Interaction of serotonin re-uptake inhibitors with perhexiline

Objective: To report two cases of perhexiline toxicity associated with selective serotonin re-uptake inhibitor (SSRI) treatment. Clinical picture: Serum perhexiline concentrations progressively increased after a 69-year-old man was concurrently prescribed paroxetine for the treatment of depression. An 84-year-old woman was admitted to hospital with severe, symptomatic perhexiline toxicity associated with fluoxetine treatment. Treatment: In both cases, perhexiline therapy was suspended and treatment with SSRIs was withdrawn. Outcome: Serum perhexiline concentrations declined following the withdrawal of paroxetine in one case, but in the case of the second patient perhexiline concentrations were extremely slow to decrease, resulting in referral to a rehabilitative care unit for convalescence. Conclusions: Serum perhexiline concentrations may be elevated during concurrent treatment with SSRls, potentially resulting in severe toxicity.