) patients in the placebo group (p-value of Fisher's exact test <0.001, risk ratio (RR) [95% CI] = 3.857 [2.039, 7.297]). There was no significant difference in the tolerability between the two regimens. CONCLUSION: Granisetron is an efficacious adjunct for the short-term treatment of patients with moderate to severe OCD and is well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: IRCT201202041556N32.