ADHD debate clouded by preconceptions and undisclosed conflicts of interest

Three separate contributors to recent editions (Levy, 2012; Paterson, 2012; Starling, 2012) were critical of my May 2012 Viewpoint ‘The rise and fall of ADHD child prescribing in Western Australia: Lessons and implications’ or my role in the National Health and Medical Research Council’s (NHMRC) decision not to approve the 2009 draft ADHD treatment guidelines. It may be instructive to identify points of both agreement and dissent.

Dr Paterson rejects my claim that over the last decade there has been a ‘massive’ decline in ADHD child prescribing rates in Western Australia (WA), although he concedes, citing superseded data, that there was a 24% decrease in WA per-capita child stimulant prescribing rates between 2004 and 2010. In October 2012, the WA Department of Health reviewed its past estimates and identified that between 2004 and 2010 the decrease in stimulant per-capita prescribing rate for children was 32% (Department of Health, 2012). However, Commonwealth Government Pharmaceutical Benefits Scheme (PBS) figures provided for me by the Department of Health and Ageing in April 2012 indicate that between 2002 and 2004 the number of children taking PBS-subsidised stimulants fell 16% despite WA’s population increasing 2%.

When adjusted for confounding factors, such as the introduction of the non-stimulant Strattera, the WA per-capita child prescribing rate for all ADHD drugs fell approximately 50% between 2002 and 2010. Although this decline is less than the previous 70%+ decrease indicated by older WA Department of Health figures, the only data source available when I wrote my May 2012 piece, or my more conservative 60% estimate, it nonetheless validates my claim of a ‘massive decline’.

Dr Paterson also rejects my assertion that tighter prescribing accountability measures were responsible for any decline. He cites significant retirements of prominent prescribers, rather than ‘bureaucratic changes’, as the reason. I agree that retirements contributed significantly but contend that these were ‘encouraged early retirements’ resulting from the pressure of ‘bureaucratic’ scrutiny. The first WA Stimulant Regulatory Report revealed a single paediatrician prescribed to 2077 children from August 2003 until December 2004. Following a significant ‘early retirement’ of a prominent ADHD advocate, this pattern of extreme prescribing to children moderated. This has not been the case for adults, with the WA Department of Health revealing that one psychiatrist prescribed to 1473 patients (including 1346 adults) in 2011 (Department of Health, 2012). Perhaps further ‘encouraged early retirements’ may reduce WA adult ADHD prescribing rates, which in 2011 were 3.3 times the national per-capita rate.

On a related issue, Professor Levy rejects my contention that heavy prescribers – such as Perth’s Dr 1473 – effectively facilitate the diversion of stimulants. She argues that: ‘dexamphetamine prescription rates have markedly decreased since the availability of slow release methylphenidate capsules, which are much more difficult to divert. Continuing reference to amphetamine diversion is thus out-dated’ (Levy, 2012).

Although methylphenidate is now the most commonly prescribed ADHD stimulant in Australia (73% of all PBS scripts in 2010), this is not the case for WA adults (Department of Health and Ageing, 2010). In 2011, the vast majority (81.3%) of WA adults prescribed stimulants were taking dexamphetamine (only 22.3% for WA children) (Department of Health, 2012). This is entirely consistent with my contention that Perth’s high child prescribing rates in the 1990s and early 2000s created a dexamphetamine abuse culture amongst young WA adults, but, as a result of the decline in child prescribing, WA’s next generation has a brighter future.

In 2005, detailed data about WA teenage prescription stimulant abuse became available, confirming anecdotal evidence of widespread abuse. Even though prescription rates had begun to drop, the 2005 Australian Secondary Students’ Alcohol and Drug Survey (ASSAD) estimated that 9492 (5.5%) of WA secondary school students had abused prescription ADHD amphetamines in the last year. It also found that amongst WA 12–17 year olds:

• 84% of those who had abused amphetamines in the last year had abused diverted stimulants

• 27% of those who had been prescribed stimulant medication either gave it away or sold it

• 45% of those who had ever taken dexamphetamine or methylphenidate were not prescribed the drugs

• between 2002 and 2008 there was a 51% reduction in ‘last 12 month amphetamine abuse’.

Rather than address the reality of WA’s experience, both Dr Paterson and Professor Levy have ignored the direct evidence of diversion in the ASSAD study. Furthermore, they have both quoted research by Wilens to support the assertion that the under-treatment of ADHD leads to future drug abuse. In 2011, Wilens, and fellow ADHD ‘experts’ Biederman and Spencer, were sanctioned by Harvard University for failing to disclose millions of dollars in pharmaceutical company support they received (Kowalczyk, 2011).

