Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry

Abstract

INTRODUCTION Transcranial direct current stimulation (tDCS), a safe and non-invasive neuromodulation technique, has re-emerged over recent years with several technical optimizations. Given the limits of extant therapeutic options in psychiatry, mainly because of its tolerability and safety profile, tDCS has elicited significant interest in clinical research studies in psychiatry, neurology, and several other medical specialties. These studies are also matched with cutting-edge investigative neuromodulation research using tDCS that has revealed critical insights advancing our knowledge about the brain in health and disease.[1] In psychiatry, tDCS has been evaluated in treating major depressive disorder, schizophrenia, alcohol use disorder, obsessive-compulsive disorder, mild cognitive impairment/dementia, and several other disorders. Given its portability and cost-effectiveness, tDCS offers the option of the remotely supervised, home-based (domiciliary) application as well. TDCS - DEFINITION tDCS uses the application of low-intensity, direct (time-invariant) current (usually in the range of 1-2 milliampere [mA]). This non-invasive neuromodulation technique, if administered as per recommended standard operating procedures, is extremely safe. The current delivery is ensured through the placement of electrodes (25-35 cm2 size [i.e., 5 X 5 cm or 7 X 5 cm]) that are made of bioconducting material (e.g., conductive rubber) placed on the scalp (corresponding to the underlying target brain area) leading to polarity-specific neuromodulation and adaptive neuroplasticity changes in the neural regions [Figure 1].Figure 1: Schematic illustration of tDCS applicationTDCS - MECHANISM OF ACTION The therapeutic utility of tDCS in disorders can be best understood when both the neuroplasticity mechanisms and how tDCS modulates those mechanisms are adequately deciphered. Studies have noted that the observed changes on account of tDCS are secondary to the adaptive neuroplasticity of the human brain.[2] Simply speaking, the mechanism through which tDCS can modify neuroplasticity is either by increasing or decreasing neuronal conductivity, differentially acting on the neuronal sites, modulating the local blood flow, and brain-derived neurotrophic factor (BDNF)-dependent mechanisms as well as glutamatergic, GABA-ergic/other neurotransmitter-mediated effects. Alteration of the neuronal resting membrane potential by varying the cation permeability is postulated to be one of the primary mechanisms through which tDCS is claimed to act. When a strong depolarizing signal is applied, it leads to more than the usual influx of calcium ions pre-synaptically. A more significant influx of calcium ions results in a greater release of glutamate post-synaptically, which subsequently causes extensive NMDA receptor activation. This cascade eventually causes an increased calcium influx post-synaptically, activating protein kinases responsible for the phosphorylation of AMPA receptors. Phosphorylation of AMPA receptors further activates more AMPA receptors resulting in further cation permeability in the postsynaptic neuron and better synaptic conductivity. The effects of tDCS on neuroplasticity can be summarized as follows: tDCS causes an increase in synaptic conductivity, both immediate and long-term. The polarity of the tDCS plays a vital role in determining the local effects of the procedure, both at the regional and neuronal levels. tDCS has been shown to induce long-lasting synaptic potentiation via augmented BDNF secretion. The long-term effects are also believed to be secondary to gene transcription secondary to tDCS. tDCS is also likely to show effects by polarity-based modulation of local blood flow. Polarity-specific effects are time-dependent, with longer duration (generally more than 40 minutes) of stimulation session provoking compensatory mechanisms and reversal of effects.[3,4] TDCS: DEVICE ASPECTS There are several types of tDCS devices. In each one, electrodes are connected to a device capable of delivering a constant low-intensity direct current (0.5 to 3.0 mA). In conventional tDCS, two large conductive siliconized rubber electrodes (typically 7 × 5 cm2), anode and cathode, complete the circuit. This administration is polarity-specific in effect, in which inhibitory stimulation at one region is counterbalanced for an excitatory stimulation of equal intensity at another region and vice versa. With this montage arrangement, we can deliver bipolar stimulation; that is, the nature of stimulation is anodal and cathodal in effect because of the electrode type and montage configuration. The tDCS devices deliver constant current – the intensity of current remains steady over time (e.g., 1 mA or 2 mA). As per Ohm’s law, the current intensity is directly proportional to voltage and inversely related to the resistance in the circuit. Ohm’s law: Voltage = Current Intensity x Resistance [V = I * R] Living biological tissue reacts to electric current as a way of adaptation, along with the flow of tissue fluids and alters the resistance being offered in the circuit. Hence, effective resistance in the circuit involves biological tissue as a combination of ohmic resistance and reactance. This effective resistance is called impedance. To keep the current constant, where changes in impedance happen dynamically, the device adjusts the voltage at every given time point. As a safety precaution, most medical-grade devices maintain a cutoff of impedance (generally 10–15 kohms) to avoid voltage surge. When the resistance increases beyond a certain threshold or when voltage reaches its limit, the device pauses/terminates the stimulation. Resistance indicators would generally be available and display the contact conditions between electrodes and the scalp during the sessions. Thus, it is recommended to use only those tDCS devices that are certified for human administration that complies with the required safety standards.