In the latest version of the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), trichotillomania (TTM) was introduced as a psychiatric disorder classified under the Obsessive Compulsive Related Dis-order category, in which sufferers persistently pull their hair [1]. Although behavioral therapy and drug therapy methods have been successful in treating TTM, but not for all patients because some patients are not willing or able to follow this treatment strategy [2]. For this reason, there is a need to investigate other effective treatment options for this group of people.

Recently, non-invasive brain stimulation techniques have shown significant clinical benefits and promise in psychiatric disorders [3-6]. One of the most common techniques is transcranial direct current stimulation (tDCS). In this method, direct current with weak intensity (2 mA) is applied to the scalp through the electrode (anode and cathode), which leads to nerve modulation and greater excitability of the areas under the electrode [7]. Recently, the use of tDCS method in the treatment of obsessive- compulsive disorder (OCD) has shown promise [7,8]. Targeting the presupplementary motor (pre-SMA)/supple-mentary motor area (SMA) areas for tDCS is recommended [9], and Inhibitory protocols including cathodal tDCS of these areas have shown promising therapeutic efficacy [10].

Trichotillomania has similarities with OCD in terms of phenomenology and neurobiology [11]. It is assumed that deficits in motor inhibition processes are common features of hair pulling in trichotillomania, compulsions in OCD and motor tics in tourette syndrome [12]. Many white matter tracts near the gray matter are abnormal in trichotillomania, these regions play a key role in the development and suppression of motor habits [13]. In all species, the pre-SMA region leads to the preparation and selection of movements and with high-level functions [14]. A role in important cognitive functions such as response inhibition, monitoring of conflicting information, and control of internally stimulated movements are important functions of the pre-SMA/SMA region [15]. Defects in SMA lead to reduced striatal inhibition and consequently striatal hyperactivity in OCD individuals and manifests as inhibitory dysfunction [12]. In addition, research evidence suggests that transcranial electrical or magnetic stimulation to reduce cortical excitability (inhi-bition) in the SMA may modify OCD symptoms [16].

A review of the evidence showed that the tDCS technique has not been used for trichotillomania so far. There-fore, the innovation of the current research is important from two aspects: 1) using tDCS technique in the treatment of trichotillomania for the first time, 2) using a new stimulation protocol with intensified and repetitive stimulation parameters. The reason for choosing this protocol is that recent evidence indicates the greater and long-term effectiveness of intensified and repeated tDCS [17-19]. According to the evidence presented above, in the present study, our aim is to investigate the effects of intensified and repeated during 16 sessions, 2 sessions one day, current intensity of 2 mA for 20 minutes, which regions dorsolateral prefrontal cortex (DLPFC) and supplementary motor area were selected as stimulation target areas on symptoms of trichotillomania and psychiatric symptoms (depression, anxiety) in a patient with TTM.

Written informed consent was obtained from the patient.

The participant in the present study was a 25-year-old woman. She is married, working and the first child in the family. She has nearly 10 years of hair pulling experience. Due to the problem of depression, he has a history of prescribing psychiatric drugs such as amitriptyline, sertraline and depakene. And among the side effects of the drugs, she has periodically had obesity and overeating. She reported that in the current situation, the hair pulling problem has intensified. Currently, she does not take any psychiatric medication (no use for almost a year) and it was agreed that she will not take any medication until the end of the intervention.

The participant was evaluated and measured in four stages approximately during two months: 1) one week before the start of the intervention (baseline), 2) immediately after finishing the stimulation sessions, 3) follow-up after three weeks, 4) second follow-up after three weeks.

Before starting the intervention process, the necessary information about the purpose of the study was fully given to the participant and the consent to participate in the research was obtained. She was evaluated in terms of inclusion and exclusion criteria for tDCS such as seizures, brain injury, being pregnant, and brain surgery. Also, since the participant was looking for a treatment method other than drug therapy, they fully welcomed our proposal, which was the tDCS method. A 16-session (every other day) protocol of electrical stimulation using tDCS was applied in a repeated and intensified manner for 20 minutes each session and two sessions in one day with an intensity of 2 mA and an interval of 20 minutes between sessions for 20 days (anodal [F3] and cathodal [SMA]). Electrodes were placed on the scalp according to the international 10−20 system. The cathode was placed on the sagittal midline at 15% of the distance between inion and nasion anterior to Cz and the anode electrode was placed on F3. For electrical stimulation, the Oasis Pro model produced by Mind Alive, Canada was used, and the size of the electrodes was 7 × 5 cm.

