Mental Health Survival Kit, Chapter 2: Is Psychiatry Evidence Based? (Part 5)

Editor’s Note: Over the course of several months, Mad in America is publishing a serialized version of Peter Gøtzsche’s book, Mental Health Survival Kit and Withdrawal from Psychiatric Drugs. In this blog, he discusses the risk of suicide and other causes of death from psychiatric drugs, focusing on depression pills. Each Monday, a new section of the book is published, and all chapters are archived here.

Suicides, other deaths, and other serious harms

Depression pills

Depression pills are the poster child for psychiatry, the pills we hear most about, and the pills which are most used, in some countries by more than 10% of the population.

As noted, it is one of psychiatry’s best kept secrets that the psychiatrists kill many patients with neuroleptics. Another well-kept secret is that they also kill many patients with depression pills, e.g. elderly patients who lose balance and break their hip.^4,96

The psychiatrists have fought really hard to hide the terrible truth that depression pills double the risk of suicide, not only in children but also in adults.^2,4,97-100 The placebo-controlled trials are hugely misleading in this respect, and a lot has been written about how drug companies have hidden suicidal thoughts, suicidal behaviour, suicide attempts, and completed suicides in their published trial reports, either by wiping the events under the carpet for no one to see, or by calling them something else.^2,4,101

This massive fraud is routine in drug companies. I devoted a huge part to the fraud in my 2015 psychiatry book,⁴ and shall therefore only mention some recent research results here.

My research group found that, compared to placebo, depression pills double the occurrence of FDA-defined precursor events for suicide and violence in healthy adult volunteers;⁹⁷ that they increase aggression in children and adolescents 2-3 times,⁵⁵ a very important finding considering the many school shootings where the killers were on depression pills; and that they increase the risk of suicide and violence by 4-5 times in middle-aged women with stress urinary incontinence, judged by FDA-defined precursor events.⁹⁸ Furthermore, twice as many women experienced a core or potential psychotic event.⁹⁸

Psychiatrists dismiss research results that go against their interests. They have also criticised our use of precursor events, but there is nothing wrong with this. Using precursor events to suicide and violence is similar to using prognostic factors for heart disease. As smoking and inactivity increase the risk of heart attacks, we recommend people to stop smoking and to start exercising.

It is cruel that most psychiatric leaders say—even on national TV¹⁰²—that depression pills can be given safely to children because there wasn’t a statistically significant increase in suicides in the trials, only in suicidal thoughts and behaviour, as if there is no relation between the two.⁴ The psychiatrists reward the companies for their fraud while they sacrifice the children. We all know that a suicide starts with suicidal thinking followed by preparations and one or more attempts.

A US psychiatrist who argued that suicidal behaviour should not count because it is “an unvalidated, inappropriate surrogate” contradicted himself, as he wrote in the same paper that, “A history of a prior suicide attempt is one of the strongest predictors of completed suicide,” and also wrote that the rate of suicide is 30 times greater in previous attempters than in non-attempters.¹⁰³ This is full-blown cognitive dissonance with deadly consequences for our children.

When I wrote my 2015 book, it became clear to me that suicides must be increased not only in children, but also in adults, but the many analyses and reports were confusing with some having found this and others not.⁴

The crux of the matter is that many suicide attempts and suicides are left out in reports. In 2019, I found additional evidence of this, when I compared a trial publication¹⁰⁴ with the corresponding 1008-page clinical study report submitted to drug regulators.¹⁰⁵ The authors of the published report did not mention that two of 48 children on fluoxetine attempted suicide versus none of 48 children on placebo.

The first author, Graham Emslie, falsely attributed the funding of the trial to the US National Institute of Mental Health, but FDA data showed that the study was sponsored by the manufacturer of fluoxetine, Eli Lilly.¹⁰⁶

Suicide attempts and suicides are not only concealed during the trial. Most often, they are also omitted when they occur just after the randomised phase is over:⁴

Sertraline trials in adults; n: number of suicides and suicide attempts; N: number of patients; follow-up: time after the randomised phase ended; RR: risk ratio; CI: confidence interval.

When the FDA did a meta-analysis of sertraline used in adults (Table 30 in their report),¹⁰⁷ they did not find an increase in suicide, suicide attempt, or self-harm combined (risk ratio 0.87, 95% CI 0.31 to 2.48).

Pfizer’s own meta-analysis found a halving of the suicidal events when all events that occurred later than 24 hours after the randomised phase stopped were omitted.¹⁰⁸ However, when Pfizer included events occurring up to 30 days later, there was an increase in suicidality events of about 50%.

A 2005 meta-analysis conducted by independent researchers using UK drug regulator data found a doubling in suicide or self-harm when events after 24 hours were included.¹⁰⁹ These researchers noted that the companies had underreported the suicide risk in their trials, and they also found that nonfatal self-harm and suicidality were seriously underreported compared to reported suicides.

