Pharmageddon (45 page)

7
. Trevor A. Sheldon and George D. Smith,
Consensus conferences as drug promotion
, Lancet 341, 100–102 (1993).

8
. J. F. Guest, W. M. Hart, R. F. Cookson, and E. Lindstrom,
Pharmacoeconomic evaluation of long-term treatment with risperidone for patients with chronic schizophrenia
, British Journal of Medical Economics 10, 59–67 (1996).

9
. Stephen Almond and Orla O'Donnell,
The cost-effectiveness of olanzapine compared to haloperidol in the treatment of schizophrenia in the UK.
Final report prepared for Lilly Industries, Personal Social Services Research Unit, University of Canterbury (1996), PharmacoEconomics 17, 383–389 (2000).

10
. Ann Mortimer et al.,
Consensus statement on schizophrenia standards in care for maintenance therapy and poorly responding/treatment intolerant patients
, CINP meeting. International Journal of Neuropsychopharmacology 1, Abstracts Supplement (1998).

11
. David Healy,
Psychopharmacology and the ethics of resource allocation
, British Journal of Psychiatry 162, 23–29 (1993).

12
. Donald Eccleston,
The economic evaluation of antidepressant drug therapy
, British Journal of Psychiatry 163, Supplement 20 (1993).

13
. Ffion Johnstone, Ian Rickard, and David Healy,
The costs of psychotropic medication
, British Journal of Psychiatry 167, 112–113 (1995).

14
. See Dwight McKee and Allen Jones v. Henry Hart, Sydni Guido, Wesley Rish, Albert Masland, James Sheehan, and Daniel P. Sattele, CIVIL ACTION No. 4: CV-02–1910, in US District Court for the Middle District of Pennsylvania; M. Petersen, “Making drugs, shaping the rules: Big Pharma is eager to help states set medication guidelines,”
New York Times
, Feb. 1, 2004, sec. 3:1, 10.

15
. Timothy Kendall, Linsey McGoey, and Emily Jackson,
If NICE was in the USA
, Lancet, doi:10.10116/5cE (2009); Fiona Godlee,
NICE at 10
, BMJ 338, 344 (2009).

16
. Carroll W. Hughes et al.,
The Texas children's medication algorithm project: Report of the Texas consensus conference panel on medication treatment of childhood major depressive disorder
, Journal of the American Academy of Child and Adolescent Psychiatry 38, 1442–1454 (1999).

17
. States that adopted the guidelines include Pennsylvania, California, Colorado, Nevada, Illinois, Kentucky, New Mexico, New York, Ohio, South Carolina, Maryland, Missouri, and Washington DC; in some cases, jurisdictions within these states adopted the guidelines.

18
. Rob Waters, “Medicating Aliah,”
Mother Jones
, May/June 2005, 50–55.

19
. Duff Wilson, “Poor children likelier to get antipsychotics,”
New York Times
, Dec. 12, 2009,
http://www.nytimes.com/2009/12/12/health/12medicaid.html?_r=2&scp=i&sq=antipsychotics&st=cse
.

20
. National Institute for Health and Clinical Excellence (NICE),
Guidance on the use of newer (atypical) antipsychotic drugs for the treatment of schizophrenia
, Technology Appraisal Guidance 43 (June 2002), available at
http://www.nice.org.uk
.

21
. L. Duggan et al., Olanzapine for schizophrenia, Cochrane Database of Systematic Reviews Issue 2, Art. No.: CD001359 (2005), doi:10.1002/1465185 8 .CD001359.pub2.

22
. David Healy et al.,
Lifetime suicide rates in treated schizophrenia: 1875–1924 and 1994–1998 cohorts compared
, British Journal of Psychiatry 188, 223–228 (2006).

23
. Joanna Le Noury et al.,
The incidence and prevalence of diabetes in patients with serious mental illness in North West Wales: Two cohorts 1875–1924 and 1994–2006 compared.
BMC Psychiatry 8, 67 (2008), doi:10.1186/1471-244X-8–67.

24
. This statement is based on my access to the data submitted to the Canadian regulator as part of a legal action on the patenting of Zyprexa.

25
. This is based on conversations with some of those involved in the process.

