Transcutaneous vagus and trigeminal nerve stimulation
                    for neuropsychiatric disorders: a systematic review

Shiozawa, Pedro; Silva, Mailu Enokibara da; Carvalho, Thais Cristina de; Cordeiro, Quirino; Brunoni, André R.; Fregni, Felipe

doi:10.1590/0004-282X20140061

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Views and Reviews • Arq. Neuro-Psiquiatr. 72 (7) • July 2014 • https://doi.org/10.1590/0004-282X20140061 copy

Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review

Estimulação transcutânea do nervo vago e do nervo trigêmeo para o tratamento de distúrbios neuropsiquiátricos: revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

We reviewed trigeminal nerve stimulation (TNS) and transcutaneous vagus nerve stimulation (tVNS). All techniques have shown preliminary promising results, although the results are mixed.

Method:

We performed a systematic review of the Medline and Embase databases, with no constraint to dates, through June 2013. The keywords were [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders.

Results:

We included four preclinical and clinical five studies on TNS. All clinical data were based on open-label studies with small samples, which diminished the external validity of the results, thus reflecting the modest impact of TNS in current clinical practice. Of the tVNS clinical trials, three assessed physiological features in healthy volunteers, and one examined patients with epilepsy.

Conclusion:

TNS and tVNS improve treatment of particular neuropsychiatric disorders such as depression.

transcutaneous nerve stimulation; trigeminal stimulation; neuropsychiatric disorders

Authors	Study design	Subjects	Diagnosis / assessment	Intervention	Main Outcome	Biases Sumary
DeGiorgio, 2006	Open Label Study	7	Epilepsy; Clinical assessment	TNS	57% of the sample experienced a ≥50% reduction in seizures after TNS intervention.	Small sample size, poor demographical sample description, low impact of results generalizability.
Pop, 2011	Open Label Study	14	Epilepsy; Clinical assessment	TNS	No signicant acute or long-term major adverse effects.	Small sample size, poor demographical sample description, low impact of results generalizability.
DeGiorgio, 2009	Open Label Study	13	Epilepsy; Clinical assessment	TNS	Mean seizure frequency reduction: 66% (3 m); 56% (6 m) and 59% (12 m).	Small sample size, poor demographical sample description, low impact of results generalizability.
Schraeder, 2011	Open Label Study	5	TRD / IDC-10; HDRS; BDI	TNS	Significant decreases in symptom severity were observed over 8 weeks.	Small sample size, low impact of results generalizability.
DeGiorgio, 2003	Open Label Study	2	Epilepsy; Clinical assessment	TNS	TNS was well tolerated and patients reported reductions in seizures during stimulation.	Small sample size, low impact of results generalizability.

Authors	Study design	Subjects	Diagnosis / assessment	Intervention	Main Outcome	Biases Sumary
Busch, 2012	Crossover	48	Health volunteers; study on pain physiology	tVNS	tVNS was related to an increase in mechanical and pressure pain threshold and a reduction of mechanical pain sensitivity.	Small sample size, poor demographical sample description, low impact of results generalizability.
Stefan, 2012	Open Label Study	10	Pharmacoresistant Epilepsy; Clinical assessment	tVNS	7 patients concluded the trial and presented an overall reduction of 71.4% of seizure frequency after a 9-month follow up.	Small sample size, poor demographical sample description, low impact of results generalizability.
Dietrich, 2008	Open Label Study	4	Health volunteers; neuroimaging study on brain activation patterns	tVNS	A positive fMRI BOLD response was detected during stimulation in different brain areas.	Small sample size, poor demographical sample description, low impact of results generalizability.
Kraus, 2007	Open Label Study	22	Health volunteers; neuroimaging study on brain activation patterns	tVNS	fMRI BOLD-signal decreases in limbic brain areas. Increased activation was seen in the insula, precentral gyrus and the thalamus.	Small sample size, low impact of results generalizability.
Hein, 2013	Double-blinded sham controled trial	37	Patients with depressive disorder	tVNS	In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI.	Small sample size, low impact of results generalizability.

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[1] Correspondence:
Pedro Shiozawa; Departamento de Psiquiatria, Faculdade de Ciências Médicas da Santa Casa de São Paulo; Rua Major Maragliano, 241 Vila Mariana; 04600-010 São Paulo SP, Brasil; E-mail: pshiozawa@yahoo.com.br