The World Journal of Biological Psychiatry, 2014; 15: 261–275

REVIEW ARTICLE

Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders?

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

MARINE MONDINO1, DJAMILA BENNABI2,3, EMMANUEL POULET1, FILIPE GALVAO1, JEROME BRUNELIN1 & EMMANUEL HAFFEN2,3,4 1Centre

Hospitalier le Vinatier, Université Claude Bernard Lyon I, Bron, France, 2Department of Clinical Psychiatry, University Hospital, Besançon, France, 3Department of Neuroscience, University of Franche-Comté, Besançon, France, and 4Clinical Investigation Center, INSERM, University Hospital, Besançon, France

Abstract Objectives. Since the discovery of psychopharmacological treatments in the early 1950s, followed by the development of second-generation antidepressants and antipsychotics, biological psychiatry has not achieved much progress. Recent technological advances in the field of non-invasive brain stimulation open new perspectives in the treatment of psychiatric disorders. Amongst them, transcranial direct current stimulation (tDCS) modulates cortical excitability and induces long-lasting effects. Here, we aimed at evaluating whether tDCS has potential to be developed as an innovative treatment in psychiatry. Methods. We conducted a systematic review of the current state of development and application of tDCS in psychiatric disorders, exploring clinical and cognitive effects, especially in major depressive disorder (MDD), schizophrenia and substance use disorder. Results. Systematic literature search yielded 40 publications: 22 in MDD, nine in schizophrenia, seven in substance use disorder, one in obsessive–compulsive disorder and one in mania. Our findings indicated beneficial clinical effects of tDCS for MDD and a promising literature in schizophrenia and substance use disorder. Conclusions. Despite methodological differences, the data published to date are promising and supports the use of tDCS as a treatment for psychiatric disorders. However, its place regarding other treatments still has to be determined before becoming a routine clinical treatment. Key words: transcranial Direct Current Stimulation, neuropsychiatry, major depressive disorder, substance use disorder,

schizophrenia

Introduction Noninvasive brain stimulation with electrical current at low amperage has been re-introduced recently under the name of transcranial direct current stimulation (tDCS; Priori et al. 1998; Nitsche and Paulus 2000). tDCS consists of applying a low-intensity current (usually 1 or 2 mA) over the scalp between two electrodes placed in saline-soaked sponges. The current delivered by a battery-driven constant current stimulator flows through the brain from the anode to the cathode and induces bidirectional polarity-dependent changes in cortical excitability. Based on neurophysiological studies investigating motor cortex excitability (Nitsche et al. 2007, 2008), it is commonly assumed that the anode induces an increase in cortical excitability while the cathode

reduces it. When the stimulation is applied continually during several minutes, commonly 10–20 min, the induced excitability changes last for up to an hour (Nitsche and Paulus 2001; Nitsche et al. 2003a). Although the accurate mechanisms underlying tDCS effects remain unknown, pharmacological studies have highlighted changes in resting neuronal membrane potential and synaptic modifications linked to glutamatergic NMDA-receptor dependent activity and GABAergic activity (Stagg et al. 2011). Compared with other stimulation devices, tDCS equipment is small and low-cost; the stimulation is easy to administer (Priori et al. 2009) and at-home deliverable (Andrade 2013). Moreover, no serious side effects were observed after tDCS; only tingling, itching, burning and mild pain sensations were

Correspondence: Jerome Brunelin, Centre Hospitalier le Vinatier, BP 300 39, 95 Boulevard Pinel, 69 678 Bron Cedex, France. E-mail: [email protected] (Received 14 May 2013 ; accepted 13 December 2013) ISSN 1562-2975 print/ISSN 1814-1412 online © 2014 Informa Healthcare DOI: 10.3109/15622975.2013.876514

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

262

M. Mondino et al.

commonly reported during the stimulation (Poreisz et al. 2007; Brunoni et al. 2011a; Kessler et al. 2012). Safety studies have reported that tDCS does not elevate levels of serum neuron-specific enolase concentration, a marker of neuronal damage, immediately or 1 h after tDCS (Nitsche and Paulus 2001; Nitsche et al. 2003b) and does not induce changes in diffusion-weighted or contrast-enhanced MRI measures (Nitsche et al. 2004) or pathological EEG changes (Iyer et al. 2005). According to its ability to modulate cortical excitability and its potential to induce longlasting effects, tDCS appears to be a safe promising tool in the treatment of conditions in which abnormal cortical activity is reported. Moreover, the use of tDCS may be relevant for patients reporting too much side effects with medication or for patients with treatment-resistant symptoms. The number of studies exploring the effect of tDCS in psychiatric disorders has relevantly increased in recent years, investigating both clinical and cognitive effects. Here, we aimed to determine whether tDCS has potential to be developed as an innovative treatment for patients with psychiatric disorders, especially depression, schizophrenia and substance use disorder. We reviewed the current state of development and application of tDCS in these indications, exploring clinical and cognitive effects. tDCS and depression In the coming decades, depression is expected to become the leading cause of disability in the world (Mathers and Loncar 2006). Despite the numerous options available, only 50% of patients with major depressive disorder (MDD) respond to their first antidepressant treatment and less than 40% achieve remission (Gorlyn et al. 2008; Kemp et al. 2008; Trivedi et al. 2008). Consequently, alternative therapeutic options are required (Giacobbe et al. 2009). In 1964, two systematic studies, conducted by Redfearn and Costain and co-workers (Redfearn et al. 1964; Costain et al. 1964) highlighted beneficial effects of brain polarization in the treatment of depression. Further investigations on the antidepressant effect induced by scalp DC have been proposed, leading to discordant results. Two open label trials (Ramsay and Schlagenhauf 1966; Baker 1970) reported a clinical improvement in a series of depressed patients, while Arfai et al. (1970) failed to detect a significant effect of tDCS on mood. Although promising, this conflicting findings and the development of antidepressant treatments resulted in a progressive loss of interest for this technique. Recently, tDCS was delivered to the dorsolateral prefrontal cortex (DLPFC) to improve depressive symptoms (Downar and Daskalakis 2012) according

to imaging studies reporting a prefrontal asymmetry with hyperactivity in the right DLPFC and hypoactivity in the left DLPFC (Grimm et al. 2009). Indeed, the repetitive application of anodal-tDCS offers the possibility of regulating cortical excitability of the DLPFC, and may exert beneficial effects on clinical symptoms in major depression. Herein, we review recent studies that have applied tDCS in patients with MDD. A systematic search of the literature was conducted using Cochrane and Pubmed databases (up to January 2013). The identification of English language articles was based on the following keywords: “transcranial direct current stimulation” or “tDCS” and “depression”. The reference lists of the selected articles were scrutinized for additional papers. The initial strategy search yielded 22 articles (when both databases were combined), including 13 randomized sham-controlled trials (RCT), seven open-label studies and two meta-analyses (see Table I). Effect on symptoms Fregni et al. (2006a) were the first to administer five consecutives sessions (20 min, 1 mA) of anodal-tDCS applied over the left DLPFC coupled with cathodaltDCS over the right supra-orbital area in 10 patients with MDD. Upon completion of the five sessions, the authors reported a significant mood improvement in the active compared with sham tDCS group, as indexed by the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) scales. The authors confirmed these results in a subsequent study including a larger sample of 18 unipolar patients (UP) with MDD (Fregni et al. 2006b). Two other RCT conducted by Boggio et al. (2007; 2008a) replicated these findings.The first one included five sessions of tDCS applied at 2 mA in 26 UP. The second study, involving 40 patients with mild to moderate depression, reported an average reduction of 40.4% in HDRS score after active DLPFC tDCS versus 21.3% after occipital tDCS and 10.4% after sham stimulation. More recently, Loo et al. (2010) performed 10 sessions of tDCS at 1 mA in 40 patients. They reported similar reduction in HDRS scores in both active and sham tDCS groups. However, they reported the superiority of active tDCS in a larger scale study, applying 15 sessions of anodal-tDCS at 2 mA in 64 UP and bipolar patients (BP), with a greater reduction in HDRS scores after active (28.4%) than after sham (15.9%) tDCS. In a study including 42 UP, Rigonatti et al. (2008) reported comparable effects of tDCS and fluoxetine after 6 weeks of treatment. The antidepressant effect occurred faster in the tDCS group than in the fluoxetine group.

