Transcranial direct current stimulation for depression and aphasia. A health technology assessment
Health technology assessment
|Published
The aim of this health technology assessment was to evaluate the efficacy and safety of tDCS for depression and aphasia. We also conducted a cost-analysis.
Key message
Depression and aphasia reduce quality of life and increase the risk of disability. Standard care for depression is psychotherapy and antidepressants, and language therapy is used for aphasia. Transcranial direct current stimulation (tDCS) is a mild form of neuromodulation. tDCS may be combined with standard care for depression and aphasia or may be used alone for depression. The aim of this health technology assessment was to evaluate the efficacy and safety of tDCS for depression and aphasia. We also conducted a cost-analysis.
We identified relevant randomized trials in systematic reviews, and in additional systematic literature searches. We included 25 trials on tDCS for depression, 27 trials on tDCS for poststroke aphasia, and two trials on tDCS for primary progressive aphasia.
The results showed that tDCS is well tolerated and:
- probably reduces depressive symptoms in patients with moderate to severe depression
- probably improves functional communication in patients with poststroke aphasia when combined with language therapy
The evidence on tDCS for primary progressiv aphasia is highly uncertain.
A 4-week tDCS treatment for depression costs about 16,000 NOK in a home-based setting, and about 81,000 NOK in an outpatient-setting. Home-based tDCS treatment combined with language therapy costs about 33,000 NOK for poststroke aphasia, and about 31,000 NOK for primary progressive aphasia. In outpatient care, the costs are about 74,000 NOK for poststroke aphasia, and about 56,000 NOK for primary progressive aphasia. The largest costs are those associated with hospital staff.
Summary
Introduction
It is estimated that 20 % of persons in Norway will experience depression during their lifetime, and depression is ranked fourth among disorders that reduce both quality of life and life years. About 9000 persons in Norway are affected by stroke every year and roughly 30 % of those affected get aphasia. The occurrence of primary progressive aphasia is uncertain, but a prevalence of 3-4 per 100 000 has been suggested.
Standard care for depression is psychotherapy and antidepressants, and for aphasia, language therapy is given. Transcranial direct current stimulation (tDCS) is a mild neuromodulation technique. During treatment, electrodes are placed on the patient’s scull and deliver a weak direct current which affects the cortical regions beneath. tDCS may be combined with standard therapy for depression and aphasia or may be offered to depressive patients that are unable or unwilling to use antidepressants.
Objective
The objective of this health technology assessment was to investigate the efficacy and safety, and to perform an economic evaluation of tDCS for depression, poststroke aphasia, and primary progressive aphasia.
Methods
We did a simple literature search for systematic reviews, and a systematic search for randomized trials published after the searches in the reviews were conducted. We included one systematic review on tDCS for depression and one on tDCS for poststroke aphasia. The review on tDCS for depression only included trials comparing tDCS with sham-tDCS (placebo). We therefore conducted a separate systematic search for randomized trials comparing tDCS with antidepressants and for studies reporting quality of life and health economic evaluations. All searches were conducted in September - December 2021.
The entire group evaluated and selected the most relevant and updated systematic reviews with the highest methodological quality. Two researchers read the titles, abstracts, and full texts of all relevant publications from the systematic searches. One researcher extracted and analyzed data from the included trials, and another verified the data extraction. We made our own judgements of the risk of bias in trials identified in the systematic searches and used the authors judgements in trials that were included from the systematic reviews. The entire group and the clinical experts evaluated our certainty of each result using GRADE.
We also conducted a cost-analysis of tDCS treatment for depression, poststroke aphasia, and primary progressive aphasia in Norway.
Results
We included 25 trials on tDCS for depression, 27 trials on tDCS for poststroke aphasia, and 2 trials on tDCS for primary progressive aphasia.
Effects of tDCS were observed at the end of treatment and were even more prominent after a period of follow-up in both depression and poststroke aphasia. Compared to sham-tDCS, tDCS increased response rates and probably improved depression scores and remission rates for patients with moderate to severe depression at 2-7 weeks follow-up (Summary of findings table). Small or no differences were found between patients given tDCS and patients given antidepressants. Compared to sham-tDCS, tDCS probably improved functional communication and naming of nouns, and may have improved naming of verbs for participants with poststroke aphasia at 1-6 months follow-up (Summary of findings table).
