Nicotine Dependence in Schizophrenia: Prevalence, Mechanisms, and Implications for Treatment

By A. Eden Evins, MD, MPH | March 1, 2008

Dr Evins is assistant professor in the department of psychiatry, Massachusetts General Hospital and Harvard Medical School in Boston. She reports that she has received research support from Janssen, GlaxoSmithKline, and Pfizer, and she has received speakers' honoraria from Primedia for CME course development and lectures.

Treatment of nicotine(Drug information on nicotine) dependence

Persons with schizophrenia are often highly motivated and persistent in their attempts to quit smoking despite having long histories of smoking and high levels of nicotine dependence.⁴⁸ In a sample of smokers with schizophrenia with a mean age of 57 years and a mean smoking history of 20 years, 70% reported a history of at least one serious attempt to quit smoking.⁴⁹

Conventional treatment regimens of 8 to 12 weeks with bupropion^50-54 or single-preparation NRT^47,55-57 added to CBT were well tolerated and moderately effective in persons with schizophrenia. However, relapse rates were high after discontinuation of bupropion, NRT, and CBT. Abstinence rates have been 4% to 19% at 3- to 6-month follow-up with bupropion, NRT, and CBT, and 0% to 6% with placebo and CBT.^47,50-57 For example, in a 12-week trial of bupropion 300 mg/d for smoking cessation in 53 schizophrenic patients, the abstinence rates at the end of treatment were 16% in the bupropion with CBT group and 0% in the placebo with CBT group. The relapse rate was 50% within 2 weeks of discontinuation of bupropion and 75% at the 3-month follow-up.⁵⁸

Tailored nicotine dependence therapy with higher-dose NRT and longer-duration pharmacotherapy may improve abstinence rates and reduce relapse rates in schizophrenic patients. Combined treatment with bupropion and NRT has shown promise in both general and psychiatric populations. The combination of bupropion sustained-release (SR) and NRT was superior to placebo and to NRT alone but not to bupropion alone for smoking cessation in a nonpsychiatric population.⁵⁹

In an open, nonrandomized smoking cessation study of 115 smokers with comorbid psychiatric and substance use disorders, patients randomized to receive a combination of bupropion SR, NRT, and CBT had significantly greater smoking reduction than those treated with the combinations of bupropion SR and CBT, NRT and CBT, or CBT alone.⁶⁰ Patients tolerated the combined treatment, and there were significantly fewer dropouts in the combined bupropion and NRT group.

Treatment with a nicotine patch combined with nicotine gum or nasal spray has shown superiority over single-form NRT (Table 1).^61-63 In a study of 51 smokers with schizophrenia randomly assigned to receive bupropion SR or placebo added to high-dose combination NRT patch and gum, 60% of those who received combination pharmacotherapy had significant reduction or abstinence compared with 31% of those who were assigned to placebo and NRT.⁶⁴ Those who received combination pharmacotherapy had significantly lower expired carbon monoxide levels than those receiving a combination of placebo and 2 forms of NRT. They also demonstrated higher rates of continuous abstinence before the NRT taper. However, as in previous studies, the relapse rate was quite high during and after discontinuation of nicotine dependence treatment: 31% of those who had quit relapsed during the NRT taper and 77% had relapsed by 12 months, which suggests a role for maintenance nicotine dependence treatment to reduce relapse rates.

Relapse prevention

In the general population, relapse rates are 41% to 58% at 1 year if pharmacological treatment is discontinued following treatment for 7 to 12 weeks.^59,65-67 In patients with schizophrenia, relapse rates of 70% to 83% have been reported 6 to 12 months after discontinuation of 8 to 12 weeks of treatment.^53,58,64 Thus, relapse rates are approximately 25% higher in patients with schizophrenia who quit smoking than in persons in the general population who quit. Longer-duration pharmacotherapy may be necessary to reduce relapse in patients with schizophrenia who are able to achieve abstinence.


	TABLE 2 Comparison of brief and extended treatment duration⁶⁹
	Treatment duration	Active treatment (%)	Placebo (%)

	Brief (8 weeks)	21	32

	Extended (52 weeks)	56	57
Abstinence rates assessed at 52 weeks. All patients were treated with cognitive-behavioral therapy, nicotine replacement therapy, and either active treatment or placebo. Missing subjects omitted in the analysis.

Longer-duration pharmacotherapy has been associated with higher rates of sustained smoking abstinence in the general population. Continuation treatment for 1 year in those who achieved abstinence with bupropion was well tolerated, and in these patients, the relapse rate at 12 months was lower than it was in those who received placebo (45% vs 58%, respectively), perhaps through reduction in craving.^67-69 Similarly, 1 year of treatment with combination CBT, NRT, and either active treatment or placebo resulted in significantly lower relapse rates compared with the same intervention over the more standard 12-week duration (Table 2).⁶⁹ Trials of longer-duration pharmacotherapy are under way in patients with schizophrenia.

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Evins AE, Cather C, Culhane MA, et al. A 12-week 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. 2007;27: 380-386.
George TP, Ziedonis DM, Feingold A, et al. Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. Am J Psychiatry. 2000;157:1835-1842.

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Nicotine Dependence in Schizophrenia: Prevalence, Mechanisms, and Implications for Treatment

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