1. Ephedrine Withdrawal Causes Severe Psychiatric Symptoms: A Case Report Gene Makela, Pharm.D., BCPP Kelly Slear Marcella Hoyland

2. Kelly Slear Marcella Hoyland Pharmaceutical Investigations course, West Virginia University School of Pharmacy

3. The Case  64-year-old woman  long history of depression  abruptly increased symptoms of depression and suicidal ideation with a plan to shoot herself with a gun  difficulty sleeping  very low energy  decreased appetite, energy, and concentration  language and memory intact

4. The Case  judgment and insight poor  some signs of paranoia: during the interview she reported “my family wants to get rid of me”  auditory hallucinations had returned recently: she heard voices of her great aunt and uncle telling her she was worthless, no good, and she should have died when she was born  major depressive disorder with psychotic features was diagnosed  Beck Depression Inventory (BDI) 63

5. Medications on Admission  mirtazepine 30mg daily  olanzapine 20mg daily  levothyroxine 0.88mg daily  conjugated estrogen 0.625mg daily  calcium carbonate 600mg twice daily  compliant with therapy, had been stable

6. Pharmacist Intervention  pharmacist faculty member with student conducted detailed medication history with following findings: l patient was taking eight Xenadrine capsules daily as a weight loss product for the past three to four months l she reported that she took this product until two days before admission to the hospital l at that time, on the advice of her daughter, she abruptly discontinued the Xenadrine

7. Components of Xenedrine ® Pantothenic acid 20mg Bitter orange - standardized to 2.5mg synephrine (similar to phenylephrine) Ma Huang (ephedra) - standardized to 10mg ephedrine Guarana extract (100mg caffeine) Ginger root 25mg White willow bark (15mg salicin) L-tyrosine, L-carnitine, Magnesium phosphate, Deanol (choline precursor). Note: normal dose is 2 capsules daily **

8. Bitter Orange  Citrus aurantium  Adrenergic amines l Synephrine and octopamine (structurally similar to epinephrine) l Hordenine l Tyramine l Methyltyramine

9. Background  Common adverse effects of ephedrine reported to FDA by consumers included elevated blood pressure, tachycardia, muscle injury, psychosis, and memory loss  FDA mandates rule in 1997 requiring manufactures of supplements containing ephedrine that products be labeled with information about risks and dangers  FDA requires stronger labeling cautions in 2003: “ephedrine has a significant risk of illness or injury to the consumer”  FDA creates new Adverse Event Reporting System (CAERS) in 2003 to enable both health care providers and consumers to more easily report adverse events from dietary supplements  In February, 2004, the FDA acts to ban ephedra-containing products

10. Resolution  mirtazepine dosage increased to 45mg at bedtime  over the next several days depression symptoms and psychosis cleared without further intervention l BDI 54 after 2 days  on the day of discharge, seven days after admission, the patient reported feeling much better l no suicidal thoughts or auditory hallucinations l hopeful about the future  discharge diagnoses included major depressive disorder, recurrent, improving, Xenadrine abuse, and Xenadrine withdrawal, resolving

11. Whatever happened to Ephedrine Products?  2008 internet search…  Ephedra products still available  many new products marketed using bitter orange as a substitute for MaHuang

12. Advertisement for ephBURN25  “this product is made from the old ephedra like the old lipodrene – smell the pills you’ll agree”  one capsule: l MaHuang extract 8% Dark (25mg) l Caffeine 200mg l Other ingredients l Dose: 1 capsule twice daily

15. Considerations  abrupt discontinuation of a stimulant taken for a long period of time may lead to depressive symptomatology  In this unique case, however, a depressed patient stable on medications was thrown into severe depression with psychosis and suicidality as a result of the abrupt withdrawal of a non-prescription dietary supplement used for weight loss  despite combined antidepressant (mirtazepine) and antipsychotic (olanzapine) treatment, discontinuation of a non-prescription weight loss product was sufficient to acutely de-stabilize this patient’s condition

16. Results / Conclusions  abrupt discontinuation of non-prescription stimulant medication may cause severe depressive symptomatology, even in a patient whose depression had been adequately controlled with prescription medication  detailed medication history important in clarifying cause of hospitalization, helpful in defining the appropriate course of treatment.

17. What Would Have Happened if:  There was no pharmacist intervention?… possible: l delayed or incorrect diagnosis l higher doses of prescribed medication… potential adverse effects l addition of other medication to stabilize patient …potential drug interactions l prolonged hospitalization

18. To Take Home  Psychiatric pharmacists can facilitate accurate diagnoses by conducting medication histories… l Resultant pharmacotherapeutic approaches may minimize length of stay for patients**  Current availability of ephedrine…need for awareness

19. Questions ???