Intra-Erythrocyte Lithium Ion Concentration and Long-Term Maintenance Treatment

Mendels, J.; Frazer, Alan; Baron, Jillian T; Kukopulos, A.; Reginaldi, Daniela; Tondo, Leonardo; Caliari, B.

doi:10.1016/s0140-6736(76)92748-3

Cited by 53 publications

(12 citation statements)

References 5 publications

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“…Some of the domains of intense search have been lithium transport in red blood cells [35] , a red blood cell/ plasma lithium ratio [36] , urinary lithium excretion [37] , platelet monoamine oxidase activity [38] , urinary 3-methoxy-4-hydroxyphenylglycol and other expressions of central amine metabolism [39,40] , serum calcium and magnesium [41] , average evoked potentials [42,43] and human leukocyte antigens [44,45] . As one example of recent studies, in an investigation by Kruger et al [46] comparing regional cerebral blood flow in valproate responders, lithium responders and their unaffected rela-tives showed significant, possibly heritable differences between the two patient groups.…”

Section: Tussle To Find a Biological Marker Of Responsementioning

confidence: 99%

Sixty Years of Lithium Responders

Grof¹

2010

Neuropsychobiology

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It has been 60 years since Cade first described patients who responded to antimanic lithium treatment. Two decades later, responders to lithium stabilization emerged in larger numbers. The responses of many severely ill bipolar patients to lithium were striking and called for an explanation. Remarkable reactions to a simple ion generated hope for an uncomplicated laboratory test of response and an extensive search for suitable biological markers ensued. But despite promising reports, particularly from molecular genetics, we are still waiting for a biological elucidation of the stabilizing effects of lithium. The most useful predictor of lithium stabilization has to date been the patient’s clinical profile, based on a comprehensive clinical assessment: complete remissions and other characteristics of episodic clinical course, bipolar family history, low psychiatric comorbidity and a characteristic presenting psychopathology. In brief, the responders approximate the classical Kraepelinian description of a manic-depressive patient. But the most intriguing findings have recently emerged from prospective observations of the next generation: the children of lithium responders, their counterparts coming from parents who did not respond to lithium and controls. Overall, they indicate that parents and offspring suffer from a comparable brain dysfunction that manifests clinically in distinct stages. If the child’s predicament starts early in childhood, it presents with varied, nonaffective or subclinical manifestations that are usually nonresponsive to standard treatments prescribed according to the symptoms. The next stage then unfolds in adolescence, first with depressive and later with activated episodes. The observations have a potential to markedly enrich the prevailing understanding and management of mood disorders.

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Section: Tussle To Find a Biological Marker Of Responsementioning

confidence: 99%

Sixty Years of Lithium Responders

Grof¹

2010

Neuropsychobiology

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“…namely the red blood cell/plasma lith ium concentration ratio (lithium ratio), which has been shown to be genetically de termined and relatively stable for a given individual [Dorus ef al., 1974[Dorus ef al., , 1975, and the HLA antigens, which are known to be located on the cell membrane surface and probably influence the membrane function in some way. Higher mean values of the lithium ratio in patients who responded to lithium prophy laxis when compared with non-responders have been claimed by a number of investiga tors [Mendels et al, 1976;Casper et al, 1976;Sacchetti et al, 1977;Flemenbaum et al, 1978], although not confirmed by others [Rybakowski and Strzyzewski, 1976;von Knorring et al, 1976;Mendlewicz and Verbanck, 1977], Moreover, an in vitro study [Fieve et al, 1978] demonstrated a positive correlation between low lithium efflux rates (which cor respond to high in vivo lithium ratios) and a good response to the treatment.…”

Section: Introductionmentioning

confidence: 88%

Cell Membrane Predictors of Response to Lithium Prophylaxis of Affective Disorders

Vecchio¹,

Farzati²,

Maj³

et al. 1981

Neuropsychobiology

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HLA antigens and RBC/plasma lithium ratio were studied in a sample of 49 patients, diagnosed as bipolar affective psychotics (n = 22), unipolar depressive psychotics (n = 18) and cycloid psychotics (n = 9), receiving prophylactic lithium for 1–4 years and maintained at lithium plasma levels of 0.6–1.2 mEq/1. Mean values of the ratio were found to be significantly higher in patients who responded to treatment when compared with non-responders, whereas the frequency of the HLA-A3 antigen was significantly higher in non-responders. The only 6 patients with a lithium ratio above the median and the absence of the HLA-A3 antigen coexistent with bipolarity and a family history of the illness were all good responders to treatment. Further research in this field will probably bring about the isolation of a subgroup of lithium-responsive patients with well-defined clinical and biological features. When patients were divided into two subgroups according to their lithium ratios (above and below the median), the HLA-A3 and Aw26 antigens were found to be significantly more frequent in those with ratios below the median. It can be hypothesized that these antigens disturb lithium transport in some way, leading to low lithium ratio values.

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“…Pandey et al (1979) have suggested that such neurotoxic effects may be due to neuroleptics increasing the intracellular lithium concentrations. In this work, the RBC has been used as a model for lithium transport in neurons, because the membranes of both cell types have features in common (Mendels et al 1976). However, it has been shown that haloperidol does not increase the entry of lithium into RBCs in vitro (Ostrow et al 1980).…”

Section: Neurotoxic Combinationsmentioning

confidence: 99%

Review of Clinically Important Drug Interactions with Lithium

Harvey

Merriman

1994

Drug Safety

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The therapeutic dosage of lithium is close to the toxic level, and drugs reducing the renal clearance of lithium can produce the most serious adverse effects. When used in combination with psychiatric drugs affecting mood, the therapeutic potential of lithium may be enhanced, and earlier concern regarding possible neurotoxic interactions with neuroleptics appear poorly substantiated. A number of specific interactions of low incidence have also been reported which should be borne in mind when new medications are introduced. The ready availability of lithium concentration monitoring in body fluids makes it possible to alter the effects of some potentially interactive drugs that may still need to be given in combination with lithium.

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Intra-Erythrocyte Lithium Ion Concentration and Long-Term Maintenance Treatment

Cited by 53 publications

References 5 publications

Sixty Years of Lithium Responders

Sixty Years of Lithium Responders

Cell Membrane Predictors of Response to Lithium Prophylaxis of Affective Disorders

Review of Clinically Important Drug Interactions with Lithium

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