Gamma Frequency Stimulation Provides Therapeutic Potential in Neuropsychiatry: A Systematic Review and Meta-Analysis

Gamma oscillation dysfunction has been implicated in neuropsychiatric disorders. Restoring gamma oscillations via brain stimulation represents an emerging therapeutic approach. However, the strength of its clinical effects and treatment moderators remain unclear. We conducted a systematic review and meta-analysis to examine the clinical effects of gamma frequency stimulation in neuropsychiatric disorders. A literature search for controlled trials using gamma frequency stimulation was performed across five databases up until April 2025. Effect sizes were calculated using Hedge's g. Separate analyses using the random-effects model examined the clinical effects in schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder, and autism spectrum disorder. For SZ and MDD, subgroup analyses evaluated the effects of stimulation modality, stimulation frequency, treatment duration, and pulses per session. Fifty-six studies met the inclusion criteria (NSZ = 943, NMDD = 916, NBD = 175, NASD = 232). In SZ, gamma frequency stimulation was associated with improvements in positive (k = 10, g = −0.60, p < 0.001), negative (k = 12, g = −0.37, p = 0.03), depressive (k = 8, g = −0.39, p < 0.001), anxious symptoms (k = 5, g = −0.59, p < 0.001), and overall cognitive function (k = 7, g = 0.55, p < 0.001). Stimulation frequency and treatment duration moderated therapeutic effects. In MDD, reductions in depressive symptoms were observed (k = 23, g = −0.34, p = 0.007). However, confidence in these estimates is limited by substantial heterogeneity and the predominance of 50 Hz theta-burst protocols.