[5,6] TDCS: STANDARD OPERATING PROCEDURES Checking for contraindication to tDCS during subject recruitment Choose the patients by ascertain the indication and any necessary precautions for tDCS administration [Table 1]. Explain to the subject the tDCS procedure in detail. Use of video would assist in annihilating the apprehensions. Ask the subject the following questions in the screening questions [Table 2] to enquire about the potential factors influencing the safe application of tDCS procedure. Table 1: tDCS indications and precautionsTable 2: Screening questions to identify potential factors influencing tDCS procedureAlthough there are no absolute contraindications for tDCS, administrators had to be cognizant of the above factors while planning the sessions. Past history of adverse effects should enable the administrators to take appropriate steps, as discussed later. Any brain-related injury, surgery, or space-occupying lesions can affect how the effect of electrical distribution and its consequent effects. History of epilepsy can theoretically increase the risk of seizures, specifically if the seizurogenic foci underlie the anode. Though tDCS has been administered safely in individuals with metallic/electrical implants, the distance from the stimulation site and the sensitivity of these devices to the electric field has to be considered. As medications can be a major confounding variable influencing the tDCS effects, it is always prudent to document it. Few patients develop headaches after tDCS, and awareness of the details of headache history in the patients will assist in its appropriate management. Preparation[4] Written informed consent has to be taken. Information regarding presence of minimal evidence for acute short-term efficacy and absence of strong evidence for long-term clinical efficacy of tDCS in the above-mentioned indications has to be clearly stated. Safety of multisession tDCS in clinical patients can be reassured. The provision of aborting the session in the event of intolerable side effects would further annihilate the patient’s safety concerns. Instruction to visit for tDCS with the dry, clean, non-oily scalp for tDCS session should be provided. Patients (and caregivers) have to be informed that fasting or other lifestyle changes are not needed for tDCS administration. Materials and their description (see Table 3 for reference)Table 3: List of materials for conventional tDCS Check if you have all materials needed before starting the procedure. The tDCS device is a battery-driven current generator capable of providing constant current stimulation to the brain with a maximum output (of ± 2.5) in milliamperes (mA) range. It operates on a rechargeable power bank. Electrodes used for tDCS are conductive rubber electrodes. These can deliver DC of either polarity - anode and cathode depending on how they are plugged into the machine. Measurement tape and skin marker can be used to mark the desired location on the subject’s scalp. The measuring tape can be further used to ascertain adequate distance between the anode and return cathodal electrode as per the study protocol requirements (minimum 3-finger distance). A comfortable chair is required to seat the subject in relaxed manner throughout the preparation and administration of tDCS procedure. Tissue or paper towels can come in handy for cleaning off either electrode due to excessive saline or cleaning the subject’s scalp after administration. Pre-administration preparations Turn on the tDCS device. Ensure the device has enough power for completion of the session. Visually inspect the rubber electrodes for signs of wear and tear. Place the rubber electrodes in sponge casings to improve tolerability and reduce adverse events like tissue injury. Never place the electrodes directly on the scalp. Apply the non-conductive water-proof bands for holding electrodes securely on the subject’s head. The placement of electrodes is described in the following sections. Administration procedure Seat the subject comfortably in a chair. Thoroughly inspect the subject’s scalp for signs of skin lesions, cuts, signs of inflammation or other cutaneous abnormalities. Localize the stimulation target regions on the subject’s head 10-20 EEG system Using tools like BeamF3 Neuro-targeting using structural with/without functional magnetic resonance imaging Mark the point on the subject’s scalp that corresponds to target locations. Part the hair at this marking. EEG paste can be used to keep hair parted - thick hair can cause higher impedance. Switch on the device before placing the electrodes on the scalp surface. This is to avoid sudden surge of current in the circuits that can lead to adverse effects. During the electrode placement, make sure that the smooth surface of the electrode (and not the wired-connected electrode surface) is in contact with the scalp. Sponge preparation: Add saline to the sponge (around 6 