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.