Do Antidepressants Cause Suicide?

Readers of comments to this blog may have noticed that I have had frequent discussions with readers who question all use of psychiatric medications. They know that I believe (actually I know) that medications can be extremely useful in some properly diagnosed patients with disorders known to respond to the medications who are also monitored for the emergence of side effects.

I have had some interesting conversations on the back channel with people who are absolutely convinced that loved ones committed suicide directly because of having taken an antidepressant. Psychiatrists counter that antidepressants prevent suicide because they treat depression, which is itself - obviously - a cause of suicide.

There is some data that indicates that antidepressants can increase suicidal ideation (but not necessarily completed suicides) in teens and young adults who take antidepressants. So what gives?

Before I answer that, I would like to point out that anti-depressants take two to six weeks to work, and often we have to increase the dose or change drugs which makes this period of time much longer, so people are at risk for suicide because of the underlying depression before the drugs have kicked in. Frequent follow up and a good suicide evaluation usually can prevent tragedy. Also, as I have posted before, there are different types of depression. The less severe type, dysthymia, will often not respond to meds at all, while significant major depression usually does.

But yes, antidepressants per se can indeed cause increased suicidal ideation, suicidal behavior, and completed suicides. However, I believe this only happens in three very specific situations, all of which can be managed by a competent psychiatrist.

The first situation is when a patient develops a side effect known as akisthesia, which is extreme agitation in which a patient can barely sit still. Milder agitation can also be a side effect. Studies clearly show that a mix of depression and anxiety greatly increases the risk for suicide. The psychiatrist can warn patients about this side effect and tell them to call the doctor if it develops. Tranquilizers usually take care of this problem, but some patients must be switched to a different antidepressant, which may or may not cause that particular side effect.

Second, if a patient has bipolar disorder but has not yet had a manic episode or has been misdiagnosed, an antidepressant can unpredictably cause them to switch into mania. Some mania is not characterized by euphoria as it is in most typical mania, but can instead be "dysphoric mania" in which the patients are miserable rather than elated. Suicide risk is high in this condition. Again, family members can be warned to look for signs of this and stop the patient from taking any more antidepressant until the doctor is reached.

Third, in a severe form of depression called melancholia, patients have a lot of clear-cut biological symptoms like thinking in slow motion and having no energy for anything. When treated with an antidepressant, their energy tends to come back well before they felt better subjectively. They suddenly develop the energy to kill themselves whereas before they did not. This is well known to psychiatrists - or should be well known - as a very dangerous time for suicide attempts.

We warn patients and families about this, and tell them to get guns and other possible means of suicide out of the house during this crucial time, as well as to keep an eye on their depressed family members. We are not seeing as much melancholia these days as we used to probably because patients usually get an antidepressant before their illness develops to the point where it is that severe - indirect evidence that the drugs are effective, by the way.

Readers of this blog also know I am highly critical of both pharmaceutical company marketing tactics and "biological" psychiatrists who think that pills can cure every human foible, that psychotherapy is a bunch of bull that has never been validated in randomized controlled studies (totally not true), and who tend to exaggerate the benefits of drugs in those conditions in which they are indicated.

I have not had many comments from these latter type of folk on the blog. So, in the spirit of being an equal opportunity critic, I thought I would post a debate I had on another blog called Medscape with other psychiatrists. Parts of the debate are somewhat technical, so I will put explanatory material in brackets and italics. I am not including every post on this particular thread, but only the ones that I respond to or that respond to me, and I've edited out some comments that are not relevant to the points I am trying to make.

The debate was started by a posting by the blogger, Nassir Ghaemi, MD about the finding that antidepressants may increase suicidal ideation in teens and young adults.

Dr. Ghaemi, MD: ...In reviewing the published FDA meta-analysis [combining the results of several different studies, often using different methodology, and running statistics on the combination] of the randomized clinical trials (RCTs) of antidepressants, [a researcher] summarized the rather clear finding that antidepressants seemed to have an age-dependent effect on suicide risk: In children and young adults below age 25, they increased the risk ...in later adult years they were neutral ...and in middle age and in the elderly they were protective... When all these age groups are summarized, antidepressants have a small protective benefit for suicide ...In all these analyses, suicidality (defined as actual suicide, suicide attempts, or notable increase in suicidal ideation) is being assessed, one should say, rather than completed suicide. There were only 8 suicides in 77382 subjects, though 2 were on placebo and 6 on antidepressant.

