Cotard’s syndrome resulting from acyclovir treatment in patients with impaired renal function – literature review

Objectives.
This article aims to review the literature on neurological and psychiatric complications of acyclovir with particular emphasis on mental disorder, such as Cotard’s syndrome, among patients with renal failure who receive acyclovir. A mechanism of neuropsychiatric effects of antiviral toxicity most likely occurs when 9-carboxymethoxymethylguanine (9-CMMG), which is acyclovir’s main metabolite, crosses the blood-brain barrier and inhibits mitochondrial DNA polymerase, which leads to mitochondrial toxicity and ultimately increased uremic toxicity. Due to the rarity of this phenomenon, both the pathomechanism and treatment are not sufficiently studied.

Literature review.
The literature review was carried out in terms of the occurrence of neurological and psychiatric side effects, especially nihilistic disorders in patients with renal failure taking acyclovir or its prodrug – valacyclovir. Case reports present the patients with no history of serious mental illnesses in the past. The possibility of using the 9-CMMG metabolite as a marker for neuropsychiatric disorders was also presented.

Conclusions.
Acyclovir is a commonly used drug, which in rare cases can be neurotoxic. Neurological side effects are: disorientation, confusion, impaired consciousness, dysarthria, agitation, visual hallucinations, auditory hallucinations, psychoses and delusions of being dead, which can be described as Cotard’s syndrome. Cotard’s sydrome is a rare psychiatric condition with strong delusions of being dead. Acyclovir is metabolized and oxidized to 9-carboxymethoxymethylguanine (9-CMMG) which may cause neuropsychiatric side effects mainly in patients with impaired renal function. Hemodialysis and reduction of the dose have been an effective treatment in some cases.