ml on either sides) to make it damp. Ensure it is sufficiently damp and not dry to be properly conductible. It should also not be dripping with saline, which may result in the shortening of circuit. Once prepared, place the electrode inside the sponge. Inspect the sponges for reusability in multisession administrations. Carefully place the cathodal and anodal electrodes kept inside the sponge case on the mark for desired/marked target regions on the cleaned subject’s scalp at an appropriate orientation. For example, tDCS electrodes for auditory hallucinations should be placed in a horizontal orientation with 7 cm as the length for the left temporoparietal junction and a vertical orientation with 5 cm as the length for the left dorsolateral prefrontal cortex. The wire connected to the electrode should be posteriorly directed in the attachment. Ascertain the distance between the two electrodes is minimum 7 cm (3 finger distance). Check for the subject’s comfort level with the attached headbands over the electrodes (This can be ascertained by asking the patients, “Is the setup too tight?”) Set-up the electrical parameters, including peak intensity, duration of stimulation, ramp-up and ramp-down rate/duration. Initiate the treatment. Ensure the impedance is below 10–15 kW - with further increase in resistance, the machine will auto-terminate the session. * Check for any sensations and reassure the pain will reduce in a few seconds with the completion of ramping up and development of tolerance. *Note: In situations of high impedance or in case of more pain, check for the following causes: a. Check if the electrodes are in full contact with the scalp. Make appropriate changes to establish better contact. b. Check if the saline is too less. Add saline as required. c. Check if the saline is too much and the current is being shunted. Use tissue to remove the extra dripping saline. d. Check if the hair parting. Remove the electrodes entirely, part the hair, apply EEG paste, and then re-attach the electrodes. In most circumstances, the above steps will resolve the impedance issues. After the session is over, remove the electrodes. Switch off the machine only after the electrodes are removed. Electrodes need to be removed from the sponge pads. Wipe the electrodes with the tissue (since dry saline over the electrodes can damage them and decrease its shelf life.) Clean the sponges with running water and allow them to completely dry before the next session. Ensure the salt deposits won’t stay for the next session. After the tDCS procedure Carefully inspect the skin regions where electrodes were placed for signs of skin irritation and/or skin damage. Any skin deterioration should be addressed in a medically appropriate way. Document the session-specific details in the session record sheet. Enquire from the subject about any possible side effects and fill in the details in the side-effect record sheet after every session. Inform the subject and their relative (or caregiver) about the timings of the next session and brief them if there were any major issues during or from the session (like appearance of skin lesion after the session, repeated sudden cessations throughout the session, difficulty in initiating stimulation due to abnormally high to side effect, Check the power the device. Make sure that the subject from and has a scalp when for tDCS session. Carefully inspect skin regions where electrodes are placed before and after every session. The subject should be and throughout the tDCS procedure. with during tDCS should be cognitive or should be during the session. not on the tDCS device before up or the electrodes for safety In a the device should be off after the administrators have the electrode following completion of the stimulation. starting the stimulation make sure that the electrodes are or where they to the machine. may with and increase the resistance in the circuit. of adverse effects due to tDCS tDCS is a if using the standard and The safety is on the stimulation that are in The adverse events are using a which the as well as the of of these adverse effects to the [Table tDCS adverse effect OF TDCS is a disorder, which also is a leading cause of The of significant cognitive and with best of the available about of patients show or no clinical and they to have resistance to about of due to that non-invasive brain stimulation increasing application in treating in several tDCS has been an increasing evidence to its clinical utility in The tDCS in have been informed by studies that between left temporoparietal region and auditory hallucinations as well as between and the of The used tDCS electrode montage cathodal stimulation over the left temporoparietal junction and anodal stimulation over the left prefrontal to target auditory hallucinations and A study that a on tDCS for auditory hallucinations in a in which for about 3 effects were in a of studies and case the effects on auditory clinical research studies have described evidence to effects of tDCS on other related to as well as depressive depressive the leading cause of is a The of and other medical further to the management. The in and tDCS is as a A brain region in is the prefrontal – the dorsolateral region – of the left side left and is postulated as one of the to This offers a to apply anodal current to the left and cathodal current to the is the most with studies using tDCS. evidence from these large of studies better efficacy of tDCS for and