Strattera’s sad story – (warning it may make you want to kill yourself)

When Strattera came onto the Australian market in 2004 it was promoted as a safer, milder alternative to ADHD amphetamines. Within two years it had the highest possible ‘boxed’ warning for suicidal ideation and a string of horrific adverse event reports for self-harm and suicidal and homicidal ideation by children (see list below) as well as a warning for potentially fatal liver damage. In 2012 a warning for ‘clinically significant increases in heart rate and blood pressure’ was added.

On 1 October 2013, the TGA advised that a nine year old boy on Strattera had ‘completed’ a suicide and other children had made ‘incomplete’ suicide attempts. The real number of children who have suffered horrific side effects on Strattera will never be known as reporting is voluntary and only a tiny fraction of the real number are reported to the TGA.

How this drug was originally licensed or approved for subsidisation, to the extent of $101.2 M over 4 years, through the Pharmaceutical Benefits Scheme will probably never be known. Commonwealth legislation exempts from Freedom of Information requests the documents used by drug manufacturer Eli Lily to support their applications. Eli Lily’s documents are given the same status as individual patients medical records. The net effect is Eli Lilly get our taxes, kids die and we are not allowed to know why.

by Martin Whitely (last updated August 30, 2012)

Strattera is Eli Lilly’s brand name for atomoxetine hydrochloride, a noradrenaline re-uptake inhibitor. Strattera’s legitimate marketing edge is that unlike dexamphetamine and methylphenidate, it is not amphetamine based and therefore has the advantage of being non-addictive and unsuitable for illicit use.

Strattera came onto the Australian market in early 2004. It was licensed by the TGA on the back of evidence from two studies chosen by its manufacturer Eli Lilly. Elli Lilly chose who conducted the studies and had the opportunity to ‘cherry pick’ favourable studies (and ignore unfavourable studies) to support its’ licensing application.

Despite claims of Strattera being a milder ADHD drug, concerns soon emerged about its safety. On 17 December 2004 the US FDA issued a talk paper, ‘New Warning for Strattera’, which stated:

‘The drug’s labeling is being updated with a bolded warning about the potential for severe liver injury in patients taking Strattera. The label warns that severe liver injury can progress to liver failure in a small percentage of patients. It cautions clinicians to discontinue the drug in patients who develop jaundice or laboratory evidence of liver injury. It also notes that the actual number of cases of severe liver injury from the drug is not known because of under-reporting.’^[1]

Less than a year later, on 29 September 2005 the FDA issued a public health advisory announcing they had put the highest possible black box warning on Strattera for suicidal ideation:

‘Strattera increases the risk of suicidal thinking in children and adolescents with ADHD. Patients who are started on therapy should be observed closely for clinical worsening, suicidal thinking or behaviours, or unusual changes in behaviour. Families and caregivers should be advised to closely observe the patient and to communicate changes or concerning behaviours with the prescriber.’^[2]

In March 2006 the Australian Therapeutic Goods Administration (TGA) followed the FDA’s lead and issued an equivalent ‘suicidality’ warning to prescribers. However, unlike the FDA the TGA made no attempt to alert the media or the public and left that responsibility to individual doctors.

In November 2011 the TGA added a warning about ‘clinically significant increases in heart rate and blood pressure’. (see http://www.tga.gov.au/safety/alerts-medicine-atomoxetine-111102.htm) The safety advisory warns ‘Atomoxetine [Strattera] is contraindicated in patients with symptomatic cardiovascular diseases, moderate to severe hypertension or severe cardiovascular disorders, whose condition would be expected to deteriorate if they experienced increases in blood pressure or in heart rate that could be clinically important’. It followed new data obtained from clinical trials sponsored by Eli Lilly.

Up until March 2012, there were one hundred and six voluntary adverse event reports made to the Australian Therapeutic Goods Administration, including over fifty of self harm or suicidal ideation for Strattera (see below).^[3] It is impossible to know the true number of actual events, as the voluntary nature of the reporting system means only a fraction of the actual incidents gets reported.^[4]

A Sample from the Adverse Drug Reactions Committee (ADRAC) adverse event reports for Atomoxetine Hydrochloride (Strattera)