28 UP 120

Double-blind, RCT, placebo or AD

Double-blind, RCT

Double-blind, RCT

Double-blind, crossover, RCT

Double-blind, crossover, RCT

Double-blind, crossover, RCT

Double-blind, RCT

Double-blind, RCT

RCT

Rigonatti et al. (2008)

Loo et al. (2010)

Blumberger et al. (2012)

Palm et al. (2012)

Loo et al. (2012)

Wolkenstein and Plewnia (2013)

Brunoni et al. (2012a)

Oliveira et al. (2013) Brunoni et al. (2013b)

28 UP

22

64

22

24 UP

40

42 UP

40 UP

Double-blind, RCT

Boggio et al. (2008a)

26 UP

Double-blind, RCT

18 UP

Double-blind, RCT

Boggio et al. (2007)

10

Double-blind, RCT

Fregni et al. (2006a) Fregni et al. (2006b)

n

Design

AuthorDate

Study

F3/F4

F3/right upper arm F3/F4

Combination with F3/F4 sertraline 50 mg

AD free BZP

AD, stable dose ⬎ 1 week, AP, lithium AD free; BZP

F3/FP2

F3/FP2

F3/F4

F3/FP2

F3/F4

No AD ⬎ 2 months

AD stable dose ⬎ 4 weeks AD stable dose ⬎ 4 weeks, BZP, AP AD stable dose ⬎ 3 weeks, BZP, AP, MS AD, stable dose ⬎ 4 weeks

F3 or O/FP2

No AD BZP

F3/FP2

F3/FP2

No AD ⬎ 3 months No AD

F3/FP2

No AD

Treatment

Anode/ Cathode placement

12

1

1

2 (1/week)

15 (3 weeks)

20 (3/week)

15 (3 weeks)

10 (3/week)

10 (10 days)

10 (10 days)

5 (10 days)

5 (5 days)

5 (5 days)

n session

2

2

2

1

2

1 or 2

2

1

2

2

2

1

1

30

30

30

20

20

20

20

20

20

20

20

20

20

Duration I (mA) (min)

tDCS Parameters

35

35

35

35

35

35

35

35

35

35

35

35

35

Electrode size (cm2) Results

(Continued)

Enhancement in working memory assessed by the n-back task after real stimulation. The combination of tDCS and sertraline increases the efficacy of each treatment. Comparable efficacy between tDCS and sertraline.

No improvement in implicit learning after real stimulation.

No significant difference in depression scores and cognitive performances after real compared with sham tDCS (TRD). Significant improvement of mood after real compared with sham. No difference in response rate. Improvement of working memory but not in CORE score. Enhancement in working memory performance and abolition of attentional bias.

Significant improvement of mood in the active compared with the sham tDCS group. Significant improvement of mood in the active compared with the sham tDCS group. Improvement of working memory performances. Significant improvement in Go-no-go task performance after 1 tDCS session, correlated with mood changes. Significant mood improvement in the active compared with sham tDCS group, 40.4% decrease in HDRS after active frontal; 21.3% decrease after active occipital, 10.4% after sham. Effect lasted 30 days. Similar antidepressant effect of tDCS and AD (fluoxetine) after 6 weeks of treatment. Antidepressant effect of tDCS appeared faster than fluoxetine. Significant mood improvement after active tDCS and sham tDCS. No significant difference in depression scores between active and sham tDCS groups (TRD).

Table I. Results and stimulation parameters of studies assessing the clinical and cognitive impact of tDCS in patients with Major Depressive Disorder.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 263

26

Monotherapy or augmentation strategy Monotherapy or augmentation strategy

AD, stable dose ⬎ 4 weeks; AP, MS, BZP AD, stable dose ⬎ 4 weeks

AD, stable dose ⬎ 4 weeks; AP, MS

AD, stable dose ⬎ 4 weeks

AD stable dose ⬎ 4 weeks, BZP, AP, Antiepileptic AD stable dose; BZP AD, stable dose ⬎ 2 weeks, BZP, AP, MS

Treatment

F3/F4 or FP2

F3/upper right arm or F4 F3/F4 or FP2

F3/F4

F3/right upper arm or F4 F3/F4

F3/F4

F3/F4

F3/F4

Anode/ Cathode placement

5 to 15

5 to 15

1 or 2

1 or 2

20

20

20

2 22.7 ⫾ 7 (3 months)

20

20

20

20

20

20

2

2

2

2

2

2

10 (5 days)

10 (5 days)

15 (3 weeks)

10 (5 days)

10 (5 days)

10 (5 days)

n session

Duration I (mA) (min)

tDCS Parameters

35

32–35

35

35

32

35

35

35

32

Electrode size (cm2)

No significant differences between active and sham tDCS in terms of both response and remission (200 MDD from 6 RCTs).

Significant reduction of depressive symptoms, according to scores on standard depression scales.

Continuation tDCS prevent relapse following clinical response.

Significant mood improvement in both study groups (63 MDD TRD including 19 BP II)

Significant mood improvement in both study groups.

Greater initial response with frontoextracephalic tDCS than with bi-frontal tDCS.

Significant mood improvement Maintenance at one month. Greater effect in severe MDD. Significant mood improvement in both study groups, persisting one week and one month after treatment.

Significant mood improvement Maintenance at one month (TRD). No effect on cognition.

Results

I, Intensity; AD, Antidepressant treatment; AP, Antipsychotic; UP, Unipolar; BP, Bipolar; BZP, Benzodiazepines; MDD, Major Depressive Disorder; MS, Mood Stabilizer; RCTs, Randomized Controlled Trials; F3, Left Dorsolateral Prefrontal Cortex (10/20 EEG system); F4, Right Dorsolateral Prefrontal Cortex (10/20 EEG system); FP2, Right Supraorbital Region (10/20 EEG system); tDCS, transcranial Direct Current Stimulation; TRD, Treatment-resistant depression.

