Neuroleptic malignant syndrome: Possible relationship between Neuroleptic Treatment And Smoking Cessation
Mª José Martín Vázquez PhD MPsych*, Teresa Jimeno Beltrán MD**
Eur. J. Psychiat. v.21 n.4 Zaragoza oct.-dic. 2007
We report the case of M., a schizophrenic patient who was treated with high doses of antipsychotics for a long time allowing him to be stable for years. He then decided to give up smoking and two weeks later he suffered a syndrome diagnosed as Neuroleptic Malignant Syndrome with somatic complications. This caused his death two months after the start of the symptoms. We discuss the implications of smoking cessation in the origin of the syndrome due to a lower metabolism of psychotropic medications, which previously had been well tolerated. We conclude that it is important to take into account the smoking and caffeine intake of these patients, as well as other metabolic inductor or inhibitor drugs.
This kind of interaction is well known. The classic examples occur in neurology, with various combinations of anticonvulsant medications. The outcomes usually are not as serious as in this case.
This case is particularly tricky because of the rarity of Neuroleptic Malignant Syndrome (NMS), and because of the time course. From eMedicine:
NMS onset ranges from 1-44 days following administration of neuroleptic drug; mean onset is 10 days. Lazarus et al reported NMS occurring in 67% of patients within 1 week and 96% of patients within 30 days following administration of neuroleptics.
This particular person had been on a stable medication regimen for two years, so the index of suspicion would have been lowered. As the authors point out, the cessation of smoking probably was a major contributing factor. He had been smoking 80 cigarettes per day, but quit about two weeks before the onset of symptoms.
Cigarette smoking lowers the levels of many antipsychotic medications:
Tobacco smoking seems to act upon cytochrome CYP1A2, inducing neuroleptic metabolism, mainly on clozapine and olanzapine, and polymorphisms within the variation in the cytochrome P450, frequent for isoenzyme 1A2, may influence drug-induced adverse effects and drug efficacy. Several studies suggest that smokers need higher levels of antipsychotics than non-smokers. Smoking can lower the blood levels of some antipsychotics by as much as 50%. Neuroleptic toxicity can appear two-to-four weeks after smoking cessation. This effect may be related to the lack of metabolic induction by smoking.
Smoking cessation may have led to an increase in the level of olanzapine, which seems to be the culprit in this case. (Risperidone is metabolized by CYP2D6.)
The patient described in the report had several risk factors. He was being treated aggressively: the antipsychotics were risperidone 3 mg/day, injectable risperidone 100 mg/15 days, and olanzapine 10 mg/day; he was male (2:1 risk); and he also was taking a high dose of topiramate (600mg), along with a modest dose of lithium (800mg). Both topiramate and lithium are thought to increase the risk of NMS. The article also mentions that working in a hot environment may have been a contributing factor.
These kinds of cases often seem obvious in retrospect. However, patients are not treated retrospectively. For that reason, it is good to study these case reports and keep a clear understanding of the risks involved in treatment.
Brain & Behavior
Medicine & Health
Comments
I've treated 2 cases of NMS, both scary as all hell...
Posted by: PalMD | July 30, 2008 8:23 AM
The dosages of risperidone are, to say the least, somewhat high. This is not an uncommon practice in Spain where polypharmacy (irrational) is rampant. The exceptional thing is not to see this more often.
Posted by: casimiro | July 31, 2008 3:06 AM