How to treat nicotine dependence in smokers with schizophrenia

Preventing relapse. Relapse is common among all smokers but especially in those with schizophrenia. In clinical trials, 70% to 83% of smokers with schizophrenia who attained abstinence relapsed to smoking within 6 to 12 months of stopping nicotine dependence treatment.^21,22,27,28

In one clinical trial, >50% of patients achieved 4 weeks of continuous abstinence on a regimen of bupropion SR, 150 mg bid; nicotine patch (21 mg/d); and as-needed nicotine gum (≤18 mg/d). However:

• 31% relapsed to smoking while NRT was being tapered from ~40 to 20 mg/d
  
• 77% relapsed after nicotine dependence treatment was discontinued.²⁷
  

Longer use of pharmacotherapy may be needed to prevent relapse to smoking in the schizophrenia population. In a recent open case series, 17 of 42 smokers with schizophrenia were able to quit for at least 2 weeks with a combination of bupropion SR, 150 mg bid, and dual NRT. Among those who quit, 13 (76%) remained abstinent for 12 additional months when offered continued pharmacotherapy and tapering CBT (AE Evins, under review).

Table 2

Suggested pharmacologic approaches for smoking cessation in patients with schizophrenia

Medication	Dosage	Specific instructions	Potential side effects
Bupropion SR	150 mg bid	Consider maintenance treatment if patient attains abstinence and tolerates medication well	Insomnia, anxiety, irritability (usually mild, time-limited); contraindicated in patients with a seizure disorder or who are at high risk for seizures; take care when prescribing in combination with clozapine
Varenicline	0.5 mg once daily for 3 days; 0.5 mg bid for 4 days; 1 mg bid ongoing	No published data in smokers with schizophrenia; several trials are underway	Nausea, headache (nausea can be managed in some patients with dose reduction)
NRT patch	21 mg/d to start	Consider combination treatment with short-acting preparation; consider maintenance treatment if patient attains abstinence and tolerates medication well	Rash, skin irritation, hypersensitivity reaction
Short-acting NRT (gum, lozenge, inhaler, spray)	≤20 mg/d as needed for craving, in 2-mg or 4-mg increments	Instruct in correct use, particularly with gum; for patients who attain abstinence, consider maintenance of as-needed short-acting NRT
NRT: nicotine replacement therapy

CASE CONTINUED: Treating nicotine dependence

Mr. V cut down to 10 cigarettes a day during a 4-week motivational enhancement/psychoeducation intervention for smokers with major mental illness.²⁹ He then enrolled in a 12-week study in which subjects received high-dose dual NRT and bupropion SR or placebo.

Mr. V was reluctant to use the NRT patch because he believed rumors that it could cause a heart attack, especially if he smoked while using a patch. He did try the patch, however, after his clinicians informed him it would increase his chances of quitting.

He received bupropion SR, 150 mg bid; NRT patch, 21 mg/d; and nicotine polacrilex gum, up to 18 mg/d as needed, and tolerated the regimen well. After 4 weeks, he quit smoking on the quit date. His blood pressure—monitored weekly for the first month then monthly thereafter—remained stable throughout the intervention.

Prescribing considerations

Metabolic changes. Smoking—but not NRT—induces hepatic clearance of many psychotropics, and smoking cessation can be associated with increased drug serum levels. Polycyclic aromatic hydrocarbons present in cigarette smoke—but not NRT—induce hepatic aryl hydrocarbon hydroxylases and cytochrome P (CYP)-450 isozymes, primarily CYP 1A1, 1A2, and 2E1, thereby increasing metabolic clearance of medications—such as clozapine—that are substrates for these enzymes.

Smoking cessation is associated with a 30% to 42% reduction in activity of CYP 1A2, and the half-life of this reduction is 27 to 54 hours. Thus, therapeutic drug monitoring and dose reduction of 10% over the first 4 days of tobacco abstinence is recommended to avoid toxicity. If the patient remains abstinent from tobacco, further reducing the antipsychotic dose may be warranted, based on individual assessment.

Weight gain. Patients who quit smoking gain an average of 3 to 5 kg.³⁰

Nicotine withdrawal. Patients are used to thinking that nicotine is calming, whereas in reality nicotine and smoking are anxiogenic, and cigarette smoking alleviates the anxiety that comes from nicotine withdrawal.³¹ Educate patients about nicotine withdrawal symptoms, which easily can be confused with early signs of a psychotic relapse but are much more time-limited:

• dysphoria and irritability
  
• anxiety
  
• insomnia
  
• reduced heart rate
  
• restlessness
  
• difficulty concentrating.
  

Bupropion SR at 150 mg bid has been well-tolerated when added to antipsychotics and modestly effective for smoking cessation in this population. It has been associated with reduced negative symptoms and greater symptom stability during the cessation attempt—compared with placebo—and is well-tolerated when combined with NRT.