valacyclovir and Mental-Disorders

The patient was a 67-year-old man with a 2-year history of peritoneal dialysis for end-stage renal disease due to hypertensive nephropathy. He presented to a dermatologist with a complaint of pain in the right femoral region. He was diagnosed as having herpes zoster and valacyclovir, 1,000 mg/day, was prescribed. After 5 days of taking valacyclovir orally, he felt fretful and hallucinations appeared. He was admitted to our hospital and was hospitalized in our urology ward. We diagnosed his condition as neurotoxicity caused by an overdose of valacyclovir. As his general condition was stable, he was treated only by continuation of peritoneal dialysis. After 7 days of hospitalization, the neurotoxicity completely disappeared and he left the hospital. His serum acyclovir concentration at admission was 20.20 μg/l, and was reduced to 0.7 μg/l when he left the hospital. This supported our diagnosis of valacyclovir-induced neurotoxicity. In this case, valacyclovir should have been reduced to 500 mg/day, considering his renal function. Although we could treat the patient only by continuation of peritoneal dialysis, hemodialysis seems to be an effective treatment method in the case of unstable general condition or severe adverse effects, because it can eliminate the serum acyclovir.

Topics: Acyclovir; Aged; Antiviral Agents; Humans; Kidney Failure, Chronic; Male; Mental Disorders; Peritoneal Dialysis; Valacyclovir; Valine

Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy.. We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis.. CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 micromol/L, range 0.6-7.0). The concentration of CMMG was below the limit of quantification (<0.5 micromol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure.. These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.

Topics: Acyclovir; Antiviral Agents; Guanine; Humans; Mental Disorders; Neurotoxicity Syndromes; Retrospective Studies; Valacyclovir; Valine

Causes and pathogenesis of psychiatric disorders is poorly understood. Infections by viruses or other agents may disturb neurotransmitters and elicit behavioral abnormalities, and induce long lasting immune reactions, referred to as mild encephalitis (ME). New findings (pathology, biochemistry, imaging) in schizophrenia and bipolar psychoses are compatible with ME hypothesis. In Chorea Sydenham and PANDAS syndrome autoimmune ME seems to explain anxiety-compulsive-hyperactivity symptoms. Add-on-therapy with Cox-II-blockers or valacyclovir improved acute schizophrenia, CSF filtration some cases of therapy resistant psychoses.

Topics: Acyclovir; Antiviral Agents; Brain; Cyclooxygenase Inhibitors; Demyelinating Autoimmune Diseases, CNS; Encephalitis, Viral; Humans; Mental Disorders; Treatment Outcome; Valacyclovir; Valine

We report three cases of neurotoxicity in patients with renal failure, treated with Zelitrex (valacyclovir).. The patients are two women and a man, aged 76 +/- 4.6 years, who presented acute mental confusion during a treatment with valacyclovir. In two cases, the patients previously had altered renal function and were under peritoneal dialysis. In the last case, the patient had simultaneous neurotoxicity and acute renal failure. After the discontinuation of the drug, the outcome was favourable in all cases.. Our cases focus attention on the possible neurotoxicity of valacyclovir, which is an amino acid ester prodrug of acyclovir, rapidly and almost completely hydrolysed to acyclovir prior to systemic exposure. The bioavailability of valacyclovir is 54% compared to approximately 20% for oral acyclovir and may account for unexpected overdoses, which may lead to serious neurological toxicity.

Topics: Acyclovir; Aged; Aged, 80 and over; Biological Availability; Drug Overdose; Female; Humans; Male; Mental Disorders; Prodrugs; Renal Insufficiency; Valacyclovir; Valine