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

Tuesday, May 23, 2017

Munich: Tannhauser




Tannhäuser

In Review Tannhauser Munich lg 817
Harteros, Bavarian State Opera’s Elisabeth 
© Wilfried Hösl

ANY NEW PRODUCTION of an opera by Richard Wagner in Munich—a city with a nearly existential association with the composer—is a very special occasion, as witness the Bavarian State Opera’s superbly cast Tannhäuser (seen May 28), led by the company’s general music director, Kirill Petrenko. Petrenko has a Midas touch with every piece of music he presents, be it symphonic or operatic; on this occasion, he once again drew sheer perfection from his orchestra, maximizing the players’ concentration on each detail while evoking a luxurious, velvety sound. Petrenko’s is not a “fire and brimstone” interpretation of Tannhäuser. His tempos were generally slower than one expects from him: the first pages of the overture sounded highly contemplative, and most of the score was delivered free of bombast.

Review: Opera Lovers, Make a Pilgrimage to Munich for ‘Tannhäuser’

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A scene from the opera, directed and designed by Romeo Castellucci. CreditWilfried Hösl
MUNICH — “Nach Rom!” the cast of Wagner’s “Tannhäuser” cries at the end of that opera’s second act, pressing the title character to make the Catholic pilgrimage to Rome and save his troubled soul.
I’d give it a new spin: “Nach München!” Opera lovers, get thee to Munich. Listening to “Tannhäuser,” which opened at the Bavarian State Opera here on Sunday, in a new production directed and designed by the provocative theater artist Romeo Castellucci, will convince you that you’ve verily been saved. I can’t say whether hearing this performance — and I mean hearingit, since the staging adds little to the purely musical experience — will secure your place in heaven, but I guarantee your faith in opera’s vitality will be renewed.
No better cast is possible in this work today, and the high priest of the podium for this production, to be webcast live at staatsoper.de on July 9, is the dazzling Kirill Petrenko. “Tannhäuser” is no easy feat to conduct: Revised again and again by Wagner — whose wife reported, three weeks before he died, that he said he “still owes the world a ‘Tannhäuser’” — it is a sometimes awkward amalgam of that master’s early and late styles.
The Bavarian State Opera’s music director and the next chief conductor of the Berlin Philharmonic, Mr. Petrenko embraces the awkwardness, and blazes through it. At the start, Tannhäuser, a chronically dissatisfied medieval knight and troubadour, has abandoned both his home and the virginal (O.K., perhaps a bit boring) Elisabeth for the sensual pleasures of Venus. The rushing lushness of the opening bacchanal music here had the complex, dizzying fervor of “Parsifal,” Wagner’s final completed opera.
But in that second-act finale — when Tannhäuser, back at court in Wartburg but disgraced once his venture to Venus’ lair has been revealed, resolves to travel to Rome — Mr. Petrenko builds the scene with a steadiness and patience that shows the music’s debt to the early 19th century and the grand finales of Rossini and Bellini.



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A scene from Wagner’s “Tannhäuser” by the Bavarian State Opera in Munich. CreditWilfried Hösl

What unites these two sides of Wagner, the early and late, here is Mr. Petrenko’s unshowy energy, which emerges from the root of the orchestra: Listen closely, and there’s always warm, full, rounded precision in the low brasses and low strings. The music down there may not be the tune you end up whistling, but it’s the scaffolding of that tune that gives intensity and purpose to the melodic lines layered on top of it.
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Mr. Petrenko brings fresh vigor to this score — not the superficial verve of loudness or fastness, but a more elusive grandeur and dignity — and his cast does, too, including the earthy Elena Pankratova (Venus) and authoritative Georg Zeppenfeld (Hermann, Elisabeth’s uncle).
As Wolfram, the stable, upstanding counterweight to Tannhäuser’s tortured confusion, Christian Gerhaher faded the end of his great “Hymn to the Evening Star” almost beyond audibility. Yet his scrupulous attention to the text kept the line vividly present, a ghost whose contours you could somehow see and feel.
A serene, queenly presence as Elisabeth, Anja Harteros focused her emotions in her attractively unsettled voice, practically vibrating with feeling. Her choices of tone color constantly surprised: Describing Tannhäuser’s disappearance, her sound palpably grayed; later, a single word, “jähen,” was a memorably sour sneer as she told how his betrayal had destroyed her. Klaus Florian Vogt, singing the title role for the first time, united his pure, boyish tone with heldentenor weight.
What convinced me to make my own Munich pilgrimage was the promise of these peerless musical forces being set in motion by Mr. Castellucci, whose enigmatic, elegant, calmly brutal theater works have brought him avant-garde acclaim since the 1980s.



