Old drug, new data

Abstract

New data have emerged over the past 10 years regarding the efficacy and mechanisms of action of lithium. This article briefly summarises the evidence for the use of lithium to treat affective disorders and psychosis, reviews its putative anti-suicidal effect, highlights new research on its mechanism of action and provides an update on some important side-effects and consequences of its use.

Lithium and chronic kidney disease: to stop or not to stop?

“…8 However, relapse in BD following cessation of lithium therapy is a well recognised risk and episodes could subsequently be more severe and more difficult to treat. 9,10 There is no way of predicting whether a patient would respond well to alternative treatments to manage BD (such as atypical antipsychotics or anticonvulsants), most of which themselves are associated with an increased risk of metabolic syndrome. To complicate matters further, there is no guarantee of slowed renal decline even after lithium is stopped.…”

“…The elevated cardiovascular risk in patients with CKD manifests as higher rates of coronary artery disease, heart failure, arrhythmias, and sudden cardiac death 8 . However, relapse in BD following cessation of lithium therapy is a well recognised risk and episodes could subsequently be more severe and more difficult to treat 9,10 . There is no way of predicting whether a patient would respond well to alternative treatments to manage BD (such as atypical antipsychotics or anticonvulsants), most of which themselves are associated with an increased risk of metabolic syndrome.…”

“…5,6 In 2012, Werneke et al carried out a decision analysis of longterm lithium treatment and the risk of renal failure, which suggested that lithium continuation, even in the presence of long-term adverse renal effects, should be recommended in most cases. 10 Broadly speaking, lithium should be continued for patients presenting with CKD stages 1 or 2, without heavy proteinuria.…”

Duodenal application of Li+ in a submaximal therapeutic dose inhibits exocrine pancreatic secretion and modulates gastro-duodenal myoelectrical activity in a conscious pig model

“…The GI side effects of lithium include nausea, emesis, and epigastric discomfort, as well as functional constipation or mild but persistent diarrhoea (Matson et al 2006;Li et al 2007;Licht et al 2010;Fosnes et al 2011). The emesis related to lithium therapy is regarded as one of the signs of incipient intoxication, and hence requires close medical monitoring, while abdominal discomfort and diarrhoea are perceived as transitory symptoms (Ferrier et al 2006), and thus they may be accepted as unavoidable side effects of lithium. However, of all the GI disturbances related to lithium therapy, epigastric discomfort as well as diarrhoea are often more upsetting for patients because they present in a continuous manner, while emesis, for example, occurs in discrete episodes.…”

Investigating light sensitivity in bipolar disorder (HELIOS-BD)

“…However, lithium has variable efficacy within the bipolar disorder population, with roughly one third of individuals having a ‘full’ response. Lithium has many reported actions – including modulation of monoamine neurotransmission ( Ferrier et al , 2006 ), inhibition of glycogen synthase kinase-3 ( Klein & Melton, 1996 ), reducing the hyperexcitability of neurons and neuroprotection ( Mertens et al , 2015 ) – but the precise mechanism of action in bipolar disorder remains an active area of research. Given the considerable etiological and clinical heterogeneity of bipolar disorder, it is possible that lithium has different modes of action within different patient subgroups.…”