Meta-analysis

200

Open label

Martin et al. (2013)

Berlim et al. (2013)

Open label

Brunoni et al. (2013a)

23 (15 UP; 8 BP) 63

180

Open label

Dell’Osso et al. (2012)

Kalu et al. (2012) Meta-analysis

Open label

31 (17 UP; 14 BP) 11

Open label

Martin et al. (2011)

32

Open label

Ferruci et al. (2009b) Brunoni et al. (2011b)

14

n

Open label

Design

Study

Ferrucci et al. (2009a)

Author Date

Table I. (Continued)

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

264 M. Mondino et al.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 265 Remarkably, only two RCT have been carried out to assess the effect of tDCS in the treatment of medication-resistant MDD. Palm et al. (2012) have assigned 22 patients to a 10-session cross-over protocol and reported significant difference in depression scores after active compared with sham tDCS. Blumberger et al. (2012) stimulated 24 medication-resistant UP with 15 sessions of anodaltDCS applied over the left DLPFC coupled with cathodal-tDCS applied over the right DLPFC and failed to report the superiority of active tDCS. The discrepancy between these results may be related to several factors. First, the use of concomitant treatment may have influenced the neurophysiological effects of tDCS. Indeed, studies reporting positive effects of tDCS only include participants free of medication prior and during the trial (Fregni et al. 2006a,b; Boggio et al. 2007, 2008a), while negative ones included patients receiving antidepressant treatment on stable dosage and antidepressantfree patients (Blumberger et al. 2012; Loo et al. 2012; Palm et al. 2012). Second, a higher degree of treatment resistance seems associated with a lack of efficacy of tDCS (Blumberger et al. 2012; Palm et al. 2012). In a blind-rater study, Dell’Osso et al. (2012) observed significant response rates in depressed patients with poor response to pharmacological treatment. Only one open-label trial to date investigated the therapeutic effects of tDCS according to symptom severity at baseline (Ferrucci et al. 2009b). Authors reported sustained antidepressant effects of active tDCS with a greater effect for severe MDD compared with mild–moderate depression at baseline. Finally, protocol design and stimulations parameters varied between and within studies, especially concerning the site of stimulations, the current strengths and the number of sessions. In two of the studies (Ferrucci et al. 2009b; Palm et al. 2012), the electrode montage was slightly different than previously described with anodal tDCS over the left DLPFC and cathodal tDCS over the right DLPFC. This last electrode montage was used in several open-label trials exploring the antidepressant effect of 10 sessions of tDCS (twice-daily 2 mA; 20 min). A total of 129 UP and 41 bipolar patients (BP) with MDD were included in these studies that all reported a significant mood improvement after active tDCS (Ferrucci et al. 2009a; Brunoni et al. 2011b, 2012a; Dell’Osso et al. 2012). In an open study, Martin et al. (2011) reported the superiority of a third electrode montage in 11 MDD patients: anodal-tDCS over the left DLPFC/cathodal-tDCS over the right upper arm. They also reported that continuation with a weekly session over 3 months, followed by a once per fortnight session over 3 months, in 26 patients, resulted in 83.7% cumulative probability of

surviving without relapse at 3 months and 51.1% at 6 months (Martin et al. 2013). Concerning interaction with pharmacology, in an open study, Brunoni et al. (2013a) highlighted the influence of the combination of tDCS and pharmacological treatments on clinical outcomes, reporting a reduction of tDCS effect with benzodiazepine and an increase with antidepressant medications. In a recent large-scale RCT, including 120 antidepressant-free UP, Brunoni et al. (2013b) compared the efficacy of tDCS, sertraline and the combination of both. They reported that the combination of tDCS (30 min, 2 mA) and sertraline (50 mg/per day) induces a greater effect on MDD symptoms after 6 weeks of treatment than each treatment separately. Finally, two meta-analyses summarizing the evidence concerning the use of tDCS have produced conflicting results. Kalu et al. (2012) have shown that active tDCS is significantly more effective than sham in reducing depressive symptoms, according to scores on standard depression scales (Hedges’ g ⫽ 0.74; 95% CI ⫽ 0.21–1.27; P ⫽ 0.006). However, focusing on response and remission rates, Berlim et al. (2013) have failed to found significant difference between active and sham tDCS in both response (23.3 vs. 12.4%, respectively; P ⫽ 0.11) and remission rates (12.2 vs. 5.4%; P ⫽ 0.22). A plausible explanation for these discrepant findings is the selection of different outcome measures and of different studies (Berlim et al. 2013 only included six RCT). However, these two meta-analyses have acknowledged the limitations of prior work including insufficient sample size, lack of consensus about stimulation parameters and concomitant use of pharmacotherapy. The number of reported side effects was extremely low, the most serious complication being the occurrence of manic or hypomanic episode after active tDCS (Galvez et al. 2011; Loo et al. 2012; Brunoni et al. 2013b; Martin et al. 2013). Effect on cognition Only a small number of RCT initially designed to investigate the antidepressant effect of tDCS have also assessed the effect on cognitive performance. Beneficial effects of a single session of anodal-tDCS on working memory and/or attention (Loo et al. 2012; Oliveira et al. 2013; Wolkenstein and Plewnia 2013) and on emotional processing (Boggio et al. 2007) have been reported, while two studies failed to demonstrate any cognitive improvement after active tDCS in MDD patients (Ferrucci et al. 2009b; Palm et al. 2012). Bifrontal tDCS has also been shown to prevent implicit learning in depressive patients, probably by inducing a decrease in the

266

M. Mondino et al.

activity of the right DLPFC (Brunoni et al. 2012a). These results suggested that tDCS might have immediate effects on some of the information processing and cognitive deficits that characterize MDD.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS and schizophrenia Some 30% of patients with schizophrenia still present psychotic and/or negative symptoms as well as cognitive deficits despite advances in pharmacological treatment (Shergill et al. 1998). There is thus a need to develop alternating approaches to alleviate treatment-resistant symptoms. A systematic search of the literature was conducted using Cochrane, ScienceDirect and PubMed databases (up to February 2013). The identification of articles was based on the following keywords: “transcranial direct current stimulation” or “tDCS” or “electrical stimulation” and “schizophrenia”. This search was completed by a manual search of relevant studies in the literature lists of published articles and yielded 95 articles. Articles only dealing with healthy volunteers or with other patients than patients with schizophrenia as well as review articles were excluded. Finally, in accordance with our inclusion criteria, 14 articles remain (see Table II). Three articles investigating neuronal plasticity in patients and showing a reduced LTP- (Hasan et al. 2011) and LTD-like plasticity (Hasan et al. 2012a,b) following tDCS were not retained in this review. One article investigating the impact of tDCS during sleep on cognition in patients with schizophrenia was not retained because of tDCS parameters (slow-oscillatory-tDCS; Göder et al. 2013). Finally, we retained seven articles dealing with the clinical interest of tDCS (five case reports, one pilot RCT and one RCT) and two articles dealing with the cognitive impact of tDCS in patients with schizophrenia. Here we review studies investigating the effect of tDCS on auditory verbal hallucinations (AVH) and other schizophrenic symptoms. In these studies, cathodal-tDCS was applied over the left temporoparietal junction (TPJ) according to neuroimaging studies incriminating a hyperactivation of the left TPJ during hallucinations (Jardri et al. 2011).