Another meta-analysis carried out in 2005 by independent researchers of the published trials was very large, as it included all drugs (87,650 patients) and all ages.¹¹⁰ It found double the amount of suicide attempts on drug than on placebo, odds ratio (which is the same as risk ratio when events are rare) 2.28, 95% CI 1.14 to 4.55.

The investigators reported that many suicide attempts must have been missing. Some of the trial investigators had responded to them that there were suicide attempts they had not reported, while others replied that they didn’t even look for them. Further, events occurring shortly after active treatment was stopped were not counted.

The reason it is so important to include suicidal events that occur after the randomised phase is over is that it reflects much better what happens in real life rather than in a tightly controlled trial where the investigators motivate the patients to take every single dose of the trial drug. In real life, patients miss doses because they forget to take the pills to work, school, or a weekend stay, or they introduce a drug holiday because the pills have prevented them from having sex (see below).

It differs from trial to trial what happens when it is over. Sometimes, the patients are offered active treatment, sometimes only the treated patients continue with active treatment, and sometimes there is no treatment.

In 2019, two European researchers finally put an end to the psychiatrists’ fierce denial that depression pills are also dangerous for adults. They re-analysed FDA data and included harms occurring during follow-up.⁹⁹ They were criticised and published additional analyses.¹⁰⁰ Like other researchers, they found that suicide events had been manipulated, e.g. “Two suicides erroneously recorded in the placebo group from the paroxetine approval program removed.”¹⁰⁰ They reported twice as many suicides in the active groups than in the placebo groups, odds ratio 2.48 (95% CI 1.13 to 5.44).

There should be no more debate about whether depression pills cause suicides at all ages. They do. Even the FDA, which has done it utmost to protect drug companies marketing depression pills,^2,4 was forced to give in when it admitted in 2007, at least indirectly, that depression pills can cause suicide at any age:^4,111

“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 … 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.”

The FDA finally admitted that depression pills can cause madness at all ages and that the drugs are very dangerous—otherwise daily monitoring wouldn’t be needed. It needs to be said, however, that daily monitoring is a fake fix of a deadly drug problem. People cannot be monitored every minute, and many have killed themselves with violent means, e.g. hanging, shooting, stabbing, or jumping in front of a train, shortly after they seemed to be perfectly fine to their loved ones.^2,4

But the organised denial continues undeterred.⁴ Two years after FDA’s announcement, the Australian government stated: “The term suicidality covers suicidal ideation (serious thoughts about taking one’s own life), suicide plans and suicide attempts. People who experience suicidal ideation and make suicide plans are at increased risk of suicide attempts, and people who experience all forms of suicidal thoughts and behaviours are at greater risk of completing suicide.”¹¹²

True, but why did suicidality not include suicide? If you want to find out how dangerous mountaineering is, and you include injuries when people have serious thoughts about climbing mountains and attend a fitness centre, and injuries when they plan to climb a mountain and when they attempt to do so, would you then exclude deaths due to falls? Of course, you wouldn’t, but this was what the Australian government did. They showed the lifetime prevalence of suicidality, divided into suicidal ideation, suicide plan, and suicide attempt, but there were no data on suicides.¹¹²

There is a long way to go. In our review of 39 popular websites in 10 countries, which we carried out in 2018, we found that 25 stated that depression pills may cause increased suicidal ideation, but 23 (92%) of them contained incorrect information, and only two (5%) websites noted that the suicide risk is increased in people of all ages.³²

Depression pills can cause violence and homicide.^2,4 But this is also one of psychiatry’s well-guarded secrets. Particularly in the USA, psychiatrists and authorities won’t tell the public if the perpetrator was on a depression pill. It can take a long time and involve Freedom of Information requests or lawsuits before anything gets revealed.

It took quite a while before we learned that the Germanwings pilot who took a whole plane with him when he committed suicide in the Alps, and that the Belgian bus driver who killed many children by driving his bus into a wall, also in the Alps, were both on a depression pill.

Even though we suspected serious underreporting of harms in the clinical study reports we examined—some outcomes appeared only in individual patient listings in appendices, which we had for only 32 of our 70 trials, and we didn’t have case report forms for any of the trials—we found alarming events, which you will never see in publications in medical journals.⁵⁵ Here are some examples:

• Four deaths were misreported by the company, in all cases favouring the active drug.
• A patient receiving venlafaxine attempted suicide by strangulation without forewarning and died five days later in hospital. Although the suicide attempt occurred on day 21 out of the 56 days of randomised treatment, the death was called a post-study event as it occurred in hospital and treatment had been discontinued because of the suicide attempt.
• Although patient narratives or individual patient listings showed they were suicide attempts, 27 of 62 such attempts were coded as “emotional lability” or “worsening depression,” which is what you see in publications, not the suicide attempts.
• One suicide attempt (intentional overdose with paracetamol in a patient on fluoxetine) was described in the adverse events tables as “elevated liver enzymes,” which is what you get if you drink a little alcohol.
• It is of particular relevance for the many school shootings that the following events for 11 patients on a depression pill were listed under “aggression” in patient narratives for serious adverse events: homicidal threat, homicidal ideation, assault, sexual molestation, a threat to take a gun to school, damage to property, punching household items, aggressive assault, verbally abusive and aggressive threats, and belligerence.

