Treatment of lithium intoxication: facing the need for evidence
Haussmann et al. Int J Bipolar Disord
Treatment of lithium intoxication: facing the need for evidence
R. Haussmann 0 3
M. Bauer 0 3
S. von Bonin 2
P. Grof 1
U. Lewitzka 0 3
0 Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden , Fetscherstr. 74, 01307 Dresden , Germany
1 Mood Disorders Center of Ottawa , Ottawa , Canada
2 Department of Internal Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany
3 Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden , Fetscherstr. 74, 01307 Dresden , Germany
Lithium has been used as the gold standard in the treatment of major depressive and bipolar disorders for decades. Due to its narrow therapeutic index, lithium toxicity is a common clinical problem. Although risk factors for lithium intoxication seem to be well-described, lacking patient education and inexperience of treatment are assumed to contribute to the probability of lithium intoxication. A review of literature shows that the treatment of lithium intoxication has not been adequately studied or standardized. The aim of this literature review is to compile and present current evidence on the treatment of lithium intoxication and contribute to a standardization regarding general treatment recommendations as well as evidence on indication for extracorporeal methods. Against the background of this common and potentially life-threatening condition, the standardization of the treatment of lithium intoxication is definitely a task for the future.
Lithium; Intoxication; Affective disorders; Bipolar disorder; Treatment; Extracorporeal methods; Hemodialysis
-
Background
Since 1970, lithium has been approved and widely used
as the gold standard for the treatment of acute episodes
and maintenance treatment of bipolar disorder (Nolen
2015; Severus et al. 2014) and frequently also used in the
treatment of recurrent major depressive disorders since
the 1950s (Bschor 2014). In addition, lithium has been
shown efficacious in augmenting response in
antidepressant non-responders and in severe treatment-resistant
unipolar major depression (Haussmann and Bauer 2013).
Due to a relatively narrow therapeutic index, lithium
intoxication has been a common clinical problem
(Timmer and Sands 1999; Hampton 2014). The effective
dose range of lithium is 0.6–1.0 mmol/l, while in
prolonged administration it may be toxic at 1.2 mmol/l or
greater (Young 2009). Since lithium is one of the
lightest elements of the periodic table, it is easily distributed
throughout total body water (Young 2009; Perrone 2015).
Lithium is an alkali metal, like potassium and sodium,
which facilitates its rapid distribution (Young 2009).
Lithium pharmacokinetics can be divided into absorption,
distribution and elimination phases (Jaeger et al. 1993).
Regarding the subtypes of lithium intoxication, there
are acute, acute-on-chronic and chronic forms, which
differ in their symptomatology due to lithium
pharmacokinetics. Acute lithium intoxication is most often
associated with gastrointestinal symptoms, cardiotoxic
effects and late developing neurological signs whereas
chronic forms manifest primarily as neurological
symptoms, including confusion, myoclonus and seizures
(Timmer and Sands 1999; Ward et al. 1994; Haussmann 2015)
(Fig. 1). The rationale for clinical differences is
compartment saturation. In the cases of acute lithium toxicity,
lithium concentrations tend to fall rapidly due to
distribution in several tissues, meanwhile chronic toxicity
faces lithium-saturated tissues. For this reason, lithium
toxicity depends on the exposure pattern which needs to
be considered regarding treatment strategy (Waring et al.
2007).
Risk factors for lithium intoxication
Drugs that alter renal function must be considered
risk factors for lithium intoxication. In particular,
© 2015 Haussmann et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International
License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any
medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made.
Fig. 1 Clinical symptoms of different lithium intoxication patterns
angiotensin-converting enzyme inhibitors,
nonsteroidal anti-inflammatory drugs and thiazide diuretics
can enhance lithium serum levels by increasing renal
reabsorption in the proximal tubule. General
medical conditions characterized by decreased circulating
volume, including viral infections with fever,
gastroenteritis with diarrhea and vomiting, great heat and
sauna and decreased oral intake of water augment
renal reabsorption of sodium and lithium, potentially
leading to toxic lithium serum levels. In this respect,
nephrogenic diabetes insipidus as a c (...truncated)