Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

Stephan A Goerigk; Frank Padberg; Adam Chekroud; Joseph Kambeitz; Markus Bühner; Andre R Brunoni

doi:10.1016/j.brs.2021.05.008

Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

Brain Stimul. 2021 Jul-Aug;14(4):906-912. doi: 10.1016/j.brs.2021.05.008. Epub 2021 May 26.

Authors

Stephan A Goerigk¹, Frank Padberg², Adam Chekroud³, Joseph Kambeitz⁴, Markus Bühner⁵, Andre R Brunoni⁶

Affiliations

¹ Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nußbaumstraße 7, 80336, Munich, Germany; Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University, Leopoldstraße 13, 80802, Munich, Germany; Hochschule Fresenius, University of Applied Sciences, Infanteriestraße 11A, 80797, Munich, Germany.
² Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nußbaumstraße 7, 80336, Munich, Germany.
³ Department of Psychiatry, Yale University, New Haven, CT, 06520, USA; Spring Health, New York, NY, 10001, USA.
⁴ Department of Psychiatry, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Straße 62, 50937, Cologne, Germany.
⁵ Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University, Leopoldstraße 13, 80802, Munich, Germany.
⁶ Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, R Dr Ovidio Pires de Campos 785, 2o andar, 05403-000, São Paulo, Brazil; Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo & Hospital Universitário, Universidade de São Paulo, Av. Prof Lineu Prestes 2565, 05508-000, São Paulo, Brazil; Laboratory of Neurosciences (LIM-27), Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, R Dr Ovidio Pires de Campos 785, 2o andar, 05403-000, São Paulo, Brazil. Electronic address: [email protected].

PMID: 34048940
DOI: 10.1016/j.brs.2021.05.008

Abstract

Background: Transcranial direct current stimulation (tDCS) presents small antidepressant efficacy at group level and considerable inter-individual variability of response. Its heterogeneous effects bring the need to investigate whether specific groups of patients submitted to tDCS could present comparable or larger improvement compared to pharmacotherapy. Aggregate measurements might be insufficient to address its effects.

Objective: /Hypothesis: To determine the efficacy of tDCS, compared to pharmacotherapy and placebo, in depressive symptom clusters.

Methods: Data from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Therapy for Treating Depression Clinical Study, ClinicalTrials.gov, NCT01894815), in which antidepressant-free, depressed patients were randomized to receive 22 bifrontal tDCS (2 mA, 30 min) sessions (n = 94), escitalopram 20 mg/day (n = 91), or placebo (n = 60) over 10 weeks. Agglomerative hierarchical clustering identified "sleep/insomnia", "core depressive", "guilt/anxiety", and "atypical" clusters that were the dependent measure. Trajectories were estimated using linear mixed regression models. Effect sizes are expressed in raw HAM-D units. P-values were adjusted for multiple comparisons.

Results: For core depressive symptoms, escitalopram was superior to tDCS (ES = -0.56; CI_95% = -0.94 to -0.17, p = .009), which was superior to placebo (ES = 0.49; CI_95% = 0.06 to 0.92, p = .042). TDCS but not escitalopram was superior to placebo in sleep/insomnia symptoms (ES = 0.87; CI_95% = 0.22 to 1.52, p = .015). Escitalopram but not tDCS was superior to placebo in guilt/anxiety symptoms (ES = 1.66; CI_95% = 0.58 to 2.75, p = .006). No active intervention was superior to placebo for atypical symptoms.

Conclusions: Pharmacotherapy and non-invasive brain stimulation produce distinct effects in depressive symptoms. TDCS or escitalopram could be chosen according to specific clusters of symptoms for a bigger response.

Trial registration: ClinicalTrials.gov, NCT01894815.

Keywords: Clinical trials; Cluster-based approach; Major depressive disorder; Non-invasive brain stimulation; Pharmacotherapy.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antidepressive Agents / therapeutic use
Brain
Cluster Analysis
Depressive Disorder, Major* / drug therapy
Double-Blind Method
Humans
Transcranial Direct Current Stimulation*
Treatment Outcome

Substances

Antidepressive Agents

Associated data

ClinicalTrials.gov/NCT01894815