Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis

BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs. AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD. METHODS We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code. RESULTS Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions. CONCLUSION Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.