Smokers May Need Different Doses of Antipsychotics

Smokers with psychiatric disorders taking olanzipine and clozapine had lower blood levels of medications than nonsmokers

(RxWiki News) Getting the correct dose of medication into the bloodstream means patients get the most from their medications. However, smoking may affect that process.

Researchers undertook a study to determine if smoking would affect how medication ended up in the blood. They wanted to know if a doctor should consider a patient’s smoking status when deciding what dose of medication to prescribe.

Their study showed that two medications taken for schizophrenia and other psychiatric disorders appeared in lower amounts in the blood of smokers than in nonsmokers.

"Tell your doctor if you smoke."

Yoshiyuki Tsuda, from the Graduate School of Pharmaceutical Sciences at Kumamoto University in Kumamoto, Japan, and a team of researchers conducted this study.

The researchers analyzed data previously published by others. They examined four studies of clozapine (brand name Clozaril) and seven studies on olanzapine (brand name Zyprexa) — both medications used to treat psychiatric disorders such as schizophrenia.

More people with schizophrenia are smokers than in the general population. It is estimated that 58 to 88 percent of patients with schizophrenia are smokers.

The body’s processing of medications (drug metabolism) is a complicated one that often involves enzymes called cytochromes. Smoking is known to increase a cytochrome enzyme important in drug metabolism.

The seven olanzapine studies included a total of 1,094 patients with schizophrenia or other psychiatric disorders, 652 of whom smoked and 442 of whom did not smoke. The four clozapine studies included 196 patients with schizophrenia or other psychiatric disorders. Of these, 120 were smokers and 76 were nonsmokers.

Since the main objective of this study was to see how smoking affected blood amounts of the two medications, Dr. Tsuda and team analyzed data in each published study on how much of each medication was given and how much ended up in the patients’ blood. These researchers compared that measurement with whether a patient was a smoker or not.

Results of the analysis were expressed as concentration of medication in blood divided by dose given, called the C/D ratio.

Comparison showed that the C/D ratio for olanzapine was an average of 0.75 units less in the blood of smokers than in nonsmokers. The C/D ratio of clozapine was 1.11 units less in the blood of smokers compared to nonsmokers.

These findings mean that when the same dose of medication was given, more of the medication ended up in the blood of nonsmokers than smokers.

"The doses of olanzapine and clozapine should be reduced by 30 percent and 50 percent, respectively, in nonsmokers compared with smokers in order to obtain an equivalent olanzapine or clozapine concentration," Dr. Tsuda and colleagues wrote.

For example, to compensate for the different medication levels in the blood of smokers and nonsmokers, the researchers estimated that if clozapine was given to smokers at 200 to 400 mg per day, nonsmokers should be given 100 to 200 mg per day.

Likewise, if smokers were given 10 to 20 mg per day of olanzapine, then nonsmokers should be given 7 to 14 mg per day, the researchers advised.

Steve Leuck, PharmD, and president and owner of AudibleRx said, "While smoking definitely alters the effects of many psychiatric medication, as does alcohol consumption and illicit drug use, when treating schizophrenia and other psychiatric disease states, the end point of treatment is symptom control."

"In my experience, working with physicians through our local behavioral health unit, the dose of anti-psychotic medication for any particular patient is titrated to effect based upon symptom relief and side effects, regardless of whether the patient is a smoker," Dr. Leuck told dailyRx News.

The authors noted some limitations of their evaluation of these studies. Other factors not considered may have affected drug metabolism. Such factors included weight, age, gender and alcohol consumption. The researchers also did not know how much the smokers smoked, so this was not factored into their analysis.

Results of this analysis were published March 4 in BMJ Open.

Grants-in-aid from the Japanese Ministry of Education, Science, Sports and Culture provided funding for this study.

The authors declared no conflicts of interest.

Review Date: 
March 13, 2014