Lithium: A Global Perspective

When speaking to psychiatrists from the United States, the mention of lithium as a treatment for mood disorders is often met with surprise. This is because the benefits and perhaps even the memory of ever having used the element has been supplanted by familiarity with newer molecules [1]. This is certainly not the case in Europe, Australia, New Zealand, China and India - in fact most other parts of the world, where the prescription of lithium remains the mainstay for managing bipolar disorder, especially in government funded hospitals and practices.

The reasons for this discrepancy are simple at first glance, but more complicated and nuanced when the issues are examined in greater detail. Americans are often caricatured as being enamoured by whatever is ‘new and shiny’, more likely to pursue fads, take risks and experiment, and to some extent all of this may be true. But the other major reason as to why an effective medication such as lithium is not more widely prescribed in the US is because medications can be marketed directly to patients through all forms of advertising, and this requires funding and support from a champion [1]. In the absence of such sponsors, the market share for any medication is likely to be slender. Furthermore, the payers – the insurance companies from which medical costs have to be reclaimed – essentially determine what is prescribed and even though the immediate and direct costs of lithium are minimal, it does require regular monitoring, blood tests and clinical follow-up, making it potentially costlier to manage longer term [2]. Furthermore, within the clinical psychiatric community it is regarded, albeit incorrectly, as more prone to causing side effects and serious complications [3].

Outside of the United States, healthcare systems are arguably more stable, and therefore more suited to providing consistent follow-up. This is because patients are ‘bound’ to primary care physicians and/or medical practices, and tend to visit the same doctors within hospitals. In other words, community models of care are more widely implemented and embedded within integrated models of management. This means that the burden of supervising the treatment of lithium long term can be shared by a number of parties and, provided there is reasonable communication between them, continuity of care can be readily achieved.

At the same time, in countries such as Australia, the UK and France, doctors have generally persevered in prescribing lithium and, in fact, there are clinics designated specifically for the prescription and management of lithium (e. g., the CADE Lithium Clinic, in Sydney). Interestingly, the evidence to support lithium’s use gets stronger day by day, with positive findings ranging from the clinical arena through to basic neuroscience, all suggesting that lithium has robust mood stabilising properties and, in conjunction with this, possesses unique anti-suicidal and neuroprotective properties. This is fantastic news, and yet, there is no fanfare, no publicity heralding lithium as the ‘new wonder drug’. Instead, remarkably, many physicians remain unaware that lithium possesses these additional qualities.

Part of the reason is that lithium has been around for a very long time and therefore it cannot be described as ‘new’ per se. And many of its properties, or at least knowledge of them, has been available to us for some time. Hence, it is perhaps understandable why both doctors and patients find it difficult to ‘get excited’ about new discoveries in relation to lithium, or to describe them as ‘breakthroughs’ when they do occur. Added to this, the concerns and negative publicity surrounding lithium remain undiminished and continue to dampen enthusiasm for its use. Furthermore, myths are mixed in with reality, making even those clinicians that usually prescribe lithium needlessly wary about whether lithium is safe [4]. A common concern is to what extent can its use be justified in patients likely to develop thyroid dysfunction or renal problems? It would seem that lithium has to battle not only against other agents, but also itself. But growing knowledge about lithium’s use in particular, how best it can be prescribed, and how its treatment effects can be optimised and its side effects limited, should be reasons for optimism [5].

Finally, it is important to note that lithium is not for everyone because not all patients with bipolar disorder will respond to it. In fact, probably only a quarter to a third benefit significantly long-term. And though there are clinical features that can potentially identify these patients, in practice, prediction of response remains a challenge. Even in those patients that do benefit initially from lithium therapy, sustained and lifelong improvement may not eventuate. In practice, lithium is often used alongside other agents although its actions in conjunction with other medications are poorly understood. However, its benefits as an augmentation strategy of antidepressants in nonresponsive depression suggest that it probably has facilitatory and synergistic properties, in addition to its own mood stabilizing effects [6].

But alas, unless we can specifically show where and how lithium can provide a significant advantage, it is unlikely that empirical evidence alone will change prescribing habits. Hence why its use has stagnated, and in some cases diminished, despite advancing knowledge and burgeoning proof in its favour. Fortunately, lithium remains cheap and is widely available. Had this not been the case its use would probably have subsided considerably by now, if not ceased altogether. Some decades ago propelling cars using electricity seemed a fantasy, but today electric cars are a reality and replacement of the combustion engine is quite conceivable. Interestingly, many of these modern electric engines are powered by lithium. And so, whilst the element is available in abundance, the hope that it will be recognised and used more widely in the treatment of mood disorders, has to be sustained.

• References

• 1 Post RM. The new news about lithium: An underutilized treatment in the United States. Neuropsychopharmacology Accepted article preview 4 October 2017; doi: doi: 10/1038npp.2017.238
• 2 Zivanovic O. Lithium: A classic drug – Frequently discussed, but, sadly, seldom prescribed!. Aust N Z J Psychiatry 2017; 51: 886-896
• 3 Malhi GS, Gershon S, Outhred T. Lithiumeter: Version 2.0. Bipolar Disord 2016; 18: 631-641
• 4 Malhi GS, McAulay C, Gershon S. et al. The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder. Bipolar Disord 2016; 18: 102-115
• 5 Malhi GS, Gessler D, Fritz K. et al. Recommendations in International Clinical Practice Guidelines for Lithium Therapy of Bipolar Disorder. In Malhi GS, Masson M. Bellivier editors. The Science and Practice of Lithium Therapy. Switzerland: Springer International Publishing; 2017. p 189-210
• 6 Malhi G, Morris G, Hamilton A. et al. The ideal mood stabiliser: A quest for nirvana?. Aust N Z J Psychiatry 2017; 51: 434-435