A pragmatic randomized controlled trial exploring the relationship between pulse number and response to repetitive transcranial magnetic stimulation treatment in depression.

BACKGROUND: Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. In particular, it is unclear whether there is a relationship between elements of the dose of stimulation (i.e., number of pulses) and clinical response. To address one aspect of dose, we conducted a trial comparing standard and high dose versions of high frequency left sided and low frequency right sided rTMS protocols (left standard = 50 trains, left high = 125 trains, right standard = 20 min, right high = 60 min, all per day in a single session). METHOD: 300 patients with treatment resistant depression were enrolled in a four arm randomized controlled trial across a four week time period. The primary outcome assessment was a comparison of response and remission rates on data from the 17-item Hamilton Rating Scale for Depression Rating Scale (HRSD-17). RESULTS: The rate of response exceeded 45% in all groups. There was no significant difference between groups on initial analysis of the primary or secondary outcome measures (response rates: standard left = 52.5%, high left = 47.3%, standard right = 49.1%, high right = 48.4%). There was a greater remission rate with high compared to moderate dose left sided treatment when controlling for illness duration. We also found significant improvements in quality of life across all treatment groups. Illness duration was weakly associated with response. CONCLUSIONS: There was no consistent association between the antidepressant effect of rTMS and the number of TMS pulses provided across the ranges investigated in this study. Increasing TMS pulse number in individual sessions seems unlikely to be a method to substantially improve clinical outcomes, and future research should explore alternative means of improving clinical response. The study was registered on the Australian and New Zealand Clinical Trials Register (ACTRN12612000321842) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362063&isReview=true.

Equivalent beneficial effects of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in a large randomized trial in treatment-resistant major depression.

Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. Recent studies have produced conflicting results as to whether unilateral rTMS is more or less effective than sequentially applied bilateral rTMS. To address this we conducted a trial comparing sequential bilateral rTMS to right-sided unilateral rTMS using a priming protocol. Patients with treatment-resistant depression (n = 179) were enrolled in a two-arm randomized controlled trial across a 4-wk time period. The primary outcome assessment was the Hamilton Depression Rating Scale. Overall, there was a substantial response rate of >50% (and a 40% remission rate); however, there were no significant differences in clinical response between the two treatment groups. rTMS was well tolerated with a very low discontinuation rate. There was no relationship between response in the current trial and previous response, or non-response, to electroconvulsive therapy. We found no significant differences in clinical response between sequential bilateral rTMS and right-sided unilateral rTMS applied with a priming protocol. The results of this study do not support superior efficacy of bilateral rTMS and instead suggest that other approaches should be explored to increase treatment efficacy.

Prevalence of hepatitis C in two inpatient psychiatry populations.

OBJECTIVE: Psychiatric populations may be particularly at risk of hepatitis C (HCV), less likely to receive appropriate interventions and at greater risk of liver damage due to comorbid substance abuse. This study sought to determine the prevalence of HCV in two inpatient psychiatric populations of seriously mentally ill patients and the relationship to risk factor screening. METHOD: Two inpatient units were chosen in similar socio-economic areas. Persons admitted to these wards over the course of the study were invited to participate and provided with pre-test counselling. Where informed consent was obtained, individuals were included in the study. It was planned to screen all consenting patients. However, funding was reduced for one site meaning that only patients with identified risk factors could be screened there. RESULTS: Around 18% of psychiatric inpatients admitted to risk factors for HCV. The prevalence of HCV with screening of all consenting patients in unit A was 3.2%. With selective screening in unit B, 41.7% of those with identified risk factors tested positive. These results compare to the Australian community rate of approximately 1.1%. CONCLUSION: Results are consistent with elevated rates of HCV in mentally ill populations elsewhere in the world, and provide support for selective screening.

A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression.

Low-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) appears to have antidepressant properties although the effectiveness of this treatment in clinical practice has not been assessed nor have the optimal stimulation parameters been adequately defined. A total of 130 patients with treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension. Non-responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria. For right-sided treatment, depression significantly improved but there was no between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05). Depression symptom scores also improved for patients who crossed over to left-sided treatment but there was no significant difference in response between 5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met clinical response criteria following treatment but response to 1 and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage over 1 Hz despite doubling pulse number.