Serum concentrations of mood stabilizers are associated with memory, but not other cognitive domains in psychosis spectrum disorders; explorative analyses in a naturalistic setting.

Monica Aas,Ingrid Melle,Anja Vaskinn,Nils Eiel Steen,Ole A. Andreassen,Mari Nerhus,Erlend Gardsjord,Ragni Mørch,Olav Spigset,Ingrid Agartz,Carmen Simonsen,Ingrid Dieset,Martin Tesli

doi:10.1186/s40345-016-0067-z

Abstract

BackgroundMood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. There is a lack of knowledge of the relationship of these medications and cognition in the psychosis spectrum. We studied the association between serum concentration of mood stabilizers and cognitive performance in a well-characterized sample of bipolar and schizophrenia spectrum disorders.MethodsSerum concentrations of valproate, lamotrigine, and lithium were analyzed for associations to performance on neuropsychological tests in six cognitive domains in individuals with bipolar disorder (n = 167) and in a combined sample of individuals with bipolar or schizophrenia spectrum disorders (n = 217). Linear regression with adjustments for gender, age, and symptom levels of depression, mania, and psychosis were applied for the association analyses.ResultsThere were negative associations between serum levels of valproate and short term delayed recall (bipolar: p = 0.043; combined: p = 0.044) and working memory (bipolar: p = 0.043). A positive association was suggested between serum level of lithium and working memory (bipolar: p = 0.039). There were no other significant relationships between serum levels of valproate, lamotrigine, or lithium and neuropsychological test performance in neither the bipolar disorder nor the combined group.ConclusionsSerum levels of mood stabilizers were unrelated to cognitive performance in most domains, indicating that higher dose does not lead to broader cognitive impairments in bipolar and related psychotic disorder patients. However, worsened memory with increasing levels of valproate suggests cautious dosing of anticonvulsants, while increasing lithium level seems to be associated with improved memory. The findings should be interpreted with caution due to the explorative, naturalistic design.

Highlights

Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders
Lithium and the anticonvulsant agents valproate and lamotrigine are classical mood stabilizers used in the treatment of bipolar disorder
Included in the current analyses were consecutively referred patients from 2003 to 2014 with a diagnostic and statistical manual of mental disorders (DSM)-IV bipolar disorders diagnosis, in the following termed “bipolar disorder” (BD, N = 167), or a schizophrenia and other psychotic disorders diagnosis, in the following termed “schizophrenia” (SCZ, N = 50), with neuropsychological testing and concurrent measurements of serum levels of lamotrigine or valproate recorded as primary anticonvulsant drug, or concurrent measurements of serum levels of lithium

Summary

Introduction

Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. Cognitive impairment is well documented in bipolar and related psychosis spectrum disorders (Bourne et al 2013; Vaskinn et al 2014). Lithium and the anticonvulsant agents valproate and lamotrigine are classical mood stabilizers used in the treatment of bipolar disorder. They are used as adjunctives in schizophrenia in attempts to optimize treatment effect (Citrome 2009). Valproate has been associated with impaired cognitive functioning in several domains, while studies of lamotrigine indicate less negative influences, even advantageous effects for certain domains such as memory and verbal fluency have been suggested (see Dias et al 2012 for an overview of mood stabilizers and cognition)

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