Lithium neurotoxicity at normal therapeutic levels

Moscovich, Daniel G.

doi:10.1192/bjp.163.3.410

Cited by 13 publications

(8 citation statements)

References 3 publications

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“…Typically signs of Li toxicity are evident with high lithium level greater than 1.5 mEq/L [5], but there have been case reports of toxicity even within therapeutic levels [6, 7]. Our patient had a level that was the upper limit of normal; however, considering that there was a 70% increase in his lithium levels shortly after the increase in the dose of Valsartan makes a very strong case for lithium toxicity.…”

Section: Discussionmentioning

confidence: 85%

Lithium Toxicity and Neurologic Effects: Probable Neuroleptic Malignant Syndrome Resulting from Lithium Toxicity

Edokpolo

Fyyaz

2012

Case Reports in Psychiatry

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Introduction. We present the case of a patient who developed lithium toxicity with normal therapeutic levels, as a result of pharmacokinetic interaction with Valsartan, and probable Neuroleptic Malignant Syndrome from the ensuing lithium toxicity. Case Presentation. A 59-year old black male with bipolar disorder maintained on lithium and fluphenazine therapy presented with a 2 week history of worsening confusion, tremor, and gait abnormality. He recently had his dose of Valsartan increased. At presentation, patient had signs of autonomic instability, he was confused, dehydrated, and had rigidity of upper extremities. Significant labs on admission were lithium level-1.2, elevated CK-6008, leukocytosis WBC-22, and renal impairment; Creatinine-4.1, BUN-35, HCO3-20.1, and blood glucose 145. CT/MRI brain showed old cerebral infarcts, and there was no evidence of an infective process. Lithium and fluphenazine were discontinued, his lithium levels gradually decreased, and he improved with supportive treatment including rehydration and correction of electrolyte imbalance. Conclusions. This case illustrates that lithium toxicity can occur within therapeutic levels, and the neurotoxic effect of lithium can include Neuroleptic Malignant Syndrome. Clinicians should be aware of the risk associated with drug interactions with lithium.

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Section: Discussionmentioning

confidence: 85%

Lithium Toxicity and Neurologic Effects: Probable Neuroleptic Malignant Syndrome Resulting from Lithium Toxicity

Edokpolo

Fyyaz

2012

Case Reports in Psychiatry

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“…Although lithium has a narrow therapeutic margin and well-known adverse effects, it is safe to use in the therapeutic dose range. Several minor side effects may occur at serum levels of lithium ranging from 0.6 to 1.2 mEq/L that have been demonstrated to be efficacious in the treatment of BD (Moscovich, 1993; Speirs & Hirsch, 1978). Symptoms associated with serum levels above 1.5 mEq/L are generally mild, including tremor, nausea, diarrhea, vertigo, and confusion (American Psychiatric Association, 2002).…”

Section: Introductionmentioning

confidence: 99%

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Chiu

Chuang

2010

Pharmacology & Therapeutics

199

198

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Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium’s main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington’s, Alzheimer’s, and Parkinson’s diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium’s neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases.

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“…Toxicity associated with lithium treatment is prevalent: 75–90% of patients treated with lithium have symptoms and signs of toxicity at some point during their treatment 2 . Many minor side‐effects may occur at serum levels of 0.6–1.2 mEq/L, although serum lithium concentrations ranging from 0.6 to 1.2 mEq/L have been demonstrated to be efficacious in the treatment of bipolar patients 3,4 . Symptoms and signs of mild intoxication (with levels >1.5 mEq/L) include marked tremor, nausea, diarrhea, blurred vision, vertigo, confusion, and increased deep tendon reflexes.…”

Section: Introductionmentioning

confidence: 99%

Implication of serum concentration monitoring in patients with lithium intoxication

Chen

Shen

2003

Psychiatry Clin Neurosci

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The aim of the present study was to determine the relationships between serum lithium level, duration of lithium intoxication, severity of symptoms, and the outcome of the disease. Subjects with a serum lithium level of ≥ 1.2 mEq/L were included in the study. Seventy-eight patients with lithium intoxication were identified between 1 July 1999 and 31 December 2002. The demographic characteristics, clinical manifestations, and concomitant medications were recorded. Most patients with acute lithium intoxication had mild symptoms, independent of the serum lithium levels. In patients with chronic lithium intoxication, the frequency of severe symptoms was higher than in those with acute intoxication. None of the 78 intoxicated patients in the present survey died or suffered from persistent neurological sequelae. Patients with concomitant medications, older age, and existing neurological illness may have an increased susceptibility to lithium toxicity. Regular monitoring of serum lithium level is essential for lithium-treated patients. Clinicians should pay attention to patients with pre-existing neurological illness, older age, or receiving medications that may interact with lithium.

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Lithium neurotoxicity at normal therapeutic levels

Cited by 13 publications

References 3 publications

Lithium Toxicity and Neurologic Effects: Probable Neuroleptic Malignant Syndrome Resulting from Lithium Toxicity

Lithium Toxicity and Neurologic Effects: Probable Neuroleptic Malignant Syndrome Resulting from Lithium Toxicity

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Implication of serum concentration monitoring in patients with lithium intoxication

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