The lithium paradox: declining prescription of the gold standard treatment for bipolar disorder

Bartoli, Francesco

doi:10.1111/acps.13525

Cited by 10 publications

(5 citation statements)

References 7 publications

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“…Some authors argued that the absence of depressive episodes would make the pharmacological prophylaxis of UM less complex than for md-BD (Angst et al, 2019 ). It is likely that lithium, the underused gold-standard treatment for BD (Bartoli, 2023 ), might represent the first-choice option for UM considering its efficacy in preventing manic episodes (Severus et al, 2014 ). In addition, considering the increased rates of concurrent psychotic features in UM and the effectiveness of second-generation antipsychotics in treating mania (Kishi et al, 2022 ), it can be hypothesized a more prominent role for these drugs in UM, especially in their long-acting formulations (Bartoli et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania

et al. 2023

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Background The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence accumulated in the last few years. We carried out a systematic review and meta-analysis of observational studies testing factors associated with UM as compared to bipolar disorder with a manic-depressive course (md-BD). Methods Studies indexed up to July 2022 in main electronic databases were searched. Random-effects meta-analyses of the association between UM and relevant correlates yielded odds ratio (OR) or standardized mean difference (SMD), with 95% confidence intervals (CIs). Results Based on data from 21 studies, factors positively or negatively associated with UM, as compared to md-BD, were: male gender (OR 1.47; 95% CI 1.11–1.94); age at onset (SMD −0.25; 95% CI −0.46 to −0.04); number of hospitalizations (SMD 0.53; 95% CI 0.21–0.84); family history of depression (OR 0.55; 95% CI 0.36–0.85); suicide attempts (OR 0.25; 95% CI 0.19–0.34); comorbid anxiety disorders (OR 0.35; 95% CI 0.26–0.49); psychotic features (OR 2.16; 95% CI 1.55–3.00); hyperthymic temperament (OR 1.99; 95% CI 1.17–3.40). The quality of evidence for the association with previous suicide attempts was high, moderate for anxiety disorders and psychotic features, and low or very low for other correlates. Conclusions Despite the heterogeneous quality of evidence, this work supports the hypothesis that UM might represent a distinctive diagnostic construct, with peculiar clinical correlates. Additional research is needed to better differentiate UM in the context of affective disorders, favouring personalized care approaches.

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Section: Discussionmentioning

confidence: 99%

Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania

et al. 2023

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“…In addition, the clinical course of bipolar disorder may be influenced by the different effectiveness of treatments for preventing relapses; however, insufficient data were available from the included studies for us to explore the role of this confounder on polarity predominance. For example, lithium, the gold-standard treatment for bipolar disorder, 72 has shown to be more effective in preventing mania than depression, 73 and, in general, there are fewer evidence-based treatments for bipolar depression than for mania. 74 Similarly, data on other important correlates, such as seasonality, 75 affective temperaments 32 and comorbid anxiety disorders, 17 were available only from a limited number of studies, suggesting a need for additional research.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and correlates of manic/hypomanic and depressive predominant polarity in bipolar disorder: systematic review and meta-analysis

Bartoli,

Bassetti,

Gazzola

et al. 2024

BJPsych open

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Background Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. Aims We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. Method The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. Results We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = −3.19, 95% CI: −5.30 to −1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = −1.57, 95% CI: −2.88 to −0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. Conclusions Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.

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“…According to most national and international guidelines, lithium is considered the first-choice long-term episode-preventing strategy, whereas anticonvulsants, such as valproate, lamotrigine, and carbamazepine also have an established role (Fountoulakis et al 2017 ). Pharmacoepidemiological data worldwide point out that SGAs are increasingly being prescribed for the maintenance treatment of bipolar disorders (Bartoli 2023 ). Also, polypharmacy is routine practice ranging from 36% up to 85% of patients in real-world hospital settings (Fornaro et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Controversies regarding lithium-associated weight gain: case–control study of real-world drug safety data

Greil,

de Bardeci,

Müller-Oerlinghausen

et al. 2023

Int J Bipolar Disord

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Background The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). Methods We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: “Arzneimittelsicherheit in der Psychiatrie”; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. Results We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9–5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7–28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3–8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1–5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. Conclusions Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.

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The lithium paradox: declining prescription of the gold standard treatment for bipolar disorder

Cited by 10 publications

References 7 publications

Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania

Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania

Prevalence and correlates of manic/hypomanic and depressive predominant polarity in bipolar disorder: systematic review and meta-analysis

Controversies regarding lithium-associated weight gain: case–control study of real-world drug safety data

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