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- Kurko, TAT, et al.
(author)
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Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies
- 2015
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In: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 1778-3585. ; 30:8, s. 1037-1047
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Journal article (peer-reviewed)abstract
- BackgroundNumerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with “for and against” debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD.MethodsSystematic review of register-based studies on long-term BZD use published in 1994–2014.ResultsFourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as “long-term” varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13–36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31–64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found.ConclusionsLong-term BZD use is common and a clinical reality. Uniform definitions for “long-term”, which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.
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- Rivera, C, et al.
(author)
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BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion
- 2002
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In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 159:5, s. 747-752
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Journal article (peer-reviewed)abstract
- Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+-Cl- cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl- extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatio-temporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.
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