ADHD treatment with Amphetamines

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Amphetamine is a stimulant that is primarily used to treat narcolepsy and attention-deficit hyperactivity disorder. It is also used recreationally as a club drug and as a performance enhancer.

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ADHD treatment with Amphetamines

  1. 1. Treatment ? Drug companies say that a pill is the cure, but pills don’t teach skills and may make addicts ill!
  2. 2. Why not use stimulants?
  3. 3. Description • Amphetamine is a stimulant that is primarily used to treat narcolepsy and attention-deficit hyperactivity disorder. It is also used recreationally as a club drug and as a performance enhancer. • Prescription amphetamines are subject to diversion and are one of the most frequently- abused drugs in high schools and colleges. • A Schedule II drug is classified as one that has a high potential for abuse, has a currently-accepted medical use under severe restrictions, and has a high possibility of severe psychological and physiological dependence. HO HO NH2 OH Norepinephrine (Noradrenaline) NH2 Amphetamine CH3 NHCH3 Methamphetamine CH3 Methylphenidate (RitalinTM) H N O O Me
  4. 4. 0 100 200 300 400 500 600 700 800 900 1000 1100 0 1 2 3 4 5 hr Time After Amphetamine %ofBasalRelease DA DOPAC HVA Accumbens AMPHETAMINE 0 100 200 300 400 0 1 2 3 4 5 hr Time After Cocaine %ofBasalRelease DA DOPAC HVA Accumbens COCAINE 0 100 150 200 250 0 1 2 3 4 5hr Time After Morphine %ofBasalRelease Accumbens 0.5 1.0 2.5 10 Dose (mg/kg) MORPHINE 0 100 150 200 250 0 1 2 3 hr Time After Nicotine %ofBasalRelease Accumbens Caudate NICOTINE Di Chiara and Imperato, PNAS, 1988 Effects of Drugs on Dopamine Release
  5. 5. Would these responses differ between controls and addicted subjects? CA PUT Striatum VTA/SN CG PreF OFC nucleus accumbens Would increasingDA enhance activity in the OFC? Compared the response to IV MP (methylphenidate given in 2 sequential doses of 0.5 and 0.25 mg/kg) in 15 controls and 21 cocaine abusers using FDG and PET to measure regional brain glucose metabolism
  6. 6. 0 2 4 6 8 10 Controls Abusers baseline First MP Second MP SelfReportCraving (0-10) 0 2 4 6 8 10 Controls Abusers SelfReportHigh (0-10) Self Reports of Drug Effects After MP in Controls and in Cocaine Abusers P < 0.001 P<0.001
  7. 7. MP-induced Increases in Metabolism OFC 1.00 1.05 1.10 1.15 1.20 1.25 1.30 Controls Abusers Baseline MP RectalGyrus/Brain -4.0 -2.0 0.0 2.0 4.0 6.0 8.0 10.0 -0.2 -0.1 0.0 0.1 0.2 0.3 Craving RectalGyrus (MP-Placebo) p < 0.005 Abusers > Controls p = 0.001 p < 0.01
  8. 8. How Much of the Differences Between Controls and Cocaine Abusers Reflect their Past Experience with Drugs? Effects of Expectation on the Brain Metabolic Responses To iv MP in Cocaine Abusers Source: Volkow, ND et al., Journal of Neuroscience, 23, pp. 11461-11468, December 2003.
  9. 9. Effects of Expectation on the Response to MP on Brain Glucose Metabolism and Behavior Increases in Metabolism Were About 50% Larger When MP Was Expected Than Unexpected “High” Was About 50% Greater When MP Was Expected Than Unexpected 0 2 4 6 8 10 Pl/PL PL/MP MP/MP MP/PL FeelDrug 0 2 4 6 8 10 Pl/PL PL/MP MP/MP MP/PL High 0 2 4 6 8 10 Pl/PL PL/MP MP/MP MP/PL LikeDrug 0 2 4 6 8 10 Pl/PL PL/MP MP/MP MP/PL Restlessness 0 5 10 15 20 25 30 %Change Source: Volkow, ND et al., Journal of Neuroscience, 23, pp. 11461-11468, December 2003.
  10. 10. Where the Rubber Meets the Road Data from Dr. Lloyd Gordon from the treatment of patients at COPAC Information obtained from CAPTASA 2012 website • Two interviewers had to agree with diagnosis (MD, PhD, PNP) • Hx of stimulant abuse not exclusionary unless DOC • Initial poor outcomes on Adderall led to switch to “safer” drugs (e.g. Concerta, Vyvanse) • One psychiatrist did all med. adjustments • Inclusion – No discussion on unit – 1 year enrollment in treatment – Leaving treatment meant no follow-up from providers – 1+ prior CD treatments • All had CBT manually/workbook driven and special groups with psychiatrist and psychiatric NP • Behavioral problems resulted in one verbal warning, then behavioral contract, then discharge • N=43 • Ages 18-55
  11. 11. AGE DISTRIBUTION CONTROL VS STIMULANT 19 10 8 2 22 12 7 2 0 5 10 15 20 25 18-25 26-35 36-45 46-55 CONTROL STIMULANT
  12. 12. RELAPSE AND LOST TO FOLLOW UP FOR STIMULANT TREATMENT OF ADHD BY QUARTER 100%(43/43) 2 13 8 1 3 10 5 1 0 2 4 6 8 10 12 14 0-3 4-6 7-9 10-12 RELAPSE LOST TO FOLLOW UP
  13. 13. Results and Conclusions of COPAC Study • 100% (43/43) participants were relapsed and/or lost to follow-up. • 31% of controls (12/39) relapsed and/or were lost to follow-up • Only 25% of the stimulant group had abused stimulants in the past • There were many more behavioral discharges in the stimulant vs. control groups though the disease severity was equal. (Some of the control group participants were given Welbutrin or Clonidine. Strattera was not available at the time of the study.) • Stimulants do not work in the 1st year of treatment.
  14. 14. The Benefits of Recovery • Living in the solution – One day at a time, easy does it, first things first, keep it simple – Acceptance – Utilize tools such as smart phones – Delegate – View the energy and creativity as wonderful gifts – Consider safe medications, but don’t expect to be “normal” (False expectation of stimulants as cure.)

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