Professor Levy concludes her commentary piece by asking: When should industry support preclude citation of peer-reviewed scientific work? I answer: when ‘industry support’ involves hidden payments like those given to Biederman, Spencer and Wilens. The NHMRC obviously came to the same conclusion when it abandoned the 2009 draft ADHD Australian treatment guidelines. Biederman, Spencer and Wilens were cited 83, 46 and 32 times in the draft guidelines (Royal Australasian College of Physicians (RACP), 2009). Other researchers cited who were involved in conflict of interest controversies include Dr Wagner and Dr Rush of the University of Texas, and Dr Christopher Gillberg of the University of Gotheburg, Sweden. Dr Gillberg has a criminal conviction for destroying research documentation (Ramshaw, 2009; Swedish Parliamentary Ombudsmen, 2006). In addition, the vast majority of members of the RACP coordinated ADHD guidelines committee, and the RACP itself, had financial ties to ADHD medication manufacturers (RACP, 2009).

Most of the above was only revealed through a US Senate investigation and Australian Freedom of Information processes. Imagine the outrage if similar hidden commercial ties existed amongst politicians determining the direction of national health policy. Or is psychiatry somehow immune to influences that are so carefully guarded against within the public sector and politics?

Both Professor Levy and Dr Starling praise the 2009 draft national guidelines as being based on sound research. The reality is that ‘the majority of the identified studies on ADHD medications’ were ‘sponsored, at least in part, by the manufacturers of the medications’. Furthermore, two-thirds of the 208 draft recommendations of the guidelines committee were made without reference to any supporting scientific evidence. They were based entirely on reference group consensus and justified as ‘best practice based on clinical experience and expert opinion’ (RACP, 2009).

Unsurprisingly, this consensus of like-minded ADHD medication advocates produced recommendations encouraging the first line, second line, third line and even fourth line use of pharmacological interventions to ‘medicate’ for ADHD or for any adverse side effects resulting from the side effects of medications. Examples of this pharmaceutical dominant approach include recommending:

• the cascading use of dexamphetamine or methylphenidate, then the other, then atomoxetine, then clonidine to treat ADHD

• that if, as is common, ADHD stimulants cause or exacerbate tics, the patient should either continue the ADHD medication alone; add an anti-tic medication; or trial another ADHD medication (followed potentially by another anti-tic medication).

The draft guidelines also encourage ‘off label’ use of methylphenidate as a second line treatment in children under 6 years of age and the concurrent prescribing of a cocktail of psychotropic drugs to children with ‘comorbid’ depression and bipolar disorder (RACP, 2009).

While it has never been suggested that individual committee members who developed the draft guidelines were corrupt, the committee disregarded submissions highlighting the issues around Biederman, Spencer and Wilens. They also ignored research that challenged their preconceptions by bringing into question the long-term safety and efficacy of ADHD medications, most notably the Oregon Health & Science University, Drug Class Review on Pharmacologic Treatments for ADHD. (McDonagh et al., 2007) It is a normal human response to ignore evidence that is inconsistent with our preconceptions. That is why it is essential that – unlike the draft guidelines process – policy development committees contain members with competing views. Competition is the best method of achieving a robust evidence-based outcome.

The same pattern of dismissive behaviour has been displayed by ADHD pharmacotherapy advocates in response to the Raine ADHD Study published in 2010. (Department of Health, 2010). I agree with Professor Levy that the finding that: ‘In children with ADHD, ever receiving stimulant medication was found to increase the odds of being identified as performing below age-level by a classroom teacher by a factor of 10.5 times (compared to never receiving stimulant medication)’, is a ‘startling figure’ (Department of Health, 2010). However, I cannot understand how the appropriate response to ‘startling’ results is to ignore them.

The education outcome and the finding that ADHD stimulant use may permanently raise diastolic blood pressure, a precursor to raised cardiovascular risk later in life, should invite fevered competition amongst researchers to pour over the Raine ADHD Study data. A further 8 years of data (from ages 14 to 22) on the safety and efficacy of stimulants for ADHD is now available, but, as Paterson points out, to date only the original non-peer-reviewed paper has been produced by the WA Department of Health. Paterson sees this as a limitation of the Raine ADHD Study analysis. I, however, see an urgent need to more systemically analyse the unique long-term data available through the Raine ADHD Study. Paediatric psychiatric pharmacological research can’t all have gone the way of Biederman, Spencer and Wilens. Surely there are independent truth seekers that are hungry to tap this important and unique long-term data source?

See Viewpoint by Whitely, 2012, 46(5): 400–403, Viewpoint by Levy, 2012, 46(5): 404–406, Commentary by Paterson, 2013, 47(2): 88–89 and Commentary by Starling, 2012, 47(1): 91–92.