Therapeutic effects of Silexan on somatic symptoms and physical health in patients with anxiety disorders: A meta-analysis.

A meta-analysis was performed to examine therapeutic effects of Silexan on somatic symptoms, including insomnia/fatigue, and physical health in patients with anxiety disorders. Five randomized, placebo-controlled trials were included in this analysis: The efficacy of Silexan (80 mg/day) was investigated in patients with subthreshold anxiety disorders (three trials) and in patients with generalized anxiety disorder (two trials). Silexan was superior to placebo in terms of the mean change from baseline in the Hamilton Anxiety Rating Scale (HAMA) subscore somatic anxiety at week 10 with a standardized mean difference of -0.31 [95% Cl: -0.52 to -0.10, p = .004]. Treatment effects of silexan on somatic anxiety were independent of gender and age. Statistically significant differences were also shown for single HAMA items somatic muscular, cardiovascular, respiratory, and genitourinary symptoms, indicating clinical relevance with small to medium effects of Silexan. Similar clinically meaningful effects of Silexan on SF-36 physical health, including reduced bodily pain and improved general health, and on insomnia complaints and fatigue, were demonstrated. In this meta-analysis including all placebo-controlled clinical trials in patients with anxiety disorders to date, statistically significant and clinically meaningful advantages of Silexan over placebo treatment were found in improving somatic symptoms and physical health.

Beneficial effects of Silexan on sleep are mediated by its anxiolytic effect.

Disturbed sleep is among the most prevalent hyperarousal symptoms in anxiety disorders. Most drugs recommended for anxiety and insomnia have a sedating effect which is related to their beneficial effect on disturbed sleep. Silexan is a proprietary essential oil from Lavandula angustifolia. This drug has significant anxiolytic and sleep improving properties. Interestingly, these effects are not associated with sedation. Here we asked whether the positive effects on sleep are due to primary pharmacodynamic or secondary, disease related effects. We used the data from a double-blind, randomized study in which 212 patients were analyzed for efficacy after ten weeks' treatment with 80 mg/day Silexan or placebo. Anxiety and disturbed sleep were assessed using the Hamilton Anxiety Scale (HAMA) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Regression-based mediation analysis was employed to estimate direct treatment effects and indirect effects mediated by anxiety control separately for each study group. Sobel's test was used to investigate the extent to which the mediator (HAMA change) contributes to the total effect of the independent variable (treatment) on the dependent variable (PSQI change). Compared to placebo, Silexan significantly reduced the total scores of the HAMA (p < 0.001) and of the PSQI (p = 0.002) after ten weeks, with clinically meaningful treatment group differences that were observed already after two and six weeks for HAMA and PSQI, respectively. Silexan had a statistically meaningful indirect effect on sleep (mediated by the effect on anxiety; p < 0.001) but no appreciable direct effect (p = 0.958). The ratio between the indirect and the total effect was determined to be 0.984, i. e., 98.4% of the total effect of Silexan on disturbed sleep were explained by the effect of Silexan on the symptoms of anxiety whereas 1.6% were attributable to a direct effect. The results indicate that Silexan exerts a secondary sleep improving effect almost exclusively through its anxiolytic action rather than by sedation. Findings are consistent with the drug's assumed mechanism of action.

Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders - Results from a double-blind, randomized and placebo-controlled clinical trial.

