The Lithium Ion: A Foundation for Psychopharmacological Specificity

Soares, Jair C.; Gershon, Samuel

doi:10.1016/s0893-133x(98)00022-0

Cited by 47 publications

(10 citation statements)

References 210 publications

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“…The mode of inheritance of lithium-responsive BD in families, as reported by Alda et al [29,30], seems to be autosomal recessive with sex-specific penetrances; relatives of lithium responders are more likely to favorably respond to treatment with lithium should they develop BD symptoms. All of the characteristics mentioned distinguish lithium responders from patients who respond better to other mood stabilizers or who do not respond well to treatment, which strengthens the evidence for a higher genetic loading for this sub-phenotype [19,31-33]. …”

Section: Heritability Of Response To Lithiumsupporting

confidence: 55%

Lithium: a key to the genetics of bipolar disorder

2009

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Since the 1950s, lithium salts have been the main line of treatment for bipolar disorder (BD), both as a prophylactic and as an episodic treatment agent. Like many psychiatric conditions, BD is genetically and phenotypically heterogeneous, but evidence suggests that individuals who respond well to lithium treatment have more homogeneous clinical and molecular profiles. Response to lithium seems to cluster in families and can be used as a predictor for recurrence of BD symptoms. While molecular studies have provided important information about possible genes involved in BD predisposition or in lithium response, neither the mechanism of action of this drug nor the genetic profile of bipolar disorder is, as yet, completely understood.

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Section: Heritability Of Response To Lithiumsupporting

confidence: 55%

Lithium: a key to the genetics of bipolar disorder

2009

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“…Lithium is primarily used in the recovery of bipolar affective disorder, with evidence supporting its role in both acute mania [Gershon and Soares, 1997; Soares and Gershon, 1998, 2000; Bowden, 2000; Poolsup et al . 2000; Shafti, 2010] and prophylactic treatment [Soares and Gershon, 1998, 2000; Burgess et al . 2001; Geddes et al .…”

Section: Introductionmentioning

confidence: 99%

Lithium: the pharmacodynamic actions of the amazing ion

Brown

Tracy

2012

Therapeutic Advances in Psychopharmacology

107

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Lithium has been used for the treatment of mood disorders for over 60 years, yet the exact mechanisms by which it exerts its therapeutic effects remain unclear. Two enzymatic chains or pathways emerge as targets for lithium: inositol monophosphatase within the phosphatidylinositol signalling pathway and the protein kinase glycogen synthase kinase 3. Lithium inhibits these enzymes through displacing the normal cofactor magnesium, a vital regulator of numerous signalling pathways. Here we provide an overview of evidence, supporting a role for the inhibition of glycogen synthase kinase 3 and inositol monophosphatase in the pharmacodynamic actions of lithium. We also explore how inhibition of these enzymes by lithium can lead to downstream effects of clinical relevance, both for mood disorders and neurodegenerative diseases. Establishing a better understanding of lithium's mechanisms of action may allow the development of more effective and more tolerable pharmacological agents for the treatment of a range of mental illnesses, and provide clearer insight into the pathophysiology of such disorders.

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“…Lithium carbonate is still, to this date, the gold standard in the treatment of bipolar disorder Soares and Gershon 1998;Schou 1999), although it may not be effective in an estimated 40-50% of cases (Guscott and Taylor 1994;Price and Heninger 1994;Goldberg et al 1996). Generally, up to 90% of typical manic patients respond to lithium (Himmelhoch et al 1976;Secunda et al 1985;Swann et al 1986), whereas the response rates are lower for patients with psychotic symptoms, mixed state, rapid cycling illness, co-morbid substance abuse, personality disorders, and secondary mania (Gaviria et al 1982;Abou-Saleh and Coppen 1986;McElroy et al 1992;Dilsaver et al 1993aDilsaver et al , 1993b.…”

Section: Introductionmentioning

confidence: 99%

Atypical antipsychotics and mood stabilization in bipolar disorder

2003

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The available literature on the use of atypical antipsychotics for the treatment of bipolar disorder was reviewed. All uncontrolled and controlled reports were identified through a comprehensive Medline search. Based on the available evidence, olanzapine was found to be the most appropriate atypical antipsychotic agent utilized for the treatment of manic bipolar patients, although there is also preliminary data suggesting the efficacy of risperidone and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. Double-blind controlled studies with atypical antipsychotics in the long-term treatment of bipolar disorder are still largely not available, but will be critical to determine the effectiveness of these agents in the maintenance treatment of bipolar disorder. There are recent uncontrolled suggestions that olanzapine may have beneficial effects in depressed bipolar patients, which deserve further investigation in controlled studies. In conclusion, atypical antipsychotics, due to lower potential for neurotoxicity and preliminary evidence suggesting better efficacy than typical antipsychotics, are increasingly having a more prominent role in the pharmacological management of bipolar patients. Nonetheless, until there is systematic data from long-term controlled follow-up studies on the comparative efficacy of these agents with mood stabilizers, atypical antipsychotics should be cautiously utilized, and preferably in combination with a mood stabilizer for the maintenance phase of treatment.

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The Lithium Ion: A Foundation for Psychopharmacological Specificity

Cited by 47 publications

References 210 publications

Lithium: a key to the genetics of bipolar disorder

Lithium: a key to the genetics of bipolar disorder

Lithium: the pharmacodynamic actions of the amazing ion

Atypical antipsychotics and mood stabilization in bipolar disorder

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