pSYCHIATRY

How to treat nicotine dependence in smokers with schizophrenia

Improve patients’ health, help them kick addiction with this practical approach

r. V, age 49, has stable but ®symptomaticDowden Health Media schizophrenia and a 33-year cigarette Mhistory. He is very concerned because his primary care physicianCopyright told him heFor has personal2 serious use only smoking-related health problems: diabetes and hypertension. He tried a smoking cessation program for the general public, but it was a poor fit because of his schizophrenia symptoms. Despite adhering to his (ziprasidone, 20 mg hs; perphenazine, 8 mg hs; lorazepam, 1 mg hs; zonisamide, 200 mg/d, and benztropine mesylate, 2 mg hs), Mr. V has residual auditory hallucinations, paranoid ideation, and impaired concentration and attention. He

smokes approximately 1.5 packs per day, particularly when VEER.COM

very ill, to alleviate chronic boredom, and to diminish 2007 © distress from the hallucinations. All of his friends smoke, and they do not support his attempts to quit. Jennifer D. Gottlieb, PhD Schizophrenia clinical and research program Massachusetts General Hospital Successfully treating nicotine dependence can seem a Instructor in psychiatry formidable challenge in patients with schizophrenia: Harvard Medical School • 72% to 90% smoke cigarettes, compared with 21% A. Eden Evins, MD, MPH of the general population1 (Box, page 66).2-12 Schizophrenia and depression clinical and research programs • They tend to smoke heavily, spending about one- Director, Center for Addiction Medicine third of their incomes on cigarettes.13 and addiction research program • Their negative symptoms (such as apathy), posi- Massachusetts General Hospital Assistant professor of psychiatry tive symptoms (such as disorganized thinking), Harvard Medical School and cognitive impairment can reduce motivation to quit and adhere to a smoking cessation strategy. • Sociologic and physiologic aspects of schizophrenia reinforce their smoking habit (Table 1, page 69).9,12,14-17 Current Psychiatry Even so, smokers with schizophrenia can be highly Vol. 6, No. 7 65

For mass reproduction, content licensing and permissions contact Dowden Health Media. Box • 4% to 19% after 3 to 6 months with bupropion or NRT and CBT Obstacles to smoking cessation 20-23 for schizophrenia patients • ≤6% with placebo and CBT.

