Increasing Cessation Increasing Cessation Rates with NRTRates with NRT

Gay SutherlandGay Sutherland

Research & Consultant Clinical PsychologistResearch & Consultant Clinical PsychologistTobacco Research Unit, Institute of Psychiatry,Tobacco Research Unit, Institute of Psychiatry,

King’s College LondonKing’s College London&&

Specialist Smoking Cessation ClinicSpecialist Smoking Cessation ClinicSouth London & Maudsley NHS Foundation TrustSouth London & Maudsley NHS Foundation Trust

ENQ Conference 29ENQ Conference 29thth – 30 – 30thth Jan 2009 (Paris) Jan 2009 (Paris)

NRT Re-Cap: Doubles quit rates of both Doubles quit rates of both

brief and intensive brief and intensive interventionsinterventions

Reduces severity of withdrawal symptomsReduces severity of withdrawal symptoms Delays weight gainDelays weight gain Reduces relapseReduces relapse Gives ~50% nicotine replacementGives ~50% nicotine replacement Very safe (if used by smokers!)Very safe (if used by smokers!)

Efficacy (Odds Ratios) of NRTCochrane 2008

GumGum 1.71.7PatchPatch 1.71.7InhalerInhaler 2.12.1Nasal SprayNasal Spray 2.52.5

Microtab/LozengeMicrotab/Lozenge 2.12.1

Consistency of NRT Efficacy(Cochrane 2008)

111 RCTs111 RCTs

22,732 smokers 22,732 smokers

106 of 111 showed positive 106 of 111 showed positive

resultsresults

NRT Re-Cap: Reduces severity of Reduces severity of

withdrawal symptoms and withdrawal symptoms and craving to smokecraving to smoke

Schematic Diagram of Smokers Nicotine Levels

Morning Afternoon Evening

ToxicToxic

OptimalOptimal

WithdrawalWithdrawal

Blo

od N

icotine

Leve

l

Dose of NRT needs to be in this range

NRT Re-Cap: Doubles quit rates of both brief and Doubles quit rates of both brief and

intensive interventionsintensive interventions Reduces severity of withdrawalReduces severity of withdrawal

Delays weight gainDelays weight gain Reduces relapseReduces relapse Gives ~50% nicotine Gives ~50% nicotine

replacementreplacement Very safe (if used by smokers!)Very safe (if used by smokers!)

But nothing like a But nothing like a cigarette!cigarette!

0 10 20 30 40 50 60

Time (mins)

0

5

10

15

20

25

30

Pla

sma

Nic

otin

e (

ng

/ml)

Comparison of Plasma Nicotine LevelsFollowing a Cigarette and the NRT Products

Cigarette

Nasal Spray

Gum / Inhaler / Tablet

Patch

Gay Sutherland, Maudsley Smokers Clinic

Common False Common False Beliefs About NRTBeliefs About NRT

Cummings (2004)

Common False Beliefs About Common False Beliefs About NRT We Need to AddressNRT We Need to Address

Cummings (2004)

What % think NRT What % think NRT does not increase does not increase quit rates?quit rates?

4141%%

Common False Beliefs About Common False Beliefs About NRT We Need to AddressNRT We Need to Address

Cummings (2004)

What % think risk of What % think risk of addiction with the patch addiction with the patch is as high or higher than is as high or higher than for cigarettes?for cigarettes?

5454%%

Common False Beliefs About Common False Beliefs About NRT We Need to AddressNRT We Need to Address

Cummings (2004)

What % think risk of What % think risk of heart attacks from the heart attacks from the patch is as high or patch is as high or higher than for higher than for cigarettes?cigarettes? 6565

%%

Common False Beliefs About Common False Beliefs About NRT We Need to AddressNRT We Need to Address

Cummings (2004)

What % think What % think nicotine causes nicotine causes cancer?cancer?

6767%%

Public Perception of NRTPublic Perception of NRT US national survey, 3,203 current US national survey, 3,203 current

and former smokersand former smokers 66% agreed that ‘66% agreed that ‘NRT is just as NRT is just as

harmful as cigarettesharmful as cigarettes’ or were ’ or were unsure if trueunsure if true

Less likely to use NRT and if used, Less likely to use NRT and if used, used less and for shorter timeused less and for shorter time

Public education needed – how to Public education needed – how to do it?do it?

