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..,. .. .. .. .. .. .r a. .. .. ~w .. .. r .. .. .. +.~ ~lr 'Ifie tntetruUonal loumal of the Addktion., 27(6). 6f3-693. 1992 Predictors of Smoking Cessation in a Sample of Italian Smokers Antonio M. Persico, M.D. Drup AddcHon .ne A,bor+oum, tla,+r canak tMfwrslry of th. S.o..d H.+rt Pb&NF*o A. (i.m.fN, Urpo A. Q.mNN d, 00108 Ront., lrtly Abstract In this study we identify several pretreatmenVicharacteristics which pre- dict abstinence at 6 months. Moreover, the persistence of withdrawal dis- comfort and of an increased frequency of night awakenings durin6 the first month of abstinence, together with a tendency to "slip" during Weeks II-IV, strongly predicted relapse. Our results suggest that: 1) Pre- dictors of outcome cannot be automatically extended from one cultural context to another; 2) a careful assessment of certain variables, made while the patient is still under treatment, provides significant prognostic hints; 3) ex-smokers' sleeping and dreaming function has been i6nored by the literature, whereas they may well be Involved into the maintenance of the drug-free state. Key wivrds. Smoking cessation; Predictors of abstinence; Nicotine dependence; Nicotine withdrawal; Dreaming function INTRODUCTION The issue of relapse in the field of smoking cessation has been the object of several studies. In Table / we list a selection of predictors of successful treatment outcome and/or absence of recidivism cited in the literature. In Table 2 we present the relative bibliography, inciudin6 some of the most recent or frequently cited works. CoyyritM O 1992 by Marcel Dekker. lnc. 683 L~TO0Mr1E!

... r .. r r .. ..r ... r. 694 j fit ~~ ~e 9 4 ~i~tlf$i?!~t i6~li(!f9t llSfsEtit~!!s~la " r t: .a ec d :! d .rc PBRSI00 I +.r .. .. .. ... r .M me.r PR81J1(.'I+ORS OF SMOKfNO C13SSATtON IN ITAL/AM SMOKERS T.UIe 2 Evtdww.v on M. Pr.4cdw hbwa o/ tM aw»a LbWin TabM 1 and R.latlw R.l.nrncas (k.m nuvpbas in Colktrnna 2 and 3+» rrhrrad to tabi. 1) PKdklive power (itetn mimber) Aulhor(s) (rer) Atrent or opposite Fresent to expeclNim Barms d Q. (1963) 2,3s,9,14,23 tlenfri ud 8aker (1994) 3.19 1lowees and QAh (1929) 3.6,30 • Buchkrerner e/ at. (19t9) Clmpben et al. (1987) s 1.2 30 oi.ninar et a1. (1988) 22 Hughet N .1. (1986) 22 lacrotx (1972) 1.4,3,9,26,27 2,7,8 Kandel and Davies (1986) 22 Mother.ill et al. (19tq 3,11,10,14,16 7,9,12,13 Pierce el al. (19=9) 1,2 Pomerkar et al. (197s) 3.8,14.17,23 SclneWer (19s) Turn1.11 el.t. (191s) s.l.,is.u 20k 16,21,24,28,29 n Vaw Aeek aed Adrlawre (19Nq 1 rVeN er al. (1977) 1,2s,7,12,17,24,25 17 693 In Italy the idea that "smokin6 can be dangerous to your health" is beEinnin6 to break through. In the wake of public concern, a recent law has imposed, for exam- ple, printed warning statements and nicotine content on cigarette packets. 'Ru Ministry of Health has invited both employers and trade unions to add tobacco smoke to the list of workplace pollutants. Nonetheless, this process is still at an early stage, as evidenced by the general lack of specific smoking cessation pra 6rams. W ithin this context, we have undertaken a study in order to reassess prognostic factors in a sample of Italian srnokers, because they may not be identical, at this ' stage and in our cultural milieu, to those Identified in other countries. Second, we wanted to establish whether the trend of single parameters, such as "cravin6" and "neaative affect," recorded while the patient is still under treatment, has prognostic value, allowing future relapsera to be differentiated from successful abstainers. METHOD The inilial sample included 28 smokers, recruited by the word-of-mouth refer- ral system. They were offered a free smoking cessation program as part of a 8~3=00VM9