BACKGROUND: Extant literature shows that adjuvant omega-3-polyunsaturated fatty acids (O3PUFAs) to a standard antidepressant medication impacts favorably on symptoms of depression in participants with major depressive disorders (MDD). The aim of the present study was to investigate, if and to what extent compared to placebo adjuvant O3PUFAs had a favorable impact on symptoms of depression, anxiety, sleep and emotion regulation among outpatients with MDD. METHOD: A total of 50 outpatients (mean age: M = 42.46; 68% females) took part in this randomized, double-blind and placebo-controlled study. They were randomly assigned either to the O3PUFA- or to the placebo-condition. Standard medication was sertraline at therapeutic dosages. At baseline, six weeks and 12 weeks later at study completion participants completed questionnaires covering symptoms of depression, anxiety sensitivity, intolerance of uncertainty, sleep disturbances, and emotion regulation. In parallel, experts blind to participants' group assignment rated participants' depression with the Montgomery-Asberg Depression Scale. RESULTS: Symptoms of depression (self- and experts' ratings) decreased over time, but more so in the O3PUFA condition, compared to the placebo condition. Likewise, anxiety sensitivity, intolerance of uncertainty and sleep disturbances improved, but again more so in the O3PUFA condition. Further, regulation and control of emotions and perception of other's emotions improved over time, but more so in the O3PUFA condition. CONCLUSIONS: Among outpatients with MDD, and compared to placebo, adjuvant O3PUFAs to a standard medication improved not only symptoms of depression, but also dimensions of anxiety and sleep, and above all patients' competencies to regulate their emotions.

Influence of adjuvant mindfulness-based cognitive therapy (MBCT) on symptoms of post-traumatic stress disorder (PTSD) in veterans - results from a randomized control study.

Even 30 or more years after the end of a war, veterans can suffer from post-traumatic stress disorder (PTSD). In the present study, we explored the influence on symptoms of PTSD among Iranian veterans of the Iran-Iraq war of mindfulness-based cognitive therapy (MBCT) as add-on to a standard treatment with citalopram. Forty-eight male veterans with PTSD (mean age: 52.97 years) took part in this eight-week intervention study. Standard treatment for all patients consisted of citalopram (30-50 mg/day at therapeutic dosages). Patients were randomly assigned either to the treatment or to the control condition. Treatment involved MBCT delivered in group sessions once a week. Patients in the control condition met at the hospital with the same frequency and duration for socio-therapeutic events. At baseline and at study completion, patients completed questionnaires covering symptoms of PTSD, depression, anxiety, and stress. At study completion after eight weeks, scores for PTSD (re-experiencing events, avoidance, negative mood and cognition, hyperarousal), depression, anxiety, and stress were lower, but more so in the intervention than the control group. Data suggest that, as adjuvant to standard SSRI medication, MBCT is an effective intervention to significantly reduce symptoms of PTSD, depression, anxiety, and stress among veterans.

Influence of adjuvant detached mindfulness and stress management training compared to pharmacologic treatment in primiparae with postpartum depression.

Ten to 15% of mothers experience postpartum depression (PPD). If untreated, PPD may negatively affect mothers' and infants' mental health in the long term. Accordingly, effective treatments are required. In the present study, we investigated the effect of detached mindfulness (DM) and stress management training (SMT) as adjuvants, compared to pharmacologic treatment only, on symptoms of depression in women with PPD. Forty-five primiparae (mean age: M = 24.5 years) with diagnosed PPD and treated with an SSRI (citalopram; CIT) took part in the study. At baseline, they completed questionnaires covering socio-demographic data and symptoms of depression. Experts rated also symptoms of depression. Next, participants were randomly assigned to one of the following study conditions: adjuvant detached mindfulness (CIT+DM); adjuvant stress management training (CIT+SMT); control condition (CIT). Self- and experts' ratings were completed at the end of the study 8 weeks later, and again at 8 weeks follow-up. Symptoms of depression decreased significantly over time, but more so in the CIT+DM and CIT+SMT group, compared to the control condition. The pattern of results remained stable at follow-up. In primiparae with PPD and treated with a standard SSRI, adjuvant psychotherapeutic interventions led to significant and longer-lasting improvements.

Rosa Damascena oil improved methadone-related sexual dysfunction in females with opioid use disorder under methadone maintenance therapy - results from a double-blind, randomized, and placebo-controlled trial.