Effect on symptoms The first open case reported by Homan et al. (2011) described the clinical improvement (hallucination and global symptoms) of a patient with schizophrenia following 10 sessions of cathodal-tDCS applied over the left TPJ (anode over the right supraorbital region). In this case study, the authors also described a decrease of cerebral blood flow in the TPJ. Later,

two other open cases were described (Brunelin et al. 2012b). tDCS was delivered with the cathode applied over the left TPJ coupled with the anode applied over the left PFC. A global clinical improvement on refractory AVH and on global symptoms was reported following 10 sessions of tDCS (two sessions/day). More recently, three open cases corroborated these results. In the first case, a complete remission of AVH was reported with the same electrode arrangement in a drug-free patient (Rakesh et al. 2013). In a second case study, tDCS induced a large decrease of AVH and associated symptoms. This improvement was sustained for 3 years thanks to once- or twice-daily maintenance sessions of tDCS delivered at home (Andrade 2013). The third case study reported the remission of a patient with catatonic schizophrenia receiving tDCS (anode applied over the left DLFPC and cathode over the right DLPFC; Shiozawa et al. 2013). Mattai et al. (2011) investigated the impact of different electrode arrangements on young subjects with childhoodonset schizophrenia. They did not measure any improvement in clinical symptoms, but reported the safety and the tolerability of tDCS in this pediatric population. Finally, a RCT investigating the clinical effect of tDCS in patients with schizophrenia presenting refractory AVH (Brunelin et al. 2012a) reported a large improvement of AVH after 10 sessions of tDCS (–31%). tDCS was delivered with the cathode applied over the left TPJ coupled with the anode applied over the left PFC. The effect lasted for 3 months. tDCS also resulted in an improvement of global symptoms immediately after the end of the stimulation period. In sum, six studies have investigated the clinical impact of tDCS in adult patients with schizophrenia. They all reported the safety of this technique in this population and the therapeutic interest of tDCS. Effect on cognition Two studies investigated the effect of tDCS on two cognitive aspects known to be impaired in patients with schizophrenia (learning capacities and visuospatial abilities). These cognitive deficits are associated with abnormal activities in two different brain regions (frontal and parietal cortex, respectively). The first study by Vercammen et al. (2011) investigated the impact of a single session of tDCS delivered with the anode applied over the left DLPFC coupled with the cathode applied over the right supraorbital region. They reported that active tDCS facilitated probabilistic association learning in patients with schizophrenia compared with sham stimulation. The second study developed by Ribolsi et al. (2013) investigated the impact of a single

15

20

30

12

1

2

NA

898 (SD 817)

1101 (SD 856)

At least 200 (clozapine)

0

ND

Patient 1: 1245 Patient 2: 900 Clozapine 400

950

Treatment (eq cpz mg/day)

Anode P3 or Anode P4

F3/FP2

2 anodes: FP1 & FP2 (n ⫽ 8; 3 sham) or 2 cathodes: T3 & T4 (n ⫽ 5; 2 sham) F3FP1/T3P3

F3FP1/T3P3

F3/T3P3

F3/F4

F3FP1/T3P3

FP2/T3P3

Anode/Cathode placement

1

1

1

2

2

2

10

10

2

1 to 3

2

2

1

I (mA)

once to twice daily 10

10

10

10

n session

tDCS Parameters

10

20

20

20

20

20 to 30

20

20

15

Duration (min)

35

35

35

25

35

ND

35

35

35

Electrode size (cm²)

Partial correction of rightward bias on line bisection task by right posterior parietal tDCS (cathode over contralateral shoulder).

Improvement of hallucinations (–31% AHRS) and global symptoms (–13% PANSS) in adults patients with schizophrenia (Sham: 1 min of active; n ⫽ 15). Facilitate probabilistic association learning (Sham: 30 sec of active).

Improvement of hallucinations (–60% HCS) and global symptoms (–20% PANSS). Decrease in Cerebral Blood Flow. Improvement of hallucinations (Patient 1: –77% AHRS/HCS; Patient 2: –48%) and global symptoms (Patient 1:–20% PANSS; Patient 2: –49%). Large decrease of catatonic schizophrenia as measured by Bush-Francis Catatonia Scale until full remission (4months). At-home deliverability of tDCS until near-normal functioning during 3years. Complete remission of hallucinations and insight gain permitting to install an AP treatment (olanzapine 5mg per day). Safety and tolerability of bilateral tDCS in childhood onset schizophrenia. No worsening of symptoms (Sham: 1 min of active; cathodes on forearm).

Results

I, Intensity; AHRS, Auditory Hallucination Rating Scale; HCS, Hallucination Change Score; PANSS, Positive and Negative Syndrome Scale; RCT Randomized Controlled Trial; ND, Not Done; F3, Left Dorsolateral Prefrontal Cortex (10/20 EEG system); F4, Right Dorsolateral Prefrontal Cortex (10/20 EEG system); FP2, Right Supraorbital Region (10/20 EEG system); FP1, Left Supraorbital Region (10/20 EEG system); T3P3, Left Temporo-Parietal Region (10/20 EEG system); T3, Left Temporal Region (10/20 EEG system); T4, Right Temporal Region (10/20 EEG system); tDCS, transcranial Direct Current Stimulation.

Ribolsi et al. (2012)

Vercammen et al. (2011)

Double blind, RCT parallel Single blind RCT cross-over Cross over

Case report

Brunelin et al. (2012a)

Case report

Andrade (2013) Rakesh et al. (2013)

Double blind, RCT parallel

1

Case report

Shiozawa et al. (2013)

Mattai et al. (2011)

1

Case report

Brunelin et al. (2012b)

1

Case report

Homan et al. (2011)

n

Design

Author Date

Study

Table II. Results and stimulation parameters of studies assessing the clinical and cognitive impact of tDCS in patients with schizophrenia.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 267

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

268 M. Mondino et al. session of tDCS in a line bisection task. tDCS was delivered with the cathode applied over the left parietal cortex coupled with the anode applied over the right parietal cortex or with the opposite electrode arrangement. They showed that the first electrode arrangement permitted a partial correction of the bias in the line bisection task in patients with schizophrenia. These two studies show that modulating cortical activity with tDCS can improve cognition in patients with schizophrenia. In conclusion, very few studies have yet investigated the use of tDCS in schizophrenia. The present results claim that it is possible to modulate cognitive deficits and symptoms in patients by acting on specific brain areas or networks (Keeser et al. 2011) underlying those deficits or symptoms. tDCS and substance use disorder Substance use disorders are characterized by a compulsive need to consume a drug despite aversive consequences and by the loss of control over substance seeking and consumption (Koob et al. 1998; Kalivas and Volkow 2005). One way to measure substance use disorder is to measure craving intensity for the substance of abuse. Since high levels of craving were associated with poorer treatment outcomes (Sinha et al. 2006; Higley et al. 2011; but for negative results see Wray et al. 2013), it was assumed that decreasing craving would allow to quit consumption and/or diminish relapse. Imaging studies have reported that craving was associated with an increased activity in the prefrontal cortex (Goldstein and Volkow 2002; Hanlon et al. 2012), especially in the DLPFC. Here we present studies investigating the effect of tDCS applied over the DLPFC on craving for tobacco, marijuana, alcohol and food. Results from studies are summarized in Table III. Impact on craving Regarding tobacco, Fregni et al. (2008a) conducted a double-blind crossover RCT on 24 tobaccodependent subjects. They compared the effect of tDCS applied over the DLPFC on cue-induced craving for tobacco under three conditions (anoderight and cathode-left; anode-left and cathode-right; sham tDCS). The authors showed a significant reduction in cue-induced craving in both active conditions compared with sham. Boggio et al. (2009) conducted a similar work on 27 smokers receiving five sessions of sham or active tDCS (anode-left and cathode-right) of the DLPFC. They showed a significant decrease in cue-induced craving, with a cumulative effect over the 4 first days of treatment (the magnitude of tDCS effects on reducing

