Assessing tDCS efficacy in reducing negative symptoms in schizophrenia spectrum disorders: A systematic review and meta-analysis.

BACKGROUND

Negative symptoms in schizophrenia spectrum disorders (SSDs) are associated with low functioning and reduced quality of life. Given the limited efficacy of current treatments, transcranial direct current stimulation (tDCS) has been studied as a potential add-on intervention, though findings to date have been mixed.

OBJECTIVE

This meta-analysis aims to assess the efficacy of tDCS for the reduction of negative symptoms in SSDs.

METHODS

A systematic review and meta-analysis were conducted on randomized controlled trials comparing active to sham tDCS treatments applied to people diagnosed with SSDs (PROSPERO registration: CRD42024530612). Standardized mean differences (SMDs) were calculated, and subgroup and moderation analyses were performed to explore possible sources of heterogeneity.

RESULTS

Across studies (k = 18; total n = 709; 361 participants in the active and 348 in the sham group), tDCS significantly reduced negative symptoms of SSDs, compared to sham stimulation, with moderate heterogeneity. Subgroup analysis showed greater efficacy when studies included only the diagnosis of schizophrenia (SMD = -0.51), and when negative symptoms were the primary outcome and the specific target of the intervention (SMD = -0.80). Stimulation over the left dorsolateral prefrontal cortex (lDLPFC) was significantly associated with symptom reduction (SMD = -0.30). No significant effects were found at follow-up, indicating limited persistence of treatment effects without maintenance sessions. tDCS was well tolerated and safe.

DISCUSSION: tDCS shows significant modest effect for the reduction of negative symptoms of SSDs as an add-on treatment to medication, particularly when protocols target these symptoms and the anode is placed over the lDLPFC. Future studies should study the long-term effects of tDCS and how to boost long-term efficacy, as well as explore individual characteristics to tailor personalized interventions.