Friday, June 30, 2017

Lithium 2017


Lithium: The Gift That Keeps on Giving in Psychiatry

http://www.medscape.com/viewarticle/881529_2

Nassir Ghaemi, MD, MPH
June 16, 2017

Wide-Ranging Benefits

At the recent American Psychiatric Association annual meeting in San Diego, an update symposium was presented on the topic of "Lithium: Key Issues for Practice."[1] In a session chaired by Dr David Osser, associate professor of psychiatry at Harvard Medical School, presenters reviewed various aspects of the utility of lithium in psychiatry.
Leonardo Tondo, MD, a prominent researcher on lithium and affective illness, who is on the faculty of McLean Hospital/Harvard Medical School and the University of Cagliari, Italy, reviewed studies on lithium's effects for suicide prevention. Ecological studies in this field have found an association between higher amounts of lithium in the drinking water and lower suicide rates.
These "high" amounts of lithium are equivalent to about 1 mg/d of elemental lithium or somewhat more. Conversely, other studies did not find such an association, but tended to look at areas where lithium levels are not high (ie, about 0.5 mg/d of elemental lithium or less). Nonetheless, because these studies are observational, causal relationships cannot be assumed. It is relevant, though, that lithium has been causally associated with lower suicide rates in randomized clinical trials of affective illness, compared with placebo, at standard doses (around 600-1200 mg/d of lithium carbonate).

Christoforos Giakoumatos, MD, from the Harvard South Shore Psychiatry residency training program, reviewed the scientific literature on lithium's neuroprotective effects. Extensive animal studies have shown that lithium keeps neurons alive longer. Some human studies also suggest a benefit of lithium in prevention or amelioration of dementia, consistent with its neurobiological benefits. These data support further work to clarify how much, and to what extent, lithium could be useful in human neurodegenerative diseases.
Othman Mohammad, MD, also from the Harvard South Shore program, examined lithium use in children and adolescents, and reviewed a number of randomized trials that showed evidence for efficacy and short-term safety with lithium in acute manic episodes, especially in adolescents. Of note, similar randomized data did not show benefit with divalproex, indicating that there is relatively more evidence for lithium's efficacy and safety in adolescence.


Lithium's Safety Profile

Dana Wang, MD, a senior resident in the Harvard South Shore program, reviewed the kidney effects of lithium and the latest studies quantifying those harms. For instance, in recent data from Sweden, lithium was associated with end-stage renal failure in about 1% of all patients who were treated with it—an effect that occurred over a mean of more than 20 years of treatment.
The rate is somewhat higher if the sample is limited to those who take lithium for a minimum of 10 years; in that case, up to 5% of patients may develop end-stage renal disease eventually. Although these numbers are important, they also indicate that over 95% of lithium-treated persons never develop end-stage renal disease.
Multiple daily dosing of lithium is a major risk factor for such chronic renal harm, and it is a preventable one, because lithium has a half-life of 24 hours and only needs to be dosed once daily. Furthermore, keeping lithium levels low, and thus avoiding acute lithium toxicity, is another preventable risk factor for chronic renal impairment. By dosing lithium once daily at night and at the lowest dose feasible, the risk for long-term kidney harm with lithium can be reduced even further.
Dr Osser ended the symposium by discussing how to manage other lithium-related side effects. He noted that lithium causes less weight gain than divalproex or commonly used antipsychotics, such as olanzapine and quetiapine. Thus, if those agents are used, so should lithium. He also noted some ways in which weight gain can be ameliorated with lithium: for example, educating patients to avoid consuming caloric beverages (such as sodas) when managing lithium-related thirst. Water retention with lithium can be managed by using amiloride. Carbohydrate craving is an important aspect of lithium-related weight gain, and the most difficult to manage.

Conclusion

I provided a commentary at the end of the symposium, where I noted that our oldest drugs are our most effective: electroconvulsive therapy, lithium, monoamine oxidase inhibitors, and clozapine. All of the new drugs developed since the 1970s have not advanced greater efficacy for any major psychiatric condition. They do have fewer side effects, which is important. But the case of lithium reminds us that we should not assume that newer is better.
All patients should be told about the potential range of benefits of lithium, in terms of mortality/suicide and neuroprotection/dementia prevention, in addition to its well-proven mood benefits. If this is understood, then many patients and doctors would perhaps also understand how these benefits could outweigh the risks of lithium. Such risks should be considered limited, with about 1% long-term kidney risk and less weight gain than other commonly used agents.

Thursday, June 22, 2017

Otello




Jonas Kaufmann and Maria Agresta in Otello at the Royal Opera
Jonas Kaufmann and Maria Agresta in Otello at the Royal Opera CREDIT: ALASTAIR MUIR

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No, he didn’t cancel and yes, he was very good indeed. Despite all the anxieties attendant on this wondrous but somewhat unreliable German tenor, Jonas Kaufmann finally made his long-awaited debut in the taxing title-role of Verdi’s Otello.
His singing is technically almost unimpeachable: perfectly in tune, even between the registers, cleanly projected. None of the challenges here were fluffed or ducked, and the sensitivity of his musicality was always evident, with some particularly lovely tone and phrasing in the love duet and the “Dio mi potevi scagliar” monologue.

Thomas Atkins and Marco Vratogna in Otello
Thomas Atkins and Marco Vratogna in Otello CREDIT: ALASTAIR MUIR
But as yet his interpretation is cautious; he ventures nowhere near the character’s emotional edge. The opening “Esultate” had no clarion authority, “Si, pel ciel” didn’t raise the rafters and he didn’t let rip on “Ora e per sempre addio”. Nor is he the world’s greatest actor: his stage presence is oddly diffident, to the point that one never sensed the mighty General or even the outsider Moor (his flesh, incidentally, was barely darkened).
Otello’s downfall is moving because it comes from a lofty height: Kaufmann radiates only a dashing young Captain who loses his cool. If the interpretation is to develop, he needs to radiate a more regal demeanour, commanding the stage through stillness and a stare, as his great predecessors Jon Vickers and Placido Domingo did. 
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The audience received him warmly, but no more warmly than his fellow principals. Maria Agresta made a maturely poised and elegant Desdemona – was I alone in craving more seraphic purity and more vivid enunciation? As Iago, Marco Vratogna (a late substitute for Ludovic Tézier) was brilliantly incisive and devilish – perhaps excessively so, as Otello emphatically deems him “onesto”.

Jonas Kaufmann and Maria Agresta in Otello
Jonas Kaufmann and Maria Agresta in Otello CREDIT: ALASTAIR MUIR
Of the remainder of the performance there is little to say. Frédéric Antoun was a pleasant but slightly underpowered Cassio, and an expanded chorus made a proportionately big noise. Antonio Pappano’s conducting of this opera, a known quantity at Covent Garden, is sharply energised but falls short of the sublime.
The real disappointment was a lame, ugly and soporifically dark staging by Keith Warner that is no improvement on what it replaces. Costuming is generically Renaissance, but the black-walled chamber with movable latticed panels designed by Boris Kudlicka evokes a Stasi HQ circa 1960; at no point does Warner bring the drama any psychological life, and his direction of the denouement is particularly ludicrous. The net result is an Otello without visceral impact.
In rep until July 15. Tickets: 020 7304 4000; roh.org.uk.
The performance on 28 June will be broadcast live in HD to cinemas around the UK and the world