26
. Jeffrey A. Lieberman et al.,
Effectiveness of antipsychotic drugs in patients with chronic schizophrenia
, NEJM 353, 1209–1223 (2005); Peter B. Jones et al.,
Randomized controlled trial of the effect on quality of life of second vs first generation antipsychotic drugs in schizophrenia
, Archives of General Psychiatry 63, 1079–1087 (2006).

27
. David Healy and David Nutt,
British Association for Psychopharmacology consensus on statement on childhood and learning disabilities psychopharmacology
, Journal of Psychopharmacology 11, 291–294 (1997).

28
. Carroll W. Hughes et al.,
The Texas children's medication algorithm project: Report of the Texas consensus conference panel on medication treatment of childhood major depressive disorder
, Journal of the American Academy of Child and Adolescent Psychiatry 38, 1442–1454 (1999).

29
. “Depression: 3 million kids suffer from it. What you can do,”
Newsweek
, Oct. 7, 2002, 52–61.

30
. Vera H. Sharav,
The impact of FDA modernization act on the recruitment of children for research
, Ethical Human Sciences and Services 5, 83–108 (2003).

31
. Martin D. Keller et al.,
Efficacy of paroxetine in the treatment of adolescent major depression: A randomized, controlled trial
, Journal of the American Academy for Child and Adolescent Psychiatry 40, 762–772 (2001).

32
. Kendall, McGoey, and Jackson,
If NICE was in the USA.

33
. Graham J. Emslie et al.,
A double-blind, randomized placebo-controlled trial of fluoxetine in depressed children and adolescents
, Archives of General Psychiatry 54, 1031–1037 (1997). The internal FDA medical review of the trial makes it clear it was a negative study.

34
. Graham J. Emslie et al.,
Fluoxetine for acute treatment in children and adolescents: A placebo-controlled randomized clinical trial
, Journal of the American Academy of Child and Adolescent Psychiatry 41, 1205–1215 (2002). It is common in clinical trials to stop previous treatments and to put everyone on placebo for a week or two before starting the trial proper. This is called either the washout or the placebo run-in period, and its stated purpose is to wash out any prior drug treatments. It is common to exclude patients responding to placebo during this period.

35
. David J. Carpenter et al.,
Safety of Paroxetine in the Treatment of Children and Adolescents with OCD
, Abstract 58, presented at the 40th annual NCDEU meeting (2001); Daniel A. Geller et al.,
Efficacy and Safety of Paroxetine in Pediatric OCD: Results of a Double-Blind Placebo Controlled Trial
, presented at the 42nd Annual NCDEU Meeting, Session 111-16 (2002) (also presented at the APA annual meeting, Philadelphia, May 2002, NR 349); Karen D. Wagner et al.,
Safety and Tolerability of Paroxetine in Children and Adolescents: Pooled Results from Four Multi-center Placebo-Controlled Trials
, presented at the 42nd Annual NCDEU Meeting, Session 11-61 (2002).

36
. Karen D. Wagner et al.,
Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: Two randomized controlled trials
, JAMA 290, 1033–1041(2003).

37
. Wagner et al.,
Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder
.

38
. Central Medical Affairs Team,
Seroxat. Adolescent Depression. Position Piece on the Phase 111 studies
, Oct. 1998, SmithKline Beecham Confidential Document, available from the author. This is also available on the Canadian Medical Association Journal website. W. Kondro,
Drug company experts advised staff to withhold data about SSRI use in children
, Canadian Medical Association Journal 170, 783 (2004),
http://www.healthyskepticism.org/files/docs/gsk/paroxetine/study329/19981014PositionPiece.pdf
.

39
. This statement is based on my knowledge of what trials had been undertaken from scrutiny of company databases and the FDA's published statements about the trials that had been submitted to them.

40
. Editorial:
Depressing research
, Lancet 363, 1335 (2004).

41
. This is based on conversations with the key players in NICE at this time.

