Smoking Patients and Psychotropic Medications

Question.

I am an R.N. at a state hospital. It has been declared a “smoke-free” environment, except for out on grounds. Many patients are smokers who will never be allowed on grounds, and so they can’t smoke. Since the rule change, the violence on my all-male unit has increased, with patients demanding cigarettes and assaulting staff members when they are denied smoke breaks. The evidence shows that nicotine has a calming effect on schizophrenics and bipolars, but the psychiatrist argues that smoking reduces the effectiveness of psychotropic medications. What is your professional opinion?

Answer.

I addressed this complicated and controversial issue in my column for the April 1998 Psychiatric Times (“Smoke, Schizophrenia, and Cytochromes”). In essence, you and your unit psychiatrist may both be right, which means that the issue requires a very careful, case-by-case assessment. Dr. Donald Goff notes that surveys of schizophrenic patients show smoking rates of 74% to 92%, compared to 35-54% for all psychiatric patients and 30-35% for the general population.

Numerous psychosocial hypotheses have been advanced to explain the high rates of smoking among patients with schizophrenia. Chronic institutionalization, boredom, impaired judgment and lack of other stimuli have all been adduced as explanations. Various “self-medication” hypotheses have also been proffered to explain these data. One study (Glynn and Sussman) noted that smoking produced relaxation and reduced anxiety in many schizophrenic patients. Twenty percent of the respondents reported that smoking reduced medication side effects, and an equal number reported smoking in response to symptoms of schizophrenia.

In a study that examined “sensory gating” in schizophrenic patients (essentially, the brain’s ability to filter out extraneous background information), Adler et al found that cigarette smoking transiently normalized the impaired auditory sensory gating often seen in schizophrenia. Since nicotinic cholinergic receptors may mediate auditory sensory gating, it is possible that cigarette smoking actually corrects a neurochemical abnormality in some schizophrenic patients.

Nicotine improves concentration in normal subjects, and may also do so in subjects with schizophrenia. The drug may also have activating effects on brain dopamine receptors (via nicotinic receptors on dopaminergic neurons), which may decrease some extrapyramidal symptoms in schizophrenic patients. Goff et al found that smokers displayed significantly less neuroleptic-induced parkinsonism than did non-smokers, but actually showed higher levels of akathisia. The effects of cigarette smoking on rates of tardive dyskinesia remain unclear, with two of three studies showing higher risk for smokers. Finally, nicotine may have antidepressant effects, perhaps via potentiation of serotonergic function, and some schizophrenic patients may use smoking to “self-medicate” affective symptoms.

In sum, cigarette smoking has some apparent “pluses” for schizophrenic patients, but may also have some serious drawbacks (besides the obvious heart and lung complications). Furthermore, the work of Ereshefsky and others has shown that cigarette smoking increases clearance – and thus decreased blood levels – of several neuroleptics, including haloperidol (Haldol), fluphenazine (Prolixin), and thiothixine (Navane).

The effects of smoking upon atypical antipsychotic blood levels are still unclear, though there are strong theoretical reasons for suspecting an interaction. Clozapine (Clozaril) and olanzapine (Zyprexa) are metabolized predominantly via the cytochrome P450 1A2 system (CYP 1A2), which is strongly induced by cigarette smoke. Haring et al (1989, 1990) found that the average clozapine level at a given dose was only about 60% as great in smokers as non-smokers, but further analysis showed that only men were so affected by smoking. (There may be differences in the number of cigarettes smoked by men and women.)

A recent MEDLINE search revealed no published studies of olanzapine or risperidone plasma levels. However, Greeman and McClellan studied the effects of a smoking ban on inpatient units at a Veterans Affairs medical center over a two-year period. The researchers found that between 20-25% of patients who smoked had difficulty adjusting to the ban, and that “some patients experienced major disruption in their treatment.” Given this complex set of pros and cons, my recommendations (see the Psychiatric Times article for references) are as follows:

• First, psychiatrists and other mental health professionals should be aware that cigarette smoking is an important activity for many of our patients with chronic illness, especially those with schizophrenia. While the precise reasons remain unclear, the patient’s needs should be considered carefully in any decision regarding a ban on smoking.
• Cigarette smoking can have both pharmacokinetic and pharmacodynamic effects in the patient with schizophrenia (and other disorders, such as depression). Smoking may reduce blood levels of antipsychotics, as well as tricyclic antidepressants (Linnoila et al, 1981). Conversely, stopping smoking could lead to elevation of antipsychotic blood levels, and to extrapyramidal side effects.
• While in principle, smoking cessation has obvious health benefits for all our patients, it may produce variable neuropsychiatric effects. Some patients may experience a worsening of negative and/or parkinsonian symptoms, or show more irritability. Others, as per the findings of West and Hajek, may actually show a decrease in anxiety, though this issue needs to be investigated in controlled, systematic studies. In any event, cessation of smoking should be enforced gradually.
• The use of atypical antipsychotics may reduce the pharmacodynamic “incentive” to smoke in some patients with chronic schizophrenia. For example, the lower rates of EPS with these atypical agents may remove one reason for nicotine self-medication.
• The issue of forcing a chronically psychotic patient to stop smoking should be examined very carefully, and on a patient-by-patient basis. Blanket policies affecting entire wards or units may not be in the best interest of our patients. Nicotine gum, skin patches or inhalers may be worth trying, but might not be sufficient for some patients.
• Nevertheless, it is probably reasonable to encourage a reduction in smoking among our chronically ill psychiatric patients, as it is with any patient. Fostering a more stimulating therapeutic milieu is also an approach worth considering.