Discussion:
This retrospective case series was inclusive of 18 patients that had
similar demographics with a median age of 48 years old compared to other
studies9. There was a marked male prevalence at 89%
in this study, which although increased when compared with previous
studies2, 9 is likely a representation of small sample
size.
The median onset of olanzapine PDSS post injection of 30 minutes (IQR
11-38min) in our series is similar to previous studies that showed
80-90% developed symptoms within 1h2, 9, 10.
Moreover, this rapid onset further supports the pathophysiology of PDSS
of partial intravascular penetration and subsequent premature
dissolution of the depot by McDonell3.
The most common first symptom displayed post injection was drowsiness
(61%) followed by dizziness (22%) and confusion (11%), which is
analogous to all reported case series (Figure 1) 2, 9,
10. These case series suggest PDSS symptomology primarily being those
of anti-cholinergic syndrome. Complications like urinary retention,
rhabdomyolysis and fever appear to be less frequent. Moreover, the
distribution of anti-cholinergic over anti-dopaminergic symptoms mimics
that of oral olanzapine overdose5,6 adding further
support to the theorised pathophysiology of PDSS being that of premature
rapid dissolution of the salt intravascularly2.
The case series revealed a median PDSS duration of 24 hours, with all
patients’ symptoms lasting within the 1.5-72 hour, duration noted also
by previous studies2, 9, 10. The most common treatment
was supportive care without any pharmacological treatment (56%) and
benzodiazepines for agitation (22%). Olanzapine PDSS has no formal
treatment to minimize the not so insignificant duration of these
debilitating symptoms, aside from supportive care2,
10. However, in the case described we propose a treatment approach with
bromocriptine and physostigmine followed by rivastigmine to manage
anti-dopaminergic and anti-cholinergic symptoms respectively. Although
physostigmine treatment is new in the scope of Olanzapine PDSS, it is
recommended to be used to manage patients with anticholinergic
delirium11. Rivastigmine was used following successful
reversal of delirium with physostigmine due to favourable
pharmacokinetics with longer duration of action (10h). Rivastigmine has
been used to treat prolonged delirium in anti-cholinergic syndrome as it
could reduce symptom recurrence and decrease need for
re-dosing12, 13. Furthermore, bromocriptine was chosen
as it has been suggested for the management of extrapyramidal symptoms
such as rigidity and dystonia14. This proposed
treatment as highlighted by the case may provide substantial opportunity
to lessen or shorten symptoms of this adverse reaction.
Conclusions: This case series demonstrated characteristics of
PDSS symptomology predominantly being those of anti-cholinergic over
anti-dopaminergic symptoms with similar onset (<1 hour) and
duration times (<72hours). A proposed treatment of
physostigmine then rivastigmine for anti-cholinergic symptoms and
bromocriptine for anti-dopaminergic symptoms is suggested for the
management of PDSS, which may provide significant possibility to reduce
symptoms.
Declaration of interests: The authors report no
declarations of interest.