Dextromethorphan Abuse in Adolescence: A Rising Trend

1. Dextromethorphan Abuse in Adolescence: A Rising Trend Ilene B. Anderson, PharmD Clinical Professor; UCSF School of Pharmacy Senior Toxicologist California Poison Control System - SF

2. Conflicts of Interest • The speaker has no conflicts of interest to disclose regarding this topic. California Poison Control System

3. Overview • Case Studies • Clinical presentation (OD, chronic abuse), Management • Pharmacology • Selected Drug Interactions with DXM • Incidence of Teenage DXM Abuse • What is being done to curb the abuse? California Poison Control System

4. What is the CPCS? • CPCS - California Poison Control System • 1 800 222-1222 OR 1 800 876-4766 • 24 hour Emergency Telephone Hotline • www.calpoison.org • Advice to health care professionals/public • Over 300,000 consultations a year • Calls to the CPCS are voluntary California Poison Control System

5. Case Study 14 year female took #24 ‘Skittles’ during a sleep-over at her friend’s house. Her friends became alarmed when she became agitated and started hallucinating. EMS called. Vital Signs: HR 150, BP 157/92, T 100 • pupils dilated, nystagmus • One Tonic Clonic seizure soon after ED arrival California Poison Control System

6. Ingested Product Active Ingredients: Dextromethorphan 30mg Chlorpheniramine 4mg California Poison Control System

7. Case Study - Outcome • Patient was observed for 9 hours • Ativan • No repeat seizures • All symptoms resolved • Toxicology screen results • Positive for phencyclidine (PCP) • Patient discharged home California Poison Control System

8. DextromethorphanPharmacology and Toxicology

9. Dextro-rotatary Isomers Levorphanol Dextromethorphan California Poison Control System

10. Pharmacology Dextromethorphan CYP 2D6 Dextrorphan (active metabolite) California Poison Control System

11. Dextromethorphan; Dextrorphan • Do Not bind to classic opiate receptors • Inhibits NMDA Receptor • (N-methyl-d-aspartate receptor) • Same site of action as ketamine, phencyclidine • Dissociative hallucinogens • Inhibits reuptake of serotonin • DXM substrate for and inhibitor of CYP2D6 California Poison Control System

12. Genetic polymorphisms of CYP 2D6 • Poor metabolizers (PMs) • Produce less Dextrorphan • Experience higher incidence of side effects • Nausea, Vomiting, Dysphoria • Less likely to abuse DXM • Extensive metabolizers (EMs) • Produce more Dextrorphan • Experience more of the euphoric, “desired” mind altering effects • More likely to abuse DXM California Poison Control System

13. Clinical Effects (“Plateaus”) • 1st Plateau: 1.5-2.5mg/kg Mild alcohol-marijuana-like intoxication, GI sxs • 2nd Plateau: 2.5-7.5mg/kg • ‘Enjoyed the best by most’ ‘CEV’ lethargy or agitation, ataxia, nystagmus, tachycardia, HTN • 3rd Plateau: 7.5-15mg/kg • Variable, often dysphoric, psychosis, disorientation, altered judgment may be severe • 4th Plateau: > 15-30mg/kg Fully dissociative, seizures, hyperthermia, aspiration California Poison Control System

14. Hidden Ingredients Do they pose a risk?

15. Case Study 2 • A 14yo M skipped school with friends and took 16 Coricidin HBP Maximum Strength Flu tablets to get high. • Friends claim he was acting goofy, slept for a while, but seemed okay. • Skipped dinner and went to sleep early. California Poison Control System

16. Case study 2; continued • Later that evening he started vomiting • Mother called the Poison Center • Patient referred into the ED • Acetaminophen poisoning • Dose (16 tabs x 500mg = 8,000mg) • Risk of liver Damage • Symptoms are delayed about 10 hours. California Poison Control System

17. Product ingested Ingredients: Acetaminophen 500mg Chlorpheniramine 2mg Dextromethorphan 15mg California Poison Control System

18. Case Study 2; Outcome • Laboratory findings • Acetaminophen 65 mg/L at 13 hours • Elevated liver enzymes by 30 hours • Patient hospitalized for 3 days • Treated with N-acetylcysteine (antidote) • Liver injury resolved • Patient discharged on Day 4 California Poison Control System

19. DXM and the Laboratory • Dextromethorphan • DXM may cause a false positive on the Phencyclidine (PCP) assay • Rule out acetaminophen • Common in many OTC cough/cold preps • Delayed hepatic toxicity California Poison Control System

20. Chronic Abuse Scant case reports ……

21. Psychosis-Vicks Formula 44-D • 25yr F ingested 800ml x 1.5 yrs (DXM, PPA, GG). Patient had a long hx of OTC abuse; No hx alcohol / DofA • Dishevelled, tangential speech, delusional (US hostage in Lebanon), hyperreflexic, nystagmus • HR 140, BP 148/102 • Supportive Care - no meds given. • No withdrawal syndrome • Resolution in 3 days Craig DF. Can Med Assoc J 1992; 146(7): 1199-1200. California Poison Control System

