Representatives for Flow Neuroscience have announced on the company’s website that a headset device that they call simply Flow is now available for sale – they claim the device can reduce chronic depression symptoms.
The British government recently gave the go-ahead to such devices (as did the EU), citing research showing such devices can be useful for treating long-term, chronic depression.
The device is now available to purchase for £399, and includes an app the company claims was created by a team of psychologists.
They also note that they are offering a 30-day trial period.
The device sits mostly on the top of the forehead and sends a small jolt of electricity through the skull into the prefrontal cortex (the part of the brain responsible for personality, decision-making and regulating emotions).
The technology, known as transcranial direct current stimulation, has been the subject of numerous tests, most of which have found that it provides some degree of relief from depression symptoms. Many have concluded that it is at least as effective as antidepressants, but without the side effects.
Thus far, none of the trials have found any adverse effects of such treatment other than reddened skin where the electrodes are placed and the occasional headache. Such treatments have been found to change the potential of neurons – in some cases, making them fire more often, and in others less often.
People with chronic depression typically experience less neural activity in the left side of their prefrontal cortex – the mild shocks are meant to increase such activity to match that in the right side.
Some of the trial results have even shown that in some cases, mild electrical stimulation can encourage the growth of new neural connections, perhaps reducing depression symptoms permanently.
Upon purchase of the device (after consulting with their own health care professional) users are directed to wear the headset for a half-hour approximately every three days over the course of six weeks.
While doing so, they are encouraged to use the app, which provides useful tips, such as reminders to get enough sleep, eat right, and exercise.
Background
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has yielded promising results in treating major depressive disorder. However, its effect on treatment-resistant depression remains to be determined. Meanwhile, as an emerging treatment option, patients’ acceptability of tDCS is worthy of attention.
Methods
This pilot study enrolled 18 patients (women = 13) with treatment-resistant unipolar (n = 13) or bipolar (n = 5) depression. Twelve sessions of tDCS were administered with anode over F3 and cathode over F4. Each session delivered a current of 2 mA for 30 min per ten working days, and at the 4th and 6th week. Severity of depression was determined by Montgomery–Åsberg Depression Rating Scale (MADRS); cognitive performance was assessed by a computerized battery.
Results
Scores of MADRS at baseline (29.6, SD = 9.7) decreased significantly to 22.9 (11.7) (p = 0.03) at 6 weeks and 21.5 (10.3) (p = 0.01) at 8 weeks. Six (33.3%) participants were therapeutically responsive to tDCS. MADRS scores of responders were significantly lower than those of non-responders at the 6th and 8th week. Regarding change of cognitive performance, improved accuracy of paired association (p = 0.017) and social cognition (p = 0.047) was observed at the 8th week. Overall, tDCS was perceived as safe and tolerable. For the majority of patients, it is preferred than pharmacotherapy and psychotherapy.
Conclusions
TDCS can be a desirable option for treatment-resistant depression, however, its efficacy may be delayed; identifying predictors of therapeutic response may achieve a more targeted application. Larger controlled studies with optimized montages and sufficient periods of observation are warranted.
Trial registration
This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR-INR-16008179).
Keywords: Transcranial direct-current stimulation, Treatment-resistant depression, Cognitive ability
Background
Major depressive disorder (MDD) is a highly prevalent mental illness associated with substantial personal impairments and societal costs [1]. Although progress has been made in the pharmacological and psychotherapeutic intervention of MDD, there are still up to 50% of patients with poor response to multiple trials of antidepressants, defined as treatment-resistant depression (TRD) [2–5]. Patients with TRD have lower quality of life. They account for more frequent medical visits and higher health care costs [6].
Empirical pharmacotherapy of TRD includes augmentation with lithium or second generation antipsychotics, often with suboptimal efficacy and poor tolerance [7]. Electroconvulsive therapy (ECT) remains as an efficient treatment for TRD, however, its application is limited due to risk of anesthesia and cognitive side effects [7–9].
Indeed, current treatment for TRD is still far from satisfactory; there is an urgent need for novel therapeutics. Recently, non-invasive brain stimulation has emerged as a promising candidate. Repetitive transcranial magnetic stimulation (rTMS) has been approved by the US Food and Drug Administration for treating TRD [10]; interests in transcranial direct current stimulation (tDCS) is growing following its demonstrated efficacy on MDD.
TDCS, a non-convulsive brain stimulation technique involves injecting a low-amplitude (generally 1-2 mA), direct electric current flows from the anode to the cathode in cerebral cortex by using two surface scalp electrodes [11, 12], which alters the membrane potentials of neurons and changes the rate of spontaneous depolarization [13–15].
The anode area becomes hypo-polarized and the cathode area becomes hyper-polarized. One well-known hypothesis of depression is hypoactivity in left dorsolateral prefrontal cortex (DLPFC) leading to psychomotor retardation and executive dysfunction [16, 17]. Researchers suppose that tDCS anodal stimulation over left DLPFC increases its cortical activity, which would lead to improvement of depression. In recent years, multiple randomized studies have confirmed the antidepressant effect of tDCS among patients with MDD [18–23].
Rigonatti et al. published that tDCS had equal but faster antidepressant effects in comparison with fluoxetine [24]. Brunoni and colleagues demonstrated that effects of tDCS plus antidepressants can be synergistic [25].