606 PERSICO T.Me3 OanrN Charaotrriuks of Ih. Sarrwf. Marh Atim 24 Smokws SuM Drup-Fia. e MaNhs aArr C.ssaUon Eca Me- a" ord range (Vears) ReIlXion Envrasfen/at b.ehpoona 44.5 (2ti-3t) Catholk, 24/24 (100%); practickg, 6/24 (237t,) urMw, as (62.s%) Srbwbsn, 9 (37.37f;) HdreMiaaw Eiknuebry 2 (t.37i) Middle 3 (12.3%) High 14 (511.7111) UWVMNr 3 (20.91i) BenptorweM: t3ire co(isr 7 (29.2S) WUUe coNa 13 (62.3%) . Hawe.rifs 2 (5.3x) M.rifal MMrs: Manied 1ri (73%) Wvaecedbep.nitA 3 (20.ti%) (lr.rr.nied 1 (4.2%) double-blind study on nicotine 6um and were then randomly allocated to form the control group. At the end of the 1-month (reatment proEram, four patients had relapsed into smoking and were excluded from our study. Because of the small number of sub- jects availabk, we decided to focus only on recidivism and to lay aside the Issue of early treatment outcome. The general characteristics of the final sample of 24 sub- jects are listed in Table 3. The items at pretreatment are listed In Table 4. W ith regard to medical history, each patient received a 0-4 point score according to number and severity of iII- rlesses as well as treatments required for their solution. The liktime prevalence of psychiatric disorders was diagnosed according to DSM-111-R criteria (Axis 1). Smokers were not included In the presence of alcohol or substance abuse/depend- ence (other than niootine), schizophrenia, an ongoing acute depressive illness, or any long-term pha.macoloairal treatment. To establish baseline scores, smokers were asked to fill out daily for I week a questionnaire includin= the following items: 12 visual analog scales (range 0-3) measuring nicotine withdrawal according to DSM-111-R criteria (craving, irritabil- ity and an6er, anxidy, difficulty concentrating, restlessrfess, increased appetite), additional DSM-111 criteria dropped in the revised version (headache, drowsiness. gastrointestinal disturbances), and other symptoms listed by Hughes and Hat- sukami (1996) (impatience, increased eating, somatic complaints); a section on sleep, with self-rated quality (visual analog scale, range 0-3), duration, presence PREDK.'1'ORS OF SMOKINO CESSATQON IN iTAUAN SMOKERS 687 Table 4 F'INwbwM CharacNrlstks and Bas.~ Soors of 13 R.faps.rs (54.2%) vs /1 Orup- Fr.e (45.8%) Ex-Smokors (mosn t standard orror of tlw m.an; for h.ms 3. 4. and A: rn.dYan ± Ant.rqvarrfl6c s.nrlditf.rarcr Stud.nr 1-r.st 22 df; X1 1 df) Vatiabk Rehpsets Ilrut-free I. Sea (MJF) 3/f 615 2. Ate (years) 44.31 12.16 44.73 2 2.67 3. Pu1 medical pobkms (range 0-4) 1.61 ±0.66 1.01 ±0.33 4. flesen/ medical probktna (an!e 0-4) 1.06 t 0.4 0.42 ± 0.43 S. Past psyehiMrk hiMory (subjeets) • I 6. Cipseftes/d.y 22.3 ± 2.24 23.2 2 9.3 7. CO levels (ppm) 64.5 2 6.2 39.8 2 7.9 •. Fatetsrrnm score (range 0-11) 6.01 ± 1.37 6.34 ± 1.94 9. Ihnation (years) 211.1) s 2.61 27.3 2 3.06 10. Age of onset 15.5 i 0.ta1 17.5 :r"1.1 • 1/. Reviors faifures 2.13 10.61 2.27 2 1.74 12. Lonsesl drug-Qee period (weeks) 19.1617.17 25.97 123.42 13. Smokers in the fatnilr I I ("kcts) 14. Smoken al wrork 10 7 13. CiXareffe cnvinX (range 0-3) 3.12 t 0.27 3.44 2 0.3 16. Wilhdrawat sympfonu (range 0-60) 9.81 2 1.92 7.32 ± 1.36 17. Heat rate (bea/s/fmin) 78.1 ± 2.39 74.42 t 2.19 IS. Systolic blood pressure (mmHg) 123 ± 4.26 124.6 ± 4.27 19. Diaswlic bfood pesnKe (n+mllt) 65.05 t 3.41 82.36 t 2.41 20. Sleer durMion (h) 7.33 i 0. 