SSRIs, Skepticism, Suicide and Suicidality.

I knew there was a reason I loved Christina.  I ask people to learn something new about SSRIs or mental illness and do a post and she cranks it up to eleven.  Did I mention she’s an occupational therapist for a living?  Women with lots of brains = sexy.

This is cross-posted from her blog.

I heard an interesting bit of information about SSRIs (a class of compounds used to treat depression and other mental illnesses) twice while at Skepticon. People (especially the media) have unfairly linked SSRI’s to suicide, especially among people under 25. Here’s how my friends explained this effect to me: Apparently SSRI’s work in a certain way, by both making you feel more motivated and by reducing depression. When an individual first starts taking SSRIs, the feeling of motivation often hits first before they ease the depression, giving the individual the ability to start completing items on their big long checklist of things to do. If “kill myself” happens to grace that list, then sometimes individuals finally find the motivation to kill themselves. Hence, an increase in suicidality/suicide crops up in the first few weeks of SSRI use.

The skeptical community has not trained many skeptical eyes upon SSRIs and suicidality/suicide. I find this rather unfortunate. I wanted to explore this bit of information myself to see what research literature actually says about suicidality/suicide. I have a stake in such a subject for many reasons, among them being because many of my friends take SSRIs. So does my husband. I have a mental illness that I have never treated chemically. Whether I should treat my illness chemically, I have not yet decided. I have not, therefore, based my information on my own personal experience.

Not wanting to jump to conclusions about why SSRIs cause suicide, I decided to look at the originating premise:

SSRIs cause suicide, or suicidal ideation, in some people.

Really, there are two separate premises here:

SSRIs cause suicide in some people.

SSRIs cause suicidality (suicidal thoughts or behavior) in some people.

Another interesting aspect of this question is the some people part of it. Studies typically look at age differences, so some people includes children/adolescents, adults, and older adults.

On to suicide and SSRIs. When you look at actual suicides, we get a pretty unconvincing picture. In analyzing the data the FDA used to establish its position on the relationship between SSRIs and suicide, researchers (Khan, et al, 2003)  found actual, completed suicides were no different among SSRI treatment, comparison and placebo groups. Age mattered not. People aren’t killing themselves as a consequence of being on SSRIs.

What would the skeptical community say about some acupuncture, homeopathy or chiropractic trial in which the results regarding a particular variable were the same whether you participated in the active treatment group, the comparison treatment group or the placebo group? We would conclude that the active treatment group had no effect with regard to that variable. We would conclude that we did not refute the null hypothesis (that SSRIs do not increase suicidality).

Another study on adolescents specifically showed that among young people who do kill themselves, only 1.6% of them had exposure to SSRIs (Dudley, et al 2010)

If the FDA warned people that SSRIs caused suicidality, and that caused a reduction in antidepressant prescriptions, what we might find is that in the general population of young people, suicides go down, assuming that SSRI’s really do cause suicide.

Except we find the exact opposite. A study done in 2003-2004 showed a decrease in SSRI prescriptions for youth, and a corresponding increase in suicide. (Gibbons, et al 2007)

At the same time, we find that as the overall rate of antidepressant prescriptions go up, the suicide rate goes down.

Why the difference? How can it be that a drug can increase suicidal thoughts, impulses and attempts, but no increase in crude suicides? The answer may lie in the inclusion criteria, which typically excludes people with suicide attempts, for obviously ethical reasons. This alone cannot account for the lack of supportive data, though excluding people with a prior history of suicide attempts does confound things, as prior suicide attempts predict future suicide attempts.

Regardless, we can’t establish that SSRI’s contribute to suicide. Perhaps, however, SSRIs cause an increase in suicidal thoughts and behaviors.

I thought Petulant Skeptic put this question to rest pretty well:

Owing to this, clinicians use suicidality as their metric instead. Suicidality generally includes suicidal ideation or planning as well as self-harming behaviors. These events are more common than actual suicide and thus much easier to catalog and compare. In a large meta analysis conducted by the BMJ they found that 0.54% of patients in clinical trials expressed “suicidality.” Helpfully, they even break down these incidences by indication group. If you do the math (they did not) 64% of the suicidality events were accounted for by those with major depressive disorder (MDD) and a further 28% had a condition categorized as “other psychiatric” (which explicitly excluded non-MDD depression). Completely unsurprisingly research has found that MDD and “other psychiatric” conditions have a very strong correlation with suicide (and, to use researcher’s own proxy here, suicidality).

What this means is that 99.5% of patients (who are high risk) never even considered suicide. Where is this number supposed to go from 99.5%? The occurrence of suicide itself in the general population is 11.4 per 100,000 (0.01%) and we’ve already covered that suicide is incredibly rare compared to suicidality. Moving on.

The BMJ trial referred to in the above quote is Stone, et al (2009). Neuroskeptic said about the same.

In a general cohort study (of 4,848 people) of the general population, the incidence of suicidal ideation was 2.7% and the incidence of suicide was .9% over a 3 year period. (ten Have, et al 2009).  Clinical trials are of a shorter duration than 3 years and include people with a clinical diagnosis warranting the use of antidepressants, but comparing the numbers doesn’t convince me that SSRIs cause suicidality.

