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Stiff-person syndrome (SPS) is a neuroimmunologic disorder characterized by painful spasms and muscle rigidity attributed to impaired inhibitory γ-aminobutyric acid (GABA) descending pathways.1 The immunopathogenesis remains unknown and the pathogenic significance of antibodies against glutamic acid decarboxylase (GAD) is controversial. Herein, we report 4 cases of anti-GAD65-positive patients with SPS (table e-1 at [Neurology.org/nn][1]) who had significant worsening of symptoms and disability with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine (table e-2). While causation cannot be proven, these observations suggest the importance of investigating the relationship between SNRI use and SPS clinical exacerbations (figure, A). [1]: /lookup/doi/10.1212/NXI.281

Serotonin-norepinephrine reuptake inhibitors may exacerbate stiff-person syndrome