A Trial of the Effects of Bupropion, Nicotine Replacement Therapy and CBT on Smoking Cessation and Smoking Relapse in Patients With Schizophrenia

Background and Preliminary Data:

Between 72% and 90% of patients with schizophrenia smoke cigarettes, and schizophrenia patients are more likely than the general population to smoke and to smoke heavily (1-6). Compared with the general population, patients with schizophrenia have low smoking cessation rates, even through they can be both highly motivated and persistent in their attempts to quit smoking (7-10) and can tolerate short-term tobacco abstinence without significant exacerbation in clinical or cognitive symptoms (11, 12). Nicotine replacement therapy (NRT) and bupropion are each well tolerated by patients with schizophrenia, and bupropion is superior to placebo for smoking cessation in this population when added to CBT (13-20). However, abstinence rates have been low (4-19%) at 3-6 month follow up, whereas placebo plus CBT has produced cessation rates of 0-6%.

It has been estimated that 45% of cigarettes sold in the US are sold to people with a mental illness (21) and that in the UK and Ireland, patients with schizophrenia spend approximately one third of their weekly income on cigarettes (22, 23). Age-adjusted mortality from smoking-related diseases such as pulmonary and cardiovascular disease are two to six times higher among people with schizophrenia compared to age matched samples (24-27). More effective pharmacologic treatments for smoking cessation in patients with schizophrenia are thus urgently needed.

Combination treatment with bupropion and NRT has shown promise. In a large study in a non-psychiatric population, a combination of bupropion SR and NRT was superior to placebo and to NRT alone but not to bupropion alone for smoking cessation (28). In an open, non-randomized smoking cessation study in 115 nicotine dependent patients with co-morbid psychiatric and substance use disorders, patients treated with bupropion SR plus NRT and weekly CBT had significantly greater reduction in smoking than those on bupropion SR plus CBT, NRT plus CBT or CBT alone (29). Subjects on a combination of bupropion SR plus NRT also had significantly greater retention in the smoking cessation program and tolerated the combination treatment well.

These findings were extended to patients with schizophrenia in a 12-week, randomized, double-blind trial of bupropion or placebo added to NRT + CBT (30). In this trial, bupropion 300 mg/d or identical placebo was added to NRT and CBT for 12 weeks. NRT was given, starting on the quit date at week 4, as nicotine patch 21 mg/d for 4 weeks, 14 mg/d for 2 weeks and 7 mg/d for 2 weeks combined with nicotine gum up to 18 mg per day prn. Combination treatment with bupropion and NRT was well tolerated and more beneficial than NRT alone for significant smoking reduction in patients with schizophrenia (Table 1 & Figure 1). The combination treatment was also superior for continuous abstinence until week 8 when the dose of NRT was reduced. When subjects were taking bupropion 300 mg per day, nicotine patch 21 mg per day and prn nicotine gum up to 18 mg per day, they had a cessation rate of 52%. See Table 1. Patients began to relapse to smoking after the dose of nicotine patch was reduced to 14 mg per day and continued to relapse through the 12 month follow up.