Critically appraised Topic

Critically Appraised Topic

Appraiser: Eric W. Terman

Date: November 3, 1997

Question: Is there an alternative way to help patients stop smoking aside from nicotine replacement and "going cold turkey?"

Clinical Bottom Lines:

1. There was a significantly increased ability to stop smoking, most of which is not durable.

2. It is most likely that you would need to use the higher doses of 150 or 300 mg per day to have any sustained effect.

Methods/Evidence:

1. Randomized, prospective, placebo-controlled, double blind and dose response trial.

2. Exclusion criteria included: presence or family history of seizure disorder, history of severe head trauma, predisposition to seizures, history or current anorexia nervosa, any unstable medical or psychiatric condition, pregnancy, lactation, history of EtOH or drug abuse, use of tobacco products other than cigarettes, use of nicotine replacement therapy, fluoxetine, clonidine, buspirone or doxepin.

3. Inclusion: Older than 18 years old, smoked on average >15 cigarettes/day, were motivated to stop smoking, and otherwise in good health.

4. Patients were assessed by history and independently by the amount of CO they exhaled.

5. Patients were randomized to placebo, 100mg, 150mg, and 300mg doses of Bupropion SR.

Percent not smoking by time						p-values
time	placebo	100 mg	150 mg	300 mg	overall	plac vs	plac vs	plac vs
	(n=153)	n=153	n=153	n=156		100mg	150mg	300mg
6 wks	19.0	28.8	38.6	44.2	<0.001	0.04	<0.001	<0.001
3 mos	14.4	24.2	26.1	29.5	0.01	0.03	0.01	<0.001
6 mos	15.7	24.2	27.5	26.9	0.06	0.06	0.01	0.02
12 mos	12.4	19.6	22.9	23.1	0.06	0.09	0.02	0.01
NNT for one year		14	9.5	9.3

Cost for each dose for one month at UNC pharmacies vs. cigarettes for a month
dose:	100 mg/d	150mg/d	300mg/d	1pack/d	2packs/d	3packs/d
cost:	$34.05	$35.00	$64.40	$60.00	$120.00	$180.00

Comments:

1. This is a fairly large and well constructed trial, with good follow up.

2. The groups were equal in major areas of interest.

3. Follow-up ends at one year, so we don’t know how long patients will remain smoke free.

4. Presumably there are no deleterious side effects that would increase the death rate from Bupropion, but hard end-points would be nice even though it would take many years to accrue.

5. The cost is significant, as is the cost of taking medication, but in the end probably better than smoking.

6. So from the NNT and the cost we know that if a physician places their patients on the 300 mg dose in order to have one patient stop smoking they need to prescribe it to 9 or 10 people. This costs about $640 for one person to stop smoking for one month. Presumably the physician would not continue to prescribe it for individuals who continue to smoke. For the individual who does stop smoking this is probably worthwhile, particularly since the cost is spread out over many people.

7. Most side effects that resulted in stopping treatment were rash, headache, and tremor.

8. For this to work in a normal office the patient must have a strong desire to stop smoking.

Reference:

Hurt RD, Sachs DPL, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder DR, Glover PN, Sullivan CR Croghan IT and Sullivan PM. A comparison of sustained-release Bupropion and placebo for smoking cessation, NEJM. 1997 337(October 23):1195-1202.