Evidence-Based Reviews

How to treat nicotine dependence in smokers with schizophrenia

Current Psychiatry. 2007 July;6(7):49-60

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

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/mmwr/preview/mmwrhtml/mm5542a1.htm.

2. Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiatry 2004;161(7):1219-23.

3. Williams JM, Ziedonis DM, Abanyie F, et al. Increased nicotine and cotinine levels in smokers with schizophrenia and schizoaffective disorder is not a metabolic effect. Schizophr Res 2005;79(2-3):323-35.

4. Tidey JW, Rohsenow DJ, Kaplan GB, Swift RM. Cigarette smoking topography in smokers with schizophrenia and matched non-psychiatric controls. Drug Alcohol Depend 2005;80:259-65.

5. Olincy A, Young DA, Freedman R. Increased levels of the nicotine metabolite cotinine in schizophrenic smokers compared to other smokers. Biol Psychiatry 1997;42(1):1-5.

6. Goff DC, Cather C, Evins AE, et al. Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists. J Clin Psychiatry 2005;66(2):183-94.

7. Himelhoch S, Daumit G. To whom do psychiatrists offer smoking-cessation counseling? Am J Psychiatry 2003;160:2228-30.

8. Carosella AM, Ossip-Klein DJ, Owens CA. Smoking attitudes, beliefs, and readiness to change among acute and long term care inpatients with psychiatric diagnoses. Addict Behav 1999;24(3):331-4.

9. Esterberg ML, Compton ML. Smoking behavior in persons with a schizophrenia-spectrum disorder: a qualitative investigation of the transtheoretical model. Soc Sci Med 2005;61(2):293-303.

10. Addington J, el-Guebaly N, Addington D, Hodgins D. Readiness to stop smoking in schizophrenia. Can J Psychiatry 1997;42(1):49-52.

11. Sacco KA, Termine A, Seyal A, et al. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 2005;62(6):649-59.

12. Barr RS, Culhane MA, Jubelt LE, et al. The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 2007 Apr 18 [Epub ahead of print].

13. McDonald C. Cigarette smoking in patients with schizophrenia. Br J Psychiatry 2000;176:596-7.

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15. Sallette J, Pons S, Devillers-Thiery A, et al. Nicotine upregulates its own receptors through enhanced intracellular maturation. Neuron 2005;46:595-607.

16. Breese CR, Lee MJ, Adams CE, et al. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 2000;23:351-64.

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18. Evins AE, Cather C, Rigotti NA, et al. Two-year follow up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction. J Clin Psychiatry 2004;65:307-12.

19. A clinical practice guideline for treating tobacco use and dependence: A US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. JAMA 2000;283:3244-54.

20. Weiner E, Ball MP, Summerfelt A, et al. Effects of sustained-release bupropion and supportive group therapy on cigarette consumption in patients with schizophrenia. Am J Psychiatry 2001;158:635-7.

21. George TP, Vessicchio JC, Termine A, et al. A placebo controlled trial of bupropion for smoking cessation in schizophrenia. Biol Psychiatry 2002;52:53-61.

22. Evins AE, Deckersbach T, Cather C, et al. A double-blind placebo-controlled trial of bupropion sustained release for smoking cessation in schizophrenia. J Clin Psychopharmacol 2005;25:218-25.

23. Williams JM, Ziedonis DM, Foulds J. A case series of nicotine nasal spray in the treatment of tobacco dependence among patients with schizophrenia. Psychiatr Serv 2004;55:1064-6.

24. Killen JD, Fortmann SP, Davis L, et al. Do heavy smokers benefit from higher dose nicotine patch therapy? Exp Clin Psychopharmacol 1999;7:226-33.

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26. Blondal T, Gudmundsson L, Olafsdottir I, et al. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow-up. BMJ 1999;318:285-8.

27. Evins AE, Cather C, Culhane MA, et al. A double-blind placebo-controlled study of bupropion SR added to high-dose, dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. J Clin Psychopharmacol. In press.

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Mr. V, age 49, has stable but symptomatic schizophrenia and a 33-year cigarette smoking history. He is very concerned because his primary care physician told him he has 2 serious 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 medications (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 very ill, to alleviate chronic boredom, and to diminish distress from the hallucinations. All of his friends smoke, and they do not support his attempts to quit.