After each stimulation session, the participant answered the electrical stimulation side effects scale. Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A) questionnaire was used to measure trichotillo-mania. Also, to check the severity of hair pulling behavior in different stages of the intervention, the participant responded to the visual analogue scale (VAS). Hamilton anxiety rating scale (HAM-A) and Beck Depression In-ventory II (BDI-II) were also used to measure psychiatric symptoms (depression and anxiety). The steps of the intervention are fully shown in Figure 1.

The results are presented in Table 1 and Supplementary Figure 1 (available online). The results indicate a significant improvement in the trichotillomania variable from the baseline stage to the follow-up stage. So that in the MIST-A scale, the percentage of changes was −63.25, and in the VAS scale, the percentage of changes until the follow-up stage was −53.33. This percentage reduction in hair pulling behavior is significant from a therapeutic point of view.

Also, the results regarding psychiatric symptoms (depres-sion and anxiety) indicated a significant improvement and reduction of these symptoms. So that in the HAM-A scale to measure anxiety, the percentage of changes until the follow-up stage was −52.38, and in the BDI-II scale to assess depression, the percentage of changes was −34.28. In both scales, the percentage of changes and reduction of symptoms.

Finally, the results of evaluating the side effects of tDCS showed that the amount of stimulation provided to the participant was tolerable and no serious side effects were reported, and in general the stimulation protocol used is safe (see supplementary results, Table 1 and Supplementary Table 1; available online).

The present study was designed with the aim of investigating the effectiveness of tDCS in the treatment of trichotillomania disorder. To the best of our knowledge, this is the first study to determine the effectiveness of electrical stimulation with tDCS in the treatment of trichotillomania. The results showed a significant effect in improving and reducing hair pulling symptoms from the baseline stage (before the intervention) to the follow-up stage.

A review of the evidence showed that no study has been conducted on the effectiveness of tDCS on tricho-tillomania. However, in the Repetitive transcranial magnetic stimulation (rTMS) method, the results of Aydın et al. [20] showed that 15-session rTMS of the over pre-SMA area, 20-minute every session led to the improvement of trichotillomania symptoms in the participants. Also, the results show that the low-frequency rTMS technique leads to the inhibition of disturbing thoughts, impulses, images and repetitive motor responses through the inhibitory effect on hyperactivity in the orbito-fronto-cortical circuits and the regulation of activity in the orbitofrontal cortex/SMA in OCD [21]. SMA has been identified as an important cortical region for OCD and is thought to mediate response inhibition [22]. The results of neuroimaging studies indicate overactivity of SMA in OCD patients and this overactivity may be related to incomplete inhibitory control of behavior [23]. Therefore, inhibition of SMA activity could be a target for brain stimulation techniques for OCD symptoms, especially in compulsive behaviors [24].

The improvement of psychiatric symptoms (depression and anxiety) was also observed in our study and there is a significant correlation between the reduction of changes in these symptoms and the reduction of hair pulling symp-toms. Considering that the anode electrode was fixed in the F3 area, these findings can be explained. Because previous studies that targeted this area for their stimulation have shown a significant improvement in the symptoms of depression [25,26] and anxiety [24,27]. Studies have shown that during depression there is hypoactivity in the left side and hyperactivity in the right side of the DLPFC [28].

The new aspect of the current research is the use of the intensified and repeated stimulation protocol. The rationale for using the intensified and repetitive stimulation protocol was that previous studies have shown more long- term effectiveness and greater excitability compared to non- repetitive stimulations [17,18]. Physiological evidence has also shown that repeated sessions of tDCS induce greater excitability [29], and clinical studies suggest greater efficacy with more frequent stimulation sessions [30]. Recent studies also indicated the effectiveness of repeated and intensified stimulation protocol in improving various mental disorders [19,31].

The present study provides evidence for the efficacy and safety of cathodal stimulation on the SMA and anodal stimulation in the F3 region in a richotillomania patient. Considering the effect of tDCS on psychiatric symptoms as a secondary outcome, one of the limitations of the present study is that it is not clear whether tDCS with a positive effect on psychiatric symptoms has led to the improvement of trichotillomania symptoms or not. Based on the findings of the present study, randomized clinical trials are needed to clarify the clinical effectiveness of this tDCS protocol. Also, experts can use this treatment method in combination with other psychotherapies and drug therapies.

The authors are grateful to the participant in the present study.

No potential conflict of interest relevant to this article was reported.

Conceptualization: Jaber Alizadehgoradel. Data acquisition: Asghar Pouresmali, Mina Taherifard. Formal analysis: Jaber Alizadehgoradel. Supervision: Jaber Alizadehgoradel. Writing−original draft: Jaber Alizadehgoradel, Asghar Pouresmali, Mina Taherifard. Writing−review& editing: all authors.