Friday, August 31, 2012

Lithium: FDA & Bipolar in Children

Until now…. only lithium has been approved to treat bipolar disorder in adolescents ages 12 and up.

Bipolar Disorder in Children

Recently a U.S. Senator uncovered something close to the Cockroach Catcher’s heart: bipolar disorder in children.

Over the last ten years or so, I kept meeting friends in the U.S. whose children seemed to progress from one psychiatric diagnosis to another with frightening regularity, the most common being from ADHD to Bipolar. One grandmother recently asked me what I thought of Bipolar illness in children.

Being an experienced and seasoned psychiatrist, I was able to bounce the question back.

“Well my grandson of five has just been diagnosed. To me he is just an imaginative bright young thing and I never really had any problems with him when he spent part of the school holidays with me. But now he is on all these medications……” she told me.

Well, a few years ago I was at an American Psychiatric Association conference, where a strong case was made for diagnosing children with Bipolar and giving them the modern anti-psychotic drug. I was impressed then.

Later I was more impressed that a single person seemed to have been able to push through a whole new agenda for the diagnosis of Bipolar disorder in children and their treatment.

ADHD was the old black. Bipolar became the new black.

Until now.

In the New York Times, the headline reads:

Researchers Fail to Reveal Full Drug Pay

“A world-renowned Harvard child psychiatrist whose work has helped fuel an explosion in the use of powerful antipsychotic medicines in children earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007 but for years did not report much of this income to university officials, according to information given Congressional investigators.”

Who is the psychiatrist?

“By failing to report income, the psychiatrist, Dr. Joseph Biederman, and a colleague in the psychiatry department at Harvard Medical School, Dr. Timothy E. Wilens, may have violated federal and university research rules designed to police potential conflicts of interest, according to Senator Charles E. Grassley, Republican of Iowa. Some of their research is financed by government grants.”
It was Dr Biederman’s presentation I heard at the conference I mentioned earlier. This is interesting!

“Like Dr. Biederman, Dr. Wilens belatedly reported earning at least $1.6 million from 2000 to 2007, and another Harvard colleague, Dr. Thomas Spencer, reported earning at least $1 million after being pressed by Mr. Grassley’s investigators.”

The New York Times was quick to point out that these figures were most likely an under-estimate.
“Dr. Biederman is one of the most influential researchers in child psychiatry and is widely admired for focusing the field’s attention on its most troubled young patients. Although many of his studies are small and often financed by drug makers, his work helped to fuel a controversial 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder, which is characterized by severe mood swings, and a rapid rise in the use of antipsychotic medicines in children. The Grassley investigation did not address research quality…..

In the past decade, Dr. Biederman and his colleagues have promoted the aggressive diagnosis and drug treatment of childhood bipolar disorder, a mood problem once thought confined to adults. They have maintained that the disorder was underdiagnosed in children and could be treated with antipsychotic drugs, medications invented to treat schizophrenia….

Doctors have known for years that antipsychotic drugs, sometimes called major tranquilizers, can quickly subdue children. But youngsters appear to be especially susceptible to the weight gain and metabolic problems caused by the drugs, and it is far from clear that the medications improve children’s lives over time, experts say.

What is the number of children involved?
“Some 500,000 children and teenagers were given at least one prescription for an antipsychotic in 2007, including 20,500 under 6 years of age, according to Medco Health Solutions, a pharmacy benefit manager.” 

Under 6 years of age!!! Take a look at this tragedy in The Boston Globe.