17 6.87 t o.bs 21. Ske* quality (range 0-3) 2.34 3 0.1 2.24 ± 0.13 22. t'ercenl of nights with awakenings 28.38 ± 7.91i 22.31 2 2.7 23. Awakeninp/niXM 1.56 2 0.24 1.07 ± 0.03 24. Coffee inrake (eupyday) 3.116 ± 0.6! 139 10. 1s 25. Wlne (gfasusJdaY) 0.79 3 0.37 1.18 2 O_l1 26. (kes (atasses/dar) 0.03 2 0.03 0.06 2 o.a 27. aher .Icoholic beveraRes 0.2110.04 0.42 ± 0.17 Difference Xi - 0.64, N.S. r- 0.12, N.S. U- 1.39, N.S. U - 2.06, p<.03 Fisher. p-.01 r- 0.79, N.S. r- 1.21, N.S. U- 0.78, N.S. r- 0.39. N.S. r- 1.51, N.S. r- 0.14. N.S. r- 0.30, N.S. Fishet, p-.W Fisher, p-.27, N.S. r- 0.11. N.S. r- 0.93, N.S. t- 1.32, N.S. r- 0.08. N.S. r- 0.62, N.S. r- 2.32. p<.02 r- 0.6. N.S. r- 0.49. N.S. r- 2.29, p<.03 r- 06. N. S. r- 0.76, N S. r- 0.14, N. S. r- 0.32. N.S. G~1•OQVMv

!iw w .. r. .. .. ... .. r ... ..r r.~ .. +r. ...~ r r +.~r ~r 680 PERSICO I PREDICTORS OF SMOKINO CESSATION IN ITALIAN SMOKERS 699 and estimated twmber of awakenints, duration of d.ytime naps; and a section on daily Intake of eoffee, wine, beer, and other alcoholic beverages. Patients were trained to measure and report their heart rate, and their skill was tested by the author on several occasions. Finally, they were asked to report the daily number of ciSarettes smoked. A quit date was then established and patients were Instructed to start chewing placebo sums whenever necessary. For I month every patient had to fill out daily the same questionnaire and was weekly reevaluated. At every visit the patient re- eeived a new supply of gum and psychological support, together with behavioral and cognitive htterventions. The 24 ex-smokers were reevaluated at posttreatment 3-Irtonth and 6-month follow-up. A relapse was defined as a smoking rate higher than an average of one ci6a- rette every 2 days and/or CO kvels above 12 ppm In the expired air. Self-reports on cigarette smoking were highly correlated with CO levels In the expired air (r -.91). Statistical analysis was carried out usin6 X2, Fisher, Student r, and Mann-Whitney tests. Point-biserial correlations were made whenever necessary. RESULTS were - Ekven (45.8%) of the 24 ex-smokers abstinent at the end of treatment still drua-free 6 months after quitting. All the pretreatment characteristics and baseline scotes taken into consideration are listed in Table 4. In reference to medi- cal history, psychosornatic syndromes (gastric and/orduocknal ulcer, S.astritis, Irri- table colon, hypettension, cephalalgy) were quite evenly distributed among relap- sers (S/11, 45.5%) and dru6-free (6J13, 46.2%) ex-smokers. On the contrary, smokin6-related disorders (emphysema, chronic bronchitis, cardiovascular heart disease, hypertension, oral or lung cancer) were siEnif icantly present in s(61.5 %) relapsers vs 1(9.1 %) dn/S-free ex-smokers (p -.01) and were almost entirely rep- resented by emphysema and chronic bronchitis. The lifetime prevalence of psychi- atric disorders was clearly hi6heramon6 relapren, with six patients referring past recurrent major depressive episodes, one patient with simple phobia, and another one with generalized anxiety disorder. Only one dru=-free ex-snwker had a history of post-partum depression requiring specific pharmacrdo6ical treatmertt. 