ABSTRACT: BACKGROUND:Panic disorder (PD) is a common type of anxiety disorder, characterized by unexpected and repeated panic attacks or fear of future panic attacks, or both. Individuals with PD are often resistant to pharmacological or psychological treatments and this can lead to the disorder becoming a chronic and disabling illness. Repetitive transcranial magnetic stimulation (rTMS) can deliver sustained and spatially selective current to suppress or induce cortical excitability, and its therapeutic effect on pathological neuronal activity in people with PD has already been examined in case studies and clinical trials. However, a systematic review is necessary to assess the efficacy and safety of rTMS for PD. OBJECTIVES:To assess the effects of repetitive transcranial magnetic stimulation (rTMS) for panic disorder (PD) in adults aged 18 to 65 years, either as a monotherapy or as an augmentation strategy. SEARCH METHODS:An electronic search of the Cochrane Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR) was conducted to 19 February 2014. The CCDANCTR includes reports of relevant randomised controlled trials (RCTs) from MEDLINE (1950 to date), EMBASE (1974 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL) (all years). Additional searches were conducted in Psyndex and the main Chinese medical databases. SELECTION CRITERIA:RCTs or quasi-randomised trials evaluating rTMS for PD in people aged between 18 and 65 years, either as a monotherapy or as an augmentation strategy. DATA COLLECTION AND ANALYSIS:Two review authors independently selected studies and extracted data and verified the data by cross-checking. Disagreements were resolved by discussion. For binary data, we calculated fixed-effect model risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated fixed-effect model standardized mean difference (SMD) and its 95% CI. MAIN RESULTS:Two RCTs (n = 40) were included in this review. The included trials compared rTMS with sham rTMS; no trials comparing rTMS with active treatments (electroconvulsive therapy (ECT), pharmacotherapy, psychotherapy) met our inclusion criteria. Both included studies used 1 Hz rTMS over the right dorso-lateral prefrontal cortex (DLPFC) for two or four weeks as an augmentation treatment for PD. However, in both studies the data for the primary outcome, panic symptoms as measured by the Panic Disorder Severity Scale (PDSS), were skewed and could not be pooled for a quantitative analysis. For this primary outcome one trial with 25 participants reported a superior effect of rTMS in reducing panic symptoms compared with sham rTMS (t = 3.04, df = 16.57, P = 0.007), but this trial had a 16% dropout rate and so was deemed as having a high risk of attrition bias. The other trial found that all 15 participants exhibited a reduction in panic symptoms but there was no significant difference between rTMS and sham rTMS (Mann Whitney U test, P > 0.05). Regarding the acceptability of rTMS, no significant difference was found between rTMS and sham rTMS in dropout rates or in reports of side effects. The quality of evidence contributing to this review was assessed as very low. Assessments of the risk of bias for the two studies were hampered by the lack of information provided in the reports, especially on methods of sequence generation and whether allocation concealment had been applied. Of the remaining sources of bias, we considered one of the studies to have been at risk of attrition bias. AUTHORS' CONCLUSIONS:Only two RCTs of rTMS were available and their sample sizes were small. The available data were insufficient for us to draw any conclusions about the efficacy of rTMS for PD. Further trials with large sample sizes and adequate methodology are needed to confirm the effectiveness of rTMS for PD.
