Psychotropic drugs and renal failure: translating the evidence for clinical practice.

INTRODUCTION: The kidney is a primary route of drug elimination; abnormal kidney function is predicted to alter the pharmacokinetics of agents metabolized and/or excreted predominantly through this route. The high prevalence of mental disorders associated with psychotropic drug use in individuals with deteriorating renal function suggests there is a need to investigate the effects of renal failure on psychotropic pharmacokinetics. The aim of this review is to provide a clinically accessible overview of the effect of chronic renal failure on the pharmacokinetics for each of the major classes of prescribed psychotropic agents. METHODS: All English language articles published between 1977 and 2008 were searched through PubMed, using the following keywords: "renal," "kidney," "pharmacokinetics," "renal impairment," "renal insufficiency," and "renal failure." Each of these search words was cross-referenced with the non-proprietary name of each psychotropic agent. The manufacturer's product insert was also reviewed for some agents for updated dosing. Owing to the lack of adequately powered studies, an inclusive manner was used. RESULTS: Chronic renal failure variably affects the pharmacokinetic parameters of psychotropic drugs. A review of each psychotropic drug is provided, with an emphasis on the individual pharmacokinetic parameters and recommended dosing. CONCLUSIONS: The adjudication of safe and effective doses for any psychotropic agent needs to be individualized. Tactics including dosage adjustment, slow titration, and careful monitoring for serious adverse events should be incorporated into practice.

Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities.

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future. Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS. An emerging paradigm regarding the pathophysiology of mood disorders posits that alterations in biological networks that mediate stress compromise optimal neuronal and glial function. A growing body of evidence indicates that central administration of insulin may enhance cognitive function in both healthy and cognitively impaired individuals. The neuroactive peptides, insulin, IGF-1 and incretins, or agents that facilitate their central effects (e.g. insulin-sensitizing agents), may constitute novel and possibly disease-modifying neurocognitive treatments.