mokers with schizophrenia are more nicotine- Multifaceted interventions. High- Sdependent, more likely to become medically dose NRT patch treatment (2 patches ill, and less likely to receive help in quitting, at a time) has not consistently shown Nicotine compared with the general population. They: additional benefi ts compared with dependence • begin smoking at a higher rate before single-patch treatment.24,25 However, diagnosis or treatment for schizophrenia, combining short-acting NRT (gum, compared with persons who do not go on lozenge, , or ) with to develop the disorder2 a long-acting NRT preparation (trans- • smoke each cigarette more intensely, extracting more nicotine per cigarette3-5 dermal patch) is well-tolerated and • have higher rates of smoking-related illness has been shown to improve sustained and medical morbidity6 abstinence rates26 (Table 2, page 70). • are much less likely to receive physician In a double-blind, placebo-con- Clinical Point advice to quit smoking.7 trolled trial,27 51 smokers with schizo- Using Many persons with severe mental illness phrenia were randomly assigned to are misinformed about the risks and nicotine replacement receive combination NRT (21-mg NRT benefi ts of smoking vs nicotine dependence patch plus ≤18 mg/d NRT polacrilex 8 plus a short-acting treatment. They often fear and overestimate gum prn) added to bupropion SR, 150 the medical risks of nicotine replacement form (gum, lozenge, mg bid, or placebo. Smoking cessa- therapies.9 Many believe smoking relieves tion—defi ned as quitting on the as- inhaler, or nasal depression and anxiety,10 whereas nicotine signed date and maintaining continu- spray) may improve actually is anxiogenic. Nicotine may improve ous abstinence for 4 weeks (measured sustained abstinence some aspects of cognitive dysfunction in schizophrenia, which could be a disincentive by expired air carbon monoxide <9 for patients to quit smoking.11,12 ppm and self-report of abstinence at weekly visits)—was achieved by: • 52% of those receiving bupropion motivated and persistent in attempting to and dual NRT quit.18 Promising results have been reported • 19% who received placebo and in trials when psychopharmacologic treat- the 2 forms of NRT. ments are combined with cognitive and be- havioral interventions. Preventing relapse. Relapse is common This article reviews these empiric stud- among all smokers but especially in those ies and suggests practical ways for cli- with schizophrenia. In clinical trials, 70% nicians to create smoking cessation and to 83% of smokers with schizophrenia who relapse prevention plans for individuals attained abstinence relapsed to smoking with schizophrenia. within 6 to 12 months of stopping nicotine dependence treatment.21,22,27,28 In one clinical trial, >50% of patients Clinical trials of smoking cessation achieved 4 weeks of continuous abstinence Inadequate interventions. Convention- on a regimen of bupropion SR, 150 mg bid; al regimens—consisting of 8 to 12 weeks (21 mg/d); and as-needed with sustained-release bupropion or nico- nicotine gum (≤18 mg/d). However: tine replacement therapy (NRT) added to • 31% relapsed to smoking while NRT supportive or cognitive-behavioral thera- was being tapered from ~40 to 20 mg/d py (CBT)19—are well-tolerated by patients • 77% relapsed after nicotine depen- with schizophrenia but only modestly ef- dence treatment was discontinued.27 fective. CBT alone (or with placebo) has Longer use of pharmacotherapy may be not been effective for smoking cessation needed to prevent relapse to smoking in in schizophrenia. In clinical trials, absti- the schizophrenia population. In a recent Current Psychiatry 66 July 2007 nence rates have been: open case series, 17 of 42 smokers with continued on page 69 continued from page 66 schizophrenia were able to quit Table 1 for at least 2 weeks with a combi- Why up to 90% of schizophrenia pSYCHIATRY nation of bupropion SR, 150 mg patients smoke cigarettes bid, and dual NRT. Among those CurrentPsychiatry.com Sociologic barriers to quitting who quit, 13 (76%) remained ab- stinent for 12 additional months • Their social groups often include a high percentage when offered continued phar- of heavy smokers macotherapy and tapering CBT • Some fear NRT is ‘unhealthy,’ causes cardiac arrest, or increases nicotine cravings9 (see Table 2, page 70, (AE Evins, under review). for an accurate NRT side effect profi le) • They are unlikely to achieve sustained abstinence CASE CONTINUED from a single cessation attempt Treating nicotine dependence Mr. V cut down to 10 cigarettes a Physiologic reinforcers and disease factors day during a 4-week motivational • Nicotine may modulate schizophrenia’s cognitive enhancement/psychoeducation dysfunction, including sensory gating (a measure of intervention for smokers with ability to fi lter out irrelevant environmental stimuli) and 12,14 major mental illness.29 He then attention Clinical Point • Nicotine may increase disease-associated reduction enrolled in a 12-week study in in nicotinic acetylcholine receptor activity15,16 For patients taking which subjects received high- • Smoking (but not nicotine) reduces antipsychotic clozapine, reduce dose dual NRT and bupropion SR blood levels by increasing metabolism and may the dose by 10% in or placebo. reduce side effects of antipsychotic medications17 Mr. V was reluctant to use the • Schizophrenia’s cognitive impairment can make the fi rst 4 days of NRT patch because he believed smoking cessation strategies diffi cult to follow abstinence; monitor rumors that it could cause a heart for the need to make attack, especially if he smoked while using a patch. He did try the patch, 1A2, and the half-life of this reduction is further reductions however, after his clinicians informed him it 27 to 54 hours. Thus, therapeutic would increase his chances of quitting. monitoring and dose reduction of 10% He received bupropion SR, 150 mg bid; over the fi rst 4 days of tobacco abstinence NRT patch, 21 mg/d; and nicotine polacrilex is recommended to avoid toxicity. If the gum, up to 18 mg/d as needed, and patient remains abstinent from tobacco, tolerated the regimen well. After 4 weeks, further reducing the antipsychotic dose he quit smoking on the quit date. His blood may be warranted, based on individual pressure—monitored weekly for the fi rst assessment. month then monthly thereafter—remained stable throughout the intervention. Weight gain. Patients who quit smoking gain an average of 3 to 5 kg.30