A girl of 4 died. These are the words in The Boston Globe;

“Finally, it's sad but true -- the field of child psychiatry is afraid of Biederman. One can hear the worries and fears whispered in the academic halls and clinics over where Biederman has taken the profession. Yet to politely challenge Biederman in public is to risk public retribution and ridicule from him and his team. Also academic researchers in child psychiatry risk losing their funding if they criticize this darling of the pharmaceutical industry, which provides most of the money these days for psychiatric research.” Dr. Lawrence Diller
The San Francisco Chronicle 
March 27,2009
“Dr Biederman appears to be promising drugmaker Johnson & Johnson in advance that his studies on the antipsychotic drug risperidone will prove the drug to be effective when used on preschool age children.”
And we do not have to wait for an eclipse. Wow! I have to declare that I have heard him at a conference and I reported this in a previous blog: Bipolar and ADHD: Boys and Breasts.

The San Francisco Chronicle article continues:

“Biederman's status at Harvard and his research have arguably made him, until recently, America's most powerful doctor in child psychiatry. Biederman has strongly pushed treating children's mental illnesses with powerful antipsychotic medicines. Diagnoses like ADHD and pediatric bipolar disorder, along with psychiatric drug use in American children, have soared in the last 15 years. No other country medicates children as frequently.”

No other country medicates children as frequently!
“Reports from court actions, along with an ongoing investigation of conflict of interest charges led by Sen. Chuck Grassley, R-Iowa, threaten to topple Biederman from his heretofore untouchable Olympian heights. Biederman has cried foul.”

“He says the drug company dollars (declared and undeclared) have not influenced him or his research. He had agreed temporarily to sever most of his financial ties with the drug industry pending the outcome of the ongoing inquiry.

“He claims his science and publications are pure, supported by a peer-review system that is supposed to verify accuracy and authenticity. Finally, he challenges as office gossip reports of his legendary anger and intolerance of those who disagree or don't support his proposals.”

The New York Times:

"In a contentious Feb. 26 deposition between Dr. Biederman and lawyers for the states, he was asked what rank he held at Harvard. 

“Full professor,” he answered.
“What’s after that?” asked a lawyer, Fletch Trammell.
“God,” Dr. Biederman responded.
“Did you say God?” Mr. Trammell asked.
“Yeah,” Dr. Biederman said.

Latest: 3 Researchers at Harvard Are Named in Subpoena 

Personal Experience:
Looking back at my career as child psychiatrist for over 30 years, I can count six bipolar cases, one at age 11, three between 13 and 16 and two over 16. All of them responded extremely well to Lithium.

Although the Grassley investigation did not address research quality, the New York Times article reported dissenting voices from other top psychiatrists:

“The group published the results of a string of drug trials from 2001 to 2006, but the studies were so small and loosely designed that they were largely inconclusive, experts say. In some studies testing antipsychotic drugs, the group defined improvement as a decline of 30 percent or more on a scale called the Young Mania Rating Scale — well below the 50 percent change that most researchers now use as the standard.

Controlling for bias is especially important in such work, given that the scale is subjective, and raters often depend on reports from parents and children, several top psychiatrists said.”
This is why I have always argued that reports from parents, teachers and children cannot entirely replace direct clinical observation.

“More broadly, they said, revelations of undisclosed payments from drug makers to leading researchers are especially damaging for psychiatry.”

Money corrupts.

Related Posts:
Lithium Bipolar and Nanking
Bipolar Disorder in Children
Bipolar and ADHD: Boys and Breasts
Bipolar Disorder: Biederman Einstein God.
Antipsychotics: Really?
Bipolar and ADHD: Boys and Breasts
Grand Round: Medicine and War
Bipolar Disorder: Lithium-The Aspirin of Psychiatry?

Thursday, August 30, 2012

Lithium-The Aspirin of Psychiatry?

The Jobbing Doctor mentioned my earlier post so I think it is worth re-posting another one on Lithium. With the number of high profiled suicides of famous people, one wonders if it was due to doctors and psychiatrists shying away from Lithium because: it is a salt, it is discovered by an Australian or it may one day lead to kidney and thyroid problems. One day, well.............

The following is an extract from The Cockroach Catcher:

“Get him to the hospital. Whatever it is he is not ours, not this time. But wait. Has he overdosed on the Lithium?”