1be evolution of sane parameters during the t-month treatment program showed an identical trend, with absolutely no difference between the groups (i.e., decrease in heart rate, systolic/diastolic blood pressta+e, intake of coffee and ako- holic beverages). The other variables evidenced a different evolution, qs presented in Figs. 1-7. tnterestin6ly, six ex-snwkers referred to smoking-related dreams (regarding themselves or other characters snakin6). Five of them were still dru6-free at 6 months, representing 45.5% of the drug-free sample, while only one had relapsed (p -.04). Time did not significantly influence this result, because three ex-smokers tFfS.1. Covins.cones (mean i standud enor of the mean; nnSe O-3).1 bseline and durin= the fint mawh afler.mokinS ceri.tlan. flt. 2. Combioed nicotine wilhdrawal syruplam' scores (range 0-60). (e): /<.I. 09T0Mt9g

r m... .r r. +.. .. .. .. r m r. 090 PiRSIOO f fk S. tt.peM a11.a.nass,, oow6i~M~ MMabi~ry .nA .n*t -tkty. nwlaarw. rd Mep.- Ilewo..oaes. PREDI(.'TORS OF SMOKINO CESSATION IN ITALIAN SMOKERS 691 l1S. S. 3e1f•rtpoAed sleep duntion (nISM sleep • dartimc nap). rp <.03. NIGHTS WITH AWAKENINGS 0 - ~tLAftt~f H ~t00-? ttt 1 0 II !II IT YEEKS ft.1. Mean.ppetile.oare, oombinia3 Yicteawed lawler and eaHnt. /%. G. Percenl.ge of nighis wilh self-reporled awakeninp..:/ <.03. I

•A . M .. .. r .. .. r .. .. .. M .. .. .. .. r .. " $92 tPEtrsaco lREDtCTORS OP SMOKING CESSATION IN iTAt.IAN SMOKERS 693 CUMULATIVE SLIPS to) I1utmIII It - an.ar•tas N /a/C-1at! ly.1 Q..ri.tMAwab.rddpntlsMAOMdAi.MitM~./MsliaaMU.Mrqdttiastie.cA~. <.Ot. t•rl~•t• r referred to having these dreams during Week III and three others during the third month, at a time when mod relapses had not yet occurred. DISCUSSION This study, though based upon a small sample, has yielded Important Initial evidence on several areas of interest. The Ixesenoe of active medical problems, especially if smoking-related, a history of previous psychiatric (affective/anxiety) episodes, and possibly the presenee of smokers In the family predicted relapse at 6 months. This is in accordance with the findings of Bowers and Glttts (1989), Olassrnan et al. (1988). Hughes et al. (1986). Kandel and Davies (1986), and West et al. (1977). Mothetsill et al. (1988) found no evidence of predictive power for the smoking statuz of family tnetnbers, while Campbell et al. (1987) found a trend to- watd higher sdcoess rates among respiratory patients. This latter work was con- ducted on 984 patients of family praditionets, and this design may have strongly h>lfuenoed ib outcome. Much more surprising thatt these findings b the complete lack of predictive power of several variabks which, In previous works„ had demonstrated a signifi- cant weight (a`e,smoking duration and intensity,nwnberofprevianunstccessful attempts, age of onset). Our data, which contradict much of the work listed in Table 2, point strongly toward a"phase" specificity of predictors of outcome In smoking cessation. In other words, during the early phase of antismoking campaitns, a sig- nificant percentage of highly dependent smokets with a long smoking history may be successful at quitting through specific smoking cessation programs not avail- able previously. As time goes on, we may expect a process of selection, which will make our smokers more similar to "hatd-core" smokers prevalent today In coun- tries where antismokin6 campaigns had an earlier starl. The