Akathisia is a horrible feeling of inner restlessness, which increases the risk of suicide, violence, and homicide. We could only identify akathisia if we had access to the verbatim terms, but we nonetheless found that, like aggression, akathisia was seen twice as often on the pills than on placebo.

In three sertraline trials where we had access to both the verbatim and the coded preferred terms, akathisia was coded as “hyperkinesia,” and miscoding seemed to have been prevalent also in paroxetine trials since we didn’t find a single case of akathisia.

For Eli Lilly’s drugs, fluoxetine and duloxetine, we compared our findings with the summary trial reports that are available on the company’s website. In most cases, adverse events were only shown if they occurred in, for example, at least 5% of the patients. In this way, the companies may avoid reporting many serious harms. We found that suicidal events and harms increasing the risk of violence were seriously underreported:

Only 2 of 20 suicide attempts (17 on drug vs 3 on placebo) were documented. None of 14 suicidal ideation events (11 vs 3) were mentioned. Only 3 akathisia events (15 vs 2) were mentioned.

Akathisia is also seen with other psychiatric drugs, e.g. neuroleptics (see below). Akathisia is a Greek word and means inability to sit still. Patients with akathisia may behave in an agitated manner, which they cannot control, and they can experience unbearable rage, delusions, and disassociation.⁸⁰ They may endlessly pace, fidget in their chairs, and wring their hands—which have been described as actions that reflect an inner torment.¹

Akathisia need not have visible symptoms but can be extreme inner anxiety and restlessness, which is how this harm is described in the product information for Zyprexa. In one study, 79% of mentally ill patients who had tried to kill themselves suffered from akathisia.¹ Another study reported that half of all fights at a psychiatric ward were related to akathisia,^5,113 and a third study found that 64 moderate-to-high doses of haloperidol, a neuroleptic, made half the patients markedly more aggressive, sometimes to the point of wanting to kill their psychiatrists.¹

Since depression pills have purely symptomatic effects and many harms, it is highly relevant to find out what the patients think about them when they weigh the benefits against the harms. They do this when deciding whether to continue in a trial till the end or to drop out of it.

It was huge work to study drop-outs in the placebo-controlled trials. We included 71 clinical study reports we had obtained from the European and UK medical agencies, which had information on 73 trials and 18,426 patients. No one, apart from my research group, had ever read the 67,319 pages about these trials before, which amount to 7 meters tall if stacked. But it was well worth the effort; 12% more patients dropped out while on drug than while on placebo.¹¹⁴

This is a terribly important result. The psychiatrists’ view is that depression pills do more good than harm,⁴ and the patients’ view is the opposite. The patients preferred placebo even though some of them were harmed by cold turkey effects. That means that the drugs are even worse than found in the cold turkey trials.

Because we had access to detailed data, we could include patients in our analyses that the investigators had excluded, e.g. because some measurements had not been made. Our result is unique and reliable, in contrast to previous reviews using mostly published data. They failed to find more dropouts on drugs than on placebo,¹¹⁴ e.g. a large review of 40 trials (6391 patients) reported that dropouts were the same (relative risk 0.99) when paroxetine was compared with placebo.

Next, we decided to look at quality of life in the same trials. Given our result for dropouts, the tiny benefit of depression pills that lacks any relevance for the patients, and the pills’ many and frequent harms, we expected that quality of life would be worse on pills than on placebo.

We were perhaps a bit naïve, because we had now come too close to the secrets of depression pills. What we found—or rather didn’t find—was shocking.¹¹⁵ The reporting of health-related quality of life was virtually non-existent.

In five trials, it was unclear which instrument was used and no results were available. We included 15 trials (4,717 patients and 19,015 pages of study reports), a substantial amount of data on which to base conclusions. However, nine of the 15 clinical study reports displayed selective reporting, and in the companies’ online registers, there was selective reporting for all 15 trials. We received 20 publications from Eli Lilly and retrieved six from the GlaxoSmithKline register. There was selective reporting in 24 of the 26 publications. Despite this extensive selective reporting, we found only small differences between drug and placebo.

