Efficacy of pregabalin augmentation for refractory pain in late-life depression

To the Editor

Pain and depression commonly coexist in the elderly. Chronic pain can contribute to subthreshold depressive symptoms and may be associated with recurrence of a major mood episode in patients with a previous mental illness. This case demonstrates that administration of pregabalin, an anticonvulsant that binds to the alpha-2-delta site of voltage-gated calcium channels, helped to reduce long-term refractory pain in a geriatric patient with depression.

A 73-year-old woman presented to our department with long-term intermittent dyspepsia, abdominal pain and an almost 20-year history of insomnia. She was often taken to an emergency department for exaggerated abdominal pain (visual analogue scale [VAS] score about 8), although her physical examination, laboratory data and imaging results were normal. She also developed severe depressive mood changes simultaneously with suicidal ideation and was given a diagnosis of major depressive disorder. Duloxetine (60 mg/day) and tramadol (400 mg/day) were concomitantly prescribed. After 6 weeks, she reported a reduction in depression (her Hamilton Depression Rating Scale [HAMD-17] dropping from 20 to 10), but the same intensity of pain. We then initiated pregabalin at a dose of 75 mg, twice daily. After 10 days, the patient reported 50% less pain, so we discontinued tramadol. After 7 days, her VAS score was 2, so we maintained her starting dosage for 6 months at the outpatient department. There were no adverse effects during this follow-up period.

The elderly may have altered pain processing, impaired function of the A-Delta fibers, altered serotonin metabolism and decreased responsiveness to opioid analgesic pathways. Pregabalin has an anti-seizure effect following from its binding to the alpha-2-delta binding site of voltage-gated calcium channels in the central nervous system, a receptor known to play a major role in pain sensitization processes. We suggest three possible mechanisms for the analgesic effect of pregabalin in senile depression. First, pregabalin might reduce depolarization-induced calcium influx at nerve terminals and then decrease the release of excitatory neurotransmitters, including glutamate, noradrenaline and substance P (Ben-Menachem, 2004). Second, decreased progressive desensitization of the µ-opioid receptor might occur after continuous administration of opioids (Bannister et al., 2011). Third, pregabalin might bind to the alpha-2-delta site of voltage-gated calcium, which is up-regulated during the hypersensitization process in senile pain (Gajraj, 2007).

Our case illustrates the benefit of augmentation with pregabalin for the treatment of refractory pain in an elderly depressed patient. However, the possible antiepileptic effect and interaction with the serotonergic system that causes mood change should be elucidated in future studies.