Prescribing considerations Nicotine withdrawal. Patients are used to Metabolic changes. Smoking—but not thinking that nicotine is calming, whereas NRT—induces hepatic clearance of many in reality nicotine and smoking are anx- psychotropics, and smoking cessation iogenic, and cigarette smoking alleviates can be associated with increased drug se- the anxiety that comes from nicotine with- rum levels. Polycyclic aromatic hydrocar- drawal.31 Educate patients about nicotine bons present in cigarette smoke—but not withdrawal symptoms, which easily can NRT—induce hepatic aryl hydrocarbon be confused with early signs of a psychotic hydroxylases and cytochrome P (CYP)-450 relapse but are much more time-limited: isozymes, primarily CYP 1A1, 1A2, and • dysphoria and irritability 2E1, thereby increasing metabolic clear- • anxiety ance of medications—such as clozapine— • insomnia that are substrates for these enzymes. • reduced heart rate Smoking cessation is associated with a • restlessness Current Psychiatry 30% to 42% reduction in activity of CYP • diffi culty concentrating. Vol. 6, No. 7 69 continued Table 2 Suggested pharmacologic approaches for smoking cessation in patients with schizophrenia Dosage Specifi c instructions Potential side effects Bupropion SR 150 mg bid Consider maintenance Insomnia, anxiety, irritability treatment if patient attains (usually mild, time-limited); abstinence and tolerates contraindicated in patients Nicotine medication well with a seizure disorder or dependence who are at high risk for seizures; take care when prescribing in combination with clozapine

Varenicline 0.5 mg once daily No published data in smokers Nausea, headache (nausea for 3 days; 0.5 mg with schizophrenia; several can be managed in some bid for 4 days; trials are underway patients with dose reduction) 1 mg bid ongoing Clinical Point NRT patch 21 mg/d to start Consider combination Rash, skin irritation, treatment with short-acting hypersensitivity reaction Take care when preparation; consider prescribing maintenance treatment if patient attains abstinence bupropion in and tolerates medication well combination with Short-acting NRT ≤20 mg/d as Instruct in correct use, clozapine because (gum, lozenge, needed for craving, particularly with gum; for of an additive risk inhaler, spray) in 2-mg or 4-mg patients who attain abstinence, increments consider maintenance of of causing seizures as-needed short-acting NRT

NRT: nicotine replacement therapy

Bupropion SR at 150 mg bid has been pendence. No reports have been published well-tolerated when added to antipsychot- on its safety and effi cacy for smoking cessa- ics and modestly effective for smoking tion in persons with schizophrenia. cessation in this population. It has been as- In our experience with open-label var- sociated with reduced negative symptoms enicline for nicotine dependence in schizo- and greater symptom stability during the phrenia, 8 of 9 patients quit smoking, re- cessation attempt—compared with place- ported reduced cravings, and remained bo—and is well-tolerated when combined clinically stable on the agent for 6 to 9 with NRT.20-22,27 months. All had previously relapsed af- ter discontinuing NRT, bupropion, or the NRT in a variety of delivery forms has been combination. well tolerated and modestly effective for Controlled trials are needed to discern smoking cessation in schizophrenia.23,27,28 this agent’s place in the treatment hierar- Combinations of short-acting NRT (gum, chy for smokers with schizophrenia, and lozenge, inhaler, or nasal spray) with the several such trials are underway. long-acting NRT patch improve long-term abstinence rates in smokers in the gen- eral population26 and may improve absti- 10-step offi ce-based approach nence rates in those with schizophrenia.27 CBT alone is not effective for smoking ces- Maintaining the pharmacotherapy used to sation in the schizophrenia population,22,28 achieve abstinence may also improve sus- but pharmacologic interventions have not tained abstinence rates. been shown to succeed without concurrent behavioral treatment. Varenicline is a partial nicotinic receptor The 10 behavioral treatments described Current Psychiatry 70 July 2007 agonist approved for treating tobacco de- below and the tools listed in Table 3 can be covered in 1 or 2 visits and individualized Table 3 for a relatively brief, offi ce-based approach. CBT tools to help schizophrenia pSYCHIATRY Using the complete list may be ideal, but patients quit smoking you can deliver a reasonable behavioral CurrentPsychiatry.com intervention by choosing tasks tailored to Create ‘reasons to quit’ card each patient’s needs. After the initial ses- Provide ‘4Ds’ card of ‘coping skills when I sion, review these interventions at follow- crave a cigarette’ (deep breathe, drink fl uids, up appointments to reinforce skills. delay (smoking), do something else) Evaluate and practice problem-solving 1 Send a clear and simple message to skills around ‘triggers and risky situations’ your patients to quit smoking. If possible, Encourage patient to develop a ‘5 things provide a handout about health risks of I will do when I feel like smoking’ card smoking and benefi ts of quitting. Develop a detailed ‘quit day’ plan