11 year old boy who ‘threw a cricket stump javelin style at a school teacher’ and ‘threatened to kill himself’
8 year old boy who ‘hit his head against a wall’ and had ‘thoughts of suicide – stating that he wants to kill himself’
18 year old male who suffered ‘swollen, painful and tender testicles’
25 year old woman who wanted to kill herself
12 year old girl who experienced; ‘anorexia, weight loss, fidgeting and compulsive behaviour that included ripping out fingernails and toenails, picking and cutting clothing, and anger outbursts’
7 year old girl who ‘became very agitated while travelling in the family car and had explosive mood swings. She said that she intended to open the door and get out of the car, and she tried to open the car door’
9 year old boy who ‘developed abnormal behaviour, including strange facial expressions with bilateral eyelid ptosis and became very emotionally withdrawn’
9 year old boy who displayed ‘aggression, was totally irrational for three days and became violent, all of which was totally out of character’
11 year old boy who ‘became agitated, emotionally labile and experienced thoughts of self-harm’
13 year old boy who ‘experienced chest pains and hostile and aggressive behaviour, but the problems immediately disappeared with the cessation of Strattera’
9 year old boy who slammed ‘his head against walls, had extreme mood swings, violent outbursts’ and was ‘always angry, depressed or sad and said he wanted to kill himself’
10 year old boy who ‘experienced nausea, then became acutely depressed, aggressive and had suicidal thoughts’
22 year old man who experienced suicidal and homicidal ideation
7 year old girl who experienced ‘abdominal pain , nausea, severe right sided headache, shooting pains, white spots in visual fields, academic regression and faecal and urinary incontinence’
7 year old boy who experienced ‘suicidal ideation and mood changes’ and suffered from ‘increased aggression’ and ‘threats to self with knife, picking his skin, poking self with knife’
12 year old boy experienced ‘very strong suicidal ideation…talking about dead bodies and about hanging himself’
11 year old boy who ‘attempted suicide’ and who experienced ‘headache(s), stomach cramps, muscle rigidity and poor concentration’
7 year old boy who experienced ‘suicidal ideation’
10 year old boy who developed ‘psychotic symptoms’ and began ‘talking about suicide’
11 year old boy who experienced ‘a psychotic episode and took an overdose of his mother’s thyroxine’
9 year old boy who ‘experienced suicidal thoughts’
11 year old boy who became ‘extremely agitated’ and ‘talked about wanting to die’
13 year old boy who experienced ‘suicidal ideation, physical and verbal aggression to family’ and became ‘angry, withdrawn, socially isolatory, impulsive, moody’
15 year old boy who was ‘expressing suicidal thoughts’
11 year old boy who ‘took Strattera for the treatment of ADHD to complement Ritalin, under the influence of which he became suicidal and depressed’
12 year old girl who ‘ripped out her fingernails and toenails’
9 year old girl who ‘experienced self-harming’
9 year old boy who expressed ‘suicidal ideation’, ‘aggression’ and ‘self harm’ and made ‘drawings of him hanging upside down from a tree, in (the) ocean’
10 year old boy who was psychotic and experienced auditory hallucinations including ‘hearing voices in his head to kill his sister’
8 year old boy who lost his appetite and experienced homicidal ideation, lost weight and was angry and confused
15 year old girl who experienced suicidal ideation and started cutting herself to the extent that was ‘life threatening’
another 15 year old girl who experienced suicidal ideation and started cutting herself with razors, scissors and knives
10 year old boy who experienced suicidal ideation
another 10 year old boy who had abnormal thoughts about ‘others jumping off buildings’
8 year old boy who talked about killing himself ‘in a boastful manner’
17 year old male who ‘was verbally and physically aggressive. These behaviours have never been seen in this man previously’’
8 year old boy who ‘had lost appetite, was homicidal, losing weight, and lashing out/angry, patient had bruising’
22 year old male who engaged in ‘psychotic behaviour’
Two reports of a 14 year old girl who ‘started cutting herself. It was reported that she felt compelled to start cutting herself and cut her arms with razors, scissors, knives. The patient had suicidal ideation while causing self-harm’
10 year old boy who ‘experienced suicidal thoughts’
10 year old boy who ‘had thoughts about others jumping off buildings’
8 year old boy who was ‘talking about killing himself/suicide. Patient was not depressed and discussed suicide in a boastful manner. Treating paediatrician continued atomoxetine and considered adding Risperidone. Past history included sexual abuse’
7 year old girl had ‘severe abdominal pain’ which ‘caused or prolonged inpatient hospitalisation’
10 year old boy who had ‘suicidal thoughts and threats, despair/depression… and violent outbursts’
8 year old boy had ‘suicidal tendencies’
6 year old boy who had ‘seizures’
12 year old girl who was ‘ripping their fingernails and toenails out.’
17 year old male who had ‘suicidal thoughts; paranoia’
13 year old boy who experienced ‘suicidal ideation’
17 year old male who experienced ‘suicidal ideation’
and a 13 year old boy who ‘commenced on Strattera … and was more agitated than usual and extremely strong suicidal ideation and urges – he climbed on a roof to jump off. Also had extremely strong ideation to seriously hurt and put in intensive care some of the other schoolchildren.’

