The science and practice of lithium therapy

CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Sydney, Australia.
Australian and New Zealand Journal of Psychiatry (Impact Factor: 3.41). 03/2012; 46(3):192-211. DOI: 10.1177/0004867412437346
Source: PubMed


Despite more that 60 years of clinical experience, the effective use of lithium for the treatment of mood disorder, in particular bipolarity, is in danger of becoming obsolete. In part, this is because of exaggerated fears surrounding lithium toxicity, acute and long-term tolerability and the encumbrance of life-long plasma monitoring. Recent research has once again positioned lithium centre stage and amplified the importance of understanding its science and how this translates to clinical practice.
The aim of this paper is to provide a sound knowledge base as regards the science and practice of lithium therapy.
A comprehensive literature search using electronic databases was conducted along with a detailed review of articles known to the authors pertaining to the use of lithium. Studies were limited to English publications and those dealing with the management of psychiatric disorders in humans. The literature was synthesized and organized according to relevance to clinical practice and understanding. Results: Lithium has simple pharmacokinetics that require regular dosing and monitoring. Its mechanisms of action are complex and its effects are multi-faceted, extending beyond mood stability to neuroprotective and anti-suicidal properties. Its use in bipolar disorder is under-appreciated, particularly as it has the best evidence for prophylaxis, qualifying it perhaps as the only true mood stabilizer currently available. In practice, its risks and tolerability are exaggerated and can be readily minimized with knowledge of its clinical profile and judicious application.
Lithium is a safe and effective agent that should, whenever indicated, be used first-line for the treatment of bipolar disorder. A better understanding of its science alongside strategic management of its plasma levels will ensure both wider utility and improved outcomes.

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    • "In fact, symptoms can be largely opposite from each other with hyperactivity being a hallmark feature of mania (DSM-V 2013), whereas lethargy or psychomotor retardation characterize depression. Lithium is commonly used to treat aspects of mania and depression as well as maintain a patient's state between periods (Malhi et al. 2012), but its effects are limited and it has a low acceptability profile (Cipriani et al. 2011). Greater understanding of the mechanisms underlying and/or overlapping different phases of BD may improve the development of novel and more efficacious therapeutics. "
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    ABSTRACT: Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD. We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment. C57BL/6 J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for "behavioral despair" (immobility) in the tail suspension test (TST) and forced swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6 J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM. Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml). Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics.
    Psychopharmacology 07/2015; 232(18). DOI:10.1007/s00213-015-4000-4 · 3.88 Impact Factor
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    • "Lithium is still considered as a first-line therapy in BD [8]. However, its narrow therapeutic range may lead to increased risk of intoxication [9]. "
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    ABSTRACT: Bipolar disorder (BD) is a chronic mental illness that is associated with substantial functional impairment, morbidity and mortality. Lithium is still considered as a first-line therapy in BD. In this study, systolic and diastolic function parameters were measured with echocardiography in BD during lithium therapy and compared to those of a control group. Thirty BD under lithium therapy and controls were included in our study. Blood samples were taken 12 hours after receiving the last dose of lithium treatment, in the meantime echocardiography were performed. Left ventricular systolic and diastolic function was assessed by conventional echocardiography and tissue Doppler imaging. Serum lithium level correlation between diastolic function parameters was measured. Baseline demographic and laboratory results did not differ significantly between the groups. Left ventricular ejection fraction (LVEF) (66.7 ± 7.1% vs 66.7 ± 4.9%), E/A ratio (1.14 ± 0.41 vs 1.28 ± 0.29), and isovolumetric relaxation time (IVRT) (77.8 ± 14.5 cm/sec vs 75.9 ± 17.7cm/sec) measured with conventional echocardiography showed no significant difference between the two groups. Em (14.8 ± 5.2 cm/sec vs 15 ± 4.6 cm/sec), Am (12.7 ± 4.0 cm/sec vs 11.1.0 ± 2.4 cm/sec) and E/Em (5.5 ± 1.8 vs 5.9 ± 2.4) measured with tissue Doppler echocardiography showed no significant difference between the two groups. Serum lithium levels were not correlated with LVEF, mitral inflow E velocity, mitral inflow A velocity, E/A ratio, deceleration time (DT), IVRT, or E/Em ratio. Left ventricular systolic and diastolic functions were preserved in BD during lithium therapy.
    International Journal of Clinical and Experimental Medicine 03/2015; 8(2):2917-2922. · 1.28 Impact Factor
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    • "This prophylactic effect and ability to stabilize emotional circuitry distinguish it as a true 'mood stabilizer'. Despite being a simple element, lithium affects many complex biological systems and, although it remains unclear which of these actions lead to its mood stabilizing properties, this clearly warrants determined investigation and the precise molecular targets need to be identified (Malhi et al., 2012). Clinically, the profiling of lithium response has identified 'responders' as those who experience recurrent episodes of illness (depression/mania ) and who have complete remission in between (Gershon et al., 2009). "

    Australian and New Zealand Journal of Psychiatry 11/2014; 48(11):973-4. DOI:10.1177/0004867414556429 · 3.41 Impact Factor
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