Suicidal Behavior During Lithium and Valproate Treatment: A Within-Individual 8-Year Prospective Study of 50,000 Patients With Bipolar Disorder

Song, Jie; Sjölander, Arvid; Joas, Erik; Bergen, Sarah E.; Runeson, Bo; Larsson, Henrik; Landén, Mikael; Lichtenstein, Paul

doi:10.1176/appi.ajp.2017.16050542

Cited by 106 publications

(80 citation statements)

References 33 publications

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“…Meta-analyses of these studies confirm the efficacy of lithium [4,27] and show that it reduces the risk of suicide as well as overall mortality known to be increased in untreated bipolar disorder [28][29][30]. The remarkable antisuicidal efficacy of lithium has recently been confirmed in a large-scale 8-year prospective study based on Swedish national registers that reported a decrease in the incidence rate of 14 % during lithium treatment [31]. This population-based study could not observe a similar effect of valproate on suicide prevention.…”

Section: Lithium In the Management Of Bipolar Disordermentioning

confidence: 69%

Genetics of Lithium Response in Bipolar Disorder

2018

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Section: Lithium In the Management Of Bipolar Disordermentioning

confidence: 69%

Genetics of Lithium Response in Bipolar Disorder

2018

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“…3 Based on a recent review of clinical practice guidelines (CPGs) and pharmaco-epidemiological data for all ages, lithium remains the first-line treatment for maintenance monotherapy despite the availability of several other choices for mood stabilization. [4][5][6] Treatment with lithium has been shown to reduce the risk of suicide 7,8 and psychiatric admissions. 4 Emerging epidemiological and neurophysiological evidence suggests that lithium may have neuroprotective properties and reduce the risk of dementia 9,10 and conceivably of cancer.…”

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confidence: 99%

Delphi survey of maintenance lithium treatment in older adults with bipolar disorder: An ISBD task force report

et al. 2018

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Objectives Despite the growing numbers and proportion of older adults with bipolar disorder (OABD), there are very limited guidelines for the use of lithium with its double‐edged potential for effectiveness and toxicity in this population. The primary aims of this Delphi survey were: (a) To determine the place of lithium among the preferred choices for maintenance treatment of OABD. (b) To provide detailed clinical guidelines for the safe and effective use of lithium in OABD. Methods In the face of limited evidence, the Delphi survey method was used to achieve consensus by a group of 25 experts in OABD from nine countries. An oversight committee monitored and analyzed the results of each survey and formulated more focused questions with each subsequent iteration. Results A 100% response rate was achieved for all three iterations of the survey. Lithium was the preferred choice for maintenance monotherapy in OABD. Serum levels of 0.4‐0.8 mmol/L were recommended for ages 60‐79 and serum levels of 0.4‐0.7 mmol/L were recommended for ages 80 and over. Specific recommendations achieved consensus for second line monotherapy as well as for other drugs to be used in combination with lithium if necessary. Guidelines for routine monitoring of lithium in OABD were provided for laboratory investigations and clinical assessments. Conclusions Lithium remains the preferred choice for maintenance monotherapy in OABD. Laboratories should report the therapeutic range for serum levels of lithium separately for older adults.

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“…Lithium, which is considered as one of the most effective mood-stabilizers used to treat bipolar disorder, decreases levels of impulsivity as measured by different outcome measures not only in bipolar patients, but also in other impulse control disorders. [33][34][35][36][37] Although impulsivity has been traditionally linked to dysregulation of serotonergic and dopaminergic systems, some authors have proposed that lithium could reduce impulsivity levels by means of its capacity to regulate the aforementioned neurotransmitter sys-mechanisms of action of lithium and amphetamine seem to be directly opposite and lithium could be prophylactic for cases of amphetamine abuse. 45 With regard to the mechanism, taking the fact into consideration that lithium has been reported to increase the volume of the prefrontal cortex and anterior cingulate gyrus, 46 it seems likely that lithium may at least partially exert its antisuicidal effect via reinforcing "top-down brakes" of impulsive action.…”

Section: Lithium and Impulsivitymentioning

confidence: 99%

“…39 Lithium may have superior antisuicidal effects relative to other mood stabilizers. 37,41,42 A recent metaanalysis 43 in 48 randomized control trials comparing lithium with placebo or active drugs in long term treatment for mood disorders, concluded that lithium is an effective treatment for reducing the risk of suicide in people with mood disorders, and the authors suggested that impulsivity might be a mechanism mediating the antisuicidal effect. John Cade (1949), 44 the Australian psychiatrist credited with discovering the effects of lithium carbonate as a mood stabilizer in the treatment of bipolar disorder, reported the original paper with the title "Lithium salts in the treatment of psychotic excitement".…”

Section: Lithium and Impulsivitymentioning

confidence: 99%

Is impulsivity in part a lithium deficiency state?

Giotakos¹

2018

Psychiatriki

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L ithium mechanisms of action are related to the function of many enzymes, hormones, vitamins, and growth factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of antiapoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor, cortical thickening, increased grey matter density, and hippocampal enlargement. Lithium, in pharmacological doses, has been used successfully in treating bipolar disorders, and has been shown to decrease suicidality and violent crime in this situation. The guidelines of major psychiatric association name lithium as a first-line therapy for bipolar disorder. From the other hand, impulsivity is a core feature of bipolar disorder. Increased levels of this dimensional trait are present not only during acute phases of the illness but also during euthymia. Increased impulsivity worsens clinical prognosis of bipolar disorder due to its association with several severity indices, such as substance abuse or dependence, suicidal behavior, and poorer functional outcome. A wide range of intracellular responses may be secondary to the inhibition of glycogen synthase kinase-3 beta (GSK3β) by lithium, while genetic variability at GSK3β gene was found to be associated with increased impulsivity in bipolar patients. Although impulsivity has been traditionally linked to dysregulation of serotonergic and dopaminergic systems, some authors have proposed that lithium could reduce impulsivity levels by means of its capacity to regulate the aforementioned neurotransmitter systems. Moreover, lithium in trace amounts, as occurs in drinking water, has been inversely related to suicidal mortality, aggression and homicidal violence. These findings pose the question of whether the prospect of adding lithium to drinking water is realistic, weighing the benefits and potential risks. It seems also that in the competition for survival, those entities that best minimized lithium toxicity and maximized the benefits of lithium action had an edge in the competition to survive and reproduce. Finally, lithium has been reported to increase the volume of the prefrontal cortex and anterior cingulate gyrus. Evidence from both basic and clinical researches support that lithium may decrease impulsivity and may at least partially, exert its antisuicidal effect via reinforcing "top-down brakes" of impulsive action. Considering the research data, we may suggest that even natural lithium level intake can influence impulsivity, a possible core factor that mediate to the manifestation of both suicidality and aggressiveness, or even criminality. Moreover, we may suggest that a lithium deficiency state may precipitate these situations.

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Suicidal Behavior During Lithium and Valproate Treatment: A Within-Individual 8-Year Prospective Study of 50,000 Patients With Bipolar Disorder

Abstract: The results suggest that lithium should be considered for patients with bipolar disorder with suspected suicidal intentions, although risk for suicide is only one of the considerations when providing clinical care.

Cited by 106 publications

References 33 publications

Genetics of Lithium Response in Bipolar Disorder

Genetics of Lithium Response in Bipolar Disorder

Delphi survey of maintenance lithium treatment in older adults with bipolar disorder: An ISBD task force report

Is impulsivity in part a lithium deficiency state?

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