The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results.

BACKGROUND: Suicide is a major health concern. Effective acute interventions are lacking. Recent studies have suggested an acute decrease of suicidal ideations following repetitive Transcranial Magnetic Stimulation (rTMS). However, placebo effects could not be excluded. We aimed to evaluate the acute effect of accelerated intermittent theta burst stimulation (TBS) on suicide risk in depression. SUBJECTS AND METHODS: In 12 suicidal therapy-resistant depressed patients accelerated intermittent TBS was delivered on the left dorsolateral prefrontal cortex in a randomized, sham-controlled cross-over fashion. Patients received 20 sessions spread over 4 days. The change in severity of suicidal ideation was measured by the Beck Scale of Suicidal Ideation (SSI) before and after treatment. RESULTS: We found a significant decrease of SSI score over time; unrelated to active or sham stimulation. Furthermore, the attenuation of suicidal thinking was not merely related to depression severity changes caused by TBS. CONCLUSIONS: Accelerated TBS treatment in depressed suicidal patients was found to be safe and well tolerated and may have the potential to acutely decrease suicidal ideations. However, the efficacy compared to sham has not yet been proven and further sham-controlled research including longer follow-up is needed to substantiate these preliminary findings.

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial.

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission?

Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.

Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based meta-analysis of structural and functional MRI studies.

OBJECTIVE: We conducted meta-analyses of functional and structural neuroimaging studies comparing adolescent and adult individuals with a history of suicidal behavior and a psychiatric disorder to psychiatric controls in order to objectify changes in brain structure and function in association with a vulnerability to suicidal behavior. METHODS: Magnetic resonance imaging studies published up to July 2013 investigating structural or functional brain correlates of suicidal behavior were identified through computerized and manual literature searches. Activation foci from 12 studies encompassing 475 individuals, i.e., 213 suicide attempters and 262 psychiatric controls were subjected to meta-analytical study using anatomic or activation likelihood estimation (ALE). RESULT: Activation likelihood estimation revealed structural deficits and functional changes in association with a history of suicidal behavior. Structural findings included reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus. Functional differences between study groups included an increased reactivity of the anterior and posterior cingulate cortices. DISCUSSION: A history of suicidal behavior appears to be associated with (probably interrelated) structural deficits and functional overactivation in brain areas, which contribute to a decision-making network. The findings suggest that a vulnerability to suicidal behavior can be defined in terms of a reduced motivational control over the intentional behavioral reaction to salient negative stimuli.

Self-directedness: an indicator for clinical response to the HF-rTMS treatment in refractory melancholic depression.

Although well-defined predictors of response are still unclear, clinicians refer a variety of depressed patients for a repetitive Transcranial Magnetic Stimulation (rTMS) treatment. It has been suggested that personality features such as Harm Avoidance (HA) and self-directedness (SD) might provide some guidance for a classical antidepressant treatment outcome. However, to date no such research has been performed in rTMS treatment paradigms. In this open study, we wanted to examine whether these temperament and character scores in particular would predict clinical outcome in refractory unipolar depressed patients when a typical high-frequency (HF)-rTMS treatment protocol is applied. Thirty six unipolar right-handed antidepressant-free treatment resistant depressed (TRD) patients, all of the melancholic subtype, received 10 HF-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). All patients were classified as at least stage III TRD and were assessed with the Temperament and Character Inventory (TCI) before a HF-rTMS treatment. Only the individual scores on SD predicted clinical outcome. No other personality scales were found to be a predictor of this kind of application. Our results suggest that refractory MDD patients who score higher on the character scale SD may be more responsive to the HF-rTMS treatment.

The role of neuroimaging in our understanding of the suicidal brain.

This paper provides a review of the literature on neuroimaging studies of suicidal behaviour, and discusses the relevance of these studies for our understanding of suicidal behaviour. Main findings from molecular imaging studies include a reduced prefrontal perfusion or metabolism and a blunted increase in activation when challenged in association with a history of suicide attempts. Moreover, impairment of the prefrontal serotonergic system in association with suicidal behaviour is demonstrated in a number of studies. Recent structural and functional imaging studies show changes in cortical and subcortical areas and their connections. A number of methodological issues hamper the interpretation of findings. Nevertheless, when findings from studies using divergent techniques are taken together there is increasing evidence of the involvement of a fronto-cingulo-striatal network in suicidal behaviour. This involvement is supported additionally by findings from neuropsychological studies, which demonstrate changes in decision-making processes in association with suicidal behaviour that rely on the same network. Further study is needed to translate the increasing knowledge from neuroimaging studies in clinical tools for the prediction and prevention of suicidal behaviour.