Shiffman et al. 2008, Addiction 103, 1371-1378Shiffman et al. 2008, Addiction 103, 1371-1378

NRT efficacy is harmed by:NRT efficacy is harmed by: Unrealistic expectations (‘magic Unrealistic expectations (‘magic

cure’, waiting for the drug to cure’, waiting for the drug to ‘make me stop smoking’)‘make me stop smoking’)

Insufficient and incorrect use (fear Insufficient and incorrect use (fear of nicotine, using only when of nicotine, using only when desperate)desperate)

Lack of preparation for the fact Lack of preparation for the fact that oral products in particular that oral products in particular may take time to get used tomay take time to get used to

John Stapleton (2008)John Stapleton (2008)

Since NRT was introduced 30 years ago its full potential has remained underdeveloped and under-researched

Licence say:• Start using NRT on day smoking stops;• Use a limited dosage while not smoking• Stop using NRT if smoking resumes• Use for only 10–16 weeks, regardless of

progress!

Addiction (2008)

One Size Does Not Fit All!One Size Does Not Fit All!

Can we do Can we do better with better with

NRT?NRT?

Better Ways of Using NRTBetter Ways of Using NRT

Pre-Treatment before Quit Pre-Treatment before Quit Day?Day?

Combination NRT?Combination NRT?

Use Higher Doses?Use Higher Doses?

Use During a Lapse or “Slip”?Use During a Lapse or “Slip”?

Adapted from Hughes (2008) UKNSCC

Possible Rationale?Possible Rationale?

Improve efficacy by separating Improve efficacy by separating nicotine levels from smoking nicotine levels from smoking and thus extinguishing and thus extinguishing smoking reinforcementsmoking reinforcement

Help smokers cut-down and Help smokers cut-down and increase their confidence in increase their confidence in quittingquitting

Might get smokers used to NRTMight get smokers used to NRT

NRT Use Prior to QuittingNRT Use Prior to Quitting Meta-analysis of 4 studies Meta-analysis of 4 studies Pre-treatment with patches for 2 Pre-treatment with patches for 2

weeks (3 studies) or 4 weeks (1 study)weeks (3 studies) or 4 weeks (1 study) 6-months abstinence OR=2.26-months abstinence OR=2.2 But: But: 3 studies by the same author3 studies by the same author 4-week pre-treatment was the only 4-week pre-treatment was the only

study with negativestudy with negative results results

Shiffman and Ferguson (2008) Addiction, 103,Shiffman and Ferguson (2008) Addiction, 103,

Better Ways of Using NRTBetter Ways of Using NRT

Pre-Treatment before Quit Day?Pre-Treatment before Quit Day?

Combination NRT?Combination NRT?

Use Higher Doses?Use Higher Doses?

Use During a Lapse or “Slip”?Use During a Lapse or “Slip”?

Adapted from Hughes (2008) UKNSCC

Rationale for Rationale for Combination NRT?Combination NRT?

Patch gives steady Patch gives steady levels of nicotine easily levels of nicotine easily plus oral “top-ups” when plus oral “top-ups” when neededneeded

Likely to lead to higher Likely to lead to higher nicotine replacement nicotine replacement levelslevels

35

30

25

20

15

10

5

0

Cues or “Triggers” to SmokeCues or “Triggers” to Smoke

Tea/CoffeeTea/Coffee

ConcentratioConcentrationn

RewardReward

DrivingDriving

(Time) (Time) HabitHabit

Daily EventDaily Event After a After a mealmeal

SocialSocial(peer (peer

pressure)pressure)

TelephoneTelephone

StressStress

BoredomBoredom

AlcoholAlcohol

Central Role of CravingCentral Role of Craving

““Background”Background” cravingcraving:: Steady during the daySteady during the day Internal - needs no environmental triggersInternal - needs no environmental triggers Gradually reduces in intensity over a few weeksGradually reduces in intensity over a few weeks