first month of abstinence provided very useful Information on the mid-/ long-term prognosis of the treatment program. Whereas both groups record a gen- eral worsening of their well-being during the first week of abstinence, successful ex-smokers present constant and steady improvement afterwards. On the other hand, except for negative effect, relapsers referred to more Intense discomfort, es- pecially during Week lll, and for several variables they reached a persistent sleady- state which was closer to their smoking baseline level than to the decreasing trend of successful ex-smokers. This result is confirmed by the clear tendency among future relapsers to have single "slips" after Week I(FiB. 7). Before Day 8 there was absolutely no difference between the two groups. Starting from Week II and espe- cially during Week Ill, nine (62.2%) future relapsers could not refnin from slip- ping, whereas no drug-free ex-smoker smoked a single cigarette after Day 8. Data on appetite and withdrawal also suggest that relapsers may have a de- creased tolerance threshold to physical stimuli and discomfort. This is entirely compatible with mockm models of addictive processes, as underlined by Pomer- kau et al. (1978), who found an increased incidence of obesity among smokers with an unsuccessful treatment outcome. y Smoking cessation should be viewed as a process rather than a single event. This process implies a continuous remodeling of ex-smokers' coping responses, dependent upon the interaction between daily life events and the patient's psycho- logical resources. Shiffman (1982) indicated a negative affect as the most frequent psychological correlate of "relapse crisis." A full-blown relapse is not so much the negative affect evoked by specific situations but rather the efficacy of the ex-smok- er's coping style. This depends upon several individual factors which together make up an "interiorized self-1tKrapeutic fundion." The extent to which this func- tion Is intedorized and becomes an integrating part of the ex-smoker's thought processes will determine the efficacy of his coping responses. We hypothesize that the cognitive, affective, and sensitive experiences con- nected with smoking cessation are interiorited during REM sl-ep and actively modify previously established patterns of behavioral response. The efficacy of ex- smoken' coping style may thus depend, among other factors, upon their sleeping and dreaming function. This hypothesis is in accordance with Dewan's and louvet's views on REM sleep and dreaming function (Dewan,1969; louvet,1978), as well as with studies on REM sleep and learning (Smith,198S; Di61i et al.,1987) or cerebral plasticity (Gigli et al., 1987). As shown in Table 3, relapsers seem to sleep longer than abstainers (point- biserial correlation: r- .42 with r- 2.32, 22 df, p<.02). Relapsers' sleep is also more disturbed during the first month of abstinence with regard both to duration (Fia. 5) and to the percentage of nights with awakenings (Fig. 6), which was si8- nificantly higher among future relapsers. Though self-reports on sleep characteris- OT00fM9

