|Year : 2021 | Volume
| Issue : 2 | Page : 305-309
A pilot study on effect of adjunctive transcranial direct current stimulation on symptom domains of depression in patients with depressive disorder
Shipra Singh1, Amit K Meena2, Gautam Sharma3, Smita N Deshpande3
1 Department of Psychiatry, Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
2 Department of Psychiatry, G.B. Pant Hospital, Delhi, India
3 Department of Psychiatry, ABVIMS, Dr. R.M.L. Hospital, Delhi, India
|Date of Submission||30-Mar-2020|
|Date of Acceptance||09-Aug-2021|
|Date of Web Publication||28-Oct-2021|
Dr. Gautam Sharma
Room No. 2, Department of Psychiatry, ABVIMS, Dr. R.M.L. Hospital, Delhi
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Depression is a highly prevalent condition and includes clusters of symptoms, namely, depressive cognition, anxiety, and visceral symptoms. Depressive symptoms often respond sub-optimally to pharmacotherapy. Adjunctive transcranial direct current stimulation (tDCS), a noninvasive brain stimulation modality, may improve depressive symptomatology. Aim: The aim of this study was to study the effect of tDCS as an augmentation strategy in depression and its various symptom domains. Materials and Methods: It is a prospective interventional study. Patients diagnosed with depressive disorder (based on International Classification of Disease- 10 criteria, diagnosed by treating psychiatrist), aged 18-70 years, who showed inadequate improvement on antidepressant selective serotonin reuptake inhibitors, were recruited after informed consent. Each participant was administered 20 sessions of tDCS over 2 weeks, each session of 20 min, with anode placement at left dorsolateral prefrontal cortex and cathode at right supraorbital region. Hamilton Rating Scale for Depression (HAM-D) was administered pre- and post-intervention to assess the change in symptoms. Results: Of a total of 35 participants, the mean score on HAM-D prior to and postintervention was 19.97 (standard deviation [SD] = 3.519) and 13.17 (SD = 3.365), respectively. The difference was statistically highly significant (P = 0.000) on paired t-test. All symptom domains of HAM-D, identified using the Cole and Motivala model (Cole et al., 2004), also showed significant reduction from pre-tDCS to post-tDCS scores (P = 0.000). Conclusion: Positive effect of tDCS on depressive symptoms, its tolerability and safety profile, and affordability makes it an effective therapeutic strategy in augmenting antidepressants in patients with depression. However, longer period studies with larger sample size may yield more generalizable results.
Keywords: Adjunctive, depression, Hamilton Rating Scale for Depression, transcranial direct current stimulation
|How to cite this article:|
Singh S, Meena AK, Sharma G, Deshpande SN. A pilot study on effect of adjunctive transcranial direct current stimulation on symptom domains of depression in patients with depressive disorder. Ind Psychiatry J 2021;30:305-9
|How to cite this URL:|
Singh S, Meena AK, Sharma G, Deshpande SN. A pilot study on effect of adjunctive transcranial direct current stimulation on symptom domains of depression in patients with depressive disorder. Ind Psychiatry J [serial online] 2021 [cited 2021 Dec 7];30:305-9. Available from: https://www.industrialpsychiatry.org/text.asp?2021/30/2/305/329367
Globally, an estimated 322 million people were affected by depression in 2015. The proportion of population with depression is estimated to be 4.4%. As per the National Mental Health Survey (2015–2016) in India, one in 20 (5.25%) people over 18 years of age has suffered at least once in their lifetime from depression, amounting to a total of over 45 million persons with depression in 2015.
Depression contributes to significant disease burden universally as well as at national level. Only one-third of depressed patients achieve clinical remission after the first antidepressant trial, but up to four different treatment trials are needed to gain remission in about 70% of patients. Moreover, about 80% of patients requiring more than one treatment relapse within 1 year. Nonresponse to antidepressant treatment involves a higher risk of illness chronicity, reduced quality of life, functional impairment, and suicidal behaviors., Tolerability is a major determinant of compliance to therapy: about 85% of patients on selective serotonin reuptake inhibitor (SSRI) medications experience at least one side effect during early stages of treatment, and side effects account for up to 20%–35% of antidepressant discontinuation.
