Antidepressants Increase the Risk of Suicide and Violence at All Ages

Peter Gøtzsche, MD
29
7100

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.

* * * * *

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 depression 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, 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.

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29 COMMENTS

  1. Peter,

    Finding causality in these studies is very difficult because in studies of human beings there are so many interpenetrating causal factors operating, with non-linear feedbacks and unseen causes of causes working in the background. Still, it’s interesting to see that the drugs may be exerting some overall malignant effect on increasing suicidality.

    One can only see such a phenomenon operating at a group level, although I have some personal experience at an individual level – my stepfather hung himself in his hospital room while on a strong dose of antipsychotics. Any single case like this is correlation (when it comes to the possible effect of drugs), although it’s also a human person and a tragedy. This experience brought home to me the truth of what you say – you can’t watch someone every minute. My stepdad was in the part of the ward where the nurse watches you every 15 minutes – and that didn’t stop him from hanging himself due to severe agitation and despair.

  2. Thank you for the good work, Dr Peter.

    There’s been a large increase in ‘out of character’ Suicide/Homicide in Ireland in the past 20 years, since antidepressants have become popular in the general population.

    I’ve suffered from Akathesia on depot ‘medication’ in the early 1980s, but I was fortunate enough to live 10 minutes away from “the Hospital” – and I was able to make the drug connection, and this is why I am still alive. Most consumers are not this fortunate.

    Ultimately, I got better as a result of not taking ‘my medication’ (carefully) – and moving to Psychotherapy.

  3. I think the problem starts with a lack of political consciousness. That is, when someone feels that something is wrong, they don’t look at it as being something about our society and about the place which they have been thrown into. They don’t look to political activism as the remedy.

    Instead they accept the view that there is something wrong with them. So they go to doctors or to motivationalism, or to evangelical religion. And of course none of these things address the real problems that they are feeling. They just make the situations worse. So from doctors they get either drugs or psychotherapy, but these accomplish absolutely nothing, other than to further convince the client that they are the problem.

    And so the susceptibility to psychiatric medications is exactly the same as the susceptibility to psychotherapy, alcohol, and street drugs.

    Nomadic

  4. It remains baffling in the face of such strong evidence that the medical community in general has not been more accepting of this data. A needed–to-harm of 16 is pretty small, and means that almost every doctor with a sizable practice will see this effect dozens or potentially hundreds of times a year. And the fact that it’s seen with women with no psychiatric diagnosis or history cuts out any argument that it’s “the disease” causing the effect. The level of denial is quite astounding!

    Thanks for your excellent summary of the recent data!

    —- Steve

    • Yes, every prescriber of SSRi’s will see the basic common denominator of AKATHISIA, but most of them have never heard of akathisia and a physician cannot include in a differential diagnosis, a condition about which such lack of awareness prevails.
      Very early and minimal experience of talking about this lack of awareness to those who have no knowledge of akathisia has been positive. – Interest certainly, and in one case a correct recognition of SSRI induced akathisia a few days later.
      The regulators seem to defend the status quo and refer to Pharma funded, KOL manipulated clinical trials where slight of diagnostic hand translates akathisia into “hyperkinesis”.
      There is a malignancy destroying the medical profession’s integrity, honour and annihilating patient’s trust in their doctors. (This trust is not an infinite commodity).
      This malignancy is apparently most prevalent in psychiatry.
      It is the self-serving belief that ethical medicine can be practiced whilst receiving powerful remunerative incentives to address marketing objectives, priorities, targets and policies of the pharmaceutical industry.
      It cannot.
      The profession and it’s regulators MUST address this, and MUST rediscover that if the patient does not truly come first, it is not medicine that is being practiced, it is deception.

      Thank you Professor Gotzsche for your further fastidious scientific analysis, deconstruction of medical mythology and for your courage and fortitude.

      Those of us who have had our own, or our dear loved ones lives destroyed, been incarcerated, ridiculed and abused, forcibly drugged and then exiled from society by the ineptitude of primary and secondary care doctors at recognising akathisia and incompetence at differentiating SSRI induced toxic psychosis from functional psychosis, afford you our utmost respect and gratitude.
      Those less “fortunate” are dead.

  5. What I’ve heard is that if a person wants legal advice to go to a lawyer; and for advice on medication to go to a doctor! And that people coming off their “antidepressants ” are in danger of suicide.

    As regards neuroleptic Fluphenazine very few prescribing doctors would be aware of the information below on potential drug toxicity:-

    From Fuller E Torrey:-
    “….For example, a study published in 1982 reported that when a group of patients with schizophrenia were each given 20 mg of fluphenazine, the difference between the highest and lowest blood level of the drug was 40-fold.5 ….”

    http://www.psychiatrictimes.com/psychopharmacology/better-without-antipsychotic-drugs

    I believe it’s established that similar potential toxicity applies to SSRI s.

