Abstract
The case report by Nama and Aftab (2012) brought to mind the old medical adage, ‘when you hear hoof beats, think horses, not zebras’. The authors have reported the case of a patient who, 2 months after an increase in his clozapine dose, presented with altered consciousness, generalized weakness, myoclonic jerks and hypotension, without pyrexia, muscle rigidity or significant elevation of serum creatine kinase. These appear to be clinical features of toxic levels of clozapine and, along with an elevated serum clozapine level of 2070 µg/l, suggests that the most likely diagnosis was a ‘typical’ case of clozapine toxicity rather than an ‘atypical’ case of neuroleptic malignant syndrome (NMS). Although the exact range of clozapine levels that corresponds to toxicity remains unclear, levels above 1000 µg/l have been linked to toxicity (Greenwood-Smith et al., 2003; Stark and Scott, 2012). It is therefore not surprising that the clinical features improved with cessation of clozapine, which was unfortunately done only on the fifth day of admission.
NMS is generally considered as a diagnosis of exclusion and virtually all cases occur within 30 days of initiation or change in dose of antipsychotic (Strawn et al., 2007). Also, this patient had myoclonic seizures which are a well-described complication of clozapine toxicity (Greenwood-Smith et al., 2003; Wong and Delva, 2007) and not NMS. The authors have rightly pointed out that a diagnosis of NMS in this case was difficult in the absence of any core feature of the same. However, there was plenty of evidence in this case to suggest clozapine toxicity.
This case highlights the importance of considering psychotropic drug toxicity as a differential diagnosis in patients with chronic psychiatric illnesses who present to emergency departments with similar clinical features. Not entertaining such a possibility could lead to continuation of the drug, as in this case, leading to prolonged effects of toxicity with potentially fatal complications. Also, the possibility of an intentional drug overdose is likely to be missed.
Once the patient has recovered from the acute illness, the most significant impact of a diagnosis of NMS is that the offending drug is unlikely to be reconsidered for ongoing treatment of schizophrenia. The same is, however, not true of drug toxicity. It is thus likely that this patient will not be given clozapine again, which in all likelihoods was started in the first place because of treatment resistance, thus precluding him of benefiting from the ‘most effective antipsychotic’.
To conclude, the tendency to look for atypical presentations of cases may lead to clinicians overlooking straightforward presentations and more common diagnostic possibilities, which can lead to significant and potentially life-threatening complications for the patient.