In 2012 the TGA stopped making individual de-identified adverse event reports available on request. They justified the decision on privacy grounds, however, it is difficult to see how any individual could be identified out of population of 22 million from information like that detailed above. Instead the TGA now provide intermittent summaries of the adverse event on their website.

On 1 October 2013 the TGA restated its’ suicide warning for Strattera: ‘Serious adverse events reported to the TGA, including one case involving the death of a child (suicide by a 9 year old boy), reinforce the importance of health professionals adequately informing parents and caregivers of the risks of suicidal ideation and behaviour in children and adolescents being prescribed atomoxetine.’ (available at http://www.australianprescriber.com/magazine/36/5/166/9 )

Strattera on the PBS

Despite its warning for suicidal ideation and potentially fatal liver damage Strattera was placed on the Pharmaceutical Benefits Scheme (PBS) on 1 July 2007 at an anticipated cost to taxpayers of $101.2 million over four years. Eli Lilly had applied unsuccessfully on at least three previous occasions to have Strattera subsidised via the PBS. Before it was placed on the PBS I wrote to the then Howard Government Health Minister (now Prime Minister) Tony Abbott highlighting to suicide and liver risks and pleading with him not to subsidise Strattera via the PBS. When in 2007 he was replaced by Rudd government Health Minister Nicola Roxon, I drew her attention to the growing number of horrific adverse events and asked her to reverse the decision. Like Abbott she dismissed my concerns.

In November 2008 I requested, via Freedom of Information, copies of all documents relating to the decision of the Pharmaceutical Benefits Advisory Committee (PBAC) to recommend Strattera’s listing on the PBS. I was particularly interested in what consideration had been given by the PBAC to Strattera’s black box warning for suicidal ideation and the numerous adverse event reports. The Department of Health and Ageing refused to release all but a tiny percentage of heavily censored and irrelevant documents.

The Administrative Appeals Tribunal heard my appeal against their refusal to release the documents in April 2010. The Department of Health and Ageing argued successfully that they had erred in giving me any documents because the Health Act 1953 prevented anyone working for the Commonwealth revealing information relating to the affairs of a (legal) person (in this case Eli Lilly). Effectively Eli Lily’s documents were given the same status as individual patients medical records

This decision created a precedent that the public has no legal right to know why the PBAC recommends taxpayers subsidising any drug. Eli Lilly and the pharmaceutical industry were the only winners benefiting from $101.2 million of public funds and the public is not allowed to know why. In the meantime more Australian children are taking Strattera and risking liver damage, cardiovascular problems, self harm and suicide.

[1] Food and Drug Administration, Warning on Liver Injury from Strattera: FDA Patient Safety News: Show #37, March 2005. Available here (accessed 18 July 2007).

[2] Food and Drug Administration, Public Health Advisory: Suicidal Thinking in Children and Adolescents Being Treated with Strattera (Atomoxetine), 17 December 2004. Available here (accessed 13 September 2009); ‘In review of 2,200 patients, 1, 357 of whom were taking Strattera, researchers found that 0.4 per cent of the children taking the drug reported suicidal thinking, compared to no cases in children taking a placebo. There was also one suicide attempt in the Strattera group.’ Amanda Gardner, ‘FDA Issues Alert on ADHD Drug Strattera’, Healthday Reporter, September 29 2005. Available here (accessed 19 May 2010).

[3] Adverse events information related to Strattera obtained from the Therapeutic Goods Administration’s Public Case Detail reports.

[4] A 2008 study by Curtin University pharmacologist Con Berbatis identified that, because reporting is voluntary, only a tiny fraction (for GP’s only 2 per cent) of adverse events are reported. Con Berbatis, ‘Primary care and Pharmacy: 4. Large contributions to national adverse reaction reporting by pharmacists in Australia’, i2P E-Magazine, Issue 72, June 2008.