Outcome After Rapid vs Gradual Discontinuation of Lithium Treatment in Bipolar Disorders

Faedda, Gianni L.; Tondo, Leonardo; Baldessarini, Ross J.; Suppes, Trisha; Tohen, Mauricio

doi:10.1001/archpsyc.1993.01820180046005

Cited by 217 publications

(134 citation statements)

References 37 publications

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“…Risks were similar with both BD I and II subtypes, but significantly higher for women with a history of 4 or more prior episodes and for women who abruptly or rapidly (< 2 weeks) discontinued lithium treatment proximate to conception. These findings are consistent with the view that either pregnancy may have little effect on recurrence risk in BD or discontinuation of maintenance treatment itself represents a major, and perhaps dominant, stressor (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Pregnancy and Recurrence Risk In Bdsupporting

confidence: 85%

Managing Bipolar Disorder during Pregnancy: Weighing the Risks and Benefits

et al. 2002

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Background: Challenges for the clinical management of bipolar disorder (BD) during pregnancy are multiple and complex and include competing risks to mother and offspring. Method: We reviewed recent research findings on the course of BD during pregnancy and postpartum, as well as reproductive safety data on the major mood stabilizers. Results: Pregnancy, and especially the postpartum period, are associated with a high risk for recurrence of BD. This risk appears to be limited by mood-stabilizing treatments and markedly increased by the abrupt discontinuation of such treatments. However, drugs used to treat or protect against recurrences of BD vary markedly in teratogenic potential: there are low risks with typical neuroleptics, moderate risks with lithium, higher risks with older anticonvulsants such as valproic acid and carbamazepine, and virtually unknown risks with other newer-generation anticonvulsants and atypical antipsychotics (ATPs). Conclusions: Clinical management of BD through pregnancy and postpartum calls for balanced assessments of maternal and fetal risks and benefits. Contexte: Les problèmes liés au traitement clinique du trouble bipolaire (TB) durant la grossesse sont profonds et peuvent entraîner des risques concurrents pour la mère et l'enfant. Méthode: Nous avons examiné les résultats récents de la recherche sur le cours du TB durant la grossesse et le post-partum, de même que les données d'innocuité reproductrice des principaux régulateurs de l'humeur. Résultats: La grossesse et surtout la période du post-partum comportent des risques élevés de récurrence du TB. Les risques semblent être limités par les traitements aux régulateurs de l'humeur et notablement accrus par la cessation abrupte de ces traitements. Toutefois, les médicaments utilisés pour traiter ou prévenir les récurrences du TB varient beaucoup en ce qui concerne les risques tératogènes: les risques sont faibles pour les neuroleptiques typiques, modérés pour le lithium, élevés pour les anciens anticonvulsivants comme l'acide valproïque et la carbamazépine, et presque inconnus pour les autres anticonvulsivants de la nouvelle génération et les antipsychotiques atypiques (APA). Conclusions: Le traitement clinique des femmes souffrant du TB durant la grossesse et le post-partum demande des évaluations équilibrées des risques et des avantages pour la mère et le foetus.

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Section: Pregnancy and Recurrence Risk In Bdsupporting

confidence: 85%

Managing Bipolar Disorder during Pregnancy: Weighing the Risks and Benefits

et al. 2002

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“…Unrecognized treatment non‐adherence can lead physicians to believe that the patient is non‐responsive, resulting in unnecessary dose increases (especially problematic for drugs with a narrow therapeutic index), medication switches, or adjunctive medications 341. Treatment withdrawal may precipitate recurrence; 50%‐90% of patients discontinuing lithium experience a recurrence within 3‐5 months,345, 346 with rapid lithium discontinuation associated with greater recurrence risk than gradual discontinuation 347. Withdrawal of other mood stabilizers also predicts recurrence 348, 349.…”

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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“…6 The clinical efficacy of lithium in preventing recurrent affective episodes requires a lag period for onset and is reversed upon discontinuation of treatment only after weeks or months. [7][8][9] By virtue of its prophylactic properties, lithium is thought to target the underlying pathophysiology of the disease, yet the precise molecular mechanism for this therapeutic action remains elusive. Evidence from both in vitro and in vivo studies has demonstrated that lithium exerts multiple effects on neurotransmitter/receptor-mediated signaling, ion transport, signal transduction cascades, hormonal and circadian regulation, and profoundly alters gene expression patterns (see reviews Lenox and Hahn, 3 Lenox et al, 10 Manji and Lenox, 11 Jope, 12 Williams and Harwood, 13 and Manji and Lenox 14 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

2003

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The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and glycogen synthase kinase-3 signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and have been implicated in modulating synaptic function in nerve terminals. These signaling pathways offer an opportunity to model critical signals for altering gene expression programs that underlie adaptive responses of neurons to long-term lithium exposure. While the precise physiological events critical for the clinical efficacy of lithium remain unknown, we propose that linking lithium-responsive genes as a regulatory network will provide a strategy to identify signature gene expression patterns that distinguish between therapeutic and nontherapeutic actions of lithium.

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Outcome After Rapid vs Gradual Discontinuation of Lithium Treatment in Bipolar Disorders

Abstract: Risk of early recurrence of BP disorder following discontinuation of lithium maintenance is elevated, but may be both predictable (timing and polarity) and modifiable by gradual discontinuation.

Cited by 217 publications

References 37 publications

Managing Bipolar Disorder during Pregnancy: Weighing the Risks and Benefits

Managing Bipolar Disorder during Pregnancy: Weighing the Risks and Benefits

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

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

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