This was more than a roadblock; it was sabotage. The companies are obliged to ensure that what they submit to drug regulators to obtain marketing approval is an honest account of what happened, and that important data or information have not been left out. We wondered why the drug regulators had not asked the companies for the missing data.

The pills that destroy your sex life are called happy pills

In the upside-down world of psychiatry, the pills that destroy your sex life are called happy pills. Half of the patients who had a normal sex life before they started on a depression pill will have their sex life disturbed or made impossible.^4,116 The sexual disturbances can become permanent and when the patients find out that they will never again be able to have intercourse (e.g. because of impotence), some kill themselves.^117,118

When I lectured for Australian child psychiatrists in 2015, one of them said he knew three teenagers taking depression pills who had attempted suicide because they couldn’t get an erection the first time they tried to have sex.

It is so cruel. And yet, the professional denial is widespread. The patients are often humiliated or ignored by their doctors who refuse to believe them. Some patients are told that such complications from taking depression pills are impossible, and others are put on neuroleptics after having been told that their problem is psychosomatic.¹¹⁸

One patient who had sent a couple of links to studies and reviews about post-SSRI sexual dysfunction received this reply: “If you wish to have such ‘syndrome’ continue what you are doing … read obscure studies and reviews in obscure databases and I can guarantee you that you will have it till the end of your life!”

By far most patients who are on a depression pill will feel something has changed in their genitals, and many complain that long after they came off the pills, their emotions continue to be numbed; they also don’t care about life or other people like they did before the pills.

Psychiatry professor David Healy has told me that some patients can rub chili paste into their genitals and not feel it. In his work as an expert witness, he has seen data no one outside the drug industry has ever seen, which are sealed as soon as the company settles out of court with the victims. Healy has described that, in some unpublished phase 1 trials, which are performed before a drug is tested in patients, over half of healthy volunteers had severe sexual dysfunction that in some cases lasted after treatment stopped.¹¹⁹

The numbness of the genitals is used in marketing. The depression pill Priligy (dapoxetine) has been approved in the European Union for treating premature ejaculation.

It is interesting to contrast this with the information provided in package inserts, e.g. for Prozac (fluoxetine).¹²⁰ Right from the start, it puts the blame on the patient rather than on the drug: “changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder.” Accordingly, an FDA scientist found out that SmithKline Beecham had hidden sexual problems with paroxetine by blaming the patients, e.g. female anorgasmia was coded as “Female Genital Disorder.”¹²¹

Healy sent a petition to Guido Rasi, the director of the European Medicines Agency (EMA) in June 2019 signed by a large group of clinicians and researchers. EMA indicated they would ask companies to mention enduring sexual dysfunction in the labels of depression pills. Six months later, Healy sent a new letter to Rasi stating that the drug agencies had responded that these conditions might stem from the illness rather than the treatment.

He added: “Melancholia, which is very rare, can lead to lowered libido but the kind of depression for which SSRIs are given does not lower libido. Indeed, just like people comfort eat when they have ‘nerves’ so they often have more sex in an attempt to handle their ‘depression.’”

In its package insert,¹²⁰ Eli Lilly stated that, “some evidence suggests that SSRIs can cause such untoward sexual experiences.” It is not some evidence. When you look at all the evidence, it becomes abundantly clear that these drugs ruin people’s sex lives.

Lilly’s denial mode continues: “Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them.” Since we have this evidence, what is then the problem Lilly has in acknowledging what it shows?

In Lilly’s trials,¹²⁰ “decreased libido was the only sexual side effect reported by at least 2% of patients taking fluoxetine (4% fluoxetine, <1% placebo).” If you don’t ask, you won’t see the problems. In a carefully conducted study, 57% of 1,022 people who had a normal sex life before they came on a depression pill experienced decreased libido; 57% had delayed orgasm or ejaculation; 46% no orgasm or ejaculation; and 31% had erectile dysfunction or decreased vaginal lubrication.¹¹⁶

There was nothing about this in Lilly’s package insert apart from: “There have been spontaneous reports in women taking fluoxetine of orgasmic dysfunction, including anorgasmia. There are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment. Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment.”

Some package inserts are more truthful, e.g. for venlafaxine:¹²² decreased libido 2%, abnormal ejaculation/orgasm 12%, impotence 6%, and orgasm disturbance 2%. But this is still far from the truth.

1. If you feel depressed, don’t go to your doctor who will very likely prescribe a depression pill for you.
2. Never accept treatment with a depression pill. It is likely to make your life more miserable.
3. Don’t believe anything doctors tell you about depression pills. It is highly likely to be wrong.
4. Depression pills are dangerous. They increase the risk of suicide, violence and homicide at all ages.
5. Depression pills are likely to destroy your sex life, in the worst case permanently.
6. Consult a psychotherapist. You might also consider if you need a social worker, counsellor or lawyer.

 

To read the footnotes for this chapter and others, click here.