in evidence effects of tDCS in beyond the studies have the of home-based application as well. situations that the of tDCS in the medical with risk in the of that to with a of is the leading causes of and human studies a in the and circuits as well as the circuits in the of These circuits and which are in patients with studies also in and are the for a of patients not adequately to these and non-invasive have been to the above circuits in patients with as an imaging studies have shown as well as in regions and which are potential of non-invasive as tDCS. it is the is related to the or is Hence, both anodal and cathodal tDCS have been with the have shown significant with tDCS the and the as to stimulation. the target has been by studies have either on the left side or as well as cathodal tDCS over the have shown results in A study to cathodal to anodal stimulation. A recent recommended anodal tDCS with Thus, there is a need for studies to the efficacy of cathodal anodal tDCS tDCS over with cathodal stimulation over left has also been shown to be in two anodal tDCS over left have shown the studies the have not been evaluated in There is also evidence for of with anodal tDCS over prefrontal evidence for anodal or cathodal stimulation of and anodal stimulation of the studies are required to these as well as to the and stimulation is a by and The off during in most in a of tDCS the has been as an in the available evidence is in the of case or treatment. Given the evidence for over the region in cathodal tDCS may be a protocol that in the evidence is at disorders disorders are the most and disorders. and are the the and are in the and are that may be in these disorders. of regions modulating these including dorsolateral prefrontal and prefrontal may be tDCS over these regions has been as a or as an for to anodal stimulation of left and/or cathodal stimulation of are the while anodal stimulation is used for in evidence from studies on disorders have shown studies have not shown In the absence of tDCS may be recommended only as for these use disorders use disorders are a of by or to take of as well as in the absence of the and to on the The above is by neuronal - and standard and are they have their in of acute and long-term tDCS has been to the with other The prefrontal is to non-invasive stimulation and has been the target in tDCS For alcohol use a protocol anodal tDCS of and cathodal tDCS of left has shown the most results in This protocol has been to reduce long-term and improve in the The efficacy of the above protocol can be augmented inhibitory It is to be noted that the above protocol is of that used in where anodal tDCS of left is with cathodal stimulation of The has not been to be in clinical in alcohol use disorders when with tDCS of the has not been to be in Thus, the most tDCS protocol for alcohol use disorders involves anodal stimulation of and cathodal stimulation of left For recent have shown significant effect of tDCS as to stimulation. and have shown more efficacy on and with anodal tDCS and left cathodal tDCS. Studies the left anodal and cathodal stimulation, have There is also evidence that cathodal stimulation of decrease the best available evidence is for anodal stimulation of and cathodal stimulation of left for which is to the protocol for alcohol A protocol has been used for and which have shown studies are to the efficacy of tDCS in these cognitive disorders in the are another in which tDCS studies have been These studies have shown there is evidence for anodal stimulation of left to be given the safety and tolerability of tDCS as well as other in the in the of medical potential for tolerability of tDCS is an and conditions tDCS is evaluated in and as well as in disorders. the site of stimulation and protocol is and the evidence is studies are to the efficacy of tDCS in these the long-term of modulation of the brain are not Hence, application of tDCS in this is and with a of The available evidence for tDCS in most disorders Table are as to or tDCS for disorders with evidence from is needed for clinical effects. tDCS may have role in certain situations for of as with for and where is for there is an absence of risk of tDCS during to be ascertained in clinical tDCS is evaluated in or and not in related to the safety and utility of tDCS and tDCS are minimal tDCS is being evaluated to disorders with of cognitive to tDCS has not shown clinical and may be The therapeutic role of stimulation like tDCS, stimulation and other of electrical like current stimulation, current stimulation, current stimulation, is due to absence of evidence or presence of of evidence of conditions with evidence from disorders like and use acute increase for alcohol and Transcranial direct current stimulation (tDCS), a safe and non-invasive neuromodulation technique, has re-emerged over the recent years with several technical optimizations. The in disorders are on this clinical on tDCS in the related to tDCS, standard operating for clinical In a brief of the studies effects of tDCS in disorders is of the potential options for the therapeutic application of tDCS major depressive disorder, auditory in use obsessive-compulsive disorder, and mild cognitive tDCS is in its with for further research to ascertain of the of this – of as well as potential for home-based - this neuromodulation a therapeutic option in and This is by the of - of interest There are no of

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