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Georg Zeppenfeld and Anja Harteros in the production. CreditWilfried Hösl

Who, on paper, would take to “Tannhäuser” better than this practiced guide to dark nights of the soul? (His “Divine Comedy,” from 2008, reflected on Dante in moody, indelible images, like that of an elderly woman gnawing on a basketball.) Who could enact a more striking battle between Venusberg and Wartburg than this purveyor of gorgeous visual responses to spiritual conflict? (His 2016 staging of Bach’s “Matthew Passion” was an eerily poignant pageant of blood, bodies, nature and science, conducted in a clinic-white box.)
This time, the result is disappointingly bland. No one wants or expects clear answers from a Castellucci production, but I wanted more suggestive images, a more charged mood.
There are ideas, particularly in the first act. During the overture, a troupe of bare-breasted Amazons shoots arrows toward a gigantic image of an eye looming at the back of the stage. (Much is made of the similar construction of an archery bow and Tannhäuser’s harp.) The eye is later replaced by a slowly rotating circular panel; when a thin stream of blood leaks onto it, it becomes a mesmerizing exercise in slow-motion spin art. Venus’s realm is a platform full of lethargically, primordially pulsing heaps of flesh — sensuality’s nightmarish overkill.
But the second act, at the Wartburg court, is slack, framed by endlessly shifting sheer, silky curtains, perhaps meant to contrast Venus’s viscous ooze. It’s a handsome set but it doesn’t quite work: Mr. Castellucci seems to have conceived Elisabeth as chilly and detached, a kind of Hitchcockian heroine, which doesn’t fit the sensitive, easily emotive Ms. Harteros. The staging isn’t so much cool as dull; the singers seem game but at sea.
The final act — in which Elisabeth dies, still praying for Tannhäuser’s redemption, and he returns from Rome, rejected, before a last-minute miracle of salvation — elicits a bit of Castelluccian meta-theater. The dead characters are placed on plinths inscribed with “Klaus” and “Anja,” the star singers’ first names, and their bodies are then replaced — and replaced, and replaced — with progressively rotting versions to simulate the process of decomposition. All that’s eventually left is two piles of dust, bits of which are sprinkled together for a cloying ending.
What wasn’t cloying in that finale on Sunday was the music — the orchestra swirling and shining, the chorus rich and full-bodied. Mr. Petrenko and the forces of the Bavarian State Opera will perform Strauss’s “Der Rosenkavalier” in concert at Carnegie Hall next season. See you there.