BACKGROUND: Methadone maintenance therapy (MMT) is provided to patients with opioid use disorder (OUD). However, as with all opioids, methadone impacts negatively on sexual function. To counter this, Rosa Damascena oil (RDO) has been used successfully for opioid-dependent male patients under MMT and with methadone-related sexual dysfunction (MRSD). In the present study, we tested the possible influence of RDO on sexual function and sex hormones of opioid-dependent female patients undergoing MMT and with MRSD. METHODS: Fifty female patients (mean age: 38.8 years) diagnosed with OUD, undergoing MMT and with MRSD were randomly assigned either to the RDO or the placebo condition. At baseline, patients completed questionnaires covering socio-demographic and OUD-related information. At baseline, and four and eight weeks later they additionally completed questionnaires on sexual function and happiness. Blood samples to assess thyroid hormones, prolactin, progesterone, and estradiol levels were taken at baseline and eight weeks later (end of the study). RESULTS: Over time sexual function and happiness increased, but more so in the RDO condition than in the placebo condition. Over time, prolactin decreased, and progesterone, and estradiol increased, but again more so in the RDO condition. Sex hormone levels and sexual function were statistically unrelated. CONCLUSIONS: Results from this double-blind, randomized, and placebo-controlled clinical trial showed that opioid-dependent females undergoing MMT and with MRDS did benefit from RDO administration, as sexual function and happiness increased, and female sexual hormone levels changed in positive directions.

Detached mindfulness reduced both depression and anxiety in elderly women with major depressive disorders.

We investigated the influence of detached mindfulness (DM) in treating symptoms of depression and anxiety among elderly women. Thirty-four elderly females (mean age: 69.23 years) suffering from moderate major depressive disorders (MDD) and treated with a standard medication (citalopram) at therapeutic doses were randomly assigned either to an intervention condition (DM; group treatment, twice weekly) or to a control condition (with leisure activities, twice weekly). At baseline (BL), four weeks later at study completion (SC), and four weeks after that at follow-up (FU), participants completed ratings for symptoms of depression and anxiety; experts blind to patients' group assignments rated patients' symptoms of depression. Symptoms of depression (self and experts' ratings) and anxiety declined significantly over time in the DM, but not in the control condition. Effects remained stable at FU. The pattern of results suggests that, compared to a control condition, a specific psychotherapeutic intervention such as DM can have a beneficial effect in elderly female patients with MDD.

Rosa Damascena oil improved sexual function and testosterone in male patients with opium use disorder under methadone maintenance therapy-results from a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Some patients with opioid use disorder (OUD) are treated with methadone maintenance therapy (MMT). However, as with opioids, methadone has major side-effects; sexual dysfunction is a particularly distressing such effect. Rosa Damascena oil has been shown to reduce subjective sexual dysfunction in patients with major depressive disorders, but its influence on testosterone has not so far been tested. The aim of the present study was to investigate the influence of Rosa Damascena oil on sexual dysfunction and testosterone levels among male patients with OUD and undergoing MMT. METHODS: A total of 50 male patients (mean age: 40 years) diagnosed with OUD and receiving MMT were randomly assigned either to the Rosa Damascena oil (drops) or a placebo condition. At baseline, and four and eight weeks later, patients completed questionnaires covering sexual and erectile function. Blood samples to assess testosterone levels were taken at baseline and eight weeks later on completion of the study. RESULTS: Over time sexual dysfunction decreased, and testosterone increased in the Rosa Damascena oil, but not in the placebo condition. Sexual dysfunction scores and testosterone levels were not consistently related. CONCLUSIONS: Results from this double-blind, randomized, and placebo-controlled clinical trial showed that Rosa Damascena oil improved sexual function and testosterone levels among males with OUD and undergoing MMT.

The current state of physical activity and exercise programs in German-speaking, Swiss psychiatric hospitals: results from a brief online survey.