cue-induced craving increased after each session). This study also showed a greater reduction in cigarette consumption (number of cigarettes smoked per day) in the active tDCS group (–30%) than in the sham group (–10%). Boggio et al. (2010) investigated the effect of a single session of tDCS on marijuana craving in 25 marijuana users. They compared active and sham bilateral tDCS of the DLPFCs with two electrode arrangements: anode-right/cathode-left and anode-left/cathode-right. Compared with sham tDCS, subjects reported significantly reduced craving for marijuana only with the anode-right/cathodeleft tDCS montage. No effect was reported on marijuana consumption. In a double-blind crossover RCT, Boggio et al. (2008b) investigated the effect of a single session of tDCS on craving for alcohol in 13 alcohol-dependent patients. All subjects were abstinent for at least 10 days. They received active and sham bilateral tDCS delivered to DLPFC (anode-left/cathode-right and anode-right/cathode-left). The craving was assessed before and after tDCS session, and before and after presentation of stimuli related to alcohol (cue-induced craving). Both active tDCS conditions showed a significant reduction in craving compared with sham. Moreover, in both active groups, the craving after tDCS was not increased by alcohol-related stimuli. In a study including 49 alcohol-dependent patients, Nakamura-Palacios et al. (2012) reported an improvement of basic cognitive performances following tDCS sessions. Regarding food, two studies investigated the effect of tDCS on food craving (Fregni et al. 2008b; Goldman et al. 2011). These studies were performed in healthy volunteers reporting frequent food craving (excluding subjects with eating disorders or other substance use disorders). In the study of Fregni et al. (2008b), 23 subjects received acive and sham bilateral tDCS delivered to the DLPFCs (anode-right/cathode-left; anode-left/cathode-right). Craving for food was significantly decreased after anode-right/cathode-left tDCS. In a shamcontrolled crossover RCT including 19 subjects, Goldman et al. (2011) reported the superiority of active anode-right/cathode-left tDCS of the DLPFCs on food craving. Impact on cognition Cognitive neuroscience studies indicated that individuals with substance use disorders displayed decision-making impairments. For instance, they showed more risky behaviors at decision-making tasks (Bechara et al. 2001; Rogers et al. 2010). The DLPFC is involved in these decision-making

25

23

13

27

VAS

VAS

VAS

AUQ

VAS

VAS

Craving assessment

F3/F4 or F4/F3

F3/F4 or F4/F3

F4/F3

F3/supradeltoid

F3/F4 or F4/F3

F3/F4 or F4/F3

F3/F4 or F4/F3

Anode/ Cathode Placement

1

3

2

2

3

5

3

n session

2

2

2

1

2

2

2

I (mA)

tDCS Parameters

20

20

20

10

20

20

20

Duration (min)

35

35

35

35

35

35

35

Electrode size (cm²)

Reduction in general and cue-induced craving for both active tDCS conditions, vs. sham. Reduction in cue-induced craving with both active tDCS conditions vs. sham. Decreased number of cigarettes smoked in active group. Reduction in general and cue-induced craving for both active tDCS conditions vs. sham. Improve cognitive functions, modify EEG signals in DLPFC. Reduction in cue-induced craving with active vs. sham stimulation. Decrease in inability to resist food with active vs. sham stimulation. Reduction in cue-induced craving with anode-right/cathode-left tDCS vs. sham. Craving reduction with anode-left/ cathode-right tDCS. Increased risk taking in decision making task with both active conditions. tDCS was delivered during task.

Results

I, Intensity; AUQ, Alcohol Urge Questionnaire; VAS, Visual Analogic Scale; F3, Left Dorsolateral Prefrontal Cortex (10/20 EEG system); F4, Right Dorsolateral Prefrontal Cortex (10/20 EEG system); DLPFC, DorsoLateral PreFrontal Cortex; tDCS, transcranial Direct Current Stimulation.

Cannabis

Food

Boggio et al. (2010)

Alcohol

Nakamura Palacios et al. (2012) Goldman et al. (2011)

Food

19

Alcohol

Boggio et al. (2008b)

Fregni et al. (2008b)

49

Nicotine

Boggio et al. (2009)

24

Nicotine

Fregni et al. (2008a)

n

Substance

Author Date

Study

Table III. Results and stimulation parameters of studies assessing the clinical and cognitive impact of tDCS in patients with substance use disorder.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 269

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

270 M. Mondino et al. processes, and neuromodulation of the DLPFC can modify decision-making processes and craving (for a review see Fecteau et al. 2010). For instance, marijuana smokers displayed an increased propensity for risk-taking during active tDCS (anodal left/cathodal right and anodal right/cathodal left) and less risky decision-making during sham (Boggio et al. 2010). Thus, tDCS seems to be a promising tool for reducing craving and cue-induced craving in patients with substance use disorder but the duration of these effects remain unknown. tDCS can also modulate cognitive functions that have been related to consumption and relapse. One limitation of these studies is the lack of gold standard instrument to define and measure craving. In the different craving rating scales, craving was not separated from behaviours, expectancies, mood, self-efficacy, intentions, or perceived behavioural control (Shiffman et al. 2004; Kavanagh et al. 2013). The inclusion of craving as a criterion for substance use disorder in DSM-5 should promote new studies with validated craving measurement. Of note, only one study assessed the change in substance consumption (cigarette) before and after tDCS (Boggio et al. 2009), showing a modest but significant decrease in number of cigarettes smoked after active versus sham tDCS. As cessation or decreasing in substance use is the optimal goal, future studies should also explore consumption and assess the efficacy of tDCS in combination with current treatments.

systematic search yielded 40 publications: 22 in patients with MDD (13 RCT, seven open-label studies and two meta-analyses), nine in patients with schizophrenia (four RCT, five case reports), seven in patients with substance use disorder (RCT), one in OCD (case report) and one in mania (case report).

Others applications

Effect on cognition

The investigation of tDCS effects on symptoms in other psychiatric disorders is still in its infancy, but initial case series illustrated its importance. Based on neuroimaging evidences suggesting that obsessive– compulsive disorder (OCD) is associated with a functional interhemispheric imbalance in the anterior neural circuits (Gonçalves et al. 2011), Volpato et al. (2013) delivered 10 sessions of cathodal-tDCS at 2 mA over the left DLPFC in a patient with severe OCD. They reported a 34% reduction in the HDRS score, and a 17.8% reduction in the anxiety score, but no improvement in OC symptoms. More recently, Schestatsky et al. (2013) suggests that anodal-tDCS in combination with pharmacological treatment can be useful for treating acute stages of mania in patients with type I BP. They observed an acute decrease on manic symptoms and a sustained decrease on psychomotor agitation following active tDCS.

The second aim of this review was to investigate the potential effect of tDCS on cognitive deficits in psychiatric populations. Cognitive deficits are a key feature in neuropsychiatric populations and are often linked to DLPFC activity. Although most of the reviewed studies targeted the left DLPFC with anodal-tDCS, only 11 of the studies investigated the impact on cognition, leading to inconsistent results. According to the link between DLPFC activity and cognitive functions, one can hypothesize that future studies will be able to distinguish a pro-cognitive effect of tDCS in patients with neuropsychiatric disorder. This hypothesis is supported by literature in healthy subjects showing the pro-cognitive effect of anodal-tDCS applied over the left DLPFC (for a review see Utz et al. 2010; Levasseur-Moreau et al. 2013).

Discussion This review is aimed at evaluating the impact of tDCS on psychiatric symptoms. Our literature

Effects on symptoms The clinical effect of tDCS on MDD symptoms seems encouraging (Kalu et al. 2012; Berlim et al. 2013). A recent large-scale RCT corroborates the clinical importance of tDCS in this indication (Brunoni et al. 2013b). The authors reported the superiority of the combination of bilateral tDCS delivered to the DLPFC (anode-left/cathode-right) and sertraline compared with each method alone. In schizophrenia, although showing promising preliminary results, clinical effects have to be studied in larger RCTs. Regarding substance abuse disorder, tDCS seems to be efficient in reducing craving for tobacco, alcohol, cannabis or food. The effects of a single session of tDCS on craving are cumulative, with a better decrease when tDCS sessions are repeated. However, effects on substance-of-abuse consumption have to be investigated in order to consider tDCS as a potential therapeutic tool in this indication. The potemtial of tDCS in other psychiatric disorders has yet to be investigated (OCD, mania, post-traumatic stress disorder).

