Does Lithium Treatment Still Work?

Baldessarini, Ross J.; Tondo, Leonardo

doi:10.1001/archpsyc.57.2.187

Cited by 145 publications

(26 citation statements)

References 43 publications

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“…Besides the broadening of diagnostic criteria, this might be attributed to a selection bias that results from the fact that the patients were recruited in university hospitals. Patients with more atypical, treatment-unresponsive illness may be overrepresented in most research centers [8,53]. In general, the use of lithium is limited by its narrow therapeutic range and its disturbing side effects [54,55].…”

Section: Discussionmentioning

confidence: 99%

Differential Efficacy of Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder: Results of the MAP Study

Kleindienst¹,

Greil

2000

Neuropsychobiology

105

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In a randomized clinical trial with an observation period of 2.5 years, the differential efficacy of lithium versus carbamazepine was compared in 171 bipolar patients (DSM-IV). In order to investigate the efficacy of the two drugs in clearly defined subsamples, a series of subgroup analyses was carried out. First, patients with a bipolar I disorder (n = 114) were analyzed separately. In these patients, lithium was superior to carbamazepine. In contrast, carbamazepine was at least equally as efficacious as lithium in the subsample of patients with bipolar II disorder or bipolar disorder not otherwise specified (n = 57). In a second analysis on differential efficacy, the whole sample was subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity; n = 67) and a nonclassical subgroup including all other patients (n = 104). Classical bipolar patients had a significantly lower hospitalization rate under lithium than under carbamazepine prophylaxis (26 vs. 62%, p = 0.012). For the nonclassical group, a tendency in favor of carbamazepine was found. In a third step, we analyzed the impact of episode sequence on differential efficacy. In a global view, the episode sequence prior to the index episode was not correlated to differential efficacy. Our results might, however, indicate that patients with an episode sequence of mania-depression-free interval responded better to lithium. Besides differential efficacy, suicidal behavior and patients’ satisfaction with treatment were investigated. Regarding suicidal behavior, a trend in favor of lithium was found. The data on patients’ satisfaction were significantly in favor of carbamazepine. In conclusion, lithium appears to be superior to carbamazepine in classical bipolar cases and might have additional impact on proneness to suicide. The distinctly larger group of patients with nonclassical features might profit more from carbamazepine which seems to be well accepted by the patients. Hence, treatment alternatives to lithium are desirable for the majority of bipolar patients.

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Section: Discussionmentioning

confidence: 99%

Differential Efficacy of Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder: Results of the MAP Study

Kleindienst¹,

Greil

2000

Neuropsychobiology

105

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“…Their main advantage usually is the length of observation, in some instances reaching several decades 363, 364, 365. This comes at the cost of generalizability, in terms of both patient selection and non‐random treatment allocation.…”

Section: Maintenance Therapy For Bipolar Disordermentioning

confidence: 99%

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

et al. 2018

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The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

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“…It is also important to acknowledge that lithium is stably effective in patients with typical BD, and that the more recent reports of reduced lithium efficacy could be attributed to expansion of the diagnostic criteria of BD in DSM-based systems. 24–27 Long term studies indicate that the distribution of response to lithium is typically bimodal, sometimes trimodal, with a smaller group of partial responders. 28 It is unclear whether partial responders are similar to responders, except that their treatment may not be optimized with respect to plasma levels or there is inadequate attention to adherence to treatment.…”

Section: Mechanismsmentioning

confidence: 99%

Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics

2015

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After decades of research, the mechanism of action of lithium in preventing recurrences of bipolar disorder remains only partially understood. Lithium research is complicated by absence of suitable animal models of bipolar disorder and by having to rely on in vitro studies of peripheral tissues. A number of distinct hypotheses emerged over the years, but none has been conclusively supported or rejected. The common theme emerging from pharmacological and genetic studies is that lithium affects multiple steps in cellular signalling, usually enhancing basal and inhibiting stimulated activities. Some of the key nodes of these regulatory networks include GSK3, CREB, and Na+-K+ ATPase. Genetic and pharmacogenetic studies are starting to generate promising findings, but remain limited by small sample sizes. As full responders to lithium seem to represent a unique clinical population, there is inherent value and need for studies of lithium responders. Such studies will be an opportunity to uncover specific effects of lithium in those individuals who clearly benefit from the treatment.

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Does Lithium Treatment Still Work?

Cited by 145 publications

References 43 publications

Differential Efficacy of Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder: Results of the MAP Study

Differential Efficacy of Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder: Results of the MAP Study

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics

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