ATTUD Journal Club Postings

Changing Treatment in Non‐Responders

A common practice in medicine is to monitor response to a treatment and, if it seems to be inadequate, to increase the intensity or add/change to a new treatment. What is the empirical evidence for such a strategy in treating smokers?

Four studies have tested changing treatment in non‐responders. Two studies found no benefit. One study provided nicotine patch to all smokers (15 mg daytime patch) and randomized them to receive a second patch of 10 mg if they had not stopped smoking or were having difficulty in the first week or to receive a placebo patch (Stapleton et a Addiction 90:31‐42, 1995). The increased dosage of patch did not improve quit rates. The other study examined increasing counseling with failing smokers (Smith et al, JCCP 69:429‐439, 2001.) In this study, all participants received nicotine patch treatment and brief advice. Those that were still smoking after 1 week were randomized to three groups a) another brief advice session or to six 90 minute sessions of b) cognitive, behavioral group treatment or c) motivational interviewing over the next 4 weeks. There were no differences in outcome across these three groups

Three studies have found positive results. One study (Jiminez et al, Mayo Clinic 88:1443‐1445, 2013), placed all patients on the standard 2 mg dose of varenicline. The investigators increased the dose to 3 mg/day in those who had not stopped or were continuing to have “severe withdrawal” but this did not occur until after 8 weeks of treatment. There was no control group, but 43% of those who were doing poorly and had their dose increased were abstinent from weeks 9 to 24 – a much larger success rate than expected. An older study found that increasing nicotine gum from 2 mg to 4 mg gum in those “still smoking” increased quit rates, but when this increase occurred was not clear (Campbell et al, Resp Medicine 85 155‐157, 1991)The fourth study began smokers on nicotine patch prior to the quit date and randomized those who did not reduce CO by 50% to either a) continue patch, b) add buproprion to the patch or c) switch to varenicline (Rose et al, Am J Psychiatry 170:860‐867, 2013) . The study also took those who lapsed after the quit and randomized them to the same three conditions. In those who did not reduce while on patch, receiving bupropion or varenicline increased success. In those who lapsed, those who received varenicline appeared to do somewhat better, but those who received bupropion did not.

In summary, the evidence that increasing or changing treatment in those who are having problems is effective is mixed. The clinician in me thinks that if one had a step‐up treatment that occurred as soon as trouble was detected and was tailored to the specific problem of the smokers (which is what is usually done in practice) this would work. In fact, in the Rose study, the effect of rescue treatment was greater when done prior to a lapse. So maybe we need a study of during‐study tailoring (preferably prior to a lapse) vs no during‐study tailoring, where the tailored treatment is not homogenous but uses insights from the smoker and the skill of the therapist. But this would be a very scary study because if it found this stepped‐up treatment did not work, it would suggest much of what we do in clinical smoking treatment is not effective. But then, that is what good science is about‐putting your cherished ideas to stringent tests.