22. DXM Withdrawal Syndrome • 66yr F hx of heavy alcohol use x 30yrs since her teens. Abstinent for a few years & switched to DXM Cough Syrup 4oz > 16oz/d (no EtOH) for > 10 years. • Last dose: 3 days prior to ED • Sxs: abdominal pain, N/V, tremor, dysphoric, depressed, insomnia • VS: HR 96, BP 183/91, T 99. • Tx: Librium, counseling. Resolved 2-5 days Desai S, et al JABFM. May-June 2006;19(3):320-322. California Poison Control System

23. Drug Drug Interactions • Do they pose a serious risk? California Poison Control System

24. Selected Drug Interactions w/ DXM • SSRIs -- Eg: fluoxetine, paroxetine • SSRIs inhibit CYP2D6 • Risk - Serotonin syndrome • AMS, seizure, rigidity, hyperthermia, arrhythmias, HTN • MDMA “Ecstasy” • Reuptake of serotonin is inhibited • Risk - Serotonin syndrome • Monoamine oxidase inhibitors • Catecholamine uptake/metabolism is altered • Risk: Increased sympathomimetic effects and Serotonin syndrome California Poison Control System

25. Why are teenagers abusing DXM ? • Euphoria and hallucinations • Commonly available over-the-counter • Legal • Relatively inexpensive • Easy to fool parents • Lacks the stigma of a ‘drug of abuse’ • False perception that use is safe • Widely advertised on the Internet California Poison Control System

26. DXM Abuse on the Internet • The 3rd Plateau: Beginner’s Guide to DXM • http://www.third-plateau.org/knowledgebase/beginners.shtml • Guide to Using Cough Syrup as DXM Source • http://www.totse.com/en/drugs/otc/guidetousingco169940.html • Dextromethorphan Extraction http://nepenthes.lycaeum.org/Drugs/DXM/extract.html • YouTube • www.youtube.com • My Space, FaceBook California Poison Control System

27. Evaluating the Problem California Poison Control System

28. CPCS DXM Abuse Study1999-2004 • Retrospective review - All DXM abuse calls to the CPCS were reviewed over 6 years (1999-2004) • Excluded: < 10 yrs, information, sxs unrelated to DXM • Charts evaluated for demographic & clinical data • CPCS Data was compared to national trends • AAPCC = American Assoc of Poison Control Centers • DAWN = Drug Abuse Warning Network • Bryner J, Wang U, Hui J, Bedodo M, MacDougall C, Anderson I. Arch Pediatr Adolesc Med. Dec 2006;160:1217-1222. California Poison Control System

29. CPCS Results • A total of 1382 Patients were included • 74% involved minors < 18 years of age • 15 and 16 year olds were the most common age • 60% Male • 93% involved minor/moderate outcome • 0.5% involved major outcomes • no deaths reported • 64% of subjects treated in a health care facility California Poison Control System

30. Dextromethorphan Abuse -- Reported to the CPCS -- CPCS total human exposure call volume only increased 1.5% ** Data from 2005-2006 from CPCS surveillance California Poison Control System

31. Age Distribution California Poison Control System

32. Most Common DXM Products California Poison Control System

33. National Trends of DXM Abuse(DAWN and AAPCC) * In 2004, DAWN reported 5,581 DXM related ED visits (1,791, minors) California Poison Control System

34. National DXM Statistics • NIDA 2006 Monitoring the Future • 4.3% of 8th graders • 5.3% of 10th graders • 6.9% of 12th graders • Partnership Attitude Tracking Study • 10% of teens admitted abusing DXM-containing OTC cough medicines to get high. • …. 2006 was the first year DXM abuse was tracked by MtF California Poison Control System

35. DXM Containing Products California Poison Control System

36. Poison Center Calls • Voluntary • Calls regarding ‘drugs of abuse’ are usually triggered by a serious adverse reaction • No study linking incidence of CPCS calls to general use in the population • Emerging DofA vs. Established DofA California Poison Control System

37. Slang Terms • Triple C’s, CCC • Robo’ing, Robotripping • Skittles, Skittling • DXM, Dex, Dexing California Poison Control System

38. What is Currently Being Done to Curb the Abuse? • Pharmacy Store Chains / Pharmacists • DXM products stored behind the counter • Selected pharmacies - Birthdate prompt at sale • Consumer Healthcare Products Association and The Partnership for a Drug-Free America • Awareness campaign, Educational commercial • Drugfree.org and dxmstories.com • Legislation to limit sale of DXM to minors: • ND, CA, NY, VA • US House of Representatives: H.R. 5280 • DXM Distribution Act -- 109/110 Congress. California Poison Control System

39. Take Home Messages • Dextromethorphan Abuse • Many OTC products contain DXM • Beware hidden ingredients (APAP) • Reasons for DXMF Teenage Abuse • Euphoria, legal, cheap, easily accessible, easy to fool parents. • Many Internet websites promote DXMF California Poison Control System