In recent years, multiple neuromodulation strategies have emerged as effective adjunctive and alternate treatment modalities for the treatment of various psychiatric disorders. Transcranial direct current stimulation (tDCS) is one such, which is safer, noninvasive and has better tolerability. tDCS is a brain stimulation procedure, which changes cortical tissue “excitability” as a result of applying a weak (0.5–2 mA) direct current using scalp electrodes overlying targeted cortical areas. In contrast to other neurostimulation modalities, tDCS does not directly trigger action potentials in neuronal cells, but instead changes overall tissue excitability, and therefore may be more aptly regarded as a “neuromodulatory” rather than a neurostimulatory approach. Cortical tissue underlying the anode (positive electrode) becomes hypopolarized, and therefore hyperexcitable; areas underlying the cathode (negative electrode) become less excitable as the average resting potential becomes more polarized.
One of its most important mechanisms of action is subthreshold modulation of neuronal membrane potentials, thereby altering cortical excitability and activity, depending on the current flow direction through the target neurons. Other biological effects include changes in neurotransmitters, effects on glial cells and on microvessels, and modulation of inflammatory processes. Unlike neuromodulation induced by psychotropics, tDCS does not induce activity in resting neuronal networks, but modulates spontaneous neuronal activity. These findings suggest that tDCS is likely to be associated not only with transient membrane polarization changes, but also with longer-lasting synaptic changes. Unlike drugs, tDCS is well tolerated and has not produced any reports of a serious adverse effect or irreversible injury across 1,000 subjects over 33,200 sessions, as reviewed by Bikson et al. tDCS has also been used in pregnancy; the evidence is sparse but promising. Hence, tDCS can prove to be an effective and safe choice for depression.
A combination of antidepressant with tDCS has shown better response as compared to the two individually. tDCS showed quicker response than fluoxetine in depression in one study. However, 6 weeks later, there was no difference in improvement. Another randomized controlled trial (RCT) showed better efficacy of sertraline with tDCS combined treatment group compared to either of them alone and sham tDCS. However, since the treatment modality is newer and relatively untested, more evidence is needed for assessing side effects and efficacy.
Considering this evidence, the present study aimed to assess the change in symptoms with tDCS augmentation in patients with depressive disorder.
| Materials And Methods|| |
Consecutive participants, diagnosed with depressive disorder (without psychotic symptoms) according to the International Classification Diseases-10 Classification of Mental and Behavioral Disorders (diagnosed by board certified psychiatrists) and receiving treatment at the out patients department of a tertiary care medical college, between 18 and 70 years of age, of either gender, and who were ready to give informed consent, were enrolled in the study. In addition, the Mini International Neuropsychiatric Interview, a structured interview tool with a high validity and reliability, was administered to rule out other coexistent psychiatric disorder. Pregnant women, those with coexistence of any psychotic symptoms, unstable medical/neurological illness or history of seizure disorder, suicidality, and concomitant substance use (except nicotine) were excluded. Participants had been given an adequate trial of at least 4 weeks of optimal doses of antidepressants (mostly SSRIs), with steady dose in the optimal dose range in preceding 4 weeks, and still had inadequate improvement. Those who were on any other psychotropic medications (except short duration of benzodiazepines) were excluded from the study.
This prospective intervention study was carried out in a tertiary care teaching hospital after approval from Institutional Ethics Committee (IEC/PGIMER/RMLH 7754/16). Written informed consent was obtained from the participants before their enrollment in the study; 20 sessions of tDCS were administered within a span of 2 weeks (with no session on Sunday). Participants received 2 sessions per day, each session of 20 min duration. Missing sessions were administered in the subsequent week up to a total of 20 sessions. The study was carried out over a period of 12 months. Sample size was calculated using “sample size calculator for designing clinical research.” Effect size was 0.5, alpha was 0.05, beta was 0.2, and standard deviation (SD) was 1. The sample size calculated was 31.