“No. my wife is very careful and she puts it out every morning, and the rest is in her bag.”

Phew, at least I warned them of the danger. It gave me perpetual nightmare to put so many of my Bipolars on Lithium but from my experience it was otherwise the best.

“Get him admitted and I shall talk to the doctor there.”

He was in fact delirious by the time they got him into hospital and he was admitted to the local Neurological hospital. He was unconscious for at least ten days but no, his lithium level was within therapeutic range.

He had one of the worst encephalitis they had seen in recent times and they were surprised he survived.

Then I asked the Neurologist (who was new, as my good friend had retired by then) if the lithium had in fact protected him. He said he was glad I asked as he was just reading some article on the neuroprotectiveness of lithium.

Well, you never know. One does get lucky sometimes. What lithium might do to Masud in the years to come would be another matter.

I found that people from the Indian subcontinent were very loyal once they realised they had a good doctor – loyalty taking the form of doing exactly what you told them, like keeping medicine safe; and also insisting that they saw only you, not one of your juniors even if they were from their own country. It must have been hard when I retired.

Some parents question the wisdom of using a toxic drug for a condition where suicide risk is high. My answer can only be that lithium seems inherently able to reduce that desire to kill oneself, more than the other mood stabilizers, as the latest Harvard research shows.

Lithium has its problems – toxic at a high level and useless at a low one, although the last point is debatable as younger people seem to do well at below the lower limit of therapeutic range.

Many doctors no longer have the experience of its use and may lose heart as the patient slowly builds up the level of lithium at the cellular level. The blood level is a safeguard against toxicity and anyone starting on lithium will have to wait at least three to four weeks for its effect to kick in. In fact the effect does not kick in, but just fades in if you get the drift.

Long term problems are mainly those of the thyroid and thyroid functions must be monitored closely more so if there is a family history of thyroid problems. Kidney dysfunction seldom occurs with the Child Psychiatrist’s age group but is a well known long term risk.
Also if there is any condition that causes electrolyte upset, such as diarrhea, vomiting and severe dehydration, the doctor must be alerted to the fact that the patient is on Lithium.
Could Lithium be the Aspirin of Psychiatry? Only time will tell!

WHO: Lithium

Cade, John Frederick Joseph (1912–1980)

Wednesday, August 29, 2012

Lithium & Manic Depressive Disorder: From Chile to Nanking

Santiago, Chile was the starting point of our cruise round Cape Horn. We had a wonderful guide who took us from Santiago city to the Valparaiso port, where we boarded our cruise liner. She was infectiously enthusiastic. She told us that apart from copper, agricultural products and wine, Chile produced something that was very important for her brother.  He suffers from Trastorno Afectivo Bipolar (Bipolar Disorder) and Chile is the world’s largest producer of lithium.

Wikimedia Commons SalarDeatacamaFromChaxa.jpg

The term "manic-depressive illness" or psychosis was coined by German psychiatrist Emil Kraepelin in the late nineteenth century. Bipolar disorder is a more recent diagnostic term.

May 09, 2008

Nanking Poster: THINKFilm
On July 2, 1996, the anniversary of Ernest Hemingway’s own suicide, Margaux Louise Hemingway, his grand daughter was found dead in her studio apartment in Santa Monica, California at age 41.

On November 9, 2004, Iris Chang (張純如), who was propelled into the limelight by her 1997 best-selling account of the Nanking Massacre “The Rape of Nanking: The Forgotten Holocaust of World War II”, committed suicide. Earlier she had a nervous breakdown and was said to be at the risk of developing Bipolar illness. She was on the mood stabilizer divalproex and Risperidone, an antipsychotic drug commonly used to control mania. There was a detailed report in San Francisco Chronicle.

My sentiments about the treatment of bipolar illness are expressed in The Cockroach Catcher:

“I am a traditionalist who believes that Lithium is still the drug of choice for Bipolar disorder. Tara’s mother was well for ten years. She was taking only Lithium and no other medication.”