Limitations Many of the reviewed studies suffered from general methodological limitations that may have contributed to discrepancies in clinical and cognitive outcomes. First, samples in each study were small with a large

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 271 variability in patient characteristics. Only 16 on the 38 reviewed studies included more than 25 subjects. The medication status of patients varied both between and within studies. This is especially relevant since pharmacological studies have highlighted an interaction between tDCS and pharmacotherapy. For instance, the administration of dopaminergic D2-receptor blockers abolishes the tDCS effects and D2 agonists decrease plasticity when they are applied at high or low dosages (Monte-Silva et al. 2009). However, when D2 agonists are applied at medium dosages, the tDCS-induced plasticity is restored. The dopamine precursor, L-dopa, converts facilitatory plasticity into inhibition, and prolongs inhibitory plasticity (Kuo et al. 2008). Serotoninergic drugs, such as the 5-HT reuptake-inhibitor citalopram, can also interact with tDCS by increasing anodal effects and turning cathodal inhibition to facilitation (Nitsche et al. 2009). As previously stated, the combination of sertraline and tDCS can lead to greater effects on MDD than tDCS alone or sertraline alone (Brunoni et al. 2013b). Nicotine can reduce or abolish both tDCS-induced inhibitory and facilitatory effects in healthy non-smokers (Thirugnanasambandam et al. 2011). A study in tobacco smokers has reported that during nicotine withdrawal, facilitatory plasticity is abolished but reinstituted by nicotine administration (Grundey et al. 2012). In a recent study, Brunoni et al. (2013a) investigated the interactions between tDCS and pharmacological interventions in MDD and reported a variation of tDCS effects according to prior pharmacological treatment: benzodiazepines can reduce tDCS effects, whereas antidepressants can lead to increased effects. Taken together these results suggest that pharmacological interventions can influence clinical outcomes and have to be taken into account in future tDCS studies. Otherwise, parameters of stimulation are heterogeneous between studies, particularly in terms of current strength, number of session and delay between sessions. Whereas repetitive tDCS sessions have been shown to induce cumulative effects (Boggio et al. 2007; 2008a), the optimal number of tDCS sessions to deliver the desired outcome remains to determined (five sessions have been delivered in patients with substance use disorders, 10 in patients with schizophrenia, up to 15 in patients with MDD). In MDD, sensitivity analyses have reported that increasing intensity (1 vs. 2 mA) or number of tDCS sessions (ⱕ 5 vs. ⱖ 10) did not improve antidepressant effects of tDCS (Kalu et al. 2012; Berlim et al. 2013). In addition, delay between tDCS sessions has an impact on outcome (Fricke et al. 2011). For example, anodal-tDCS excitatory effects were initially reduced but prolonged when a second tDCS session was applied during the

after-effects of the first (0–20 min after). These effects were abolished when the second tDCS session was applied 3 or 24 h after the first (MonteSilva et al. 2013). The lasting inhibitory effects of cathodal-tDCS were enhanced if the sessions were separated by 24 h, but not when the interval was 3 h (Monte-Silva et al. 2010). Moreover, studies have reported that daily tDCS leads to greater increases in cortical excitability than tDCS administered every second day (Alonzo et al. 2012). Finally, electrode placement has to be discussed. Most studies targeted the left DLPFC because of its implication in psychiatric disorders, in addiction and also in many cognitive deficits, but the electrode montage varied between studies. In MDD, the first studies employed a bi-frontal montage in which the anode was placed over the left DLPFC and the cathode over the contralateral supraorbital area. Other tDCS montages were used in recent studies, such as anode over the left DLPFC and cathode over the right DLPFC. This commonly used bilateral electrode montage is considered to be useful in conditions that involve an imbalanced interhemispheric activity, such as depression. More recently, a fronto-extracephalic montage in which the cathode is placed over the right upper arm has been hypothesized to result in a more widespread pattern of cortical activation compared with the standard bi-frontal montage, and has been hypothesized to induce more significant antidepressant effects (Martin et al. 2011). These three different montages have to be compared directly. Despite these limitations, the studies reviewed here highlight the potential of tDCS for treating psychiatric populations. More than just being an “easy-to-use” and “less-expensive” technique with low side-effects, tDCS offers many opportunities. The place of tDCS has been investigated in two main directions with encouraging results: as a monotherapy (Fregni et al. 2006a,b; Boggio et al. 2007, 2008a; Rigonatti et al. 2008; Brunoni et al. 2012a, 2013a; Rakesh et al. 2013) or as an add-on treatment for psychiatric disorders (Loo et al. 2010, 2012; Brunelin et al. 2012a,b; Blumberger et al. 2012; Palm et al. 2012). The most recent studies have even suggested that tDCS might act to enhance pharmacological interventions (Brunoni et al. 2013b) and to permit the subject improved insight, leading to better compliance with treatment (Rakesh et al. 2013). Moreover, tDCS has been successfully delivered at home in a 3-year maintenance protocol in a patient with schizophrenia (Andrade 2013). Conclusion To conclude, the place of tDCS as a treatment for psychiatric disorders still has to be determined

272 M. Mondino et al. but seems promising. Further studies comparing parameters of stimulation (current parameters, electrodes placement, duration number and frequency of sessions) are needed to determine optimal parameters. A better understanding of the neurophysiological effects of tDCS may help us to improve stimulation parameters according to the pathophysiology of the disorders, and thus may result in a better alleviation of clinical symptoms and a better improvement of cognitive functions.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

Acknowledgements The authors thank the French Association for the development of transcranial non-invasive stimulation in psychiatry (STEP section from AFPBN). Marine Mondino held a doctoral fellowship from La Region Rhone-Alpes.

Statement of Interest None to declare.

References Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. 2012. Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stim 5:208–213. Andrade C. 2013. Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia. J ECT 29:239–242. Arfai E, Theano G, Montagu JD, Robin AA. 1970. A controlled study of polarization in depression. Br J Psychiatry 116: 433–434. Baker AP. 1970. Brain stem polarization in the treatment of depression. S Afr Med J 44:473–475. Bechara A, Dolan S, Denburg N, Hindes A, Anderson SW, Nathan PE. 2001. Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39:376–389. Berlim MT, Van den Eynde F, Daskalakis ZJ. 2013. Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and metaanalysis of randomized, double-blind and sham-controlled trials. J Psychiatr Res 47:1–7. Blumberger DM, Tran LC, Fitzgerald PB, Hoy KE, Daskalakis ZJ. 2012. A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression. Front Psychiatry 3:74. Boggio PS, Bermpohl F, Vergara AO, Muniz AL, Nahas FH, Leme PB et al. 2007. Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression. J Affect Disord 101:91–98. Boggio PS, Liguori P, Sultani N, Rezende L, Fecteau S, Fregni F. 2009. Cumulative priming effects of cortical stimulation on smoking cue-induced craving. Neurosci Lett 463:82–86.

