Lithium Neurotoxicity Due to Second-Generation Antipsychotics Combined With Lithium

Netto, Ivan; Phutane, Vivek H.; Ravindran, Bipin

doi:10.4088/pcc.17r02225

Cited by 8 publications

(3 citation statements)

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“…There are two opposing hypotheses regarding interactions between antipsychotics and lithium. One posits that combining antipsychotics with lithium may increase lithium toxicity ( 21 ), which could be due to the anticholinergic effects of antipsychotics, including decreased urine output and delayed lithium elimination, resulting in elevated serum lithium levels. Another hypothesis found no significant differences in serum lithium concentrations between groups combining antipsychotics versus single antipsychotic use.…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report

Wei,

Yang,

Wang

et al. 2024

Front. Psychiatry

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Background and aimLithium is considered to be the first-line treatment for bipolar disorder, and paliperidone was approved for the treatment of schizophrenia and acute bipolar manic/mixed episodes. However, both agents have been associated with thyroid dysfunction and cardiovascular adverse effects like subclinical hypothyroidism, bradycardia, and sinus arrest, even at therapeutic doses.Case presentationHere, we reported a case of a 17-year-old Han Chinese female who developed symptomatic hypothyroidism, sinus bradycardia, and sinus arrest while being treated with lithium and paliperidone for bipolar disorder with psychotic features including auditory hallucinations. Her workup suggested that these adverse effects might be related to the combined lithium and paliperidone treatment, although other causes could not be ruled out. After discontinuing both medications, her thyroid function and heart rhythm normalized over 20 days.ConclusionTo our knowledge, hypothyroidism, sinus bradycardia, and sinus arrest associated with the combined use of lithium and paliperidone had not been reported previously. Further research is warranted to elucidate the potential risks and benefits of this combination therapy for bipolar disorder with psychotic symptoms.

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Section: Discussionmentioning

confidence: 99%

Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report

Wei,

Yang,

Wang

et al. 2024

Front. Psychiatry

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“…Compared to lithium monotherapy, lithium plus valproic acid or -pine drugs can enhance therapeutic effects by increasing lithium concentration, partially supporting our findings. In addition, some case reports have found that the combined use of lithium and antipsychotics can cause neurotoxicity, but serum lithium levels may not increase at the same time [ 56 , 57 , 58 ]. The feature importance ranking of our model can also partially explain it, that is, different types of antipsychotics have different effects on lithium concentration.…”

Section: Discussionmentioning

confidence: 99%

Predicting Serum Levels of Lithium-Treated Patients: A Supervised Machine Learning Approach

et al. 2021

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Routine monitoring of lithium levels is common clinical practice. This is because the lithium prediction strategies available developed by previous studies are still limited due to insufficient prediction performance. Thus, we used machine learning approaches to predict lithium concentration in a large real-world dataset. Real-world data from multicenter electronic medical records were used in different machine learning algorithms to predict: (1) whether the serum level was 0.6–1.2 mmol/L or 0.0–0.6 mmol/L (binary prediction), and (2) its concentration value (continuous prediction). We developed models from 1505 samples through 5-fold cross-validation and used 204 independent samples to test their performance by evaluating their accuracy. Moreover, we ranked the most important clinical features in different models and reconstructed three reduced models with fewer clinical features. For binary and continuous predictions, the average accuracy of these models was 0.70–0.73 and 0.68–0.75, respectively. Seven features were listed as important features related to serum lithium levels of 0.6–1.2 mmol/L or higher lithium concentration, namely older age, lower systolic blood pressure, higher daily and last doses of lithium prescription, concomitant psychotropic drugs with valproic acid and -pine drugs, and comorbid substance-related disorders. After reducing the features in the three new predictive models, the binary or continuous models still had an average accuracy of 0.67–0.74. Machine learning processes complex clinical data and provides a potential tool for predicting lithium concentration. This may help in clinical decision-making and reduce the frequency of serum level monitoring.

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“…Neurotoxicity can be favored by intracellular levels higher than those expected at a given lithium serum concentration in geriatric patients, due to lithium’s pharmacokinetics alterations emerging with age [ 123 , 124 ]. Importantly, the risk to develop neurotoxicity is particularly increased when lithium is prescribed in combination with antipsychotics [ 125 - 127 ]. When neurotoxicity occurs, symptoms are usually reversible after lithium discontinuation [ 128 ], and the reintroduction of lithium at a lower dose is not precluded [ 129 ].…”

Section: Pharmacological and Physical Treatment Of (Hypo)manic Sympto...mentioning

confidence: 99%

Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

Elefante

Brancati

Torrigiani

et al. 2023

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Background: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. Objectives: The main aim of this study is systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated with negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD or FTD and BD or (hypo)mania have been included. Results: Manic symptoms seem to be associated with disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincides with or precedes cognitive impairment in FTD. Overall, mood stabilizers and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert a neuroprotective activity in patients with AD. Conclusion: Prevalence, clinical features and treatment response to pharmacotherapy of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.

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Lithium Neurotoxicity Due to Second-Generation Antipsychotics Combined With Lithium

Cited by 8 publications

References 0 publications

Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report

Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report

Predicting Serum Levels of Lithium-Treated Patients: A Supervised Machine Learning Approach

Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

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