Predictors of antidepressant-related suicidality with antidepressants were interesting: Suicide attempts (i.e., actual behavior) were more associated with antidepressants rather than increase in suicidal ideation (thoughts without behavior). Also, non-depressed persons (e.g., studies of antidepressants in other conditions such as anxiety disorders or PTSD) were more likely to be suicidal with antidepressants than those diagnosed with clinical depression (major depressive disorder).

[The researcher] also addressed the common critique that adolescent suicides increased after the FDA warning, which led to a decrease in antidepressant prescriptions in children. He reviewed data showing that suicides per 100,000 population for adolescents occurred at rate of 7.3 in 2003, 8.2 in 2004, 7.6 in 2005, and 7.2 in 2006. The FDA warning came out in 2004, but that increase in suicide rates occurred before the decline in antidepressant prescription rates for adolescents, which happened more in 2005 and 2006, corresponding to a decrease in adolescent suicide rates.

It is a not entirely appealing aspect of our profession that we wish to criticize, but not be criticized: Many of us are critical of the pharmaceutical industry, or of diagnosing mental illnesses like bipolar disorder in children, and yet we react angrily when asked to restrain our use of drugs. Instead, we should think seriously about the clear question arising from these data: Why are antidepressants preventive of suicide in later adulthood, and causative of it in younger age?

MD #1: "Why are antidepressants preventive of suicide in later adulthood, and causative of it in younger age?"
The qualifier there is in RCTs for FDA drug approval. There are many reasons these days why clinical populations are different.

My only criticism of the pharmaceutical industry is that they have not found many safe and effective drugs. I would like to be able to prescribe a mood stabilizer to a bipolar patients where I did not have to warn them that in 20 years there is a small but substantial risk of kidney failure. I would be quite happy to provide psychotherapy alone to bipolar patients if it prevented them from killing themselves or otherwise destroying their lives. In fact, it would be much easier to provide therapy than obsessing about lithium toxicity.

MD #2: It's a peculiar to read criticism of pharmaceutical industry for "not found[ing] many safe and effective drugs" along with favorable (at least the way I read it) mentioning of psychotherapy which failed to provide anything substantial and replicable for suicide prevention whatsoever. While pharmaceutical limitations are measurable and evident, psychotherapeutic shortcomings are hidden behind self-congratulatory process. It's de rigueur in psychiatric narrative nowadays to insert reverences toward "psychotherapy" together with BigPharma admonitions (a form of psychiatric PC, I suppose) without any critique of the former or balanced view about the latter.

The response to the criticism 'why the pharmaceutical industry have not found many safe and effective drugs' is unprecedented, enduring assault on the industry from angry psychoanalysts, greedy selfish government, opportunistic politicians, and many busybodies. I am surprised BigPharma stayed in business this long - there are less vexing ways to make a buck.

Me: What a bizarre conversation! Talking about "drugs" or "psychotherapy" or even "depression" as if they were monolithic entities is insane.

Treating a melancholic depression with any type of psychotherapy is indeed a waste of time, as is treating most cases of dysthymia with just drugs alone.

As to suicide with antidepressants, [I list the clinical situations mentioned earlier in this post].

And of course we need better drugs. With all current antipsychotics, for instance, you get to pick between a significant risk for metabolic syndrome and a significant risk of tardive dyskinesia [a long-term neurological side effect]. What a wonderful choice. And of all the things one can choose to criticize big pharma for, I don't think that problem is one of them.

MD #2: It would be nice if one could comfortably tell one type of depression from another and expect at least half of his colleagues to agree. But your dysphoric mania is another man's agitated depression and the third one's depression with ADHD. And someone else's frontotemporal dementia. Before we start claiming superiority of one treatment over another shouldn't we first sort out the nomenclature?

The irony about "wonderful choice" is misdirected. Consider oncological drugs and their side effects. I don't see oncologists mocking BigPharma. Psychoanalytic/dynamic psychiatrists, OTOH, do. They are still convinced that the world is flat and if you keep moving ahead you can fall from the edge of the earth.

Me: I agree there is a lot of diagnonsense around, but if a psychiatrist can't tell a severely melancholic depression from a typical dysthymia, he or she needs to go back to medical school. While the DSM contains a lot of b.s., much of it is also highly consistent with both clinical presentation and treatment response.

About the "wonderful choice," what I said was that should NOT be blamed on big Pharma. However, if you think big PhARMA science is so honest, perhaps you should read The Truth About the Drug Companies by Marsha Angell, former editor of the New England Journal of Medicine, and see if you still think so. Or check out the Zyprexa marketing documents on FuriousSeasons.com, or the US Justice Department settlements with FIVE different big Pharma companies, available on the DOJ website, for a description of highly misleading and pervasive marketing of psychotropic drugs - including ghostwriting journal articles and paying big name "experts" to sign on as authors. Get your head out of the sand!