2 Elicit the patient’s reasons for wanting Role-play cigarette refusal skills to quit, and help him or her list these rea- Prepare a smoking cessation ‘survival kit’ sons as specifi cally as possible, such as: Clinical Point • “I want to have more spending To help the patient money.” • visiting a family member who smokes cope with craving, • “I want to improve my health.” • dealing with a stressful situation. • “I want to make my sister proud.” Problem-solve with patients about how provide a card listing Copy this list on index cards for the pa- to cope with smoking triggers (Table 4, page ‘4Ds’: deep breathe, tient, and encourage him or her to carry 1 72). For example, switch from coffee to tea drink fl uids, delay and post others around the house. or “decaf,” listen to music to cope with au- (smoking), or do ditory hallucinations, use nicotine gum or 3 Prescribe pharmacotherapy, as sup- lozenges while waiting for the bus, or surf something else ported by clinical trial results. Explain the the Internet at day treatment instead of go- rationale for its use, and encourage adher- ing outside to smoke during breaks. Have ence. Review proper techniques for using patients make an index card with a list of “5 NRT patches and gum, lozenge, inhaler, or things I will do when I feel like smoking.” nasal spray. 6 Set a quit date with a detailed “quit 4 Teach the patient skills to cope with crav- day” plan. When the patient has some mas- ings. The “4 Ds” are a helpful mnemonic: tery over triggers and risky situations, work • Deep breathe. with him or her to prepare for quit day • Drink fl uids. (such as throw out cigarettes and lighters, • Delay (smoking). tell family he or she will be quitting). • Do something else. Plan the day, often hour by hour, to Give the patient an index card listing the help the patient make new choices (such 4Ds, and help him or her memorize them. as go to the park in the morning instead of the convenience store, do a puzzle while 5 Discuss the patient’s smoking triggers watching TV at night). Schedule in some and risky situations. These vary from patient rewards and pleasant activities to substi- to patient, but common triggers include: tute for cigarettes. • fi nishing a meal or drinking coffee • seeing other people smoking 7 Work on ‘refusal skills.’ Patients will • psychological stressors or psychiatric likely need to practice saying no to ciga- symptoms such as anxiety or auditory rettes offered to them in their social environ- hallucinations ments. Discuss these skills, and role-play to • boredom, such as waiting for a bus. increase patients’ likelihood of success. Common risky situations include: • going to a day treatment center where 8 Provide a ‘survival kit’ for use during Current Psychiatry most patients and staff smoke the fi rst week without cigarettes. Include Vol. 6, No. 7 71 Table 4 6-step problem-solving skills to help prevent smoking relapse Step (with sample therapist question) Sample patient response 1. Identify the problem (What is the situation I am tempted to buy cigarettes every time I walk that is making it diffi cult for you to stay quit?) by the convenience store in my neighborhood

2. Brainstorm 1. Walk a different way to the bus so I don’t pass Nicotine (What are some possible solutions?) the convenience store 2. Tell the people at the convenience store that I dependence quit smoking 3. Don’t carry extra money so I can’t buy cigarettes

3. Evaluate pros and cons (What are the good Walking a different route to the bus: things and the not-so-good things about each Pros: less temptation, more exercise possible ?) Cons: longer trip, different routine Don’t carry money: Pros: can’t buy cigarettes Clinical Point Cons: can’t buy other things; might need money in an emergency