BACKGROUND: Physical activity and exercise programs (PAEPs) are an important factor in increasing and maintaining physical and mental health. This holds particularly true for patients with psychiatric disorders undergoing treatment in a psychiatric hospital. To understand whether the benefits reported in the literature are mirrored in current treatment modalities, the aim of the present study was to assess the current state of PAEPs in psychiatric hospitals in the German-speaking part of Switzerland. METHODS: All psychiatric hospitals (N=55) in the German-speaking part of Switzerland were contacted in spring 2014. Staff responsible for PAEPs were asked to complete an online questionnaire covering questions related to PAEPs such as type, frequency, staff training, treatment rationale, importance of PAEPs within the treatment strategy, and possible avenues to increase PAEPs. RESULTS: Staff members of 48 different psychiatric hospitals completed the survey. Hospitals provided the following therapeutic treatments: relaxation techniques (100%), sports therapy (97%), activity-related psychotherapeutic interventions (95%), physiotherapy (85%), body therapies (59%), far-east techniques (57%), and hippotherapy (22%). Frequencies ranged from once/week to five times/week. Approximately 25% of patients participated in the PAEPs. Interventions were offered irrespective of psychiatric disorders. PAEP providers wanted and needed more vocational training. CONCLUSION: All participating psychiatric hospitals offer a broad variety of PAEPs in their treatment curricula. However, the majority of inpatients do not participate in PAEPs. Furthermore, those who do participate cannot continue to do so following discharge. PAEP providers need specific extended vocational trainings and believe that the potential of PA should be improved.

Efficacy of Hypericum extract WS(®) 5570 compared with paroxetine in patients with a moderate major depressive episode - a subgroup analysis.

OBJECTIVES: efficacy and tolerability of WS(®) 5570 for the treatment of acute mild-to-moderate depression, has been demonstrated in various studies. Here, we present a subgroup analysis of a double blind, randomised trial to compare the therapeutic efficacy of WS(®) 5570 with paroxetine in patients suffering from a major depressive episode with moderate symptom intensity. METHODS: moderate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Patients received, after a single blind placebo run-in phase of 3-7 d, either 3 × 300 mg/d WS(®) 5570 or 20 mg/d paroxetine for six weeks. The change of the HAM-D total score was used to describe the efficacy of WS(®) 5570 compared with paroxetine in the subgroup of patients with moderate depression. RESULTS: the reductions of the HAM-D total score were significantly more pronounced in patients treated with 3 × 300 mg/d WS(®) 5570 compared to 20 mg/d paroxetine. CONCLUSIONS: patients treated with WS(®) 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine. Keypoints Various studies showed the efficacy and tolerability of WS(®) 5570 for the treatment of acute mild-to-moderate depression. Beneficial effects of WS(®) 5570 have been also shown in patients with moderate-to-severe depression. In this study reductions of the HAM-D total score were significantly more pronounced in patients with moderate depression treated with WS(®) 5570 compared with paroxetine. Patients treated with WS(®) 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine.

Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial.

Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B1) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.

Effects of psychotherapy in combination with pharmacotherapy, when compared to pharmacotherapy only on blood pressure, depression, and anxiety in female patients with hypertension.

We investigated effects of metacognitive detached mindfulness therapy and stress management training on hypertension and symptoms of depression and anxiety, as compared to a control condition. A total of 45 female patients (mean age: M = 36.49 years) were randomly assigned to one of three conditions: metacognitive detached mindfulness therapy, stress management training, and the control condition. Blood pressure and symptoms of depression and anxiety decreased from baseline to post-test, to follow-up. Group comparisons showed that blood pressure and symptoms of depression and anxiety decreased more in psychotherapeutic groups than in the control group. Psychotherapeutic treatment of hypertension reduced blood pressure and symptoms of depression and anxiety. Positive effects were observable at follow-up 8 weeks later.