Transcranial direct current stimulation treatment
tDCS was administered by one of the study authors, through FOCUS V2 device, which is a certified standard equipment and implements recommended safety guidelines. Anodal tDCS was administered over the left dorsolateral prefrontal cortex (DLPFC), identified as pF3 on the 10/20 EEG system. Cathode was placed over the right supraorbital region. Conductive rubber electrodes (2 inch × 2 inch or 5.08 cm × 5.08 cm) covered by sponges soaked in saline were used, held in place by a headband. Stimulation was given at 2 milliampere for 20 min, with gradual ramping up of the current over 30 s. Two sessions of tDCS were given per day and all sessions were given forenoon.
The outcome measure was change in Hamilton Rating Scale for Depression-17 items (HAM-D). Average duration of the HAM-D interviews was 12 min. Scores between 0 and 6 did not indicate the presence of depression, scores between 7 and 17 indicated mild depression, between 18 and 24 indicated moderate depression, and over 24 indicated severe depression., HAM-D was applied at the baseline, i.e. prior to commencing the tDCS intervention and on the day of the 20th tDCS session. Two other study authors (not including the one administering tDCS) applied HAM-D and frequent reliability checks were performed. After every session, participants were asked about any uncomfortable symptoms to assess side effects.
Paired t-test was done to study the difference in HAM-D scores pre- and post-tDCS intervention. Cole et al. model was used to study the response to tDCS on components of depressive symptomatology. This model suggests that 17 items of HAM-D are related to four latent variables, namely core depression (including items 1–3, i.e. depressed mood, feelings of guilt, suicide), insomnia (items 4–6, i.e. insomnia-initial, insomnia-middle, insomnia-delayed), anxiety (items 9–13, and item 15, i.e. agitation, anxiety-psychic, anxiety-somatic, somatic symptoms-gastrointestinal, somatic symptoms-general, hypochondriasis), and visceral (items 7, 8, 14, 16, 17, i.e. work and interest, retardation, genital symptoms, weight loss, insight).
| Results|| |
A total of 35 participants consented. Their mean age was 37.42 years, ranging 19–67 years; 57.14% (20) were male, 65.7% were married, and 34.3% were single. 71.4% of patients belonged to urban and 28.6% to rural background. The mean age of onset of depressive disorder was 30.64 years.
The mean score on HAM-D prior to intervention was 19.97 (SD ± 3.519) and postintervention was 13.17 (SD ± 3.365). The difference between two scores was statistically highly significant (P = 0.000) on paired t-test.
On further analysis, using the Cole and Motivala model, means of different variables of HAM-D were calculated pre- and post-intervention [Table 1]. On paired t-test, the difference in the scores of all individual variables showed significant change suggesting highly significant reduction of symptoms in all domains (P = 0.000), as shown in [Table 1].
|Table 1: Mean and paired t-test analysis of Hamilton Rating Scale for Depression and individual variable scores pre- and post-transcranial direct current stimulation|
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No serious adverse effect was noticed or mentioned by participants with administration of tDCS. However, one patient developed rash with itching on the application site after eighth session, after which he was monitored with continued tDCS sessions, and rash subsided in 2–3 days without any intervention.
| Discussion|| |
In our study, 35 participants underwent tDCS sessions over a period of 2 weeks, and at the end of sessions, a significant reduction was observed in all depressive variables. Literature yields studies with varying outcomes, probably due to the diversity in participant selection, tDCS methodology, electrode sizes, electrode placements, duration of stimulation, and amplitude of current. Fregni et al., 2006, in a RCT investigated the effect of 5 days of anodal stimulation (1 mA strength for 20 min/day) of the left DLPFC in 10 patients with major depression, randomly assigned to active or sham tDCS, and found 4 treatment responders in active versus no responders in the sham group. Boggio et al. reported 40.4% reduction in HAM-D scores in the tDCS group with 10 consecutive sessions in 2 weeks interval with strength of 2 mA for 20 min when compared to 10.4% in the active sham group, where participants were off antidepressants for at least 2 months prior to enrollment in the study.