Boggio PS, Rigonatti SP, Ribeiro RB, Myczkowski ML, Nitsche MA, Pascual-Leone A, et al. 2008a. A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. Int J Neuropsychopharmacol 11:249–254. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A et al. 2008b. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug Alcohol Depend 92:55–60. Boggio PS, Zaghi S, Villani AB, Fecteau S, Pascual-Leone A, Fregni F. 2010. Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Drug Alcohol Depend 112:220–225. Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, et al. 2012a. Examining transcranial directcurrent stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 169:719–724. Brunelin J, Mondino M, Haesebaert F, Saoud M, Suaud-Chagny MF, Poulet E. 2012b. Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. Brain Stimul 5:431–432. Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. 2011a. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol 14: 1133–1145. Brunoni AR, Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Boggio PS, et al. 2011b. Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 35:96–101. Brunoni AR, Zanao TA, Ferrucci R, Priori A, Valiengo L, de Oliveira JF, et al. 2012a. Bifrontal tDCS prevents implicit learning acquisition in antidepressant-free patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 43C:146–150. Brunoni AR, Ferrucci R, Bortolomasi M, Scelzo E, Boggio PS, Fregni F, et al. 2013a. Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: Findings from a naturalistic study. Eur Psychiatry 28:356–361. Brunoni AR, Valiengo L, Baccaro A, Zanão TA, de Oliveira JF, Goulart A, et al. 2013b. The sertraline vs electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. J Am Med Assoc Psychiatry 6:1–9. Costain R, Redfearn JW, Lippold OC. 1964. A controlled trial of the therapeutic effect of polarization of the brain in depressive illness. Br J Psychiatry 110:786–799. Dell’Osso B, Zanoni S, Ferrucci R, Vergari M, Castellano F, D’Urso N, et al. 2012. Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients. Eur Psychiatry 27:513–517. Downar J, Daskalakis ZJ. 2012. New targets for rTMS in depression: a review of convergent evidence. Brain Stimul 2012 (September 7). Fecteau S, Fregni F, Boggio PS, Camprodon JA, Pascual-Leone A. 2010. Neuromodulation of decision-making in the addictive brain. Subst Use Misuse 45:1766–1786. Ferrucci R, Bortolomasi M, Brunoni AR, Vergari M, Tadini L, Giacopuzzi M, et al. 2009a. Comparative benefits of transcranial direct current stimultation (tDCS) treatment in patients with mild/moderate vs. severe depression. Clin Neuropsychiatry 6:246–251. Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Salvoro B, Giacopuzzi M, et al. 2009b. Transcranial direct current

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

tDCS in psychiatry 273 stimulation in severe, drug-resistant major depression. J Affect Disord 118:215–219. Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A. 2006a. Treatment of major depression with transcranial direct current stimulation. Bipolar Disord 8: 203–204. Fregni F, Boggio PS, Nitsche MA, Rigonatti SP, Pascual-Leone A. 2006b. Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression. Depress Anxiety 23:482–484. Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS. 2008a. Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cueprovoked smoking craving: a randomized, sham-controlled study. J Clin Psychiatry 69:32–40. Fregni F, Orsati F, Pedrosa W, Fecteau S, Tome FA, Nitsche MA, et al. 2008b. Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods. Appetite 51:34–41. Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC. 2011. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J Neurophysiol 105:1141–1149. Galvez V, Alonzo A, Martin D, Mitchell PB, Sachdev P, Loo CK. 2011. Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS). J ECT 27:256–258. Giacobbe P, Mayberg HS, Lozano AM. 2009. Treatment resistant depression as a failure of brain homeostatic mechanisms: implications for deep brain stimulation. Exp Neurol 219:44–52. Göder R, Baier PC, Beith B, Baecker C, Seeck-Hirschner M, Junghanns K, et al. 2013. Effects of transcranial direct current stimulation during sleep on memory performance in patients with schizophrenia. Schizophr Res. 2013 Jan 18. Goldman RL, Borckardt JJ, Frohman HA, O’Neil PM, Madan A, Campbell LK, et al. 2011. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Appetite 56:741–746. Goldstein RZ, Volkow ND. 2002. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652. Gonçalves ÓF, Carvalho S, Leite J, Pocinho F, Relvas J, Fregni F. 2011. Obsessive Compulsive Disorder as a functional interhemispheric imbalance at the thalamic level. Med Hypotheses 77:445–447. Gorlyn M, Keilp JG, Grunebaum MF, Taylor BP, Oquendo MA, Bruder GE, et al. 2008. Neuropsychological characteristics as predictors of SSRI treatment response in depressed subjects. J Neural Transm 15:1213–1219. Grimm S, Boesiger P, Beck J, Schuepbach D, Bermpohl F, Walter M, et al. 2009. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology 34:932–943. Grundey J, Thirugnanasambandam N, Kaminsky K, Drees A, Skwirba AC, Lang N, et al. 2012. Neuroplasticity in cigarette smokers is altered under withdrawal and partially restituted by nicotine exposition. J Neurosci 32:4156–4162. Hanlon CA, Jones EM, Li X, Hartwell KJ, Brady KT, George MS. 2012. Individual variability in the locus of prefrontal craving for nicotine: implications for brain stimulation studies and treatments. Drug Alcohol Depend 125:239–243. Hasan A, Nitsche MA, Rein B, Schneider-Axmann T, Guse B, Gruber O, et al. 2011. Dysfunctional long-term

potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav Brain Res 224:15–22. Hasan A, Aborowa R, Nitsche MA, Marshall L, Schmitt A, Gruber O, et al. 2012a. Abnormal bihemispheric responses in schizophrenia patients following cathodal transcranial direct stimulation. Eur Arch Psychiatry Clin Neurosci 262:415–423. Hasan A, Nitsche MA, Herrmann M, Schneider-Axmann T, Marshall L, Gruber O, et al. 2012b. Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study. Brain Stimul 5:475–483. Higley AE, Crane NA, Spadoni AD, Quello SB, Goodell V, Mason BJ. 2011. Craving in response to stress induction in a human laboratory paradigm predicts treatment outcome in alcohol-dependent individuals. Psychopharmacology (Berlin) 218:121–129. Homan P, Kindler J, Federspiel A, Flury R, Hubl D, Hauf M, et al. 2011. Muting the voice: a case of arterial spin labelingmonitored transcranial direct current stimulation treatment of auditory verbal hallucinations. Am J Psychiatry 168: 853–854. Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM. 2005. Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology 64:872–875. Jardri R, Pouchet A, Pins D, Thomas P. 2011. Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. Am J Psychiatry 168:73–81. Kalivas PW, Volkow ND. 2005. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162: 1403–1413. Kalu UG, Sexton CE, Loo CK, Ebmeier KP. 2012. Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychol Med 42:1791–1800. Kavanagh DJ, Statham DJ, Feeney GF, Young RM, May J, Andrade J. et al. 2013. Measurement of alcohol craving. Addict Behav 38:1572–1584. Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, et al. 2011. Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI. J Neurosci 31:15284–15293. Kemp AH, Gordon E, Rush AJ, Williams LM. 2008. Improving the prediction of treatment response in depression: integration of clinical, cognitive, psychophysiological, neuroimaging, and genetic measures. CNS spectrums. 13:1066–1086; quiz 87–88. Kessler SK, Turkeltaub PE, Benson JG, Hamilton RH. 2012. Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimul 5:155–162. Koob GF, Rocio M, Carrera A, Gold LH, Heyser CJ, MaldonadoIrizarry C et al. 1998. Substance dependence as a compulsive behavior. J Psychopharmacol 12:39–48. Kuo MF, Unger M, Liebetanz D, Lang N, Tergau F, Paulus W et al. 2008.Limited impact of homeostatic plasticity on motor learning in humans. Neuropsychologia 46:2122–2128. Levasseur-Moreau J, Brunelin J, Fecteau S. 2013. Non-invasive brain stimulation can induce paradoxical facilitation. Are these neuroenhancements transferable and meaningful to security services? Front Hum Neurosci 7:449. Loo CK, Sachdev P, Martin D, Pigot M, Alonzo A, Malhi GS, et al. 2010. A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression. Int J Neuropsychopharmacol 13:61–69. Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P. 2012. Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry 200:52–59.

