Challenges to Effective Medication Use

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Challenges to Effective Medication Use

• February 19, 2003
• Richard D. Hurt, M.D.Professor of
  MedicineDirector, Nicotine Dependence
  CenterMayo Clinic
• www.mayoclinic.org/ndc-rst

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46 y/o Neurosurgeon

• Began smoking age 11, currently smokes 20-30 cpd
• Multiple prior attempts to stop cold turkey,
  acupuncture, nicotine patch, hypnosis, bupropion,
  and aversion therapy
• Withdrawal symptoms anxiety, impatient, craving,
  ? appetite, and irritability
• Longest previous smoking abstinence 2-3 days
• Persistent and chronic cough

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46 y/o Neurosurgeon (cont.)

• Admitted for residential treatment, CO25 ppm
• Bupropion 150 bid begun before admission
• Nicotine patch dose 35 mg/d
• Severe cravings and loss of concentrating ability
• Baseline cotinine 621 mg/mL

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46 y/o Neurosurgeon (cont.)

• Day 3 Nicotine patch dose ? to 42 mg/d but still
  had constant low grade urge to smoke. Add
  nicotine gum.
• Day 5 Struggling with withdrawal symptoms and
  emotional lability. ? patch dose to 63 mg/d.
  Steady state cotinine 259 mg/mL.

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46 y/o Neurosurgeon (cont.)

• Day 6 Improved. Less emotional lability. Appears
  more relaxed. Still has urges. Doesnt recall
  very much of the first 3 days after admission.
  She critiqued a video on day 2 but had no recall
  of that. ? nicotine patch dose to 77 mg/d.
• Days 7-8 Comfortable on 77 mg nicotine patch
  dose bupropion 6-10 pieces of nicotine gum/d.

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46 y/o Neurosurgeon (cont.)

• Week 2 Patch dose reduced to 70 mg/d (2 - 21 and
  2 - 14 mg patches) bupropion nicotine gum.
  Some emotional lability.
• Week 8 Symptoms of depression insomnia, loss
  of appetite and some suicidal ideation. She had
  ?d her dose of bupropion to 200 mg/d at week 4.
  Also had ?d nicotine patch dose to 35 mg/d 6
  pieces of nicotine gum/d. Returned to work
  half-time.

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46 y/o Neurosurgeon (cont.)

• Week 13 Her internist had ?d her bupropion dose
  to 450 mg/d and added mitrazapine 60 mg/d. Off
  nicotine patch therapy. 6 pieces nicotine gum/d.
• Week 16 Saw psychiatrist in Rochester. Major
  depression in partial remission.
  Obsessive-compulsive personality traits.
• Weeks 28-40 Begin reducing mitrazapine. Continue
  bupropion 450 mg/d but begin reducing week 32.
  Nicotine gum 4-6/d. Therapy visit with
  psychiatrist every 2 months.

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46 y/o Neurosurgeon (cont.)

• Week 48 Had reduced bupropion to 150 mg/d and
  mitrazapine to 15 mg/d. ? dysphoria and ?
  insomnia ? bupropion to 150 mg/d. Still
  vulnerable to reemergence of significant
  depression.
• Week 52 Bupropion 150 mg BID. Nicotine gum
  1-3/d. Therapy visit with psychiatrist.
• Week 64 Final therapy session with psychiatrist.
  Bupropion 150 mg/d. Mitrazapine 15mg HS. Nicotine
  gum 6/d. Dismissed back to her internist.

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53 y/o WM Executive

• Smoked cigarettes as early as age 5
• 20 cpd until 1991 MI ? CABG x 3
• 3 mos post-MI relapse to smoking cigarettes
• Switched to pipe I knew I couldnt smoke
  cigarettes anymore
• Inhaled the pipe smoke from outset
• 3-5 bowls of pipe tobacco per day

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53 y/o WM Executive (cont.)

• Multiple attempts to stop cold turkey never
  more than a day
• Abstinence with nicotine patch bupropion but
  serious w/d symptoms decreased mood, inability
  to concentrate, anxiety, and craving
• Relapsed during high stress at work
• Admitted for residential treatment Rx bupropion
  21 mg nicotine patch

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53 y/o WM Executive (cont.)

• Persistent anxiety symptoms ? ? patch dose to 2
  - 21 mg patches
• PFT COPD
• Baseline cotinine 516 ng/ml, steady state 265
  ng/ml
• ? patch dose to 3 - 21 mg patches NNS ? less
  anxiety symptoms
• Dismissed on 3 - 21 mg nicotine patch dose
  bupropion ad lib nicotine gum and NNS for crises

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Hurt RD, et al. Clin Pharmacol Ther 5498-106,
1993
13
Lawson GM, et al. J Clin Pharmacol 38502-509,
1998
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High Dose Patch TherapyConclusions

• High dose patch therapy safe for heavy smokers
• Smoking rate or blood cotinine to estimate
  initial patch dose
• Assess adequacy of nicotine replacement by
  patient response or percent replacement
• More complete nicotine replacement improves
  withdrawal symptom relief
• Higher percent replacement may increase efficacy
  of nicotine patch therapy

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Therapeutic Drug Monitoring

• Clinicians recognize limitations of empirical
  dosing (standard or fixed dose regimens)
• Clinical observations have led to individualizing
  patient drug doses
• Allows scientific approach to selecting drug
  regimen to achieve targeted serum concentration
• Serum drug analyses are critical adjunct to
  optimal therapeutic drug utilization

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Pharmacotherapy for Tobacco DependenceMultifactor
al Problem

• Relatively few medications
• Virtually no changes in existing medications
  since introduction
• ONE new medication (nicotine lozenge) introduced
  in past 5 years
• Multiple barriers to use clinicians, patients,
  payers, tobacco industry

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Pharmacotherapy for Tobacco DependenceClinicians

• Lack of familiarity with and understanding of
  existing medications
• Concern about safety overdosing and abuse
  liability
• Perceived low efficacy

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Pharmacotherapy for Tobacco DependencePatients

• Low self-esteem and embarrassment
• Expense
• Inadequate relief of withdrawal and craving
• Concern about safety underdosing and short
  duration of use
• Hard to use products gum, inhaler, nasal spray
• Pharmaceutical marketing focus on competition
  rather than the problem

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Pharmacotherapy for Tobacco DependencePayers

• Perceived low efficacy
• Concern about costs fear of herd effect
• Perception it is the patients responsibility
  choice and self-quitting
• Not buying cigarettes should offset cost to
  patient

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Pharmacotherapy for Tobacco DependenceTobacco
Industry

• Highly sophisticated products and marketing
• Underregulated and politically protected
• Enormous resources and pervasive influence
• Constantly preempting or adapting to public
  health environment
• Morally and ethically bankrupt

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Pharmacotherapy for Tobacco DependenceNicotine
Withdrawal Syndrome

• Needs to be revisited with more scientific vigor
• Spectrum of symptoms is broader than presently
  defined
• Better understanding of neurophysiology of
  withdrawal and craving
• Pharmacotherapy targeted toward withdrawal and/or
  craving

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Pharmacotherapy for Tobacco DependenceIdeal Drug

• High efficacy withdrawal and craving relief,
  tobacco abstinence plus relapse prevention
• Few side effects
• Easy to administer
• Long duration of action
• Positive ancillary effects no weight gain or
  weight loss, improved mood, eliminates wrinkles