W-.. .. .. .. .. .. .. .. .. .. .. M .. .. .. M .. ra . 6% PEItSICO tks ate psttialiy biased (Cuskadon et al.,1976), th..e dNa provkle initial erid«we that, at 1ad in sann niap.ars, sleeping function may be relatively disturbed. Longer sleeping duratiow may be interpreled aa an attempt to comperrate for re- 4 dtx~ed sleeping efficiency. Futthermore, this may partly ezpbin why the Inodifia- tbn of smoking-related cognitive, affective, and behavioral patterns seems to be . Impaired among relapeels (Shiffman, 1982). ., The presenoe of anwking-ie/a/ed dreams should be " signal fhat such a modl- fica(ion is taking place. It Is highly suggestive that smoking-related dreams oc- curred with an elevated itequency in the same period of time (i.e., Week 111) when future relapsers who, with one exception, did not remember makin` such dreams, referred to an increase in cravinE and the frequency of slips. Psychiatrists h.ve long known that /he.ppenauo. of delu.ional ot depnesdre thtMnes in the dnstms of pa- tients with psychotic or affioliw disotdnsi respet:ti.ely, is usually followed by a tapid inlprovemaM of theit clinical conditions. Smokint-ralaled dteatrls may play the same role In smoking cessation (except when possibly functioning as oondi- Noned cues, hwessins craving the following morldn6)., Future research will have to further clarify the chancteristics of Italian smok- ets and of predictive factors In this population. Crofas-cultural studies are needed to provide oomparabie data fwnl diffel+ent settings. Finally, the significance and full implications of the sleeping and dreaming function in smoking cessation should be thorvu6hly investigated REFERENCES tSARNBS.O. t3., VIIt.CANO. S. A...n+ORt3AV6S, L(19fr3). Chu.eleri.lic. a(teetiwt.ucceafui a.*ome (w Ifie eerMiow of smoking. lat !. Aldlct. 20(9k 1429-1434. 13BNPARI, R. C., rtd t3AKER, f3. ( I9i4). 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A., a.d BBROONZI, P. (19t7). 8uloet.wtlde (ry8vjcw..ocMrle.nd MMetilve Iesodo .S .csaians: F/feds uw dSlil .lee, of Du.n.•..yuawwte patienla Skq 1o(6)r 363-369. OLASSMAN. A. H., STETNER, R, rVALSH. T., RAIZMAN. r. s., li.81SS.1. L. COOrFJt. T. B., and COVBY, L. !. (19111). He.vy snwUas,.nwkini ce.rNoa,.ad cioddine../. Aa.. Aled Ar- •.e. s39(19): 2163-2966. Antonio M. Persko received his M.D. from the Catholic University of the Sa- cred Heart, Rome, In 1986. He is em- ployed in the Drug Addiction and Alco- holism Unit at that institution. His prin- cipal interests Include molecular Senet- ics In psychiatry; neurophysioloaical re- sponses to microiontophoretically ap- plied psychoactive substances !n vivo; neurobiology, clinical aspects, dia6no• sis, and treatment of drug dependence and alcoholism; and psychosocial, neuropsychoioaical, and psychophar- macological aspects of AIDS. i d t'REDI(.'hORS OF SMOKING CESSATION IN ITALIAN SMOKERS 695 HUGHES, l. R., ad HATSUfCAMI, D. (19f6). 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HtedMoes otoutcane ud rrcidivisn in.mokiei ce..Mion tKaunenM. Adact te/b.: 3: 63-70. SCHNEIDER. S.1. (19a4).1Niw quits smoking Ma behaviouw.l tteabnetM poSramT Addict QeMr. 9: 373-381. SHfFFMAN, S. (1902). Relapse following smoking cessation: A situdion.l an.lysit l. Conrub. CNk r.rycW 30(1): 71-t6. SMITH, C. (1915). Skep pates and IeaininS: A review on 1he.wimalliterMure. NerroscL S/obeAav. Ittv. 9: 137-168. TUNSTALL, C. D., OINSBERO, D., and HALL, S. M. (19tp). Qdininj -+twlcinS. bu. J. Addkt. 20(6!7): 1019-11 lI. VAN REEK. )., rd ADRIAANSE, H. (19it). CipnNle rnokin: oes.tion rate.6y aex in five weateie cowMries. e.. J. Addkr. 83: 385. W EST, D. rV., ORAHAM. S., S WANSON, M., md NItJCINSON, 0. (1977). PWe year foi{ow-uq ol. rnoklnS withdrawal clinic Popul.lion. Aw. J. Arb!(c Health 67(6): 336-543. THE AUTHOR