The anti-suicidal effect of lithium has been confirmed by a number of recent studies in both the U.S. and in Europe.

According to the results of a population-based study published in the 2003 Sept. 17 issue of The Journal of the American Medical Association (JAMA. 2003;290:1467-1473, 1517-1519), Lithium reduced suicide rates of patients with bipolar disorder but divalproex did not. Risk of suicide death was about 2.5-fold higher with divalproex than with lithium.

Another paper published in 2005 (Arch Suicide Res. 2005;9(3):307-19) reviewed the existing evidence.

“The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithium's episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.”

The JAMA paper highlighted the declining use of lithium by psychiatrists in the United States and observed that:

"Many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."

One might ask why there has been such a shift from Lithium.

Could it be the simplicity of the salt that is causing problems for the younger generation of psychiatrists brought up on various neuro-transmitters?

Could it be the fact that Lithium was discovered in Australia? Look at the time it took for Helicobacter pylori to be accepted.

Some felt it has to do with how little money is to be made from Lithium.

My questions are: Will the new generation of psychiatrists come round to Lithium again? How many talented individuals could have been saved by lithium?

Bipolar disorder: divalproex er vs placebo

May 19, 2009

Just before I retired, it has become fashionable to use anticonvulsants as a mood stabiliser. Being a traditionalist, I felt then that the evidence was not clear and I tended to stick with the trusted lithium.

Well my doubts were confirmed:Journal of the American Academy of Child & Adolescent Psychiatry:

May 2009 - Volume 48 - Issue 5 - pp 519-532
doi: 10.1097/CHI.0b013e31819c55ec
New Research

A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

Conclusions: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(5):519-532.

An earlier Harvard study showed that Lithium reduced suicide risks by as much as 9 fold.

Cade, John Frederick Joseph (1912 - 1980)
Taking lithium himself with no ill effect, John Cade then used it to treat ten patients with chronic or recurrent mania, on whom he found it to have a pronounced calming effect. Cade's remarkably successful results were detailed in his paper, 'Lithium salts in the treatment of psychotic excitement', published in the Medical Journal of Australia (1949). He subsequently found that lithium was also of some value in assisting depressives. His discovery of the efficacy of a cheap, naturally occurring and widely available element in dealing with manic-depressive disorders provided an alternative to the existing therapies of shock treatment or prolonged hospitalization.

In 1985 the American National Institute of Mental Health estimated that Cade's discovery of the efficacy of lithium in the treatment of manic depression had saved the world at least $US 17.5 billion in medical costs.

And many lives too!

Anorexia Nervosa: Breasts, Wine & French Health Care!

In my post on PIP implant I suggested that the French should stick to wine making: I was unfortunately wrong. They only make the labels it would seem.

****PIP implants manufactured by a French farm using non medical grade material: read it all here>>>>

In the wine worlds most dramatic news since the Austrians added anti-freeze to their winesyears ago one of the big Burgundian houses is in serious trouble.

 ©2008 Am Ang Zhang

Four directors of Maison Labouré-Roi, the 180-year-old Burgundy negociant house, have been accused of various counts of wine fraud.

…..Public Prosecutor Eric Lallement said during a press conference held in Dijon last night (13 June) that the fraud office was first alerted due to a disparity in figures between what the company was actually bottling and what it should have been, given the yields declared at harvest time. ‘It was as if the company was managing to vinify 100% of its musts, which is impossible,’ he said.

On investigating this, he said police found evidence of several specific frauds: firstly bypassing legal blending limits, affecting every level of the production from Grand Cru, Premier Cru and Village appellations, and adding table wine to wine musts to top up the ‘angel’s share’, Lallement said. He said the suspected fraud related to 500,000 bottles of wine, worth €2.7m in sales.

The second fraud detailed was over wine quality and labeling. ‘When the company needed to fulfil an order of a wine that it had run out of, it swapped labels with other wines,’ said Lallement. The magnitude of this fraud is estimated to be around 1.1m bottles.

