Treating neuropathic pain and comorbid affective disorders: Preclinical and clinical evidence

Abstract Introduction Neuropathic pain (NP) significantly impacts quality of life and often coexists with affective disorders such as anxiety and depression. Addressing both NP and its psychiatric manifestations requires a comprehensive understanding of therapeutic options. This study aimed to review the main pharmacological and non‐pharmacological treatments for NP and comorbid affective disorders to describe their mechanisms of action and how they are commonly used in clinical practice. Methods A review was conducted across five electronic databases, focusing on pharmacological and non‐pharmacological treatments for NP and its associated affective disorders. The following combination of MeSH and title/abstract keywords were used: “neuropathic pain,” “affective disorders,” “depression,” “anxiety,” “treatment,” and “therapy.” Both animal and human studies were included to discuss the underlying therapeutic mechanisms of these interventions. Results Pharmacological interventions, including antidepressants, anticonvulsants, and opioids, modulate neural synaptic transmission to alleviate NP. Topical agents, such as capsaicin, lidocaine patches, and botulinum toxin A, offer localized relief by desensitizing pain pathways. Some of these drugs, especially antidepressants, also treat comorbid affective disorders. Non‐pharmacological techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and photobiomodulation therapy, modulate cortical activity and have shown promise for NP and mood disorders. Conclusions The interconnection between NP and comorbid affective disorders necessitates holistic therapeutic strategies. Some pharmacological treatments can be used for both conditions, and non‐pharmacological interventions have emerged as promising complementary approaches. Future research should explore novel molecular pathways to enhance treatment options for these interrelated conditions.