A reappraisal of the role of fever in the occurrence of neurological sequelae following lithium intoxication: a systematic review

Abstract

Aim We aimed to review cases of Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) characterized by neurological sequelae following acute lithium toxicity and to explore whether cerebellar sequelae are more frequent in cases presenting with fever and/or infection. Methods Case reports were identified from: (i) 6 reviews published up to 2005; (ii) MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search. Results We identified 123 SILENT cases published from 1965 to 2019, in which cerebellar sequelae were observed in an overwhelming proportion (79%). Nearly two out of three cases (63%) had maximal lithium plasma level <2.5 mEq/l (low/mild toxicity). Fever and/or infection were reported in nearly half of the patients (48%). The likelihood of presenting with cerebellar vs. other neurological sequelae was independently increased by elevated plasma lithium level ( 2.5 mEq/l) (OR=4.36, 95%CI 1.31-14.52, p = 0.02) and by a history of fever and/or infection (OR=6.48, 95%CI 2.0-21.0, p = 0.002). Conclusions During the SARS-CoV-2 pandemic, prescribers have to be aware of the risks of cerebral sequelae associated with infection and fever in lithium users, and should warn them of the need to consult in case of fever to adjust their lithium dosage. As the occurrence of SILENT is exceptional, there is no need to modify lithium treatment preventively because of the pandemic as the benefit/risk balance of this drug remains largely positive.

Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder

“…There appears to be a historic assumption that lithium could be stopped abruptly because it did not induce any withdrawal effects. 49 However, lithium is shown to have clear withdrawal effects not related to relapse of primary illness. 30 This was perhaps first demonstrated by Bunney et al in 1968 when patients in the placebo arm of abrupt lithium discontinuation had an increased mania reading even if the placebo period lasted for only a day.…”

“…30 This was perhaps first demonstrated by Bunney et al in 1968 when patients in the placebo arm of abrupt lithium discontinuation had an increased mania reading even if the placebo period lasted for only a day. 30 In the case of lithium, some of the withdrawal effects reported in literature include anxiety, irritability and sleep disturbances, 25,30,32,49,50 symptoms that are also consistent with withdrawal from other psychotropic medications. Blockade of the development of supersensitive dopamine receptors; changes in neuronal membranes, cell transport function or other neurotransmitter systems; rebound increase in noradrenaline; and psychogenic-anxiety due to the discontinuation of an effective medication have been suggested as possible explanations of the lithium withdrawal phenomenon.…”