Factors influencing anxiety and depression in postherpetic neuralgia patients

Table 1 Summary of risk factors, mechanisms, evidence levels, and clinical recommendations for anxiety and depression in postherpetic neuralgia patients

Risk factor	Evidence type	Underlying mechanism	Clinical recommendation
Advanced age	Direct (PHN) + indirect (population)	Reduced neuroplasticity; amygdala enlargement; social isolation	Geriatric assessment; sleep optimization; social support
Female sex	Direct (PHN cohort)	Hormonal pain sensitivity; stronger amygdala response; stress susceptibility	Early psychological screening; emotional support
Severe pain intensity	Direct (PHN)	Amygdala/ACC activation; central sensitization; inflammatory disturbance	Timely analgesia (gabapentin/pregabalin); pain control to VAS ≤ 4
Prolonged pain duration	Direct + indirect (chronic pain)	Cumulative stress sensitization; HPA axis hyperactivity	Early intervention; regular follow-up; multidisciplinary care
Extensive rash	Direct (PHN)	Nerve damage; body image disorder; social isolation	Skin care; appearance support; psychosocial counseling
High PHQ-9 score	Direct (PHN)	Somatic-affective overlap; neurotransmitter disturbance	PHQ-9 screening; referral if ≥ 10; antidepressant therapy
Negative coping	Indirect (cross-population)	Maladaptive stress response; cognitive avoidance	Cognitive behavioral therapy; positive coping training

The evidence levels presented in this table are derived from studies with heterogeneous designs and populations. “Direct” evidence refers to findings from postherpetic neuralgia (PHN) specific cohorts (mostly retrospective or crosssectional), whereas “indirect” evidence comes from other chronic pain populations, general population cohorts, or preclinical studies. Direct PHN evidence provides the highest specificity for risk prediction but may be subject to selection bias and limited generalizability across different clinical settings. Indirect evidence supports biological plausibility and helps fill knowledge gaps, but extrapolation to PHN patients requires caution owing to differences in disease pathophysiology and comorbidity profiles. The proposed mechanisms and clinical recommendations integrate both levels of evidence; however, their applicability should be validated in prospective PHN-focused studies. PHQ-9: Patient Health Questionnaire-9; PHN: Postherpetic neuralgia; ACC: Anterior cingulate cortex; HPA: Hypothalamic-pituitary-adrenal; VAS: Visual Analogue Scale.