In another study of people with depressive spectrum disorders (Spijker, et al 2010), 16.6% report suicidal ideation while 3.2% make a suicide attempt. So, those in the BMJ meta analysis are actually much less likely to have suicidal ideation or attempts while using SSRIs.

There really isn’t a link between SSRIs and suicidal ideation generaly. Yet, here we have this:

[5/2/2007] The U.S. Food and Drug Administration (FDA) today proposed that makers of all antidepressant medications update the existing black box warning on their products’ labeling to include warnings about increased risks of suicidal thinking and behavior, known as suicidality, in young adults ages 18 to 24 during initial treatment (generally the first one to two months).

Okay. Notice the FDA does not warn of a risk of suicide – no risk of suicide exists given the many studies. The FDA does not warn of the risk of suicidal ideation for adults, nor for older people. The warning only applies to suicidality of young adults.

The FDA came to this conclusion because their data show that while 1.62% of people under 25 in a placebo treatment group experience suicidality, 2.3% of people under 25 in an active SSRI treatment group experience suicidality. That’s double the risk of suicidality, which sounds scary. However, that’s a vanishingly small amount of people. Apparently, this suicidality isn’t leading to suicide. I think this small risk of suicidality is worth the help that antidepressants give to people. For the record, the studies also show that there is no increased risk of suicidality in people aged 25-59, and a decreased risk for those over 60.

Of course, one could also question whether antidepressants work at all.

A 2010 meta analysis (Fournier et al 2010) lit a fire under the media. Articles abound, but a good example is this Newsweek article titled, “The Depressing News About Antidepressants“. Most media outlets reported that this meta-analysis concluded that antidepressants do not work.

The meta-analysis concluded no such thing. The meta-analysis concluded that antidepressants had a large clinically meaningful effect over placebo for severe depression, and only a small clinically meaningful effect for mild to moderate acute depression. If I could make journalists who write about science understand one thing, I would make them understand effect size.

In other words, SSRIs work for people who have a problem between their ears, not in their external world. SSRIs won’t help you if you are grieving over the end of your relationship or if you feel sad occasionally. A lot of the time, depressive episodes surrounding environmental factors will resolve when the issue in the environment resolves. Major depression follows you around, crushing you even if you consider your life otherwise completely awesome. In depression, your brain gets in the way of your life.  Treat depression with SSRIs and most people see results. Treat depression brought about by environmental triggers and you might not, unless your brain is concurrently imbalanced.

I’m pretty convinced this fear that SSRIs cause suicide does far more harm than good. The data do not establish causality and barely establish a link between suicidality among young people. Get your friends, family or yourself the help you need.

TL:DR – The data do not support the notion that SSRI’s cause an increase in suicide. It does support a slight increase in suicidal thoughts in young people under 25. There exists much evidence that SSRIs help people with chemical depression. If we dispel the myth  that SSRIs cause suicide, people may fear them less.

References:

Khan A, Khan S, Kolts R, Brown W. Suicide Rates in Clinical Trials of SSRIs, Other Antidepressants and Placebo: Analysis of FDA Reports. Am J Psychiatry 2003;160:790-792. Online here.

Fournier JC, DeRubeis RJ, Hollen SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J. Antidepressant Drug Effects and Depression Severity: a Patient-Level Meta-Analysis. JAMA 2010;303(1):47-53. Online here.

Gibbons RD, Brown CH, Hur K, Marcus SM, Bhaumik DK, Erkens JA, Herings RM, Mann JJ. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007 Sep;164(9):1356-63. Abstract here.

ten Have M, de Graaf R, van Dorsselaer S, Verdurmen J, van ‘t Land H, Vollebergh W, Beekman A. Incidence and Course of Suicidal Ideation and Suicide Attempts in the General Population. Canadian Journal of Psychiatry. 2009;4:824-833 Online here.

Spijker J, de Graaf R, ten Have M, Nolen WA, Speckens A. Predictors of suicidality in depressive spectrum disorders in the general population: results of the Netherlands Mental Health Survey and Incidence Study. Social Psychiatry & Psychiatric Epidemiology May2010, Vol. 45 Issue 5, p513-521 Abstract here.

Dudley M, Goldney R, Hadzi-Pavlovic D. Are adolescents dying by suicide taking SSRI antidepressants? A review of observational studies. Australas Psychiatry. 2010 Jun;18(3):242-5. Abstract here.

Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ. 2009 Aug 11;339:b2880. doi: 10.1136/bmj.b2880. Abstract here.

P.S. Yes, I know that there are problems with the pharmaceutical industry, and I am not holding the industry up as bastions of good ethics. Physicians often prescribe antidepressants for people without a psychiatric diagnosis. I question the ethics of direct-to-consumer marketing, for example. I also highly disapprove of coupons for brand name pharms when generics would suffice and are much cheaper to you and your insurance.

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About JT Eberhard

When not defending the planet from inevitable apocalypse at the rotting hands of the undead, JT is a writer and public speaker about atheism, gay rights, and more. He spent two and a half years with the Secular Student Alliance as their first high school organizer. During that time he built the SSA’s high school program and oversaw the development of groups nationwide. JT is also the co-founder of the popular Skepticon conference and served as the events lead organizer during its first three years.


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