1. WADA’s Prohibited Substance List: A Psychiatric Perspective 15 th FINA World Sports Medicine Congress Indianapolis, October 12 th, 2004 Presenter – Saul I Marks, M.D. Toronto, Ontario, Canada

2. Goals Consistency in Doping Control is paramount Is there consistency with the “Psychotropic Medications”? Consistency with Therapeutic Use Exemption Continuing review of “Psychotropic Medications” is needed

3. Drug Classification Psycho-stimulants The sedative-hypnotics and alcohol The anti-depressants Analgesics, anti-psychotics and the mood stabilizers

4. Attention-Deficit Disorders Attention-deficit/hyperactivity disorders (ADHD), inattentive type, hyperactive- impulsive type, combined type 3-5% of children and adolescents 2-3 times more prevalent in males then females Most common reason for children to be referred to mental health services DSM - IV

5. Etiology Many variable studies Involvement of both the dopaminergic and catechoaminergic systems Mesolimbic system involved in hyperactivity, prefrontal cortex involved in symptoms of inattention and impulsivity. Beh and Brain Res, 130 (2002) 65-71

6. Treatment First-line treatment are Methylphenidate and Dextroamphetamine Side effects– sleeplessness, appetite suppression, weight loss and emotional lability Side effects controlled by decreasing the dose Prohibited Substance Therapeutic Use Exemption? Consistency and guidelines Int J Sports Med 2003; 24: 535-540

7. Guidelines Proper documentation History of ADHD and meet criteria for the disorder Symptom control on stimulant therapy Documented evidence of response by rating scale Treatment reviewed regularly, yearly? Relapse off of treatment

8. Sedative-Hypnotics and Alcohol Very few studies, older studies, although alcohol is banned in particular sports and not in others (banned in gymnastics, not in diving) Limited studies with benzodiazepines and newer agents Many questions remain regarding performance and these agents with different half-lives, and the newer agents zolpidem and zopiclone One study showed longer acting benzo caused morning drowsiness and decreased psychomotor performance vs. zopiclone

9. Further Research? Could short-acting sedative-hypnotics, and/or newer agents aid sleep night before performance and enhance performance? Could longer-acting benzodiazepine help performance in low dose or in tolerant person? Consistency regarding alcohol as a prohibited substance Cl Jour Sport Med, 10; 123-128, 2000

10. Antidepressant Classes Monoamine oxidase inhibitors Tricyclic antidepressants Selective serotonin reuptake inhibitors Serotonin-norepinephrine reuptake inhibitor – BUPROPION Alpha-2 antagonist - mirtazapine Serotonin antagonist/reuptake inhibitor - nefazadone

11. Bupropion Increases levels of both dopamine and norepinephrine, similar to stimulants? Second-line agent in treatment of ADHD along with Venlofaxine Does Bupropion warrant further investigation as a potential ergogenic agent? Consistency

12. Analgesics, anti-psychotics and the mood stabilizers Codeine is a permitted substance, morphine is prohibited Codeine is metabolized to morphine in the liver - ? Consistency? In prohibited substance list? Anti-psychotics need to be classed alone (tendency to be forgotten as a separate class of drugs?) Mood Stabilizer – Topiramate – weight loss agent of abuse in the literature, out of competition use?

13. Summary TUE in Attention Deficit Disorder Sedative-Hypnotics and Alcohol deserve further evaluation Bupropion deserves further evaluation

14. Questions?

15. QUESTIONS? /