When compared to antidepressant treatment alone, tDCS yielded response of similar magnitude but of more rapid onset. Brunoni et al. in their double-blind, placebo-controlled trial applying tDCS-alone and combined with sertraline found that tDCS alone as well as in combination with sertraline improved concentration difficulties and pessimistic and suicidal thoughts; compared to sertraline, tDCS showed superior improvement on items of “sadness” and “suicidal thoughts” of long form first Montgomery-Asberg Depression Rating Scale (MADRS). However, contrary result has also been seen where the difference between tDCS and sham group was not significant.
Further studies were done to assess if tDCS was effective in cases with severe symptoms or treatment resistance. Ferrucci et al. reported more than 30% reduction in HAM-D scores in severely depressed, treatment-resistant patients after 10 tDCS sessions over 5 days at 2 mA for 20 min per session, with anode placed at left DLPFC. Similar findings and contrary results have been reported. A recent meta-analysis suggested that tDCS may be an effective treatment option for patients presenting with major depressive episode, but its use in treatment-resistant depression or as an add-on augmenting strategy in patients already receiving antidepressants was less investigated.
In order to ascertain the symptoms that showed response to tDCS stimulation, we used Cole and Motivala model, and all the four variables, i.e. “core depression,” “insomnia,” “anxiety,” and “visceral,” showed significant reduction of scores. A similar study using a different model for factor analysis of HAM-D reported that “anxiety/somatization,” “cognitive disturbances,” and “retardation” factors showed more significant reduction in scores than other variables. However, a study by Loo et al. using CORE (core measures of psychomotor disturbance), which has been proposed as a predictor of response to other physical antidepressant treatments, reported that the CORE scores did not correlate significantly with percentage change in MADRS scores, and thus did not predict response to active tDCS.
Symptoms of depressive cognition, insomnia, anxiety, and other somatic complaints (which have been discussed earlier) have been found to improve with tDCS in otherwise non-depressed patients with different electrode placements, number of sessions, and other parameters.,,,,, Individual case reports and case series reported improvement in various anxiety symptoms. A case study of generalized anxiety disorder showed improvement in anxiety symptoms after 15 sessions of tDCS with cathode at right DLPFC. Similar electrode placement in a case of panic disorder also reported positive results. Our participants did not report any panic symptoms, nor had co-morbid anxiety disorders, although anxiety symptoms were present in a number of them; mean score of “anxiety” pre-tDCS was 6.54 and post-tDCS was 5.14.
Anodal tDCS targeting the left DLPFC significantly attenuated the increase on Defense and Veterans Pain Rating Scale ratings following the cold pressor task involving immersing the participant's dominant hand and arm in an ice water bath. Another study using anodal tDCS at dorsolateral prefrontal cortex showed lower pain unpleasantness ratings in the participants where diagnosis of depression was excluded.
tDCS has been used in sleep-related issues in various disorders. Anodal tDCS improves the quality of subsequent sleep during a wake period, as assessed by higher scores on the Pittsburgh Sleep Quality Index, in cases of postpolio syndrome and euthymic phase of bipolar disorder (when placement of cathode is on cerebellum)., A review by Annarumma concludes that oscillatory stimulation on frontal areas at 0.75 Hz during nonrapid eye movement sleep can be effective in enhancing slow wave sleep, whereas a stimulation at 5 Hz during resting state may be a suitable method to induce and increase sleepiness in patients with insomnia disorder. Since sleep-related symptoms commonly occur in many neuropsychiatric conditions, tDCS can be investigated as a potential safer adjunctive treatment modality instead of pharmacological agents. In our own participant group, sleep improved significantly.
| Conclusion|| |
The present study demonstrates that tDCS augmentation improves depressive symptoms in the short term. Nearly all domains or variables of depressive symptomatology responded to tDCS in our sample. In clinical practice, this may help in reducing sequential trials of multiple antidepressants or adjunctive drugs and avoid their burdensome side effects, thus giving an alternate safer modality for the treatment of depression. However, open label nature, absence of control group, modest sample size, lack of uniform treatment doses of antidepressants, and lack of long-term assessment of outcome measures are the limitations which restrict the generalizability of this study.
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Conflicts of interest
There are no conflicts of interest.
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