Discussion
Upon review of the literature, there is only limited reports ofcases of NMS especially in the last 15 years. This could be due because this condition is rare and unpredictable.
An interesting question prompted by this particular case is whether there is a correlation between NMS and Intellectual Disability. A retrospective case note analysis (15) failed to demonstrate a higher than expected prevalence of NMS in clients with learning disability exposed to neuroleptics.Over a one-year period, from 2000 to 2001, a retrospective case note analysis was completed on all case notes of two Mental Health Learning Disability services in the West Midlands in the UK, providing a total of 570 cases. There was evidence of regular neuroleptic (did not specify individual antipsychotics or differentiate between typical or atypical antipsychotics) administration in 301 cases, a rate of 47%. It was discovered only two cases in which a patient hadsymptoms which would give a possible diagnosis ofneuroleptic malignant syndrome.This gives a lifetime prevalence of 0.33% (95% confidence interval of 0.0%- 1.8%)that is not high, in comparison toother published incidence rates (e.g. between 0.2% and 3%). (4-6)
On the other hand, a more recent cohort study from 2017 (16) of9013 adults with intellectual disability and 34 242 adults without intellectual disabilityreported that although occurring infrequently, Neuroleptic Malignant Syndrome was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013).
It is relevant to differentiate NMS from Serotonin Syndrome (SS) as many of the symptoms of both can overlap. A case report (17) described a case of dual onset of both NMS and SS following a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine). However, we are confident that our patient suffered from NMS from a clinical perspective and from a medication timeline perspective. Her Mirtazapine medication that may provoke SS (18) was reduced two months prior to the onset of her physical symptoms.
From a review of English language literature, there are cases of NMS caused by Quetiapine (19).We were unable to identify any cases of NMScaused by Mirtazapine. Also with this case both Quetiapine and Mirtazapine doses were reduced prior the onset of the NMS symptoms, NMS symptoms demonstrated a temporal causality with the increase specifically of Olanzapine.
It is relevant to consider that patientswith diagnoses of Intellectual Disability are more vulnerable. As in our case, patients with moderate/severe ID can find it difficult to communicate their needs. Furthermore, some core NMS symptoms such as changes in mental state can be interpreted as behavioural symptoms, leading to a diagnostic overshadowing that can delay the treatment of NMS. Our case was also complicated by the concomitant onset of bronchitis. In fact, infections can confound a picture of NMS by sharing symptoms such as hyperthermia, autonomic changes and also changes in behaviour such as decreased motivation and social withdrawal and lack of interest in previous enjoyable activities.
One study of relevance in relation to thissuggested that elevation of CK is a non-specific finding, particularly in patients who become pyrexial while on psychotropics; therefore, theinclusion of elevation of CK as a diagnosticcriterion may potentially lead to over-diagnosis of NMS if this happens just in the presence of non-specific features as pyrexia, tachycardia, tachypnoea and diaphoresis. (20)
It is relevant that our patient developed all the four main symptoms of NMS (changes in mental state, muscular rigidity, hyperthermia, autonomic instability) and laboratory tests showed raised CK and increased WBC. All these classical symptoms highlight all the relevant aspects of NMS and this is very important from an academic point of view.
In our case, patient was taking Olanzapine 5mg BD regularly when she developed NMS. This is not a high dose. The maximum dose is 20mg daily (21). A case review (2) of 26 cases on NMS probably secondary to Olanzapine reported that the dose of Olanzapine responsible was not always high, being 10mg OD in 16 cases and 7.5mg OD and 5mg OD in other two cases. It is relevant to note that in three cases, patients had intellectual disability (one mild, one severe, one mild/moderate) and developed NMS at a dose of Olanzapine of respectively 10mg OD, 10mg QDS, 12.5mg OD.
In summary, olanzapine needs to be considered as a risk factor for potential NMS in patients with Intellectual Disability.