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.