Outcome |
Anticipated absolute effects (95% CI) |
Relative effect |
Number of participants |
Certainty (GRADE) |
||
|
sham-tDCS |
tDCS |
|||||
|
tDCS for depression |
||||||
|
Depression score
|
- |
SMD 0.60 SD lower |
- |
472 |
⨁⨁⨁◯ |
|
|
Response |
237 per 1 000 |
471 per 1 000 |
RR 1.99 |
411 |
⨁⨁⨁⨁ |
|
|
Remission |
134 per 1 000 |
267 per 1 000 |
RR 1.99 |
411 |
⨁⨁⨁◯ |
|
|
Drop-out |
89 per 1 000 |
69 per 1 000 |
RR 0.78 |
1062 |
⨁⨁◯◯ |
|
|
tDCS for poststroke aphasia |
||||||
|
Functional communication |
- |
SMD 0.29 SD higher |
- |
103 |
⨁⨁⨁◯ |
|
|
Naming of nouns |
- |
SMD 0.66 SD higher |
- |
113 |
⨁⨁⨁◯ |
|
|
Naming of verbs |
- |
SMD 0.94 SD higher |
- |
12 |
⨁⨁◯◯ |
|
|
Drop-out and serious adverse effects |
70 per 1 000 |
49 per 1 000 |
RR 0.69 |
428 |
⨁⨁⨁◯ |
|
The outcomes were measured at 2-7 weeks follow-up in patients with depression and at 1-6 months follow-up in patients with poststroke aphasia.
- Broad confidence interval including large and small effects
- Broad confidence interval including no effect and both positive and negative effects
- High risk of bias in multiple studies
- Few participants (low statistical power)
tDCS probably resulted in small or no differences in the proportion of drop-out and serious adverse effects, but mild and transient side effects such as skin redness, tingling, and itching under the electrodes were reported in most of the included trials.
The evidence on tDCS for primary progressive aphasia was highly uncertain.
A 4-week tDCS treatment for depression costs about 16,000 NOK in a home-based setting, and about 81,000 NOK in an outpatient setting. The costs of home-based tDCS combined with language therapy are about 33,000 NOK for poststroke aphasia and about 31,000 NOK for primary progressive aphasia, in which the additional costs of tDCS are about 15,000 NOK and 12,000 NOK respectively. tDCS combined with language therapy in an outpatient setting costs about 74,000 NOK for poststroke aphasia and about 56,000 NOK for primary progressive aphasia, in which the additional cost of tDCS is about 2500 NOK. The number of tDCS treatments needed each year, is estimated to be 1-2 for depression and 1-4 for aphasia.
Discussion
The evidence on tDCS for depression and poststroke aphasia addresses all the research questions of this health technology assessment. The trials on depression mainly included patients with moderate to severe depression. The treatment-induced effects reported here are therefore valid for this patient group but are not necessarily valid for patients with mild depression. The evidence is also less comprehensive for bipolar than for unipolar depression. However, subgroup analysis did not indicate that patients with these indications differed in the response to tDCS treatment. For poststroke aphasia, most trials combined tDCS with language therapy and we do not know whether tDCS can provide similar effects if applied alone. Nevertheless, one will probably combine tDCS with language therapy also in Norwegian practice. The number of participants in the trials of primary progressive aphasia was too low to detect clinically important differences (low statistical power). Novel studies investigating the effect of tDCS for primary progressive aphasia are therefore warranted.
To conduct a cost-analysis, we had to make several assumptions on how tDCS may be applied in a home-based and an outpatient setting. The assumptions were made by consulting clinical experts and suppliers of tDCS devices, but are, despite these efforts, to some degree uncertain. The costs may thus have been both over- and underestimated.
Conclusion
tDCS treatment probably reduces symptoms of depression in patients with moderate to severe depression. The effect of tDCS is probably not greater than antidepressant effects. tDCS treatment probably reduces language impairment in patients with poststroke aphasia when combined with language therapy. tDCS treatment did not increase the proportion of drop-out and serious adverse effects, but mild and transient side effects must be expected. The evidence on tDCS for primary progressive aphasia is highly uncertain. Based on the current evidence it is impossible to estimate whether tDCS is cost effective, but we have estimated approximate costs based on certain assumptions. The largest costs are those associated with hospital staff, and home-based treatment is thus less expensive than outpatient care.
