# Presentation: 159833

## Challenges to Effective Medication Use

**February 19, 2003 **
**Richard D. Hurt, M.D.****Professor of Medicine****Director, Nicotine Dependence Center****Mayo Clinic**
**www.mayoclinic.org/ndc-rst**

## 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**

## 46 y/o Neurosurgeon (cont.)

**Admitted for residential treatment, CO=25 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**

## 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.**

## 46 y/o Neurosurgeon (cont.)

**Day 6:**** Improved. Less emotional lability. Appears more relaxed. Still has urges. Doesn’t 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.**

## 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.**

## 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.**

## 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.**

## 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 couldn’t smoke cigarettes anymore**
**Inhaled the pipe smoke from outset**
**3-5 bowls of pipe tobacco per day**

## 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**

## 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**

## Hurt RD, et al. Clin Pharmacol Ther 54:98-106, 1993

**Hurt RD, et al. Clin Pharmacol Ther 54:98-106, 1993**

## Lawson GM, et al. J Clin Pharmacol 38:502-509, 1998

**Lawson GM, et al. J Clin Pharmacol 38:502-509, 1998**

## High Dose Patch TherapyConclusions

**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**

## 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**

## Pharmacotherapy for Tobacco DependenceMultifactoral 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**

## Pharmacotherapy for Tobacco DependenceClinicians

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

## Pharmacotherapy for Tobacco DependencePatients

**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**

## Pharmacotherapy for Tobacco DependencePayers

**Perceived low efficacy**
**Concern about costs – fear of “herd” effect**
**Perception it is the patient’s responsibility – choice and self-quitting**
**Not buying cigarettes should offset cost to patient**

## Pharmacotherapy for Tobacco DependenceTobacco 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**

## Pharmacotherapy for Tobacco DependenceNicotine 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**

## Pharmacotherapy for Tobacco DependenceIdeal 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......**