Discuss rewards 4. Pick a solution (Which solution or Walk a different way to the bus so I don’t patients can give combination of solutions looks the best?) pass the store themselves (a new 5. Make a plan (What do you need to do to I need to test out other routes to the bus, set alarm concept to many) try it out?) earlier so have enough time for longer route to help them depend 6. Rate the solution (How well did it work? Since I planned my route in advance, I don’t feel Do you need to try something else?) nervous about it. I think about cigarettes less in less on cigarettes the morning now for gratifi cation tools to help with cravings and provide After 12 months, Mr. V’s bupropion dosage distractions, such as a small bag with sug- was tapered to 150 mg/d for 2 weeks and arless gum or candy, toothpicks and straws then discontinued, and the NRT patch was to chew, rubber bands to keep hands busy, a tapered to 14 mg/d for 2 weeks, 7 mg/d for water bottle, cough drops, healthy snacks, 2 weeks, then discontinued. At the same and a card with the 4 Ds. time, he gradually decreased his use of short- acting nicotine gum. 9 Discuss rewards patients can give Mr. V realized early in treatment that if themselves instead of cigarettes. This con- he quit smoking he could save $1,000 per cept will be new to many but is important year in the price of cigarettes. The camera he to help patients depend less on cigarettes bought with the money he saved served as a for gratifi cation. motivator and helped alleviate the boredom that had kept him smoking. 10 Call patients on their quit date or the day after to make sure they are on track. References 1. Tobacco use among adults: United States, 2005. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly 2006 Oct 27;5(42):1145-8. Available at: http://www.cdc.gov/ CASE CONTINUED mmwr/preview/mmwrhtml/mm5542a1.htm. An improving picture 2. Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of With CBT, Mr. V grasped that he had to make schizophrenia: a historical-prospective cohort study. Am J important changes to quit smoking and Psychiatry 2004;161(7):1219-23. 3. Williams JM, Ziedonis DM, Abanyie F, et al. Increased nicotine reduce his risk of relapse. He embraced the and cotinine levels in smokers with schizophrenia and “4 Ds” and successfully adhered to the plan schizoaffective disorder is not a metabolic effect. Schizophr Res 2005;79(2-3):323-35. for his quit date. He maintained abstinence 4. Tidey JW, Rohsenow DJ, Kaplan GB, Swift RM. Cigarette through the 12-month relapse prevention smoking topography in smokers with schizophrenia and matched non-psychiatric controls. Drug Alcohol Depend treatment period with the same bupropion 2005;80:259-65. and NRT dosage he had used to quit smoking 5. Olincy A, Young DA, Freedman R. Increased levels of the Current Psychiatry nicotine metabolite cotinine in schizophrenic smokers 72 July 2007 (and tapered CBT sessions). compared to other smokers. Biol Psychiatry 1997;42(1):1-5. continued on page 77 continued from page 72 6. Goff DC, Cather C, Evins AE, et al. Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists. J Clin Related Resources Psychiatry 2005;66(2):183-94. pSYCHIATRY 7. Himelhoch S, Daumit G. To whom do psychiatrists offer • U.S. Public Health Service. Clinical practice guideline. smoking-cessation counseling? Am J Psychiatry 2003;160: Treating tobacco use and dependence. www.surgeongeneral. 2228-30. CurrentPsychiatry.com gov/tobacco/tobaqrg.htm. 8. Carosella AM, Ossip-Klein DJ, Owens CA. Smoking attitudes, beliefs, and readiness to change among acute and long term • Agency for Healthcare Research and Quality. Treating care inpatients with psychiatric diagnoses. Addict Behav tobacco use and dependence: clinician’s packet. A how-to 1999;24(3):331-4. guide for implementing the Public Health Service Clinical 9. Esterberg ML, Compton ML. Smoking behavior in persons Practice Guideline. www.ahcpr.gov/clinic/tobacco. with a schizophrenia-spectrum disorder: a qualitative investigation of the transtheoretical model. Soc Sci Med 2005; • Massachusetts Department of Public Health. 