Introduction: Mitochondrial disorders are a group of metabolic conditions caused by impairment of the oxidative phosphorylation system. The treatment of mitochondrial diseases is still inadequate. Therapies that have been attempted include: respiratory chain cofactors, other metabolites secondarily decreased in mitochondrial disorders, antioxidants, and agents acting on lactic acidosis. However, their role in the treatment of the majority of mitochondrial diseases is still unclear. Furthermore, some drugs may potentially have detrimental effects on mitochondrial dysfunction.

Areas covered: To critically review this still unclear field, this paper attempts to answer, on the basis of the basic and clinical literature available to date, the ‘frequently asked questions', such as: Is valproic acid safe in mitochondrial patients? What about other antiepileptic drugs? May metformin trigger lactic acidosis in mitochondrial patients? Are statins safe in these subjects?

Expert opinion: Randomized clinical trials are necessary to establish efficacy and safety of drugs. Multicenter collaboration is essential for the advancement of therapy for mitochondrial disorders.