““Episodic”Episodic” cravingcraving:: Occasional intense burstsOccasional intense bursts Triggered by environmental cues or moodTriggered by environmental cues or mood Decreases in frequency but NOT intensity for monthsDecreases in frequency but NOT intensity for months Caused by being in situations ex-smoker has not yet Caused by being in situations ex-smoker has not yet

got “habituated” togot “habituated” to

PatchPatch

Faster Self-D

osed NRT

Faster Self-D

osed NRT

Usually patch + Usually patch + faster self-faster self-administered productadministered product

7 trials included in 7 trials included in Cochrane review Cochrane review show overall benefit show overall benefit (OR=1.42)(OR=1.42)

Combining 2 Different NRT’s

Silagy et al. (Cochrane Library) Silagy et al. (Cochrane Library)

0

2

4

6

8

10

12

14

16

18

Single NRT CombinationNRT

% Q

uit

>6

mon

ths

What time of day do people relapse? (%) Brandon et al 1986

0

5

10

15

20

25

30

35

2.00am-11.00am

11.00am-1.00pm

1.00pm-5.00pm

5.00pm-8.00pm

8.00pm-2.00am

NICE Endorses NICE Endorses Combination TherapyCombination Therapy

‘‘Consider offering a Consider offering a combination of nicotine combination of nicotine patches and another form of patches and another form of NRT… to people who show a NRT… to people who show a high level of dependence on high level of dependence on nicotine or who have found nicotine or who have found single forms of NRT single forms of NRT inadequate in the past.’inadequate in the past.’

This meeting is sponsored GlaxoSmithKline Consumer Healthcare [NCQ/CW/0608/005]

Feb 2008Feb 2008

……Craving predicts Craving predicts who is most likely who is most likely

to relapse….to relapse….

0 1 2 3 4

Craving Score After 1 Week

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Lik

elih

oo

d o

f R

elap

seCraving After 1 Week of Abstinence

and Relapse by 3 MonthsStapleton et al (1995) n=1200

Bars=95% CI

Essential to get good Essential to get good craving relief early on craving relief early on

in the quit attemptin the quit attempt

Quitting early matters!Quitting early matters! Cease Trial: 25% of smokers abstinent in Cease Trial: 25% of smokers abstinent in

their 1their 1stst week stayed quit for 1 yr vs only week stayed quit for 1 yr vs only 2.7% of those who smoked in 12.7% of those who smoked in 1stst week week

A Patch study of 1,686 smokers also found early quitting the strongest predictor of sustained abstinence

Of the 1st week quitters, 25% of those on NRT and 28% on placebo became long-term quitters vs only 4% (NRT) and 2% (placebo) if they smoked in the 1st week

Another study of 1,200 smokers found all but 1 of the 96 subjects who quit long-term, had quit during their 1st week

Better Ways of Using NRTBetter Ways of Using NRT

Use it for Longer?Use it for Longer?

Pre-Treatment before Quit Day?Pre-Treatment before Quit Day?

Use Higher Doses?Use Higher Doses?

Use During a Lapse or “Slip”?Use During a Lapse or “Slip”?

Adapted from Hughes (2008) UKNSCC

European Respiratory Journal (1999)European Respiratory Journal (1999)

Higher Higher DDosesoses of NRT for of NRT for Greater % Nicotine Greater % Nicotine

Replacement? Replacement?

European Multi-Centre CEASE European Multi-Centre CEASE TrialTrial RCT to see if higher dose and longer duration of use RCT to see if higher dose and longer duration of use

of 16hr daytime-only patches increase quit ratesof 16hr daytime-only patches increase quit rates 36 chest clinics in 17 countries36 chest clinics in 17 countries 3,575 smokers took part (>14 cigs per day)3,575 smokers took part (>14 cigs per day) Smokers randomized to 1 of 5 groups: Smokers randomized to 1 of 5 groups:

25mg patch (15 + 10mg) for 22 wks - 15mg for 2 wks - 10mg for 2 wks

25mg patch (15 + 10mg) for 8 wks - 15mg for 2 wks - 10mg for 2 wks -14 wks of placebo patches

15mg patch + placebo for 22 wks - 10mg for 4 wks 15mg patch + placebo for 8 wks - 10mg for 4 wks - 14 wks of

placebo patches 2 x placebo patches for 26 wks

Smokers also received behavioural supportSmokers also received behavioural support