61(2):293-303. www.trytostop.org. 10. Addington J, el-Guebaly N, Addington D, Hodgins D. • Centers for Disease Control and Prevention. Tobacco Readiness to stop smoking in schizophrenia. Can J Psychiatry 1997;42(1):49-52. Information and Prevention Source (TIPS). www.cdc.gov/ 11. Sacco KA, Termine A, Seyal A, et al. Effects of cigarette tobacco. smoking on spatial working memory and attentional Drug Brand Names defi cits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 2005;62(6):649-59. Benztropine mesylate • Cogentin Nicotine/polacrilex 12. Barr RS, Culhane MA, Jubelt LE, et al. The effects of transdermal Bupropion SR • Zyban • Nicorette nicotine on cognition in nonsmokers with schizophrenia and Clozapine • Clozaril Perphenazine • various nonpsychiatric controls. Neuropsychopharmacology 2007;Apr 18 Lorazepam • Ativan Varenicline • Chantix [Epub ahead of print]. Nicotine/transdermal Ziprasidone • Geodon 13. McDonald C. Cigarette smoking in patients with schizo- phrenia. Br J Psychiatry 2000;176:596-7. • Nicotrol, Prostep Zonisamide • Zonegram Clinical Point Nicotine/nasal spray 14. Adler LA, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic • Nicotrol NS Call patients on their patients. Am J Psychiatry 1993;150:1856-61. Disclosures 15. Sallette J, Pons S, Devillers-Thiery A, et al. Nicotine upregulates quit date or the day its own receptors through enhanced intracellular maturation. Dr. Gottlieb reports no fi nancial relationship with any Neuron 2005;46:595-607. company whose products are mentioned in this article or after to make sure 16. Breese CR, Lee MJ, Adams CE, et al. Abnormal regulation of with manufacturers of competing products. high affi nity nicotinic receptors in subjects with schizophrenia. they are on track Neuropsychopharmacology 2000;23:351-64. Dr. Evins receives research support from Janssen 17. Miller D, Kelly M, Perry P, Coryell W. The infl uence of Pharmaceutica. cigarette smoking on haloperidol pharmacokinetics. J Clin Psychiatry 1990;28:529-31. 18. Evins AE, Cather C, Rigotti NA, et al. Two-year follow up of a smoking cessation trial in patients with schizophrenia: 25. Hatsukami D, Mooney M, Murphy S, et al. Effects of high increased rates of smoking cessation and reduction. J Clin dose transdermal nicotine replacement in cigarette smokers. Psychiatry 2004;65:307-12. Pharmacol Biochem Behav 2007;86:132-9. 19. A clinical practice guideline for treating tobacco use and 26. Blondal T, Gudmundsson L, Olafsdottir I, et al. Nicotine nasal dependence: A US Public Health Service report. The Tobacco spray with nicotine patch for smoking cessation: randomised Use and Dependence Clinical Practice Guideline Panel, Staff, trial with six year follow-up. BMJ 1999;318: 285-8. and Consortium Representatives. JAMA 2000;283:3244-54. 27. Evins AE, Cather C, Culhane MA, et al. A double-blind 20. Weiner E, Ball MP, Summerfelt A, et al. Effects of sustained- placebo-controlled study of bupropion SR added to high-dose, release bupropion and supportive group therapy on cigarette dual nicotine replacement therapy for smoking cessation or consumption in patients with schizophrenia. Am J Psychiatry reduction in schizophrenia. J Clin Psychopharmacol. In press. 2001;158:635-7. 28. George TP, Ziedonis DM, Feingold A, et al. Nicotine 21. George TP, Vessicchio JC, Termine A, et al. A placebo controlled and atypical antipsychotic medications trial of bupropion for smoking cessation in schizophrenia. Biol for smoking cessation in schizophrenia. Am J Psychiatry Psychiatry 2002;52:53-61. 2000;157:1835-42. 22. Evins AE, Deckersbach T, Cather C, et al. A double-blind 29. Steinberg ML, Ziedonis DM, Krejci J, Brandon TH. placebo-controlled trial of bupropion sustained release for Motivational interviewing with personalized feedback: a brief smoking cessation in schizophrenia. J Clin Psychopharmacol intervention for motivating smokers with schizophrenia to 2005;25:218-25. seek treatment for tobacco dependence. J Consult Clin Psychol 23. Williams JM, Ziedonis DM, Foulds J. A case series of nicotine 2004;72(4):723-8. nasal spray in the treatment of tobacco dependence among 30. Williamson DF, Madans J, Anda RF, et al. Smoking cessation patients with schizophrenia. Psychiatr Serv 2004;55:1064-6. and severity of weight gain in a national cohort. N Engl J Med 24. Killen JD, Fortmann SP, Davis L, et al. Do heavy smokers 1991;324:739-45. benefi t from higher dose nicotine patch therapy? Exp Clin 31. Cooke JP, Bitterman H. Nicotine and angiogenesis: a new Psychopharmacol 1999;7:226-33. paradigm for tobacco-related diseases. Ann Med 2004;36:33-40. Bottom Line Multifaceted treatment with pharmacotherapy and a 10-step cognitive-behavioral intervention increases the likelihood of smoking cessation in patients with schizophrenia. To reduce nicotine dependence, consider combining bupropion SR with patch and short-acting NRT. Develop a ‘quit day’ plan, teach coping skills, build in self-rewards, and provide cues written on index cards to reinforce abstinence.

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