valacyclovir and Cognition-Disorders

Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint.. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group.. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.. NCT00031486.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cognition Disorders; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life; Valacyclovir; Valine; Young Adult

To test our hypothesis that valacyclovir, an antiherpes virus-specific medication, added to antipsychotics (APs) would improve cognitive performance and psychopathology among schizophrenia subjects exposed to neurotropic herpes simplex virus, type 1 (HSV1).. Using a double-blind placebo-controlled design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily orally. At each visit, subjects were evaluated for severity of psychopathology and side effects using standardized scales and a study-specific semistructured checklist. A computerized neurocognitive battery validated on both schizophrenia and healthy subjects was administered at baseline and follow-up. Intent-to-treat analysis, using linear regression models that included all randomized subjects, were used to examine differential changes in cognition and psychopathology scores over 18 weeks between valacyclovir and placebo, accounting for placebo response.. Valacyclovir group improved in verbal memory, working memory, and visual object learning compared with placebo group. The effect sizes (Cohen's d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for the visual object learning. Psychotic symptom severity did not improve.. Supplemental valacyclovir may alleviate impairments in cognitive domains that are often observed in schizophrenia but not psychotic symptoms in those exposed to HSV1. If replicated, this approach could provide a novel strategy to treat cognitive impairments in a subgroup of schizophrenia subjects who can be reliably identified using a blood test.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Learning; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Psychotic Disorders; Schizophrenia; Valacyclovir; Valine; Young Adult

Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia - even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable.. In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N=226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5G twice daily for 16weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT).. PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p=0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved in VAL-treated patients (p=0.048, Cohen's d=0.43).. A proportion of age related decline in EMOD is attributable to HSV-1 infection.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Emotions; Female; Follow-Up Studies; Herpes Simplex; Humans; Male; Middle Aged; Neuropsychological Tests; Randomized Controlled Trials as Topic; Severity of Illness Index; Valacyclovir; Valine; Young Adult