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

274

M. Mondino et al.

Martin DM, Alonzo A, Mitchell PB, Sachdev P, Galvez V, Loo CK. 2011. Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study. J Affect Disord 134:459–463. Martin DM, Alonzo A, Ho KA, Player M, Mitchell PB, Sachdev P, et al. 2013. Continuation transcranial direct current stimulation for the prevention of relapse in major depression. J Affect Disord 144:274–278. Mathers CD, Loncar D. 2006. Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine. 3:e442. Mattai A, Miller R, Weisinger B, Greenstein D, Bakalar J, Tossell J, et al. 2011. Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia. Brain Stimul 4:275–280. Monte-Silva K, Kuo MF, Thirugnanasambandam N, Liebetanz D, Paulus W, Nitsche MA. 2009. Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans. J Neurosci 29: 6124–6131. Monte-Silva K, Kuo M-F, Liebetanz D, Paulus W, Nitsche MA. 2010. Shaping the optimal repetition interval for cathodal transcranial direct current stimulation (tDCS). J Neurophysiol 103:1735–1740. Monte-Silva K, Kuo MF, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W, et al. 2013. Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul 6:424–432. Nakamura-Palacios EM, de Almeida Benevides MC, da Penha Zago-Gomes M, de Oliveira RW, de Vasconcellos VF, de Castro LN, et al. 2012. Auditory event-related potentials (P3) and cognitive changes induced by frontal direct current stimulation in alcoholics according to Lesch alcoholism typology. Int J Neuropsychopharmacol 15:601–616. Nitsche MA, Paulus W. 2000. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527:633–639. Nitsche MA, Paulus W. 2001. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57:1899–1901. Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. 2003a. Modulation of cortical excitability by weak direct current stimulation–technical, safety and functional aspects. Suppl Clin Neurophysiol 56:255–276. Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell J, Paulus W. 2003b. Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clin Neurophysiol 114:600–604. Nitsche MA, Niehaus L, Hoffmann KT, Hengst S, Liebetanz D, Paulus W, Meyer BU. 2004. MRI study of human brain exposed to weak direct current stimulation of the frontal cortex. Clin Neurophysiol 115:2419–23. Nitsche MA, Doemkes S, Karakose T, Antal A, Liebetanz D, Lang N et al. 2007. Shaping the effects of transcranial direct current stimulation of the human motor cortex. J Neurophysiol 97:3109–3117. Nitsche M, Cohen LG, Wassermann E, Priori A, Lang N, Antal A, et al. 2008. Transcranial direct current stimulation: state of the art. Brain Stimul 1:206–223. Nitsche MA, Kuo MF, Karrasch R, Wächter B, Liebetanz D, Paulus W. 2009. Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biol Psychiatry 66:503–508. Oliveira JF, Zanao TA, Valiengo L, Lotufo PA, Bensenor IM, Fregni F, et al. 2013. Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder. Neurosci Lett 14:60–64.

Palm U, Schiller C, Fintescu Z, Obermeier M, Keeser D, Reisinger E, et al. 2012. Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. Brain Stimul 5:242–251. Poreisz C, Boros K, Antal A, Paulus W. 2007. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull 72:208–214. Priori A, Berardelli A, Rona S, Accornero N, Manfredi M. 1998. Polarization of the human motor cortex through the scalp. Neuroreport 9:2257–2260. Priori A, Hallett M, Rothwell JC. 2009. Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? Brain Stimul 2:241–245. Rakesh G, Shivakumar V, Subramaniam A, Nawani H, Amaresha AC, Narayanaswamy JC, et al. 2013. Monotherapy with tDCS for schizophrenia: a case report. Brain Stimul 6:708–709. Ramsay JC, Schlagenhauf G. 1966. Treatment of depression with low voltage direct current. South Med J 59:932–934. Redfearn JW, Lippold OC, Costain R. 1964. A preliminary account of the clinical effects of polarizing the brain in certain psychiatric disorders. Br J Psychiatry 110:773–785. Ribolsi M, Lisi G, Di Lorenzo G, Koch G, Oliveri M, Magni V, et al. 2013. Perceptual pseudoneglect in schizophrenia: candidate endophenotype and the role of the right parietal cortex. Schizophr Bull 39:601–607. Rigonatti SP, Boggio PS, Myczkowski ML, Otta E, Fiquer JT, Ribeiro RB, et al. 2008. Transcranial direct stimulation and fluoxetine for the treatment of depression. Eur Psychiatry 23:74–76. Rogers RD, Moeller FG, Swann AC, Clark L. 2010. Recent research on impulsivity in individuals with drug use and mental health disorders: implications for alcoholism. Alcohol Clin Exp Res 34:1319–1333. Schestatsky P, Janovik N, Lobato MI, Belmonte-de-Abreu P, Schestatsky S, Shiozawa P, et al. 2013. Rapid therapeutic response to anodal tdcs of right dorsolateral prefrontal cortex in acute mania. Brain Stimul 6:701–703. Shergill SS, Murray R, McGuire P. 1998. Auditory hallucinations: a review of psychological treatments. Schizophr Res 32: 137–150. Shiffman S, West R, Gilbert D; SRNT Work Group on the Assessment of Craving and Withdrawal in Clinical Trials. 2004. Recommendation for the assessment of tobacco craving and withdrawal in smoking cessation trials. Nicotine Tob Res 6: 599–614. Shiozawa P, da Silva ME, Cordeiro Q, Fregni F, Brunoni AR. 2013. Transcranial direct current stimulation (tDCS) for catatonic schizophrenia: a case study. Schizophr Res 146: 374–375. Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ. 2006. Stress-induced cocaine craving and hypothalamic-pituitaryadrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatry 63:324–331. Stagg CJ, Nitsche MA. 2011. Physiological basis of transcranial direct current stimulation. Neuroscientist 17:37–53. Thirugnanasambandam N, Grundey J, Adam K, Drees A, Skwirba AC, Lang N, et al. 2011. Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans. Neuropsychopharmacology 36:879–886. Trivedi MH, Hollander E, Nutt D, Blier P. 2008. Clinical evidence and potential neurobiological underpinnings of unresolved symptoms of depression. J Clin Psychiatry 69:246–258. Utz KS, Dimova V, Oppenländer K, Kerkhoff G. 2010. Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive

tDCS in psychiatry 275

World J Biol Psychiatry Downloaded from informahealthcare.com by Gazi Univ. on 12/28/14 For personal use only.

brain stimulation in neuropsychology – a review of current data and future implications. Neuropsychologia 48:2789–2810. Vercammen A, Rushby JA, Loo C, Short B, Weickert CS, Weickert TW. 2011. Transcranial direct current stimulation influences probabilistic association learning in schizophrenia. Schizophr Res 131:198–205. Volpato C, Piccione F, Cavinato M, Duzzi D, Schiff S, Foscolo L et al. 2013. Modulation of affective symptoms and resting state

activity by brain stimulation in a treatment-resistant case of obsessive-compulsive disorder. Neurocase 19:360–370. Wolkenstein L, Plewnia C. 2013. Amelioration of cognitive control in depression by transcranial direct current stimulation. Biol Psychiatry 73:646–651. Wray JM, Gass JC, Tiffany ST. 2013. A systematic review of the relationships between craving and smoking cessation. Nicotine Tob Res 15:1167–1182.