Barbiturate-related connective tissue disorders

Development of Dupuytren's contractures, frozen shoulder, Ledderhose's syndrome, Peyronie's disease, fibromas, and general joint pain has been linked in retrospective studies and case reports to the use of antiepileptic drugs. We undertook a prospective survey of the incidence of connective tissue disorders in 622 patients newly treated with carbamazepine, phenobarbital, phenytoin sodium, or primidone. Ten of the 406 patients who were treated for 6 months or more developed connective tissue disorders. All affected patients were taking a barbiturate (primidone, 4 patients; phenobarbital, 6 patients). Seven of the 10 problems occurred during the first year of treatment. These data are prospective evidence of a statistically significant relationship between barbiturate use and the development of connective tissue disorders, and timing of appearance.