Effects of antidepressants and benzodiazepine-type anxiolytic agents on hepatic porphyrin accumulation in primary cultures of chick embryo liver cells

Patients with any of the acute porphyrias may suffer from acute attacks. If these patients are treated with certain drugs, such as barbiturates, the l ikelihood of developing an attack is increased. Patients treated with antid epressants or benzodiazepine-type anxiolytics also could be placed at incre ased risk of developing porphyric attacks because little is known about the potential for some of these drugs to induce attacks. Primary cultures of c hick embryo liver cells were used to study the effects of selected antidepr essants and anxiolytics on porphyrin accumulation. Cells were treated with desferrioxamine (to partially block heme synthesis, simulating conditions e ncountered in porphyric patients) and increasing concentrations (3.16-1000 mM) of the evaluated drugs. Twenty hours later, porphyrin accumulation was measured. The drugs included four antidepressants and five benzodiazepine-t ype anxiolytics. The antidepressants bupropion and nefazodone significantly increased porphyrin accumulation when given with desferrioxamine, whereas neither fluoxetine nor paroxetine increased porphyrin accumulation. The ben zodiazepine-type anxiolytic agents oxazepam, lorazepam, diazepam, triazolam , and midazolam all significantly increased porphyrin accumulation when giv en with desferrioxamine. Dose-response studies showed that diazepam, midazo lam, and triazolam produced significant increases even at the lowest concen tration tested (3.16 mM), whereas lorazepam and oxazepam required higher co ncentrations (greater than or equal to 10 mM). These studies suggest that p atients with acute porphyrias may be at greater risk for developing porphyr ic attacks when treated with bupropion or nefazodone compared with fluoxeti ne or paroxetine, and that the evaluated benzodiazepine derivatives should be administered with caution. Among the latter, low doses of lorazepam and oxazepam may be safer than those of diazepam, midazolam, and triazolam.