"Neuromodulation Treatment" Effects on Suicidality: ECT Stands Out
Out on PubMed, from investigators at the Mayo Clinic and the University of Minnesota, is this paper:
A Systematic Review of Neuromodulation Treatment Effects on Suicidality.
Front Hum Neurosci. 2021 Jun 25;15:660926. doi: 10.3389/fnhum.2021.660926. eCollection 2021.PMID: 34248523
Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality. Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality. Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality. Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.
Keywords: deep brain stimulation; electroconvulsive therapy; repetitive transcranial magnetic stimulation; suicide; transcranial direct current stimulation; vagal nerve stimulation.
The pdf is here.
And from the text:
Recent ECT studies consistently showed significant clinical effects of ECT on suicidality (Kellner et al., 2005; Bradvik and Berglund, 2006; Patel et al., 2006; Ambade et al., 2009; Keshtkar et al., 2011; Ahmadi et al., 2016; Kawoos et al., 2018; Liang et al., 2018), whereas earlier studies did not show any difference between ECT-treated groups and control patients (Avery and Winokur, 1976, 1978; Tsuang et al., 1979; Black et al., 1989; Sharma, 1999). This difference may be the result of standardization of ECT techniques, which allowed for retained clinical efficacy and fewer adverse effects (Tirmizi et al., 2012). Another explanation might be the increase in numbers of prospective and controlled studies. These higher quality studies may have provided more accurate results. Similarly studies in which suicidality was a primary outcome often showed improvement in suicidality. There were 11 studies which suicidality was the primary outcome. Seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT (Avery and Winokur, 1978; Rich et al., 1986; Black et al., 1987; Ciapparelli et al., 2001; Kellner et al., 2005; Bradvik and Berglund, 2006; Patel et al., 2006; Ahmadi et al., 2016; Kawoos et al., 2018). Two of them could not show any significant difference (Avery and Winokur, 1976; Black et al., 1989), while two of them showed a higher rates of completed suicide in the patients treated with ECT (Munk-Olsen et al., 2007; Jorgensen et al., 2020). Two of all the studies mentioned an association of improvement in suicidal ideation and intent with the improvement in depression (Kellner et al., 2005; Patel et al., 2006). Yet it is hard to reach a conclusion regarding if improvements in suicidal ideation or intent was barely a result of improvement in depression.
Although the mechanism of action is still unclear, multiple theories may explain how ECT contributes to improvement in suicidality. ECT may exert its effect on suicide indirectly by improving symptoms of depression and directly by improving suicidality. Treatment with ECT increases neurotrophic factors, such as brain-derived neurotrophic factor in hippocampal neurons, although data are not clear regarding whether depression improves with increasing levels of brain-derived neurotrophic factor (Gedge et al., 2012; Rapinesi et al., 2015). Normalizing the hypothalamic-pituitary-adrenal axis hyperfunction after ECT treatment in patients with depression and ensuing decreased cortisol levels in response to ECT could also improve suicidality (Singh and Kar, 2017). Treatment with ECT may also normalize GABA/glutamate levels, which have been reported as higher in the prefrontal cortex and hippocampus in rodent models of depression (Sartorius et al., 2007; Dong et al., 2010). Correcting altered glutamatergic activity in various areas of the brain in patients with depression (Michael et al., 2003) underscores the potential role of the glutamatergic system in efficacy of ECT. Improved plasticity and alterations in the functional connectivity of various networks are other possible mechanisms through which ECT, which exerts a positive effect on depression, might contribute to improvement in suicidality (Singh and Kar, 2017). ECT may also directly address the mechanistic neurobiology of suicide. An increase in noradrenergic activity could explain its anti-suicidal activity. Postmortem analyses of brains of patients who committed suicide showed an increase in a2-noradrenergic binding, and ECT decreased this binding, implying an increase in noradrenergic hormone levels (Lillethorup et al., 2015). Another suggested mechanism of action is recovery of neuropeptide Y levels, which are lower in suicidal patients with depression (Ozsoy et al., 2016).
This is a long, detailed paper, the ECT part of which is really the only relevant content for this blog. The article contains a good review of suicidality assessment instruments. But I found several errors in the description of the reviewed studies that I know well; thus, the quality of this review is a bit suspect...
Suicidality remains one of the most important clinical presentations that compels the recommendation of ECT. Clinical wisdom and experience suggest that ECT has rapid and profound effects that decrease suicidal ideation and drive for many patients. Lesser "neuromodulation" modalities should not be conflated with ECT in the presence of acute and urgent patient treatment needs.
I suggest a full read of this systematic review only for those readers with a special interest in the suicidality literature, ~30 minutes. Please see also blog post of April 22, 2021.
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