Atypical Neuroleptic Malignant Syndrome and Atypical Antipsychotics

Abstract

Clarithromycin-Induced ManiaTO THE EDITOR: This letter presents a case of clarithromycin-induced mania.Ms. A, a 52-year-old woman with a history of three depressive episodes, was admitted for hyperenergetic, loud, and unfocused behavior. She was also elated and delusional. Two days earlier, she had been prescribed a regimen of clarithromycin, 500 mg b.i.d., and prednisone, 60 mg q.i.d., followed by a taper, for severe sinusitis. Results of a neurologic examination were within normal limits; laboratory data were also within normal range. The results of a drug-of-abuse screen were negative; Ms. A's blood alcohol concentration was zero. Her clarithromycin was discontinued; the prednisone taper continued. Within 1 week, Ms. A responded to haloperidol and lithium treatment. She was tentatively diagnosed as having steroid-induced psychosis. Lithium was discontinued after 4 months because of the appearance of hypothyroidism, probably induced by lithium. Two years later, again 2 days after starting treatment with clarithromycin for an acute episode of sinusitis, Ms. A became agitated and acutely delusional. She believed she was "Jesus Christ," a singer and a superstar. She would scream intermittently. She had an expansive mood, flight of ideas, an intense affect, and looseness of associations, but no hallucinations. Her physical examination and laboratory results were unremarkable. Clarithromycin was discontinued, and Ms. A was started on a regimen of haloperidol and lithium. An unequivocal improvement was noted the next day with mildly pressured speech and an expansive mood, but a denial of delusions. Ms. A was discharged 6 days after her admission. Ms. A had two similar episodes with clear evidence of mania and psychosis. During the first episode, she was taking both clarithromycin and prednisone; the mania and psychosis were thought to be due to the prednisone. Before the second episode, Ms. A was taking clarithromycin alone. We think that Ms. A's case represents clarithromycin-induced mania. Her dose of clarithromycin in both episodes was 500 mg b.i.d. as opposed to the relatively high doses (1000 mg b.i.d.) described in the treatment of disseminated Mycobacterium avium-complex infections in two AIDS patients who developed manic episodes (1), similar to the results reported by Cone et al. (2). Clarithromycin has excellent CSF penetration (3), but no reports of possible interaction with central neurotransmitters were found in the literature, although such interaction is a plausible assumption. There have been several reports of CNS side effects of clarithromycin: dizziness, lightheadedness, confusion, and insomnia (4), as well as visual hallucinations (5). 2. Cone LA, Sneider RA, Nazemi R, Dietrich EJ: Mania due to clarithromycin therapy in a patient who was not infected with human immunodeficiency virus. Clin Infec Dis 1996; 22:595-596 3. Schmidt T, Froula J, Tauber MG: Clarithromycin lacks bactericidal activity in cerebrospinal fluid in experimental meningitis. J Antimicrob Chemother 1993; 32:627-632 4. Wallace RJ, ...

Neuroleptic malignant syndrome and its controversies

“…It has been suggested that the decrease of incidence could be a consequence of more conservative prescribing patterns, and of a shift to the use of atypical antipsychotics, but also of increased awareness of the disorder, earlier recognition and intervention. 1,27 A logical question to ask would be how such earlier recognition and intervention could decrease the incidence of the condition assumed to be an unpredictable idiosyncratic drug reaction.…”

Ileus as a Sign of Neuroleptic Malignant Syndrome: A Case Report and Review of the Literature

“…Diagnosis of NMS is largely based on clinical history and the presence of specific clinical symptoms (14). Unlike the patient introduced here, NMS occurs less in patients on stable dose of antipsychotic drugs for long periods of time or those with appropriate long-term compliance (20,21). However, antipsychotics polypharmacy increases the risk of NMS (22).…”

Atypical Neuroleptic Malignant Syndrome or Serotonin Toxicity Associated with Atypical Antipsychotics?

“…However, it is still controversial whether the "atypical NMS" is more likely with atypical antipsychotics than with conventional antipsychotics. Since the presentation of NMS even with typical antipsychotics can be heterogeneous and variable, some investigators are cautious in hastily ascribing milder and atypical cases associated with novel antipsychotics to NMS [29,33,43,77]. Ananth et al [36] concluded that atypical antipsychotic drug-induced NMS manifestations were of similar nature and severity as those produced by conventional antipsychotics.…”