Tricyclic antidepressants (TCAs) modulate neurotransmitter activity by inhibiting serotonin and norepinephrine reuptake, potentially alleviating the emotional dysregulation and anxiety associated with Depersonalization-derealization disorder. By enhancing synaptic neurotransmitter concentrations, TCAs may help reduce the disconnective symptoms and emotional numbness characteristic of DPDR, though their efficacy is not conclusively established through large-scale clinical trials.