High dose

Standard dose

Placebo

CEASE Trial ResultsCEASE Trial Results1 yr sustained quit rates were: 1 yr sustained quit rates were:

High dose long duration = 15.4%High dose long duration = 15.4% High dose standard duration = 15.9%High dose standard duration = 15.9% Standard dose long duration = 13.7%Standard dose long duration = 13.7% Standard dose standard duration = 11.7%Standard dose standard duration = 11.7% Placebo = 9.9% Placebo = 9.9% No sign. difference in quit rates between long No sign. difference in quit rates between long

and standard duration patch useand standard duration patch use

High dose patches increased long-High dose patches increased long-term quit ratesterm quit rates

But no advantage in using for longer But no advantage in using for longer than 8-12 weeksthan 8-12 weeks

Higher nicotine doses Higher nicotine doses also gave better relief also gave better relief of tobacco withdrawal of tobacco withdrawal

symptomssymptoms

0 1 2 3 4 5 6 7 8

Weeks After Start of Treatment

-0.5

0.0

0.5

1.0

1.5

Adv

erse

Moo

d (c

hang

e fr

om w

k 0)

15mg patch25mg patch

Placebo

p<0.05

p=0.2

p<0.001

p=0.001

Adverse Mood Tobacco Withdrawal SymptomsCEASE Trial (Tonnesen et al 1999)

CEASE Trial - SafetyCEASE Trial - Safety

Higher doses were well Higher doses were well tolerated tolerated

Side-effects were mild and Side-effects were mild and typical of NRT (eg skin typical of NRT (eg skin irritation)irritation)

No unexpected or serious No unexpected or serious adverse eventsadverse events

Higher Doses or TailoringHigher Doses or TailoringNRT NRT (Cochrane 2008)(Cochrane 2008)

Higher Doses of Patch:Higher Doses of Patch:7 trials = 1.2 (OR)7 trials = 1.2 (OR)

Tailoring Dose to Blood Tailoring Dose to Blood Levels:Levels:

2 small trials both report 2 small trials both report improvementimprovement

The Implications?The Implications?

A 25mg/16 hr patch will soon be A 25mg/16 hr patch will soon be launched in some European launched in some European countriescountries

Many clinicians are too cautious Many clinicians are too cautious about dosingabout dosing

SPCs for NRT usually have cut-offs SPCs for NRT usually have cut-offs based on cigs/day which are unduly based on cigs/day which are unduly conservative and not supported by conservative and not supported by the evidencethe evidence

Better Ways of Using NRTBetter Ways of Using NRT

Use it for Longer?Use it for Longer?

Pre-Treatment before Quit Day?Pre-Treatment before Quit Day?

Use Higher Doses?Use Higher Doses?

Use During a Lapse or Use During a Lapse or “Slip”?“Slip”?

Adapted from Hughes (2008) UKNSCC

Importance of Continuing NRT Importance of Continuing NRT During a Lapse or “Slip”During a Lapse or “Slip”

(Shiffman 2006)(Shiffman 2006)

Prevention of a lapse or Prevention of a lapse or slip to full relapse = 7.1slip to full relapse = 7.1

Lapse RecommendationsLapse Recommendations

Keep using NRT!Keep using NRT!

Increase Dose of PatchIncrease Dose of Patch

Increase Dose of Acute Increase Dose of Acute NRTNRT

Add a 2Add a 2ndnd NRT NRT

John Hughes 2008

Bottom LineBottom Line Max effort early on. Get good NRT Max effort early on. Get good NRT

dosing from the beginningdosing from the beginning Be flexible - switch NRTs if smoker Be flexible - switch NRTs if smoker

prefersprefers Use combinationsUse combinations Use higher dosesUse higher doses Continue with NRT during lapsesContinue with NRT during lapses Most important - keep re-treating Most important - keep re-treating

“failures”!!!“failures”!!!

John Hughes (2008 UKNSCC)John Hughes (2008 UKNSCC)

““Using NRT via guidelines is Using NRT via guidelines is suboptimalsuboptimal treatment and treatment and should be should be discourageddiscouraged””

““Allowing fear of complaints Allowing fear of complaints or lawsuits to prevent optimal or lawsuits to prevent optimal care is care is unethicalunethical””