Bipolar disorder in children
Mental illness is becoming more common in children.
Diagnosis of bipolar disorder in children has increased dramatically in the US, and Australia is struggling to resist temptations to follow suit, writes Margaret Rice.
Australian scientists and psychiatrists looking over their shoulders at the 44-fold increase in diagnosis of bipolar disorder in US children between 1994 and 2003, and wondering whether diagnosis rates here are appropriately far more modest.
But how can mania be detected in a small child? By their nature children can be raucous one minute, and tearful and aggressive the next.
According to The New York Times the high US rate relative to other countries is due largely to the influence of the child psychiatrist Joseph Biederman, at Harvard, who has given the lead to many other American child psychiatrists.
Biederman's arguments for broadening the diagnosis to include symptoms such as extreme moodiness and irritability have been taken up over the past 10 years by the American Academy of Child and Adolescent Psychiatry. Its journal is littered with papers and reviews supporting Biederman, who has in recent years reassessed as bipolar disorder sufferers a quarter of the children he previously thought had attention-deficit/hyperactivity disorder, another controversial childhood diagnosis.
In the US today four-year-olds are regularly diagnosed with bipolar disorder; rarely the diagnosis extends to two-year-olds and younger. But since June Biederman has been under a cloud. A congressional investigation found he had not told university officials of the $US1.6 million ($2.2 million) he had received in grants from pharmaceutical companies. He breached US disclosure law in declaring only $US20,000.
By late November parents were starting to sue Eli Lilly (maker of Zyprexa), AstraZeneca (Seroquel), Pfizer (Geodon, sold as Zeldox in Australia), Bristol-Myers Squibb (Abilify) and Johnson & Johnson (Risperdal, mainly sold by Janssen-Cilag but also by generic manufacturers in Australia).
All these drugs are second-generation antipsychotics, traditionally prescribed for schizophrenia and increasingly for bipolar disorder. The American parents' lawsuits claim their children were injured after taking these medications.
Bipolar disorder is characterised by a pattern of depression and mania. Mania, its most telling feature, is defined by euphoric mood, accompanied by at least three of the following symptoms - distractibility, indiscretion, grandiosity, flight of ideas, activity, sleeplessness and talkativeness.
But how can mania be detected in a small child? By their nature children can be rowdy, raucous and inappropriately dominating one minute, and tearful and aggressive the next.
Young children are often uninhibited about how they express themselves and do not "layer" their moods, as adults cleverly do in presenting as more upbeat than they feel.
And isn't moodiness a right for someone leaving the cocoon of babyhood and experiencing huge leaps in awareness of the world around them?
The British National Institute for Health and Clinical Excellence rejects as theory the suggestion that children suffer bipolar disorder. It warns it could lead to overmedication.
In Australia the increase in childhood diagnosis worries Peter Parry, an Adelaide child psychiatrist who published a paper with Stephen Allison in last April's issue of Australasian Psychiatry. This prompted letters in the August issue, with one contributor arguing it is "currently one of the most active and controversial areas of clinical and research interest in child psychiatry".
Parry and colleagues recently surveyed 199 Australian and New Zealand child psychiatrists for future publication in Child And Adolescent Mental Health. Ninety per cent thought bipolar disorder was overdiagnosed in the US, 53 per cent said they had never encountered a case in a prepubescent child and another 29 per cent said they had seen only one or two cases.
"If you'd told me three years ago that two-year-olds were being diagnosed with bipolar disorder my reaction would have been 'that's impossible', " Parry said.
"Most of us in the psychiatric profession consider it extremely rare prior to puberty, let alone in a two-year-old."
A solid majority of Australian child psychiatrists see diagnoses such as ADHD, anxiety and emotional- and stress-related problems as sufficient explanations for children who are moody and given to behaviour outbursts.
Parry said the training of Australian child psychiatrists, more than their US counterparts, emphasised treating children's problems in the context of upbringing and environment. The US also has what is known as diagnostic up-coding, in which diagnoses are given elevated seriousness to qualify for private medical insurance cover.
In the US, where government makes no contribution to medical costs, a child suffering an ordinary, out-of-sorts episode that requires treatment not covered by medical insurance may have the condition upgraded to attract a financial rebate.
If diagnoses of bipolar disorder did not have serious consequences, it might just make for an interesting debate.
The rise in US bipolar disorder diagnoses coincided with an almost five-fold increase in childhood prescriptions for antipsychotics.