Given the encouraging findings of tDCS in MDD, several pilot studies have explored its effect in TRD patients, with mixed results. In a randomized controlled study applying 10 sessions of tDCS, there were no significant differences of depressive symptoms between active and sham groups after 4 weeks [26].
Blumberger and his team extended that a 15-session tDCS was not efficacious in TRD [27]. In another controlled study, tDCS efficacy on psychomotor and neuropsychological functioning in TRD is limited [28]. On the contrary, the promising result from Dell’Osso el al. revealed that tDCS administered twice a day for 5 consecutive days help reduce depressive symptoms, particularly melancholic features [29].
Another encouraging study conducted by Ferrucci applied the identical tDCS protocol among hospitalized patients with severe MDD; improvement was observed on day 5 after ten tDCS sessions and persisted to the end of 5 weeks [30].
It has been observed that the effect of brain stimulation can be delayed [31], with its effect manifesting beyond treatment periods. However, existing research often completed follow-up at the end of treatment.
The majority of studies examined the effect of tDCS on depressive symptomatology, few have comprehensively assessed cognitive performance, a crucial determinant of functional recovery. Moreover, as a novel treatment modality, the acceptability of tDCS needs to be further established. Thus, in the present study, we examined, at the 8th week, the antidepressant and cognitive effects of a 6-week tDCS treatment for TRD, identified potential predictors for treatment responsiveness, and elaborated the subjective experiences receiving tDCS.
Discussion
The present study demonstrated that tDCS could be advantageous to patients with treatment-resistant depression (TRD) in improving depressive symptoms and cognitive performance. Its effect may be delayed, with marked discrepancy between responders and non-responders. TDCS is well accepted and preferred than other treatment modalities.
The findings here need to be interpreted with a number of limitations considered, including a relatively small sample size, an open-label design, lacking of a controlled group, and less stringent definition of TRD.
It is likely that response rates may increase in open-label studies due to positive expectations from both un-blinded patients and un-blinded raters. With the multiple tests for cognitive performance, the 2 significant outcomes may be prone to type-I errors. Also, the inclusion of bipolar patients is likely to increase heterogeneity. Prior studies examining the efficacy of tDCS on TRD were universally small (i.e. sample size < 25), yielding conflictual results.
Our positive findings are in agreement with those of Dell’Osso et al. and Ferrucci et al., both applying augmented, F3-F4 tDCS with a five-days, twice-daily protocol [29, 30]. In contrast, in three controlled studies, reduction of depressive symptoms was similar in active and sham groups [26–28]. Results from another open-label study also showed no benefit of tDCS in patients with TRD [34].
The montages of tDCS in these negative studies are mostly different from the established F3-F4 positioning, and their period of observation is, at most, 4 weeks. Comparatively, our tDCS application spans for 6 weeks, with the lengthiest follow-up of 8 weeks, which is more likely to capture its full effect.
Due to the differential antidepressant effect of tDCS, it raises the need to investigate predictors of treatment response. It has been shown that pre-treatment verbal fluency predicts the response of tDCS on depression [35]. In a recent report pooled from 3 tDCS trials with 171 depressed patients, pre-treatment cognitive disturbance, retardation, anxiety and somatization played a role in prediction of response to tDCS [36].
Nonetheless, in our study, no demographic, clinical or cognitive characteristics at baseline could predict response to tDCS, potentially owing to limited sample size, higher severity of depression and unmeasured covariates.
We observed an improvement of visual learning and social cognition at the end of 8 weeks. The result is in accordance with a report by Boggio et al., that, in depressed patients, tDCS stimulation of left DLPFC had a significant effect on improving the accuracy of identifying figures with positive emotional content [37].
Wolkenstein et al. [38] and Brunoni et al. [39] reasoned that tDCS may improve cognition via modifying the emotional inhibitory control and negative attentional bias. Effects of tDCS may extent to cortico-subcortical regions, which can modify the cognitive dysfunction and emotion processing.
In contrast, several studies found no effect of tDCS on cognition in patients with TRD [26, 28, 30]. One recent systematic review could not conclude the cognitive benefits of tDCS in depressed patients [40]. Future research is needed to clarify the equivocal findings.
We observed a delayed effect of tDCS over depressive symptoms. In an animal study, cathodal stimulation combined with task assignment showed effects 3 weeks later [41]. In another controlled study examining effects of tDCS in MDD, antidepressant effect in the 3-week masked face was only modest, but the number of responders in the following 3-week, open-label phase was much more encouraging [22]. The after-effects of tDCS have been linked to non-synaptic mechanisms involving neurogenesis [42–44]. TDCS may also induce long-term cortical plastic change via metabolic pathways, for example, increasing BDNF release [41, 45, 46].
Conclusions
Given that available treatments of TRD had unsatisfactory efficacy or tolerability [9], the high acceptance, perceived benefits, and preference of tDCS demonstrated here have important clinical implications. TDCS is inexpensive and easily administered, which has a potential to serve as a scalable treatment. Our preliminary findings suggest that tDCS can be a desirable option for TRD, however, its efficacy may be delayed; identifying predictors of therapeutic response may achieve more targeted application. Larger controlled studies with optimized montages and sufficient periods of observation are warranted.
