Risks of Ephedra Use Are More Than Just Physical

Evidence continues to mount about the potential ill effects—including psychiatric effects—of herbal supplements containing ephedra.

A spokesperson for the Food and Drug Administration told Psychiatric News that the comment period for receiving public input about potential ill effects of ephedra has ended and that the agency is assessing evidence to determine whether there exists a “significant or unreasonable risk of illness or injury” from dietary supplements containing ephedra.

Ephedra is an adrenaline-like stimulant that can have potentially dangerous effects on the nervous system and heart.

This year the RAND Corporation’s Southern California Evidence-Based Practice Center issued the report “Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects.” The report provided evidence that ephedra is associated with important health risks—including psychiatric effects—and found only limited evidence of health benefits resulting from its use.

The RAND Corporation’s review of some 16,000 adverse-event reports revealed two deaths, four heart attacks, nine strokes, one seizure, and five psychiatric cases involving ephedra in which the records appeared thorough and no other contributing factors were identified. RAND called such cases “sentinel events,” because they may indicate a safety problem but do not prove that ephedra caused the adverse event.

The study recognized that such case studies are a weak form of scientific evidence. Other unmeasured factors may have contributed, and such serious adverse events are likely to happen (albeit at very low rates) among the millions of users of ephedra anyway. The study also identified other such events potentially associated with ephedra, in which other factors may have contributed to the adverse events or in which records were inadequate, according to the FDA.

In addition, three cases of psychosis related to use of ephedra-containing herbal supplements were reported in the July Southern Medical Journal.

One patient was a 19-year-old man referred for psychiatric evaluation because of decreased sleep, increasingly aggressive and disorganized behavior, and paranoid delusions during a one-week period. The patient had been using over-the-counter herbal weight-training supplements that contained ephedra and had been escalating the doses and inhaling the supplements in powder form.

He was observed in the hospital for two days without medications, during which time he became increasingly hostile, assaultive, and disorganized. He was administered valproate, clonazepam, and haloperidol for persistent manic and psychotic symptoms. Gradually, the symptoms abated, and he was released for outpatient follow-up. The antipsychotic and benzodiazepine medications were discontinued after approximately 60 days without further psychotic symptoms.

A second patient was a 21-year-old man who presented with recurrent manic and psychotic symptoms. The patient had used Hydroxycut, a weight-training supplement containing ephedra. In the hospital, he was administered olanzapine and discharged on the 10th day with continued follow-up.

The third patient was a 33-year-old man with a two-week history of depressive symptoms, suicidal ideation, auditory hallucinations, and paranoid and grandiose delusions. These symptoms coincided with use of the diet aid Metabolife, which contains ephedra. He was hospitalized and observed without medication use, then discharged after five days with apparent resolution of his symptoms. But he presented in the emergency department 10 days later with a recurrence of the symptoms, though he denied resumption of the herbal product. Treatment with antipsychotic medication resulted in remission of symptoms over the next three weeks.

Study authors Ruth Walton, M.D., and Gail H. Manos, M.D., of the department of psychiatry at Portsmouth Naval Medical Center in Portsmouth, Va., said that a search of English-language publications revealed only four previously reported cases of psychosis following use of products containing ephedra. “Toxicity may occur at only two or three times the maximum therapeutic dose of 150 mg/d,” the authors observed. “Most reports have focused on medical complications such as stroke, seizure, hepatic toxicity, or even death.”

Secretary of Health and Human Services Tommy Thompson issued a statement cautioning against use of ephedra-containing products, especially under conditions of strenuous exercise and in combination with other stimulants, including coffee.

The RAND report, “Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects,” is posted on the Web at www.fda.gov/OHRMS/DOCKETS/98fr/95n-0304-bkg0003-ref-07-01-index.htm. ▪