Am J Psychiatry. 2012 Jul 1;169(7):719-24
Authors: Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E
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Abstract
OBJECTIVE: Some 25%–30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs. Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms, respectively. The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms.
METHOD: Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays.The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex.
RESULTS: Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation, with a mean diminution of 31% (SD=14; d=1.58, 95% CI=0.76–2.40). The beneficial effect on hallucinations lasted for up to 3 months. The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale (d=0.98, 95% CI=0.22–1.73), especially for the negative and positive dimensions. No effect was observed on the dimensions of disorganization or grandiosity/excitement.
CONCLUSIONS: Although this study is limited by the small sample size, the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia.
PMID: 22581236
All patients were maintained on their treatment throughout the study period.
A randomized double-blind parallel- arm (raters, experimenters, and patients were blind to randomized treatment assignment) tDCS protocol was used in the study. Stimulation was done using an Eldith DC stimulator (www. neuroconn.de/dc-stimulator_plus_en/) with two 7×5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl). Electrodes were placed on the basis of the international 10-20 electrode placement system.
The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left prefrontal cortex: dorsolateral prefrontal cortex, assumed to correspond to a region including Brodmann’s areas [BA] 8, 9, 10, and 46, depending on the patient) and the cathode located over a point midway between T3 and P3 (left temporo-parietal junction, assumed to correspond to a region including BA 22, 39, 40, 41, and 42, depending on the patient).
In accordance with recent studies of tDCS in other psychiatric or neurological illnesses (24, 25, 30), the stimulation level was set at 2 mA for 20 minutes. In line with our previous study using 1-Hz rTMS for auditory verbal hallucinations (31, 32), stimulation ses-sions were conducted twice a day on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours. In sham stimulation, the chosen stimulation parameters were displayed, but in fact after 40 seconds of real stimulation (2 mA), only a small current pulse occurred every 550 msec (110 mA over 15 msec) through the remainder of the 20-minute period.
Acute effect. Compared with the sham condition, a large effect of tDCS on auditory verbal hallucinations was seen in the active group after 5 days of tDCS (d=1.58, p<0.001). The active group showed a mean improvement of 31% (SD=14.4) in AHRS score (from 28.3 [SD=4.1] to 19.9 [SD=5.8]), whereas the sham tDCS group had a mean re- duction of 8% (SD=13.7) in AHRS score (from 27.2 [SD=6.9] to 25.1 [SD=7.7]) (Figure 1).
Maintenance effect. In the active tDCS group, AHRSscore was reduced 36% (SD=21.8) at 1 month and 38% (SD=25.0) at 3 months, whereas in the sham tDCS group, AHRS score was reduced 3% (SD=18.3) at 1 month and 5% (SD=13.7) at 3 months (Figure 1).
Our results suggest that tDCS, an easy-to-use, low-cost stimulation tool with few side effects (26, 29, 30, 40), by acting antagonistically on two distinct brain areas in- volved in the pathophysiology of schizophrenia, could constitute a new tool in the treatment of refractory symp toms.
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Transcranial direct current stimulation (TDCS) is the application of a constant low current directly to the brain target areas. It was originally developed to help victims of brain injury and stroke.
TDCS is a very inexpensive treatment. Its competitor, the highly aggressively commercially promoted repetitive transcranial magnetic stimulation (rTMS), in comparison costs $10,000 to $15,000 per treatment series – of which nearly $5000 is dismayingly for the disposable supplies that is paid to the manufacturer for each patient. Additionally there is a much expense for the large amount of time devoted to simply positioning the magnets on the patient’s skull. TDCS on the other hand has much more easily placed electrodes.
TDCS thus far also has very low risk of adverse effect – unlike Electroconvulsive treatment.
TDCS is very exciting for the fairly robust response patients exhibited for the relatively low investment in time. They showed a reduction in hallucinations of 38% – in addition to the response they already had with antipsychotic treatment. Additionally, the effect lasted at least 3 months – for an investment of about 1 hours a day over 5 days. Given the low cost of treatment, this can easily be given four times a year. RTMS on the other hand is limited by the $10,000 to $15,000 expense from each series of treatment.
It would have been nice to follow the patients for longer than 3 months in this study to determine the actual duration of action and its diminishment over time.
TDCS and rTMS do not address the complete pathophysiology of schizophrenia. They are more like bandages that have to be repeatedly applied. None of the patients had complete remission of symptoms.
However, if the patients significantly improve in their ability to function in their daily lives, TDCS would be a highly worthwhile, inexpensive, and exciting addition to the psychiatrist’s toolkit.