Over time, more and more people reported serious problems with this drug - with claims of children committing suicide as a reaction to this drug. These concerns were repeatedly dismissed by GSK, but in 2003 the UK Committee on Safety of Medicines issued a warning against the use of Seroxat in children. At around this time GSK issued a letter to all medical practitioners here in the UK actively discouraging the use of paroxetine in patients under 18 years of age as trial results showed “unacceptable risk of serious adverse effects, including hostility and suicidality.” 3
It took until 2012 for the law to catch up with GSK for misleadingly promoting this drug (and some other drugs too). GSK agreed to plead guilty and pay the US Government a settlement of $3 billion to resolve fraud allegations and their failure to report safety data. The US Department of Justice’s complaint included the assertion that: “GSK published an article that misstated Paxil’s efficacy and safety for children and adolescents.” (More here). A Lancet medical journal editorial neatly summarised the case against GSK: “What is particularly egregious about GSK's fraud is the calculated deceit and potential human cost of its aggressive and misleading marketing. For instance, while evidence was emerging that showed an increased suicide risk in adolescents prescribed selective serotonin reuptake inhibitors for depression, GSK was actively encouraging off-label prescription of paroxetine to individuals younger than 18 years. This was not an isolated incident… Such behaviour is not only illegal, it is immoral 4.”
I recognise that you may think I am overly cautious, even sceptical, when it comes to trusting drug company data. But Study 329 is a stark warning. We need this healthy scepticism as we take a closer look at Prozac.
Prozac can be prescribed for children, but is it as safe and effective as claimed?
To many people it seemed that matters were resolved with the exposing of the risks and deception associated with Seroxat in paediatric use. There is, however, one exception permitted: fluoxetine/Prozac. Here in the UK a doctor is advised, if prescribing an antidepressant to someone under 18, to make fluoxetine the first choice (in keeping with NICE Guideline 28 here). But there is a key problem that has not been resolved: a closer look at the evidence-base supporting fluoxetine’s use in youngsters is fraught with problems. It is true that doctors here in the UK are clearly informed of the potential risks of suicide by antidepressant drugs, including Prozac. Even so, I raise concerns that the data supporting the use of Prozac for paediatric use minimises the risks and thus misleads physicians and patients.
As we have seen, doctors are largely reliant on published studies (and drug company summary data) when deciding if a drug is worth prescribing. Doctors were, quite rightly, outraged when a meta-analysis 5 (an analysis of data from a number of trials/sources) clearly showed that studies showing antidepressants (for children) in a positive light were being published – while those with negative findings were almost always remaining unpublished. An editorial in the Lancet described this practise as “an abuse of the trust patients place in their physicians 6”. But the study (Whittington et al) central to this contention stopped short: it recognised risks of antidepressants in paediatric use, but still concluded that Prozac/fluoxetine “has a favourable risk-benefit profile”. The problem is, a closer look at studies on Prozac show it too has been presented more favourably than the data shows to be true.
Graham Emslie was lead author of two studies that were submitted to the FDA in 2003 when Prozac was licensed as a treatment for children/adolescents 7, 8. Emslie is in fact listed as one of the authors of the dubious and misleading Seroxat Study 329, which we referred to earlier. It is also noteworthy that neither of these studies on Prozac was independent: both were directly or indirectly funded by Eli Lilly, the maker of Prozac (For details see: Jureidini, J. et al. 2004). According to Professor Healy, one of these studies showed that “on the primary end-point measure, Prozac was no better than placebo…In addition, there was a 29% drop-out rate on Prozac and the rate of behavioural side effects was greater on Prozac than on placebo 9.”
Professor Leo, writing about the same study (Emslie, G. et al. 1997) also points out that “There is no mention in the paper about any children attempting suicide” in the trials, even though evidence that there were “two suicide attempts in the group of 48 Prozac-treated patients” 10 was later to become evident. Furthermore, this and similar studies were designed to give Prozac a head start over placebo: this is not illegal but it produces misleading results (For more about this see Leo, J. 2006). Thus Prozac was initially approved for use with children by an inadequate representation of the facts. Dr Emslie is, by the way, also one of the TAD authors, that we will come to next (listed here under Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression).
Concerns have also been raised about later studies on Prozac for adolescents, including the TADS studies. The TAD (Treatment for Adolescents with Depression) series of studies were heavily influenced by the pharmaceutical companies in that so many of the authors had (or still were receiving) received funding from the drug companies – see the conflicts of interest with makers of antidepressants here – and therefore a biased investment in the outcome of the studies.
In the Suicidal Events in the Treatment for Adolescents with Depression Study (TADS) 11, there is a failure (observes the psychiatrist and retired academic Dr Mickey Nardo) “to mention that 82% of the suicidal events were in kids on Prozac and 94% of the suicide attempts were by kids on Prozac. What other explanation is there besides those conflicts of interest for leaving out the most obvious thing in their data?” (More here). Dr Nardo adds that: “the actual suicidality information is buried in layers of numerology” and this “is deliberately deceitful science” (More here). Dr Nardo’s clear analysis of the TAD study data shows an alarming risk of suicide with the use of Prozac in adolescents, as shown here (as copied from his more in-depth analysis here) in the chart below:
And yet, the authors of the TADS study failed to produce a chart like this which is based on their data. Did they chose to deliberately try and conceal the data? When it comes to the studies of antidepressants and young people, it is evident that researchers not only have financial conflicts of interest with the makers of these drugs but some researchers seem determined to deliberately distort the data to show these drugs as less hazardous than they are.
Another study “reported the emergence of self-destructive phenomena in 14% (6/42) of children and adolescents (ages 10-17) who were being treated with fluoxetine” 12. It is worth noting that this particular study was with those youngsters being treated for with Prozac for so-called obsessive-compulsive disorder, so the self-destructive acts shouldn’t be attributed to depression.
Although we have focussed here on the suicidal risks, there are other significant side-effects produced by fluoxetine in paediatric use, including mania, “hypomania or restlessness, insomnia or sleep disturbance, general irritability or social disinhibition, and gastrointestinal distress 13”. A key concern here is that it would be far too easy to attribute these to the child/adolescent without recognising that they are adverse reactions to the drug. Furthermore, a child who becomes hyper is soon likely to be diagnosed as “Bipolar” and then prescribed further drugs (with additional side-effects).
Some concluding thoughts
Alarmingly, it transpires that drug companies have tried to play down the risks and to exaggerate the benefits of antidepressants for use with children (as detailed in this meta-analysis 5). An editorial in The Lancet medical journal reported this “Confusion, manipulation, and institutional failure” as “an abuse of the trust patients place in their physicians”.14