So should they now stick to Health Care; best in the world according to WHO a few years back!

A reprint:

Reading a new book sometimes brings you the unexpected.

In Ahead of the Curves, the author told of the story he heard of Jacques Chirac and his pact with West African marabouts, witch doctors. He was told to sacrifice one of his daughters if he wanted his presidency. Soon after his younger daughter, began suffering from anorexia nervosa.

So, I Googled Chirac’s daughter:

Telegraph: By Colin Randall
Published: 07 Dec 2004
President Jacques Chirac's wife has broken a 30-year silence to talk publicly about the anorexia that drove their elder daughter to try repeatedly to kill herself.

"A mother who fails with a child, who cannot bring a sick child back to health, always feels guilty," Bernadette Chirac said on French television. "And a father, too."

Laurence Chirac, now 46, was a promising medical student and worked for a short time after her studies with Samu, the emergency medical service, in Paris.

But she had suffered from an acute form of the eating disorder since she was 15, leading to several stays in hospitals and clinics.

Sixteen years ago, during her father's second presidential campaign, she was taken to hospital amid widespread rumours that she had died.

"Being famous can be harmful when one is faced with illness," Mrs Chirac said. "Confronting this kind of difficulty, you just want to hide from the gaze of others."

Laurence, whose younger sister Claude is a key member of the president's team at the Elysée, continued to suffer from the condition. In 1990 she tried to commit suicide by jumping out of the window of her fourth-floor flat.

A nurse assigned to her round-the-clock care was unable to stop Miss Chirac, who survived with a broken pelvis and head injuries.

Little has been heard of her since and Mrs Chirac said merely that she always kept the hope "pinned to my heart" that her daughter would recover.

Mrs Chirac has been the president since 1994 of a charity seeking to create better conditions for children and teenagers in hospital, enabling them to listen to or play music and play sports. She agreed to talk about her daughter on a France 3 discussion programme, “You Cannot Please Everyone”, to help publicise a new clinic for adolescents, La Maison de Solenn, funded by her charity.

"These children need some gaiety in their lives, to be able to see the sun," said Mrs Chirac,

She contrasted this ideal with the conditions in which her daughter was sometimes treated, "enclosed behind brick walls in a bedroom with a small window". She added: "That is why this mother wants to create a facility specific to adolescents' needs.

French Health Care as experienced by the President’s daughter.

We did not do too badly with our own Adolescent Psychiatric Units.

Saturday, August 25, 2012

Anorexia Nervosa: Let Her Die!

A reprint:

©Am Ang Zhang 2005

Can a patient be allowed to die? 
Can a seventeen year old patient be allowed to die?
Can a seventeen year old Anorexia Nervosa patient be allowed to die?

Are we not supposed to save lives?

Could doctors be held to ransom? By?

Here is a Play: Let Her Die!

The Players:

The parents:
Father used to run a business security agency specialising in industrial counter espionage. Or was it espionage? I cannot be sure.

Too often there is this bizarre desire by some parents to make sure that if they cannot do it, no one else should either. We need to recognise it early enough. We are doomed otherwise, and so is the patient.

The patient: Nicola
It was really quite painful to sit there and talk to someone who looked worse than the worst they showed from Auswitz. Why could Nicola not realise that if she wanted any man to like her she would need to look a lot better, which involved doubling her weight for starters.

The Doctors:
Dr Hillman:

This was a family given up even by Dr Hillman, my most fervent supporter of family therapy. Father used to run a business security agency specialising in industrial counter espionage. Or was it espionage? I cannot be sure.

The Consultant:
        I did not go round looking like a hippie or pretending that I liked the music the teenagers listened to. I told them to me it was trash. I did not pierce my ear or have a tattoo. I certainly did not wear trainers to work.
        In short, you do not have to gain respect by becoming like them or worse, by pretending that you are like them.