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The soprano Anja Harteros. The conductor Christian Thielemann describes her voice as “one of the most beautiful which has been ever around.” CreditLaetitia Vancon for The New York Times
MUNICH — The joy of Elisabeth’s entrance aria in Wagner’s “Tannhäuser” recedes for a line of sadness as she recalls her beloved’s departure. The soprano Anja Harteros, whose performance of the role at the Bayerische Staatsoper here will be streamed at staatsoper.tv on Sunday, July 9, makes of that passing moment an entire anatomy of melancholy.
Her voice suddenly turns gray and hazy, without losing its steely core. Sinking to its depths, its texture is like weathered velvet. She transforms before our eyes from a cheerful girl into a woman who’s peered into the heart of grief. The conductor Christian Thielemann put it simply: “The voice is one of the most beautiful which has been ever around.”
In the great operas of Verdi, Puccini, Strauss and Wagner, Ms. Harteros is as good — as powerful yet lyrical in her singing, as sensitive in her acting — as anyone in the world. Nikolaus Bachler, the Staatsoper’s director, called her “one of the major singers of our time.”
“I always compare her to a river, in her clearness and her purity,” Mr. Bachler said in an interview. “But she can grow, like rivers can grow, in a second — and go back, in a second, to a calm, shining beauty.”
Anja Harteros sings "Pace, pace, mio dio!" from LA FORZA DEL DESTINO Video by BayerischeStaatsoper
Why, then, have her appearances outside of a small circle of theaters in and near Germany been so limited over the past decade? Why has she developed a reputation for cancellations? Why has she not performed since 2008 at the Metropolitan Opera, where she had acclaimed runs over several seasons?
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Ms. Harteros as Elisabeth, with Georg Zeppenfeld as Hermann, in “Tannhäuser” in May. CreditWilfried Hösl
“I’ve told her this: I would turn the schedule inside out to make it possible, even on short notice,” said Peter Gelb, the Met’s general manager. “Because I think it would be a great artistic event to have her back on the Met stage.”
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Speaking in May over lunch at a restaurant here, Ms. Harteros, 44, politely but firmly deflected certain questions about her personal life. “These are private reasons,” she said, “that I didn’t want such big travel, with big distance from home.”
But interviews with past and present collaborators point to a major reason for the unusual limitations on her dazzling career: Her husband, who is also an artistic mentor of hers, has been ailing for some time, so she is unwilling to venture far from where they live, outside Cologne, Germany.
This commitment to her family has earned Ms. Harteros the admiration of many in the opera world, even as they regret the performances they and their audiences are missing. “She’s a very responsible person, and she has a responsibility: end of story,” said Antonio Pappano, the music director of the Royal Opera in London. “It doesn’t make me feel wonderful. But it is what it is.”
Mr. Thielemann, one of the world’s leading Strauss and Wagner conductors, expressed similar feelings: “If you have somebody at home you want to take care of, and need to,” he said, “it’s more than logical that you do it.”
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Ms. Harteros in Munich.CreditLaetitia Vancon for The New York Times
Her restrictions on her travel, along with her lack of a large body of recordings — a deal with Sony fizzled out years ago — have made Ms. Harteros perhaps the most elusive important singer in the world, a star who can seem like a secret.
Born in 1972 near Cologne, the middle of three children of a Greek father and German mother, Ms. Harteros grew up playing the violin. But from early on, she was encouraged to explore her voice. She sang Zerlina in a school production of “Don Giovanni” when she was just 13, and while she made a mistake — the performance even needed to be briefly stopped — it was ineffably right.
“I felt that even if I failed,” she said, “it was not like playing violin in front of an audience. It was a free feeling.”
She entered the conservatory in Cologne, and in her early 20s joined the ensemble at the theater in nearby Gelsenkirchen, before moving on to a larger house in Bonn. In 1999, though she didn’t much like stilted aria contests, she entered the BBC Cardiff Singer of the World competition and won a surprising victory.
“She was an artist that did not arrive at the competition with a kind of buzz around her,” said Anthony Freud, one of the jurors that year and now the general director of the Lyric Opera of Chicago.
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Ms. Harteros as the Countess in “Le Nozze di Figaro” at the Met in 2003.CreditKen Howard/Metropolitan Opera
A young lyric soprano, Ms. Harteros was at that point concentrating on Mozart and the lighter Verdi; one of the things she sang in the final round in Cardiff was the famous “Sempre libera” from “La Traviata,” with its insouciant coloratura. Her voice was full and creamy, but it didn’t give away the dramatic depths it would be plumbing a decade or two hence.
