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Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population. We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook. The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P < .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS. rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.

Purpose of Review Co-occurring substance use disorders (SUDs) are highly common in individuals with psychiatric illnesses. Individuals with comorbid psychiatric illness and SUDs may experience poorer mental health and decreased treatment efficacy. However, there are no FDA-approved treatments for co-occurring substance use and psychiatric disorders. Repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation that uses an electromagnetic field to change brain activity and behavior, may be a promising treatment for co-occurring disorders. A comprehensive literature search of PubMed, MEDLINE, and Google Scholar databases was conducted, and records were manually reviewed to include all studies testing the effects of rTMS for co-occurring SUDs. Recent Findings Eleven studies met our inclusion criteria. The majority (7/11) assessed rTMS for the treatment of schizophrenia and co-occurring substance use, and the remaining three studies assessed rTMS for the treatment of SUDs in mood and anxiety disorders. Potential neural circuitry targets for the treatment of co-occurring substance use and post-traumatic stress disorder, anxiety disorder, and bipolar disorder are discussed. We identify future directions and considerations for rTMS treatment and research. Namely, we recommend identification of novel treatment targets, the use of pragmatic treatment approaches, the evaluation of rTMS for substance withdrawal, the evaluation of state dependence as a predictor of treatment efficacy, the use of neurobiological measurements to identify underlying neural circuitry, and the assessment of individual predictors of rTMS treatment response. Summary There is preliminary evidence suggesting rTMS may be effective to treat co-occurring disorders, but additional research is needed.

Negative symptom severity predicts functional outcome and quality life in people with psychosis. However, negative symptoms are poorly responsive to antipsychotic medication and existing literature has not converged on their neurobiological basis. Previous work in small schizophrenia samples has observed that lower cerebellar-prefrontal connectivity is associated with higher negative symptom severity and demonstrated in a separate neuromodulation experiment that increasing cerebellar-prefrontal connectivity reduced negative symptom severity. We sought to expand this finding to test associations between cerebellar-prefrontal connectivity with negative symptom severity and cognitive performance in a large, transdiagnostic sample of individuals with psychotic disorders. In this study, 260 individuals with psychotic disorders underwent resting-state MRI and clinical characterization. Negative symptom severity was measured using the Positive and Negative Symptoms Scale, and cognitive performance was assessed with the Screen for Cognitive Impairment in Psychiatry. Using a previously identified cerebellar region as a seed, we performed seed to whole brain analyses and regressed connectivity against negative symptom severity, using age and sex as covariates. Consistent with prior work, we identified relationships between higher cerebellar-prefrontal connectivity and lower negative symptom severity (r=-0.17, p=.007). Higher cerebellar-prefrontal connectivity was also associated with better delayed verbal learning (r=.13, p=.034). Our results provide further evidence supporting the relationship between cerebellar-prefrontal connectivity and negative symptom severity and cognitive performance. Larger, randomized, sham-controlled neuromodulation studies should test if increasing cerebellar-prefrontal connectivity leads to reductions in negative symptoms in psychosis.

Abstract The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies—particularly in persons with Crohn’s disease—combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes. Lay Summary This article reviews studies on treatment for inflammatory bowel disease (IBD). IBD is a disease that causes the bowels to become inflamed. Many treatment options exist for people with IBD in Canada. Some of these options are drugs, surgery and diet. Many drugs used to treat IBD are very expensive. New biosimilar drugs may lower costs and increase how available these drugs are. It is very important to make sure that the right drug for the right person at the right time is found. New studies must seek to understand what the right treatments are for each person. We have come a long way in treating IBD over the last 60 or so years. However, people with IBD may still need surgery at some point. New drugs being tested offer hope that more ways to treat IBD will soon be available. We hope that these new drugs will prove safe an effective for people with IBD and reduce complications of disease.