Clinical Point

Using transdermal nicotine replacement plus a short-acting form (gum, lozenge, inhaler, or nasal spray) may improve sustained abstinence

Successfully treating nicotine dependence can seem a formidable challenge in patients with schizophrenia:

72% to 90% smoke cigarettes, compared with 21% of the general population¹ (Box).^2-12
They tend to smoke heavily, spending about one-third of their incomes on cigarettes.¹³
Their negative symptoms (such as apathy), positive symptoms (such as disorganized thinking), 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).^9,12,14-17

Even so, smokers with schizophrenia can be highly motivated and persistent in attempting to quit.¹⁸ Promising results have been reported in trials when psychopharmacologic treatments are combined with cognitive and behavioral interventions.

Box

Obstacles to smoking cessation for schizophrenia patients

Smokers with schizophrenia are more nicotine-dependent, more likely to become medically ill, and less likely to receive help in quitting, compared with the general population. They:

begin smoking at a higher rate before diagnosis or treatment for schizophrenia, compared with persons who do not go on to develop the disorder²
smoke each cigarette more intensely, extracting more nicotine per cigarette^3-5
have higher rates of smoking-related illness and medical morbidity⁶
are much less likely to receive physician advice to quit smoking.⁷

Many persons with severe mental illness are misinformed about the risks and benefits of smoking vs nicotine dependence treatment.⁸ They often fear and overestimate the medical risks of nicotine replacement therapies.⁹ Many believe smoking relieves depression and anxiety,¹⁰ whereas nicotine actually is anxiogenic. Nicotine may improve some aspects of cognitive dysfunction in schizophrenia, which could be a disincentive for patients to quit smoking.^11,12

This article reviews these empiric studies and suggests practical ways for clinicians to create smoking cessation and relapse prevention plans for individuals with schizophrenia.

Table 1

Why up to 90% of schizophrenia patients smoke cigarettes

Sociologic barriers to quitting
Their social groups often include a high percentage of heavy smokers Some fear NRT is ‘unhealthy,’ causes cardiac arrest, or increases nicotine cravings⁹ (see Table 2, for an accurate NRT side effect profile) They are unlikely to achieve sustained abstinence from a single cessation attempt
Physiologic reinforcers and disease factors
Nicotine may modulate schizophrenia’s cognitive dysfunction, including sensory gating (a measure of ability to filter out irrelevant environmental stimuli) and attention^12,14 Nicotine may increase disease-associated reduction in nicotinic acetylcholine receptor activity^15,16 Smoking (but not nicotine) reduces antipsychotic blood levels by increasing metabolism and may reduce side effects of antipsychotic medications¹⁷ Schizophrenia’s cognitive impairment can make smoking cessation strategies difficult to follow

Clinical trials of smoking cessation

Inadequate interventions. Conventional regimens—consisting of 8 to 12 weeks with sustained-release bupropion or nicotine replacement therapy (NRT) added to supportive or cognitive-behavioral therapy (CBT)¹⁹—are well-tolerated by patients with schizophrenia but only modestly effective. CBT alone (or with placebo) has not been effective for smoking cessation in schizophrenia. In clinical trials, abstinence rates have been:

4% to 19% after 3 to 6 months with bupropion or NRT and CBT
≤6% with placebo and CBT.^20-23

Multifaceted interventions. High-dose NRT patch treatment (2 patches at a time) has not consistently shown additional benefits compared with single-patch treatment.^24,25 However, combining short-acting NRT (gum, lozenge, inhaler, or nasal spray) with a long-acting NRT preparation (transdermal patch) is well-tolerated and has been shown to improve sustained abstinence rates²⁶ (Table 2).

In a double-blind, placebo-controlled trial,²⁷ 51 smokers with schizophrenia were randomly assigned to receive combination NRT (21-mg NRT patch plus ≤18 mg/d NRT polacrilex gum prn) added to bupropion SR, 150 mg bid, or placebo. Smoking cessation—defined as quitting on the assigned date and maintaining continuous abstinence for 4 weeks (measured by expired air carbon monoxide

52% of those receiving bupropion and dual NRT
19% who received placebo and the 2 forms of NRT.