42
. Anyone involved in framing guidelines is now involved in business and their judgments can have far-reaching financial consequences, as the money involved in the patent extensions for the SSRIs demonstrates. The story of another SSRI given to children may make this clear. Celexa (citalopram) was discovered by the Danish company Lundbeck and marketed by Forrest Laboratories in the United States. In 1996, Lundbeck started a trial of Celexa in children that wasn't published until 2006. In 2002, Forrest ran another study of Celexa in children in the United States. As the controversy surrounding antidepressants for children grew, Forrest personnel made presentations of their “data” for Celexa, which appeared to show it worked and was free of risks. A ghostwritten report on the results of the second study was published in June 2004; see Karen D. Wagner et al.,
A randomized placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents
, American Journal of Psychiatry 161, 1079–1083 (2004). There was no mention in all this of the earlier, unpublished Lundbeck study in which Celexa had failed to beat placebo and in which the rate of suicidality on Celexa was dramatically higher than on placebo (A. L. Von Knorring et al.,
A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder
, Journal of Clinical Psychopharmacology 26, 311–315 (2006). To the stock market analysts reviewing company share prices, Celexa looked good compared to the other drugs, which were running into trouble at the time. The Teamsters Union invested pension funds in the stock, while company board members sold stock and made money. As news of the earlier study spread, however, the value of Forrest's stock dropped. The Teamsters Union then took a securities action that resulted in a $65 million settlement in their favor (B. Maier and B. Carey, “Drug maker accused of fraud,”
New York Times
, Feb. 25, 2009,
http://www.nytimes.com/2009/02/26/business/26drug.html?_r=3&ref=health
). There is clearly a lot more at stake in these exercises than there ever had been in traditional medical trials.

43
. Melanie Newman,
The rules of retraction
, BMJ 341, 1246–1248 (2010).

44
. Erick H. Turner et al.,
Selective publication of antidepressant trials and its influence on apparent efficacy
, NEJM 358, 252–260 (2008).

45
. Jean Delay and Pierre Deniker,
38 Cas de psychoses traitées par la cure prolongée et continue de 4560 RP
, C.R. Congrès Méd Alién Neurol France 50

497–502 (1952).

46
. National Institute for Health and Clinical Excellence (NICE),
Bipolar disorder: Clinical Guideline 38
(2006), available at
http://www.nice.org.uk
.

47
. Sumant Khanna et al.,
Risperidone in the treatment of acute mania: Double-blind, placebo-controlled study
, British Journal of Psychiatry 187, 229–234 (2005).

48
. Sandhya Srinivasan et al.,
Trial of risperidone in India—concerns
, British Journal of Psychiatry 188, 489–492 (2006).

49
. There are two versions of the guideline. A longer technical version makes it clear childhood bipolar disorder should not be diagnosed unless children meet the criteria for the adult form of the illness; the shorter version does not mention this. The shorter version is the one that has been disseminated.

50
.
http://www.best-practice.net
(accessed Jan. 4, 2010).

51
. In the case of overactive bladder, in clinical trials patients on anticholinergic drugs like Detrusitol used in instances of what once was called urge incontinence go to the toilet one less time in forty-eight hours. Renaming the condition as overactive bladder increased the numbers of patients from twelve to thirty million in the United States with trials showing the same minimal benefit—but substantial side effects.

52
. P. Colbrook,
Can you ignore guidelines?
BMJ Careers, 143–144 (April 9, 2005).

53
. Tim Croudace et al.,
Impact of the ICD-10 primary health care (PHC) diagnostic and management guidelines for mental disorders on detection and outcome in primary care: Cluster randomized controlled trial
, British Journal of Psychiatry 182, 20–30 (2003); Peter Tyrer, Michael King, and J. Fluxman,
Treatment of common mental disorders in general practice: Are current guidelines useless?
British Journal of Psychiatry 183, 78 (2003).

54
. Edward Evarts, “A discussion of the relevance of effects of drugs on animal behavior to the possible effects of drugs on psychopathological processes in man.” in
Psychopharmacology: Problems in Evaluation
, ed. Jonathan O. Cole and Ralph W. Gerard, 284–306, esp. 302 (Washington, DC: National Academy of Sciences/National Research Council, 1959).

55
. David Healy et al.,
Psychiatric bed utilisation: 1896 and 1996 compared
, Psychological Medicine 31, 779–790 (2001).

56
. Healy et al.,
Lifetime suicide rates in treated schizophrenia
.