The Experts:
I spent one session with them and agreed with Dr Hillman. They were good. We looked like a bunch of amateurs dealing with professionals. None of the family therapy tricks work, Minuchin or Haley.

The NHS Trust & GMC

To me, suspension on full pay is a risk every doctor takes nowadays, as the basis is no longer limited to bad practice. It is no longer a reflection on whether you are good or bad clinically. Many psychiatrists are no longer prepared to use techniques that might upset their patients or parents of their patients.

The Main Action:

A family meeting was called and it lasted only a few minutes.
          I was in top form.

          “Nicola has been eating but after two months has not put on any weight. I cannot see any reason for her to continue to stay here. She might as well do the eating at home. She can then sort out for herself why she is not gaining weight without the pressure from us.”
          I tried to put it in the calmest way possible.
          “You mean you will let her die?” Father sounded a bit annoyed.

        With that father got up and left the room without saying another word.

          “What do I do now? You have upset him!” said mother.
          Good, something got to him at last, but I did not say it.
Nicola gave a wry smile to me as if to say, “You found me out.”
          She turned to mum, “Let’s pack and leave this dump.”
          We all kept still.
Six months later, one of the nurses bumped into Nicola in a nearby town. She was kicked out by father and moved in with another ex-anorectic. She was with a boy friend. More importantly she was wearing a very sexy dress to show off her then very good figure.
          She did not die.

                                           Based on an extract from my book The Cockroach Catcher

The Cockroach Catcher on Amazon Kindle UKAmazon Kindle US


Dr No said...
CC - Dr No rather suspected that if you didn't turn up and comment on badmed, then you were probably doing a post of your own!

Dr No reads the moral of your post as less is more, ie the more doctors try to control patients (admission, section, forced feeding), the more the patient resists. Do the opposite (patient can go home, even die if the want to) and the patient still resists - in Nicola's case by gaining weight...even if she did do so rather rapidly...and, of course, having a spook for a dad is enough to put anyone on edge...

E's case (the one recently in the news) is very different. She was almost twice N's age, very different family by the sound of things, significant co-morbdities and a long history of failed forced feeding attempts (albeit with one early success). She was, if such a concept is meaningful, in end-stage anorexia nervosa.

Can a patient be allowed to die? Yes - we do it all the time.

Can a seventeen year old patient be allowed to die? Yes - we reluctantly and with great sadness do it from time to time.

Can a seventeen year old Anorexia Nervosa patient be allowed to die? Not if we can possibly help it. But anorexia nervosa is truly pernicious illness, and sometimes it defeats us all - although usually a bit later in the patient's life.

Would Dr No have discharged Nicola as you did? Almost certainly, and probably for the same reasons!
Cockroach Catcher said...
It is perhaps The Cockroach Catcher's own experience with young Anorexia Nervosa Patients that has coloured his views. There is in him a genuine feeling that doctors should be allowed to doctor pure and simple and in that sense he feels that psychiatrists should be doctors too, real doctors.

Remember the early days of treating phobia when bus loads of phobic patient from none other than the Maudsley were taken to Piccadilly Circus and dumped there. It was known as implosion therapy. then later suicidal patients were given the sharpest razor blades so that they can get on with it.

In Psychiatry, the best treatment is without doubt Placebos. But placebos only works if neither the patient nor the parents knew.

In reading DN's blog I reposted my patient where I let her die.

Well, did I or was that part of Haley/Minuchin treatment? You can decide.

No the early day psychiatrists did not mean harm to come to the Picadilly or Razor patients, but when non-doctors are involved, good luck to the said patients.

Perhaps DN;s patients was of Millennium Trilogy quality and ooops, what was the state doing?

Please let the real doctors or better still the real psychiatrist get on with their real work, if only they are allowed to remember how to give all the guidelines floating around.

The Cockroach Catcher retired partly because he sensed he would not be allowed to carry on his own doctoring ways.