madinamerica
By Peter Gøtzsche, MD November 16, 2016
Drug agencies warn against using antidepressants in children and adolescents because they increase the risk of suicide. It is more difficult to know what the risk is in adults, as there has been massive underreporting and even fraud in the reporting of suicides, suicide attempts and suicidal thoughts in the placebo-controlled trials(1,2). The US Food and Drug Administration (FDA) has contributed to the obscurity by downplaying the problems, by choosing to trust the drug companies, by suppressing important information, and by other means(2).
In a meta-analysis of the placebo-controlled trials from 2006, the FDA reported only five suicides in 52,960 patients on SSRIs (one per 10,000 patients)(3), but there were many more suicides in these trials(2). Five years earlier, in 2001, Thomas Laughren, who was responsible for the FDA’s meta-analysis, published a paper using FDA data where he reported 22 suicides in 22,062 patients randomised to antidepressants(4), which is 10 per 10,000, or 10 times as many as he reported in 2006. In Laughren’s 2001 paper, there were four times as many suicides on antidepressants as on placebo, which was statistically significant (P = 0.03, my calculation). However, Laughren did not tell his readers about this but wrote: “There is obviously no suggestion of an excess suicide risk in placebo-treated patients.” No, but there surely was in the drug-treated patients!
In its meta-analysis, the FDA found that paroxetine increased suicide attempts significantly in adults with psychiatric disorders, odds ratio 2.76 (95% confidence interval 1.16 to 6.60)(3). GlaxoSmithKline also found an increase in suicide attempts in adults and in 2006, GSK USA sent a “Dear Doctor” letter that pointed out that the risk of suicidal behaviour was increased also above age 24(2).
The FDA was inconsistent. The agency claimed in 2009 that it is only in those below 24 years of age that these drugs are risky(5). But in 2007, the agency admitted, at least indirectly, that SSRIs can cause suicide at all ages(6): “All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants.” The FDA also noted that, “Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt.” It seems that the FDA finally admitted that SSRIs can cause madness at all ages and that the drugs are very dangerous; otherwise daily monitoring wouldn’t be needed. Such daily monitoring is, however, a fake fix. People cannot be monitored every minute and many have committed SSRI-induced suicide within a few hours after everyone thought they were perfectly okay.
Since there is pervasive scientific misconduct in the published trial literature related to suicidality and aggression on antidepressants, we decided to look elsewhere. We obtained 64,381 pages of clinical study reports from the European Medicines Agency, which proved to be very revealing(7). In January 2016 we showed, for the first time, that SSRIs in comparison with placebo increase aggression in children and adolescents, odds ratio 2.79 (95% CI 1.62 to 4.81). This is an important finding considering the many school shootings where the killers were on SSRIs.
In October, we showed in a systematic review of placebo-controlled trials in adult healthy volunteers that antidepressants double the occurrence of events that can lead to suicide and violence, odds ratio 1.85 (95% CI 1.11 to 3.08)(8). The number needed to treat to harm one healthy adult person was only 16 (95% CI 8 to 100).
On November 14th, we showed that adverse effects that increase the risk of suicide and violence were 4-5 times more common with duloxetine than with placebo in trials in women with stress urinary incontinence(9). The results were similar for FDA-defined activation events, and there were also more women on duloxetine that experienced a core or potential psychotic event, relative risk RR 2.25 (95% CI 1.06 to 4.81). Many women were hit by the harms of duloxetine. There were 187 who had at least one core or potential activation event on duloxetine out of 958, whereas only 42 of 955 women on placebo experienced such events, i.e. 15% more women were harmed when on active drug than on placebo, or one out of every seven treated.
Duloxetine was never approved for use in stress incontinence in the US or in Canada whereas it is approved in Europe. We performed a meta-analysis of 4 randomised placebo-controlled trials of duloxetine (involving a total of 1913 patients) submitted to the European Medicines Agency for marketing approval. We used data from the clinical study reports (totalling 6870 pages and including individual patient data). It would have been quite impossible to demonstrate how dangerous duloxetine is, if we had only had access to published research.
Our systematic review underlines that antidepressants not only increase the risk of suicide and violence in children and adolescents, but also in much older people: The women in the trials had a mean age of 52 years. In accordance with this, the FDA has previously announced that women who were treated with duloxetine for incontinence in the open-label extension phase of the clinical studies had 2.6 times more suicide attempts than other women of the same age(2).
I have no doubt that the manufacturers of antidepressants and their paid allies among the psychiatrists will argue that there is nothing to worry about because we did not find an increase in suicides or suicide attempts in adult healthy volunteers or in women with urinary incontinence, only an increase in precursors to such events. But this argumentation is faulty. Looking at precursor events to suicide is just like looking at prognostic factors for heart disease. We say that increased cholesterol, smoking and inactivity increase the risk of heart attacks and heart deaths and therefore recommend people to do something about it. Psychiatric leaders, however, routinely try to get away with untenable arguments. Many say, for example, that antidepressants can be given safely to children arguing that there were no more suicides in the trials, only more suicidal events, as if there was no relation between the two, although we all know that a suicide starts with suicidal thoughts, followed by preparations and one or more attempts.
Conclusions
Although the drug industry, our drug regulators and leading psychiatrists have done what they could to obscure these facts(2), it can no longer be doubted that antidepressants are dangerous and can cause suicide and homicide at any age(2,10,11). Antidepressants have many other important harms and their clinical benefit is doubtful(2). Therefore, my conclusion is that they shouldn’t be used at all. It is particularly absurd to use drugs for depression that increase the risk of suicide when we know that psychotherapy decreases the risk of suicide(12). The psychotherapy trials have been criticised for lack of blinding(12) but it is difficult to blind such trials. Furthermore, suicidality is a pretty hard outcome.
We should do our utmost to avoid putting people on antidepressant drugs and to help those who are already on them to stop by slowly tapering them off under close supervision. People with depression should get psychotherapy and psychosocial support, not drugs.
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References:
1. Healy D. Did regulators fail over selective serotonin reuptake inhibitors? BMJ 2006;333:92–5.
2. Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015.
3. Laughren TP. Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). 2006 Nov 16. www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf.
4. Laughren TP. The scientific and ethical basis for placebo-controlled trials in de¬pression and schizophrenia: an FDA perspective. Eur Psychiatry 2001;16:418-23.
5. Stone M, Laughren T, Jones ML, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 2009;339:b2880.
6. FDA. Antidepressant use in children, adolescents, and adults. http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm096273.htm.
7. Sharma T, Guski LS, Freund N, Gøtzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016;352:i65.
8. Bielefeldt AØ, Danborg PB, Gøtzsche PC. Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. J R Soc Med 2016;109:381-392.
9. Maund E, Guski LS, Freund N, Gøtzsche PC. Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports. CMAJ 2016;14 November. http://www.cmaj.ca/lookup/doi/10.1503/cmaj.151104.
10. Healy D. Let them eat Prozac. New York: New York University Press; 2004.
11. Breggin P. Medication madness. New York: St. Martin’s Griffin; 2008.
12. Hawton K, Witt KG, Taylor Salisbury TL, Arensman E, Gunnell D, Hazell P, Townsend E, van Heeringen K. Psychosocial interventions for self-harm in adults. Cochrane Database Syst Rev 2016; 5: CD012189.
Thank You Dr Gotzsche and MIA.
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