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metabolism, reduced blood levels
and hence reduced benefits from
mirtazapine. Secondly, cigarette
smoking induces CYP1A2 enzymes.
Increasing his cigarette use may have
further reduced the blood levels of
mirtazapine and hence its effects.
Mirtazapine is generally well
tolerated. The histamine H1
antagonistic activity of mirtazapine
may cause a degree of sedation in the
first weeks of treatment.2 Sedation
is decreased at higher doses of
mirtazapine (more than 15 mg daily).3
Therefore, reduced mirtazapine
concentrations due to increased
tobacco smoking in conjunction
with being a CYP1A2 ultrarapid
metaboliser may have reduced the
benefits of mirtazapine but also
increased the risks of sedation and
falls. Mr York may be experiencing
dizziness, which might be
contributing to his decline in mobility;
perhaps he is reluctant to stand up
due to dizziness and/or drowsiness.
Other causes of his behavioural issues
may include urinary tract infections
(UTIs), other infections (note elevated
white blood cells and neutrophils),
interpersonal issues with particular
staff, ambient temperature of his
living areas and/or boredom. Pain and
constipation appear to be managed
well at this stage.
Quetiapine is metabolised by
CYP2D6 (see Table 2), which has
slightly reduced activity in Mr
York. This means that if quetiapine
doses are increased, Mr York will
be at an increased risk of side
effects from quetiapine (e.g.
orthostatic hypotension, impaired
alertness, somnolence, dizziness,
eosinophilia, elevated LFT results, dry
Mr York takes medicines that may
increase his risk of falls by reducing his
blood pressure and/or causing central
nervous system (CNS) depression (e.g.
mirtazapine, quetiapine, ramipril,
and oxazepam occasionally). Regular
colecalciferol (OsteoVit-D) 1,000 IU in
paracetamol (Panamax) 500 mg two
tablets three times a day plus two
daily when required
salbutamol (Ventolin) 100 mcg
metered dose inhaler (MDI) with
spacer two to six doses every four
hours when required
oxazepam (Serepax) 7.5 mg three
times a day when required.
All oral medicines are being crushed/
dispersed due to resistive behaviours.
Weight: 71.1 kg (stable).
Body mass index (BMI): 21.7 kg/m2
Vaccinations: Influenza (05/2015) and
Relevant recent pathology
Urea, electrolytes, creatinine (UEC):
Na 139 mmol/L (135–145 mmol/L),
K 5.1 mmol/L (3.5–5.5 mmol/L),
urea 7.0 mmol/L (3.0–8.0 mmol/L),
creatinine 105 micromol/L
(60–110 micromol/L). Calculated
creatinine clearance (CrCl)
Liver function tests (LFTs): all within
Full blood examination (FBE):
haemoglobin (Hb) 122 g/L (130–
180 g/L), platelets 582 x 109/L (150–
400 x 109/L), white cell count (WCC)
15.1 x 109/L (4–11 x 109/L), neutrophils
10.5 x 109/L (2.0–8.0 x 109/L).
Therapeutic drug monitoring (TDM):
valproate 174 micromol (350–
Mr York has a sister and other
family members who visit often. He
demonstrates unpredictable physical
and verbal behaviours, is dismissive with
mood swings and can be aggressive
and swear, which can be distressing for
family and staff. Waiting for his hourly
cigarette often triggers his aggression,
so staff have been giving extra
cigarettes to manage this behaviour.
His pain is managed well but his
mobility has declined over the last few
months to the point where he mostly
pushes himself in a wheelchair. Mr York
has had three falls in the past 12 months
with no injuries.
Mr York’s general practitioner
(GP) decided Mr York needed a
pharmacogenomic test due to the
difficulties in stabilising his patient
on various antipsychotic and
antidepressant therapies (see Table 1).
His GP had previously been part of a
pharmacogenomics study conducted by
GenesFX in various psychogeriatric care
• Mr York’s depression may not
be adequately controlled with
mirtazapine, which may be
contributing to his difficult
behaviours. Firstly, mirtazapine
is metabolised by both CYP1A2
and CYP2D6 (see Table 2). The
pharmacogenomic test results
show that Mr York has slightly
reduced activity of CYP2D6 and
ultrafast activity of CYP1A2 enzyme.
The net effect being increased
Table 1. Pharmacogenomic test results
ultrarapid metaboliser (fast)
slightly reduced activity (reduced by ~30%)
slightly reduced activity (reduced by ~30%)
high warfarin sensitivity
possible improved response to a selective serotonin reuptake
Note: There are currently no reliable genetic tests to determine differences in CYP3A4 activity.
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