  6. I’m not a paid ally of a drug manufacturer but do worry that apparent potential side effects of SSRIs such as nervousness and tremor are seen as precursors to suicidality and violence. And, although it may well be difficult to get information about blinding, I’m surprised that Peter doesn’t consider the implications of unblinding for measurement of side effects because he regards it as important when assessing efficacy (as I do).

    • It is akathisia which is the precursor to suicidality.
      I find that many prescribers are unfamiliar with akathisia, if indeed they have heard of it.
      They do not appreciate that it may also be the precursor of a toxic psychosis.
      The term “inner restlessness” completely fails to convey the agony and intensity of this SSRI induced ADR,
      the most dangerous of so many adverse responses.

        • “Antidepressants can also induce the appearance of akathisia, due to increased serotonin signalling within the central nervous system. This also explains why serotonin antagonists are often a very effective treatment. The 2006 UK study by Healy et al. observed that akathisia is often miscoded in antidepressant clinical trials as “agitation, emotional lability, and hyperkinesis (overactivity)”. The study further points out that misdiagnosis of akathisia as simple motor restlessness occurs, but that this is more properly classed as dyskinesia.”
          https://en.wikipedia.org/wiki/Akathisia

          • “The combination of medication, fluctuating restlessness, suicidality, aggression and toxic hallucinations are pathognomic of akathisia.
            We cannot find any other diagnosis in the medical taxonomy that combines suicidal and aggressive thoughts with medication, nor any other that recedes when the culprit drug has been taken away”.

            Ref. The Relevance of Cytochrome P450 Polymorphism in Forensic Medicine and Akathisia related Violence and Suicide.
            Eikelenboom-Schieveld SJM.
            Lucire Y. Fogelman JC.
            Journal of Forensic and Legal Medicine. 2016. doi: 10. 1016.

            Please also see: –
            Antidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolising genes of the CYP450 family.
            Lucire Y. Crotty C.
            Journal of Pharmacogenomics and Personalised Medicine. 29 July. 2011.
            .

    • I used to believe in the BNF too until I saw the consequences of SSRI induced akathisia misdiagnosed as “psychotic depression”.
      The patient was immediately sectioned inappropriately and subject to enforced fluoxetine and olanzapine.
      This patient had been persuaded to take SSRIs for college stress, and was never depressed.
      This further, akathisia exacerbating, combination prescribing triggered a generalised neuroleptic malignant syndrome as failure to respond resulted in a futile cascade of psychotropic drugging and case entries such as “Manipulative Behaviour”.
      I believe that the misleading literature, misleading drug information inserts and the misgivings that you have regarding this debate reflect the SSRI manufacturers remarkably successful manipulation of clinical trials such as 329 and revealed in The Citalopram CIT-MD-18 Pediatric Depression Trial De-construction paper by Jureidini et al – 2016.
      I respect disagreement but would ask that all who share your misgivings observe patients (who are initiated on SSRIs, ceased by taper, subject to SSRI dose change, SSRI brand change and/or combination prescribing recipients) – for acute, subacute or chronic emergent akathisia.

  7. There are objective signs of akathisia as well as the inner restlessness, such as pacing on the spot. I’ve seen this several times with neuroleptics but never with SSRIs. Is it just that I haven’t been looking hard enough?

    Surely the issue about antidepressants and suicide/violence doesn’t boil down to whether antidepressants cause akathisia, does it? Perhaps Peter can clarify.

    • Dear Duncan,

      My experience with Akathesia has been with neuroleptics. The inner restlessness was very distressing but even more frightening was the state of mind I was in at the time, which was beyond anything I had ever experienced. In that state I was completely out of control and a risk to myself – while I might have appeared quite calm and reasonable to an observer.

      Akathesia can take different forms.

      I would imagine akathesia with SSRIs might be more subtle, than with neuroleptics – as people on SSRIs seem to be able to plan events.

      I experienced acute instances of suicidal reaction but I also suffered movement problems constantly while I costumed neuroleptics at any maintenance level.

    • “Over the years many case reports have associated extra-pyramidal symptoms, (EPS) with the use of antidepressants.
      All kinds of EPS are seen in patients taking antidepressants but AKATHISIA appears to be the most common presentation followed by dystonic reactions, parkinsonian movements and tardive dyskinesia.
      AKATHISIA appears to be more common in younger patients as compared with the other EPS symptoms.
      Among antidepressants, SSRIs have the highest number of case reports of EPS”.

