1. Transcranial direct current stimulation (tDCS) in therapy-resistant depression: Preliminary results from a double-blind, placebo-controlled study.
U. Palm, D. Keeser, C. Schiller, Z. Fintescu, E. Reisinger, C. Mulert,
O. Pogarell, H.-J. Möller and F. Padberg
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University Munich, Germany
Background:
Transcranial direct current stimulation (tDCS) for modulating membrane potentials in neurons is known since the 1960s and was used to investigate motor cortex neurophysiology. More recently, tDCS has also been investigated as therapeutic intervention in various neuropsychiatric disorders. Based on the role of the dorsolateral prefrontal cortex (DLPFC) in the pathophysiology of depression and on previous studies with repetitive transcranial magnetic stimulation (rTMS), Fregni and co-workers investigated anodal tDCS of the left DLPFC in three consecutive trials in patients with depression yielding promising results.
However, no data are available so far in therapy-resistant depression where new effective interventions are urgently needed. Here, we report preliminary findings from a double-blind, placebo-controlled cross-over trial in subjects with therapy-resistant depression (Fig. 1).
Methods:
18 patients with moderate to severe major depression (DSM-IV criteria) were included in a four week cross-over trial, 10 of them received 1 mA tDCS, 6 received 2 mA tDCS, 2 dropped out. All patients had undergone at least two ineffective trials with antidepressants prior to tDCS. Patients received add-on tDCS under a stable antidepressant treatment over 3 weeks and were randomized to active or sham tDCS treatment. The sham condition was evaluated in 10 healthy volunteers and was indistinguishable.
Both, active (1 mA resp. 2 mA) and placebo tDCS were applied for 20 min per day and for two weeks and then switched to the other condition. The anode was positioned over F3 and the cathode over the contralateral supraorbital region. For placebo tDCS a novel sham device (neuroconn, Ilmenau, Germany) was used which is indistinguishable for the applying person. Severity of depression was assessed by HAMD, BDI, CGI and CORE scales and raters were blind to treatment conditions.
Results:
Overall there was no significant difference between real and sham tDCS in terms of clinical improvement. Group 1 receiving active tDCS first showed a decrease in mean HAMD scores from 34.5 at baseline to 30.5 after two weeks treatment and to 23.5 after further two weeks of sham treatment and group 2 receiving sham tDCS first showed a decrease in mean HAMD from 34.0 at baseline to 28.0 after two weeks sham treatment and to 23.0 after further two weeks of active treatment (Fig 2, 3, Table 1). tDCS was well tolerated and there were little side effects apart from skin lesions occurring mainly with 2 mA tDCS which are reported elsewhere (Palm et al. in press) (Fig. 4).
Conclusion:
Though active tDCS did not appear to be superior to sham treatment and previous findings could not be replicated in therapy-resistant patients, we observed hang-over effects in weeks 3 and 4 depending on the first condition. Thus, real tDCS may induce improvement continued over a prolonged period of time and extended trial protocols should further address this issue.
Fig. 1
Study Design
Fig. 2
HAMD Ratings group A (active-sham) versus B (sham-active). Median + Range
Fig. 4
Skin lesion after 5x tDCS, 2 mA
Phase 1 - Baseline
Phase 1 - End of Week 1
Phase 1 - End of Week 2
= Phase 2 Basline
Phase 2 - End of Week 1
Phase 2 - End of Week 2 18 20 22 24 26 28 30 32 34 36 38
Zellmittelw. B A
Table 1: HAMD Rating. Patient 1-10: 1 mA, Patient 11-18: 2 mA. Patient 16+17: drop-out.
Fig. 3
BDI Ratings group A (active-sham) versus B (sham-active). Median + Range
Phase 1 - Baseline
Phase 1 - End of Week 2
= Phase 2 Basline
Phase 2 - End of Week 2
References:
Boggio PS, Rigonatti SP, Ribeiro RB, et al. A randomized, double-blind clinical trail on the efficacy of cortical direct current stimulation for the treatment of major depression. Int Journal of Neuropsychopharmacology 2008;11:249-54
Fregni F, Boggio PS, Nitsche MA, et al. Treatment of major depression with transcranial direct current stimulation. Bipolar disorders 2006;8:
Palm U, Keeser D, Schiller C, Fintescu Z, Reisinger E, Padberg F. Skin lesions after treatment with transcranial direct current stimulation (tDCS). Brain Stimulation, in press.
Acknowledgement: We thank the NeuroConn GmbH, Ilmenau, Germany for their kind support and providing tDCS devices.