Exercising Impacts on Fatigue, Depression, and Paresthesia in Female Patients with Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) is a chronic progressive autoimmune disease impacting both body and mind. Typically, patients with MS report fatigue, depression, and paresthesia. Standard treatment consists of immune modulatory medication, though there is growing evidence that exercising programs have a positive influence on fatigue and psychological symptoms such as depression. We tested the hypothesis that, in addition to the standard immune regulatory medication, either yoga or aquatic exercise can ameliorate both fatigue and depression, and we examined whether these interventions also influence paresthesia compared with a nonexercise control condition. METHODS: Fifty-four women with MS (mean age: M = 33.94 yr, SD = 6.92) were randomly assigned to one of the following conditions: yoga, aquatic exercise, or nonexercise control. Their existing immune modulatory therapy remained unchanged. Participants completed questionnaires covering symptoms of fatigue, depression, and paresthesia, both at baseline and on completion of the study 8 wk later. RESULTS: Compared with the nonexercise control condition and over time, fatigue, depression, and paresthesia decreased significantly in the yoga and aquatic exercise groups. On study completion, the likelihood of reporting moderate to severe depression was 35-fold higher in the nonexercise control condition than in the intervention conditions (yoga and aquatic exercising values collapsed). CONCLUSION: The pattern of results suggests that for females with MS and treated with standard immune regulatory medication, exercise training programs such as yoga and aquatic exercising positively impact on core symptoms of MS, namely, fatigue, depression, and paresthesia. Exercise training programs should be considered in the future as possible complements to standard treatments.

In a randomized, double-blind clinical trial, adjuvant atorvastatin improved symptoms of depression and blood lipid values in patients suffering from severe major depressive disorder.

BACKGROUND: The administration of statins seems to be a promising new avenue in the treatment of patients suffering from major depressive disorder (MDD), though patients suffering from severe MDD remain unstudied in this respect. The aim of the present study was therefore to investigate, in a randomized double-blind clinical trial, the influence of adjuvant atorvastatin on symptoms of depression in patients with MDD. METHODS: A total of 60 patients suffering from MDD (mean age: 32.25 years; 53% males) received a standard medication of 40 mg/d citalopram. Next, patients were randomly assigned either to the atorvastatin group (20 mg/d) or to the placebo group. Blood lipid values were assessed at baseline and on completion of the study 12 weeks later. Experts rated depressive symptoms via Hamilton Depression Rating Scales (HDRS) at baseline and 3, 6 and 12 weeks later. RESULTS: HDRS scores decreased over time; the significant Time by Group interaction showed that symptoms of depression decreased more in the atorvastatin than in the placebo group. Compared to the placebo group, in the atorvastatin group cholesterol, triglyceride, and Low Density Lipids (LDL) significantly decreased, and High Density Lipids (HDL) significantly increased over time. HDRS scores and blood lipid values were generally not associated. CONCLUSIONS: The pattern of results suggests that adjuvant atorvastatin favorably influences symptoms of depression among patients with severe MDD. Given that after 12 weeks of monotherapy and adjuvant atorvastatin patients were still moderately to severely depressed, more powerful treatment algorithms such as augmentation and change of medication are highly recommended.

Influence of mindfulness practice on cortisol and sleep in long-term and short-term meditators.

BACKGROUND: There is growing scientific interest in assessing the biological correlates of non-pharmacological interventions such as mindfulness. Examinations of the beneficial effects of mindfulness on hypothalamus-pituitary-adrenocortical system activity (HPA SA) and sleep are sparse. The aim of the present study was to explore the impact of long- and short-term meditation experience on HPA SA and sleep. METHOD: There were 20 participants, 9 of whom had long-term experience in meditation (mean = 264 months) and 11 novices. Novices underwent an 8-week course in Mindfulness-Based Stress Reduction (MBSR), and cortisol samples were taken in the lab at the beginning and end of the course. To assess the cortisol awakening response, 4 morning cortisol samples were collected. Sleep and mindfulness were assessed by self-rating questionnaires. RESULTS: Among participants with long-term meditation experience, morning cortisol decreased with length of experience. For novices, after an 8-week introductory MBSR course, morning cortisol levels had decreased, while both sleep and self-attribution of mindfulness significantly improved. Cortisol levels did not, however, change between the beginning and end of individual MBSR sessions. CONCLUSIONS: The pattern of results lends support to the view that MBSR/meditation has a favorable influence both on biomarkers of stress regulation, such as cortisol secretion, and on sleep.