      The Safety, Tolerability and Risks Associated with the use of Newer Generation Antidepressant Drugs: A Review of The Literature.
      Carvalho A.F. Sharma M.S. et al.
      Psychother. Psychosom. 2016: 85. 270-288.
      (Editors Choice. Free Access).

      Why is AKATHISIA, – the most dangerous and life threatening ADR of SSRIs so poorly understood by prescribers and virtually unknown to “consumers”?

    • Dr. D, I was misdiagnosed as ‘bipolar’ due to antidepressant (given for smoking cessation, not depression) withdrawal induced “pacing.” I paced once in my life, when trying to convince someone I later learned was a child molester to behave in a rational manner, no twice, the other time was just after an idiot psychiatrist prescribed Risperdal to “cure” the common symptoms of antidepressant discontinuation syndrome. Trying to “cure” the ADRs of an antidepressant by adding a neuroleptic drug makes a person ‘psychotic,” too, via anticholinergic toxidrome poisoning. It’s rather a shame the medical community is so ignorant about the effects of the drugs they prescribe.

  8. Deadly Psychiatry and Organised Denial. Peter C. Gotzsche. 2015.
    Page 103.
    Anti-depressant Induced Homicides.

    “That antidepressants can cause homicide is beyond doubt”.
    “As stated earlier, we know what the main mechanism of action is for suicide and homicide, the extreme form of restlessness we call akathisia”.

    Fiachra and Duncan,
    I am sorry. These two comments were intended as replies to Duncan Double.
    Perhaps they are best presented together. TRM 123.

  9. Dear Duncan
    Please see also this excellent website http://missd.co . By the way, chatting with a psychiatrist colleague just now, who like me often sees this adverse effect with SSRI / SNRI’s, we think that we doctors are just narrowly taught to think “akathisia = dopaminergic S/E” hence calling it “nervousness and tremor”, or agitation, or whatever. Feeling very very uncomfortable and restless (without necessarily putting on a nice pacing “sign” for the doctor) is reasonably termed akathisia – and those who’ve taken the MANY drugs which can cause it WELL know it’s one of the key experiences leading to harming self or others. If the patient / client / person experiences it, they’re experiencing it, and for doctors, validating, caring, and minimising potential contributors are our key responsibilities.
    Best wishes,

    Rob
    Dr Robert Purssey
    MBBS FRANZCP
    Psychiatrist and ACT Therapist
    Director – Brisbane ACT Centre
    7 Marie Street, Milton Q 4064
    [email protected]
    http://www.brisbaneactcentre.com.au

    • Dr. Robert Purssey,
      Thank you for your invaluable statement of fact, which is also the repeated clinical observation of yourself and your psychiatry colleague.
      May I ask why both of you can observe, recognise and correctly interpret SSRI/SNRI induced AKATHISIA, and yet so many regular prescribers are unable to do so?
      Those of us striving to achieve akathisia awareness in the UK are finding GPs do listen to our akathisia concerns, and listen to our dreadful experiences of the outcomes of missed akathisia diagnosis.

      It now comes as expectation, rather than surprise, to have a sincere and caring GP admit: –
      “I have never heard of it”.

      The heartbreaking image of the emaciated young girl on this current M.I.A Home Page alerts us to another akathisia induced, mistaken and dreadfully damaging, false diagnosis.

      Intense akathisia, exacerbated by increased dosing, and/or change of SSRI leaves a patient in extremis who is unable to eat and drink.
      An akathisic girl of this age, in this condition, is immediately and catastrophically mis-diagnosed as anorexic.
      (As was the patient I referred to above).
      More labels for life.
      No drip to rehydrate.
      No help with feeding.
      More SSRI and antipsychotic (enforced) drugging.
      Denial that tardive dyskinesia had developed.
      Cruel contempt from the “nursing” staff.
      Records state “manipulative behaviour”.
      “Rehabilitation plan”: – “To wash her own clothes and only to eat in the dining area”.

      The suffering of the soul, and the iatrogenic destruction of
      self-worth which adds to the neurotoxicity of misdiagnosed SSRI/SNRI akathisia is truly appalling and a disgrace to the practice of medicine.
      Your welcome and authoritative comment affords hope.

  10. Speaking of which:

    Sorry to interrupt with this but people need to know:

    MURPHY ALERT!!! THE 21ST CENTURY CURES BILL IS THE REPACKAGED MURPHY BILL INCLUDING AOT! This has not been made clear — it’s vital to CALL YOUR CONGRESS PEOPLE TODAY (Tuesday). Watch for further posts tonight and/or check out the organizing forum. (Don’t reply to this here, we don’t want to divert the discussion.)