Raloxifene augmentation in men and women with a schizophrenia spectrum disorder:A study protocol

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered

Treating auditory hallucinations with transcranial direct current stimulation in a double-blind, randomized trial

Objective: Transcranial direct current stimulation (tDCS) could be a treatment option for medication-resistant auditory hallucinations (AH), but so far results have been inconclusive, and large sample trials have been missing. This study used tDCS as a treatment method for these hallucinations in a double-blind, placebo-controlled study with a relatively large sample size. Methods: Fifty-four patients of several diagnostic categories with medication-resistant AH were randomized and treated during 10 sessions of 20 min each, with either 2 mA tDCS or placebo, administered on five consecutive days (i.e., two sessions per day). Anodal stimulation was targeted at the left dorsolateral prefrontal cortex, cathodal stimulation at the left temporoparietal junction. AH severity was assessed using the Auditory Hallucination Rating Scale (AHRS). Other outcome measures were assessed with the Positive and Negative Syndrome Scale (PANSS), the Stroop, and the Trail Making Test. Results: AH frequency and severity decreased significantly over time, as did the scores on the total and general subscales of the PANSS. However, there was no significant interaction effect with the treatment group on any of the main outcome measures. Conclusions: We found no evidence that tDCS is more effective for medication-resistant AH than placebo, even though AH frequency and severity decreased in both groups. An alternative strategy may be to offer tDCS at an earlier stage of illness. In the light of recent investigations into the neurophysiological mechanisms behind tDCS, we may also have to consider the possibility that tDCS is not able to induce any long-lasting brain changes

Physical exercise improves quality of life, depressive symptoms, and cognition across chronic brain disorders: a transdiagnostic systematic review and meta-analysis of randomized controlled trials

We performed a meta-analysis to synthesize evidence on the efficacy and safety of physical exercise as an add-on therapeutic intervention for quality of life (QoL), depressive symptoms and cognition across six chronic brain disorders: Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Parkinson’s disease, schizophrenia and unipolar depression. 122 studies (= k) (n = 7231) were included. Exercise was superior to treatment as usual in improving QoL (k = 64, n = 4334, ES = 0.40, p < 0.0001), depressive symptoms (k = 60, n = 2909, ES = 0.78, p < 0.0001), the cognitive domains attention and working memory (k = 21, n = 1313, ES = 0.24, p < 0.009), executive functioning (k = 14, n = 977, ES = 0.15, p = 0.013), memory (k = 12, n = 994, ES = 0.12, p = 0.038) and psychomotor speed (k = 16, n = 896, ES = 0.23, p = 0.003). Meta-regression showed a dose–response effect for exercise time (min/week) on depressive symptoms (β = 0.007, p = 0.012). 69% of the studies that reported on safety, found no complications. Exercise is an efficacious and safe add-on therapeutic intervention showing a medium-sized effect on QoL and a large effect on mood in patients with chronic brain disorders, with a positive dose–response correlation. Exercise also improved several cognitive domains with small but significant effects

Simvastatin augmentation for recent-onset psychotic disorder : A study protocol

Background: There is ample evidence that inflammatory processes play a role in the pathophysiology of schizophrenia. Randomized controlled trials have shown benefit of some (but not all) anti-inflammatory drugs on symptom severity. So far, these drugs have been given for a relatively short period. Simvastatin combines well-established vascular protection with reduction of the inflammatory status of the brain, thus offering an attractive potential to further improve treatment of schizophrenia and related disorders. Methods/design: We are currently undertaking a double-blind placebo-controlled trial, including 250 patients (18-50. years of age) whom are diagnosed with a schizophrenia spectrum disorder. Onset of their first psychosis should be no longer than three years ago. Patients are randomized 1:1 to either 40. mg simvastatin or placebo daily during one year, next to their regular antipsychotic treatment. Primary outcome measures are symptom severity and cognitive decline as measured by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), at baseline and end of treatment. Secondary aims are to establish an attenuation of brain tissue loss and an improvement in general functioning, presence and severity of metabolic syndrome and degree of movement disorders. Lastly, immunological and metabolic parameters are assessed in blood samples to possibly predict treatment response. Discussion: We hypothesize simvastatin to lower symptom severity and to prevent or reduce excessive brain tissue loss and cognitive decline, compared to placebo. We expect that simvastatin will be well-tolerated and lead to decreased prevalence of metabolic syndrome. Trial registration: ClinicalTrails.gov NCT01999309; EudraCT-number 2013-000834-36