Serious but uncommon side effects are linked to antipsychotics. These include diabetes, movement disorders, Parkinson's disease-type symptoms and liver and blood disorders. The most common side effects include weight gain and sedation, and these can be particularly troubling in children. In 2006 the deaths of 29 antipsychotic-taking children were reported to the US Food and Drug Administration.
Australian Medicare figures show the use of second-generation antipsychotics (SGA) has increased dramatically in the past five years. Compared with six years ago, pharmacists are filling 52 per cent more scripts for Zyprexa, Seroquel, Zeldox, Abilify and Risperdal. The figures do not tell us about children's use, but there is evidence prescriptions for children are increasing.
In last August'sissue of Australasian Psychiatry, Professor Garry Walter and his co-authors said SGAs "were among the most commonly prescribed psychotropic [mind-affecting] agents" in their survey group of child psychiatrists. They surveyed 126 child psychiatrists throughout Australia and New Zealand and found 112 acknowledged prescribing SGAs to patients under 18 within the past two years. Seventy-three patients had bipolar disorder, and 100 had schizophrenia.
Use of Zyprexa, Seroquel, Zeldox, Abilify and Risperdal (permitted for children with disruptive behaviour caused by intellectual impairment) was discussed by psychiatrists in the Walter survey.
Representatives of Pfizer, the maker of Zeldox, and Bristol-Myers Squibb (Abilify) told the Herald their SGAs were not promoted for childhood use in Australia. Eli Lilly and Janssen Cilag, makers of Zyprexa and Risperdal, issued general statements saying their companies adhered to Australian codes of conduct, and AstraZeneca, the maker of Seroquel, did not respond to our queries.
There are also reports that Australian pediatricians and GPs prescribe SGAs to children with emotional and behavioural problems, without waiting for a clear diagnosis of psychosis.
The monitoring and control of prescriptions of these drugs to children is left to child psychiatrists' professional bodies.
The Royal Australian and New Zealand College of Psychiatrists said "the evidence base, in terms of controlled trials in children, is substantially less developed thanin adults".
"Accordingly clinical decisions regarding medication in childhood presentations of disorders such as suspected bipolar disorder are made only after comprehensive assessment occurring over multiple appointments - usually including family and contextual assessment, reports from multiple informants such as the child's parents and teachers and consideration of alternative explanations for the child's presentation."
The college wants to make a high priority of further research "to develop the evidence base in this important area".
But it is hard to see a hospital-based ethics committee approving a study that would require a large number of children to take SGAs.
In the wake of the Biederman exposure, questions are again being asked in the US about relationships between doctors and the pharmaceutical industry.
"In the area of child psychiatry in particular, we know much less than we should, and we desperately need research that is not influenced by industry money, " said Dr E. Fuller Torrey of the Stanley Medical Research Institute.
In Australia, too, the relationship between pharmaceutical companies and doctors is often questioned.
Critics argue that doctors rely too heavily on the pharmaceutical industry for their drug education. Most doctors point out that if drug education did not come from pharmaceutical companies they would get none. A minority disagrees.
Medicines Australia, the self-regulatory body of the pharmaceutical industry, now requires pharmaceutical companies to report on their websites all the doctor education events they sponsor. In the first half of last year, psychiatrists were the exclusive beneficiaries of 576 education events put on by the makers of Risperdal, Zyprexa, Seroquel, Zeldox and Abilify.
Eli Lilly, the maker of Zyprexa, sponsored 1060 events for doctors and other health professionals (568 involved a mental health theme) and 320 for psychiatrists. The pharmaceutical industry also picks up the tab for some RANZCP events.
The only child psychiatrist we could find who was willing to talk - albeit anonymously - about industry sponsorship received funding from four pharmaceutical companies for six projects.
He has received three education grants - typically $10,000 each but one of nearly $20,000 - for his contributions to consumer and carer information and doctors' guidelines in managing dual diagnoses. A research grant to study bipolar disorder has not yet started. He also received travel assistance to a conference, and a speaking fee of between $400 and $1000.
A general psychiatrist said pharmaceutical companies met venue hire, food and other expenses in examination meetings he ran through the hospital where he works. Pharmaceutical companies had also financed his travel to conferences in London and Milan. In January Eli Lilly paid $56,117 to take seven Australian psychiatrists to a bipolar disorder meeting in India.
Such relationships are increasingly questioned. An outspoken British child psychiatrist, Sami Timimi, argued in the January issue of Advances In Psychiatric Treatment that industry's undue influence had skewed "literature towards biological disease models of childhood mental health in order to support the use of the pharmaceutical companies' products".
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