Reversible neurotoxicity lithium

Originally, it was thought that, except in extreme cases, lithium-induced neurotoxicity was reversible. However, it eventually became apparent that many patients develop irreversible brain damage and dysfunction, often involving the cerebellum (Grignon et al., 1996). In the last two decades, researchers have defined a syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). Adityanjee et al. (2005) reviewed the literature from 1965 to 2004 for cases of lithium neurotoxicity with the persistence of sequelae for at least 2 months after cessation of treatment. They found 90 cases of SILENT, with persistent cerebellar dysfunction as the most commonly reported persistent aftereffect. These... 

Lee SH, Yang YY. Reversible neurotoxicity induced by a combination of clozapine and lithium a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1999 62(3) 184-7. 

The combination of clozapine and lithium has been studied in a randomized controlled trial in 10 patients with schizophrenia and 10 with a schizoaffective disorder taking clozapine with either lithium or placebo for 4 weeks (299). The combination was well tolerated, except for reversible neurotoxic reactions in two patients with schizophrenia, and safety measures showed no significant variations. The authors concluded that the lithium added to clozapine appears to afford potential benefit in schizoaffective disorders without harmful effects for schizophrenia, however, it did not afford improvement but posed a risk of lithium toxicity. 

Keitner GI, Rahman S. Reversible neurotoxicity widi combined lithium-haloperidol administration. J Clin Psychopharmacol (1984) 4,104-5. 

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

A retrospective study of patient records revealed 5 patients with bipolar affective disorder, treated with lithium carbonate 900 mg to 2.4 g daily, who had developed a reversible neurotoxic syndrome with ataxia, dysarthria. 

Nervous System Reversible Neurotoxicity. Reversible neurotoxicity can occur with lithium. A review of 52 cases in the literature in which patients presented with neurotoxic manifestations, but recovered with time was published [82review] Patients ranged from 10 to 80 years old, and women were over-represented. Patients frequently presented with delirium, along with dyscoordination, tremor, and hyperreflexia. Most patients had serum levels below 1.5 mM. Only eight cases had levels greater than 1.5 mM [82 ]. 

Non-reversible lithium neurotoxicity continues to be reported (165,166), including a case of lithium overdose (serum lithium concentration 3.9 mmol/1) with persistent severe ataxia for 9 months that improved markedly when inadvertently treated with high-dose buspirone (120-160 mg/day) (167). 

Garcia-Resa E, Blasco Fontecilla H, Valbuena Briones A. Sindrome de neurotoxicidad irreversible por litio. [Non reversible lithium neurotoxicity a case report.] Med Clin (Bare) 2001 116(9) 357. 

Netto 1, Phutane VH. Reversible lithium neurotoxicity review of the literature. Prim Care Companion CNS Disord 2012 14(1). PCC.llr01197. ] Baek JH, Kinrys G, Nierenberg AA. Lithium tremor revisited pathophysiology and treatment. Acta Psychiatr Scand 2014 129 17-23. 

---