E strano... Sempre liebera (La traviata) - Anja Harteros Video by Bernardo Kim
“I can’t honestly say I was sitting there saying, ‘This lady is going to become a great Elsa or Leonora or Elisabetta di Valois,” Mr. Freud recalled, referring to some heavier Wagner and Verdi roles in which Ms. Harteros has recently triumphed.
Winning the Cardiff competition “was like a passport,” opening her international career, Ms. Harteros said. She rarely faltered in those early years as she traveled from San Diego to New York to Tokyo to Vienna. “Her singing was beautifully cool, clear-toned and full bodied,” Anthony Tommasini wrote in The New York Times of a Met “Don Giovanni” in 2004.
But she recalled the tension of making tough choices as a newcomer. She turned down a prestigious offer to sing Musetta, a supporting part in “La Bohème,” in London; the lead, Mimì, was already in her repertory. She rejected major theaters that wanted to build her up in uncongenial minor roles, preferring to sing the characters she loved in smaller houses.
“That’s the hardest part of the career,” she said. “You have sleepless nights. I needed to learn to say no and to stay with my no.”
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Ms. Harteros as Donna Leonora, with Jonas Kaufmann as Don Alvaro, in “La Forza del Destino” in 2013.CreditWilfried Hösl
Her most important debut came just months after the Cardiff competition here in Munich, where Peter Jonas, who had also been on the Cardiff jury, was the Bayerische Staatsoper’s artistic leader and Zubin Mehta was music director. They embraced her, and the theater quickly became her home base, though she feared her secure position would be threatened when the administration changed in 2008.
“When Herr Bachler began, I was so frightened,” she said. “But he said, ‘You are a wonderful singer and so important to this house, and we want to continue this work and deepen it.’”
A turning point, when you could say she went from house soprano to house star, came in 2009, when she was paired with the galvanizing tenor Jonas Kaufmann in a new production of Wagner’s “Lohengrin.” (“A Hollywood moment,” Mr. Bachler called it.) It was part of Ms. Harteros’s careful pivot from the light, agile heroines of Mozart to Wagner’s Sieglinde, Puccini’s Tosca and Verdi’s Aida.
“It’s mainly a lyric voice that slowly is gaining in power and in potential for bigger and bigger dramatic roles,” said Mr. Pappano, who cast her, alongside Mr. Kaufmann, in an atmospheric recent recording of “Aida.”
Donald Runnicles, the music director of the Deutsche Oper in Berlin, called her embrace of this repertory “a door you can ecstatically walk through — but can you walk back? You can become typecast, or take on roles that are too big for you. And you can’t find your way back. I think that is why Anja is prudent.”
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Ms. Harteros as Amelia, with Plácido Domingo in the title role of “Simon Boccanegra” in 2009.CreditLieberenz/ullstein bild, via Getty Images
Her performances of these queenly characters are memorable because of the passion quaking beneath her serene, regal bearing. Her big blue eyes are full of what the stage director Christof Loy called in an interview “something fragile always.” Singing “Tu che le vanità,” Elisabetta’s climactic aria near the end of Verdi’s “Don Carlo,” Ms. Harteros makes sensational drama out of balancing almost martial control with an undercurrent of rhythmic freedom, her pianissimos seeming to hold back floods of forte.
“From the outside there is purity,” Mr. Bachler said. “But in the inside, you can feel the volcano, and the fire that she doesn’t live, really, or let out, really. And this makes the personality so rich.”
There are not terribly many more major roles for her to explore; no one expects her essentially lyric instrument to push much further, into dramatic parts like Salome or Isolde. Mr. Thielemann said that he had recommended Puccini’s Madama Butterfly to her and thinks that her interpretations of the mature, subtle women of Strauss — the title character in “Ariadne auf Naxos,” the Marschallin in “Der Rosenkavalier,” the Countess in “Capriccio” — will be touchstones in the years to come.
“You need someone with experience,” he said of these characters, “who dominates the scene without doing too much.”
The question, of course, is how widely Ms. Harteros will be able to range in the time she has left, given her personal circumstances. She recalled a rare visit to London, for Verdi’s “Otello” in 2012, a period she called “maybe the hardest or second-hardest time of my life.”
“I went onstage and did Desdemona,” she said. “And the feeling I had when I did ‘Ave Maria,’ that was so special. I put it into the music, and something really special happened with the audience. I don’t want to live that again, but it makes me strong, to know that in difficult times you can reach very high points.”
The opera world, for its part, seems to have tacitly agreed to be patient.
“I have not lost hope, and I believe she will come back to the Met,” Mr. Gelb said. “For her, I would make it work.”