Lofepramine--a safe anti-depressant in acute hepatic porphyria?

The acute porphyrias are a group of neuropsychiatric disorders in which a life-threatening crisis can be precipitated by a variety of drugs, including antidepressants. Because of the need to find an antidepressant that is safe for porphyria patients, we have studied the effects of lofepramine on porphyria in laboratory rats and porphyria patients. The rats did not exhibit a significant rise in hepatic δ-aminolaevulinic acid synthase activity (a marker of drug porphyrinogenicity) when given the drug compared with its solvent alone. Four porphyria patients exhibited no clinical evidence of disease activation after exposure to the drug. The biochemical activity of their disease was assessed by measurement of the 24-h urinary excretion of δ- aminolaevulinic acid and porphobilinogen (haem precursors formed prior to the metabolic block). No patient exhibited a sustained rise compared to pre-treatment levels, or between low dose and high dose lofepramine. We suggest that lofepramine is probably safe in acute porphyria, but should be used with caution.