Lithium as the drug of choice for maintenance treatment in bipolar disorder

Kessing, Lars Vedel

doi:10.1111/acps.13070

Cited by 22 publications

(21 citation statements)

References 14 publications

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“…The apparently high prescription of lithium by Spanish psychiatrists agrees with the results that have recently been observed in the Netherlands, where 70% of patients diagnosed with BD or Schizoaffective Disorder were treated with lithium (Renes et al, 2018). Nevertheless, as it is mentioned above this percentage is signi cantly higher than in other neighboring countries (Kessing, 2019). In Sweden, the prescription rate for lithium in BD is 55%, in Denmark 41.7%, in Germany 26.2% and in Scotland 22% (Bohlken et al, 2020;Karanti et al, 2016;Kessing et al, 2016;Lyall et al, 2019) (Table 1).…”

Section: Discussionsupporting

confidence: 87%

“…In fact, over the last two decades, the decrease in lithium´s use is not widespread and in certain countries the lithium´s prescription rate has remained high. In some countries, more than 50% of bipolar patients are treated with lithium while in the US for example, only the 17% (Kessing et al, 2019;Parabiaghi et al, 2015;Renes et al, 2018, Rhee et al, 2020 (Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Overview of Lithium´s Use: A Nationwide Survey

Mendiola

Hidalgo‐Mazzei

Vieta

et al. 2020

Preprint

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Background: Lithium is considered the gold standard treatment for bipolar disorder (BD). Its use as a first-line treatment in BD is supported by current clinical guidelines and scientific evidence. However, over the last two decades it has been observed a downward tendency in lithium´s use in several developed countries. Based on a nationwide survey, the objective of this study is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD.Methods: Data were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of the use of lithium (indication, dosage, monitoring and information for patients).Results: 212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6-0.8 mmol/L) and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients who are on lithium treatment.Conclusions: From the results of the present study it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease that has a typical onset in adolescence, the reasons for the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Overview of Lithium´s Use: A Nationwide Survey

Mendiola

Hidalgo‐Mazzei

Vieta

et al. 2020

Preprint

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“…The LR phenotype is often deemed ‘classical’ in terms of its resemblance to the original Kraepelinian descriptions . However, Hui et al and Kessing , in his accompanying editorial, note that the existing body of literature on clinical predictors of LR warrants a cautious interpretation: There appears to be substantial meta‐analytic heterogeneity, sample sizes have tended to be small, and response has often not been defined using validated instruments. Therefore, the predictive utility of clinical information is promising but warrants further scrutiny.…”

Section: Introductionmentioning

confidence: 99%

Prediction of lithium response using clinical data

Nunes

Ardau²,

Berghöfer

et al. 2019

Acta Psychiatr Scand

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Prediction of lithium response using clinical data.Objective: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. Method: Our data are the largest existing sample of direct interviewbased clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. Results: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. Conclusion: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial betweensite heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between-and within-site heterogeneity, and further testing such models on new external datasets.• Lithium response can be predicted accurately (area under the receiver operating characteristic curve of 0.80) in previously unobserved subjects based on data collected by careful clinical interview.• Variables related to clinical course of illness and absence of rapid cycling are particularly informative. Limitations• Our data were retrospective in nature, although data of such as scope would be difficult to collect prospectively.

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“…Individual clinical trials, cohort studies and meta‐analyses of pooled data have demonstrated the broad clinical benefits of lithium (Li) (e.g. ), and Kessing notes that all international clinical practice guidelines identify Li as a first‐line continuation treatment for BD. However, patient and clinician preference for Li is lower than might be expected .…”

Section: Introductionmentioning

confidence: 99%

“…A critical element of any treatment of BD‐I is the need for long‐term efficacy . Individual clinical trials, cohort studies and meta‐analyses of pooled data have demonstrated the broad clinical benefits of lithium (Li) (e.g.…”

Section: Introductionmentioning

confidence: 99%

Can network analysis shed light on predictors of lithium response in bipolar I disorder?

Scott

Bellivier

Manchia

et al. 2020

Acta Psychiatr Scand

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investigators involved in the ConLiGen collaboration. Can network analysis shed light on predictors of lithium response in bipolar I disorder?.Objective: To undertake a large-scale clinical study of predictors of lithium (Li) response in bipolar I disorder (BD-I) and apply contemporary multivariate approaches to account for interrelationships between putative predictors. Methods: We used network analysis to estimate the number and strength of connections between potential predictors of good Li response (measured by a new scoring algorithm for the Retrospective Assessment of Response to Lithium Scale) in 900 individuals with BD-I recruited to the Consortium of Lithium Genetics. Results: After accounting for co-associations between potential predictors, the most important factors associated with the good Li response phenotype were panic disorder, manic predominant polarity, manic first episode, age at onset between 15-32 years and family history of BD. Factors most strongly linked to poor outcome were comorbid obsessive-compulsive disorder, alcohol and/or substance misuse, and/ or psychosis (symptoms or syndromes). Conclusions: Network analysis can offer important additional insights to prospective studies of predictors of Li treatment outcomes. It appears to especially help in further clarifying the role of family history of BD (i.e. its direct and indirect associations) and highlighting the positive and negative associations of different subtypes of anxiety disorders with Li response, particularly the little-known negative association between Li response and obsessive-compulsive disorder.• Using network modelling may help clarify predictors of lithium response and understand any differences associated with two commonly employed definitions of outcome: change in illness activity or change in illness activity after consideration of potential cofounders.• The network model highlighted that whilst family history of bipolar disorders has a weak direct connection with good lithium response, it is a highly influential node in the network and is linked to other predictors such as age at onset of illness.• This study identified that obsessive-compulsive disorder was one of the most robust predictors of poor lithium response, a finding that may have been obscured in previous studies due to lack of statistical power of other analytic approaches. Limitations• We focused only on bipolar I disorder, measured treatment outcome using only one rating scale and used a strict definition good response to lithium. Using these approaches, the overall rate of good outcome was about 14%.• The original data set available for this study lacks information on some factors previously identified as being associated with good response to lithium.• We created a binary network model, which may have over-or under-estimated some co-associations between putative predictors. As such, findings will need replicating in another large-scale, independent data set.

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Lithium as the drug of choice for maintenance treatment in bipolar disorder

Cited by 22 publications

References 14 publications

Overview of Lithium´s Use: A Nationwide Survey

Overview of Lithium´s Use: A Nationwide Survey

Prediction of lithium response using clinical data

Can network analysis shed light on predictors of lithium response in bipolar I disorder?

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