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Do neuromodulatory treatments, such as transcranial magnetic stimulation, really reduce depressive symptoms?

Hadden, Lowri 2020. Do neuromodulatory treatments, such as transcranial magnetic stimulation, really reduce depressive symptoms? ClinPsy Thesis, Cardiff University.
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Depression is a serious mental health condition, which can have fatal effects, with over 800,000 people dying by suicide each year. It is also the leading cause of disability across the globe (WHO, 2017). Given the high rates of mortality, and disability, it is paramount to have evidencebased and clinically relevant treatments. One emerging treatment, with a relatively new evidencebase, is transcranial magnetic stimulation (TMS). TMS treatment protocols for depression are endorsed by two regulatory bodies, NICE (2015) and the FDA (2008). However, the basic scientific validity and mechanisms of action of these protocols remain vague, particularly relating to how excitatory TMS reduces a key depressive symptom, anhedonia. For our empirical chapter, we replicate two core studies (e.g. Ahn et al., 2013; Duprat et al., 2016) that have informed the clinical evidence-base of TMS for depression. One of these core studies, Ahn et al., (2013) demonstrated an increase in reward responsiveness in controls, following excitatory TMS compared to sham TMS, as measured on a probabilistic learning task (PLT). However, in a pseudo-replication study of Ahn et al., (2013), Duprat et al., (2016) only found an increase in reward responsiveness, following excitatory TMS, when including an exploratory variable, trait hedonic capacity, as a covariate. Our empirical chapter did not replicate the core effects of neither Ahn et al., (2013) nor Duprat et al., (2016), that is we did not find an effect of excitatory TMS compared to sham for reward responsiveness, nor did we demonstrate any effect with the inclusion of trait hedonic capacity. However, our results on the PLT were commensurate with the wider PLT evidence-base, evidencing that learning had occurred across the task, as was expected. In contrast to Ahn et al., (2013) and Duprat et al., (2016), we had also included mood ratings, using the Positive and Negative Affect Schedule (PANAS), both pre and post stimulation. Intriguingly, following active TMS, participants exhibited a significant decrease of positive mood, indicative of increased anhedonia. Negative mood was unaffected by TMS. These mood findings call into question the fundamental premise of TMS, which is thought to decrease symptoms of anhedonia, rather than increase them. For our systematic review and meta-analysis, we examined the efficacy of TMS as a treatment for depression, taking into account the clinical relevance of these findings, which previous 8 TMS studies have failed to do. Previous “gold” standard randomised controlled trials (RCTs) assessing the effectiveness of active compared to sham TMS have generated variable estimates of treatment efficacy, with active compared to sham TMS evidencing small, medium, and large effect sizes, or indeed, no effect at all. These divergent findings may lie in the heterogeneous patient samples with comorbid disorders, and concurrent antidepressant medication included in these RCTs. Thus, we conducted a systematic review and meta-analysis of TMS for depression, controlling for previous heterogeneity through the inclusion of double-blind RCTs that included depressed patients who were anti-depressant free. We considered the questionnaires used to assess depressive symptom change, typically the Hamilton Depression Rating Scale (HDRS), and calculated the standardised mean difference (SMD/ hedges ‘g’) for scores on the HDRS post stimulation (active and sham). We found a small effect (SMD) of active compared to sham stimulation (SMD = -0.29), indicating that active TMS is effective in reducing symptoms of depression. However, the clinical relevance of this effect is negligible, based on the % change of depressive symptom reduction, as outlined in Lepping et al., (2014). We found a -31% reduction in depressive symptoms for active and -14% reduction for sham stimulation, which corresponds to “no change/ minimally improved” depression, commensurate with the findings of Lepping et al., (2014). Similarly, the participants, on average failed to move out of “casedness” for their depressive symptoms. Combined, the results of our empirical paper and systematic review & meta-analysis, fail to provide convincing support for the use of TMS for treating depression. In particular, we were not able to replicate the main findings of Ahn et al., (2013) and Duprat et al., (2016). Moreover, TMS reduced positive affect, and made no difference to negative affect, when measured on self-report questionnaires. Our meta-analysis provided evidence towards the use of active TMS for depression, prior to calculating the clinical relevance of this effect, which generated no meaningful changes, or a reduction from “casedness”. Thus, our studies highlight the importance of triangulating clinical and statistical methods to truly assess the efficacy and effectiveness of TMS as a treatment for depression. Not doing so, leads to an inconclusive and vague answer about treatment effects, which could result in potentially worse treatment outcomes for patients (i.e. increased anhedonia).

Item Type: Thesis (DClinPsy)
Date Type: Completion
Status: Unpublished
Schools: Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Date of First Compliant Deposit: 13 October 2020
Last Modified: 09 Feb 2022 02:30

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