By the way, I'm not a psychoanalyst in the least. I agree that old line psychoanalysis was wrong about a lot of stuff, but not everything, and hardly any therapists practice it anymore anyway. I mean, biological psychiatrists have stopped doing insulin shock, so I don't continue to hold that against them now.

MD#2: I see the fine line separating constructive criticism from vilification is permanently erased by critics. Even if we dispense with objectivity, slamming BPharma is plain impractical. We see several leading manufacturers exiting the stage. Another Pyrric victory?

It was refreshing to see your trust in the US DOJ as a pillar of fairness. When thugs put on suits and badges, does it make shake-down palatable? One can grudgingly accept governmental thuggery but applauding would be a bit exuberant, wouldn't it? Any other gov organization in line for blind love and trust? BTW, the data on Zyprexa side effects were available from the get go for anyone who cared to check, but laziness and ignorance of our colleagues found excuses in pharma bashing.

And why shouldn't pharm co's aggressively advertise and market? Are there laws against it?

After descending from planet Utopia to our sinful Earth, maybe misdeed of E Lilly & Co won't look so evil and the US government so white and fluffy.

PS I am curious what entails "not everything" that "old line psychoanalysis were wrong about"? In regard to psychiatry, I mean.

Me: I am not out to vilify the drug companies. We need them. I'm a capitalist myself. I have no objection to marketing if it's even relatively honest. Make your best case. Buy me lunch, even. I don't care. However, the horrendous tactics described in the DOJ agreements go far far beyond that, and they can readily be observed every day at sponsored promotional talks, in regular and throw-away journals, and in DTC advertising. I don't have to make it up. The so-called science behind sponsored clinical trials has become almost comically biased.

You think the government has been too hard on big business? I'd say they're more often partners in crime. We all know that unrestrained big business never does bad things - just look at those paragons of virtue, Enron and BP. And don't big insurance companies always give both patients and us physicians a fair shake?

You're right about the side effects of Zyprexa being (or should have been) common knowledge a long time ago. I actually wasn't concerned about that. What I was concerned about was that, according to the company own memos (which were not even supposed to be released according to the agreement with the "thugish" DOJ, but a journalist got a hold of them), there was a conscious marketing decision to deceive doctors into expanding the definition of bipolar disorder to include any patient who was both anxious and depressed, without regard to any duration criteria, in order to sell more atypicals [expensive brand named anti-psychotic medications].

I have to admit I'm shocked by how many doctors fell for this, but if all you have is medication to offer, everything looks like a brain disease. There's an excellent study by Zimmerman and others that showed that in his sample, 40% of patients who had seen a previous psychiatrist and who clearly met DSM criteria for borderline personality disorder, and who did not even come close to meeting DSM criteria for bipolar disorder, had been diagnosed as bipolar by the previous doctor. Argue with the DSM definitions if you will, and I often do, but I think they got a lot things right.

There's plenty of b.s. in the psychotherapy literature as well. Your question about what is right and wrong about analytic theory would take a book to answer, so I won't even try. What I will say is that any neuroscientist can tell you that the brain is plastic and is literally shaped by interactions with primary attachment figures and other social influences on an ongoing basis. There's a ton of hard science available to back up that assertion.

MD #3: What a profoundly dispiriting exercise reading these comments has been. With one or two exceptions the desire to make a point has created only a painful experience of heat and smoke with precious little light.
Let's face a few facts:

What we don't know is enormous, for all of us. What we don't know we don't know is even greater. Therefore it behoves us all, myself included, to have humility in the face of our ignorance....

I am saddened to see that the arguments which rage for and against Big Pharma, necessary but venal, and psychoanalysis, unpalateable and frequently misused, are just infantile. They each have a place and each have contributed to where we are today. The exciting findings of today in neurophysiology in relation to infant attachment and trauma confirm the prescience of early psychoanalysts, their other failings not withstanding.

The absence of healthy doubt is dangerous. Let's have more doubt.

MD #2: It's unusual to see anyone to be so emotionally perturbed with tepid professional discourse and experience pains while reading opinions different from his/her own. "Let's have more doubts" appeal might work for dogmas (psychoanalytical and others), not for emerging, vibrant, and already highly controversial field like biological psychiatry..

"The exciting findings of today in neurophysiology in relation to infant attachment and trauma", IMO, are not exciting, specific, replicable, practical, and measurable. They serve a purpose, though, - resurrection of fading psychoanalytical orthodoxy. Good luck with that.

Suicide is too serious problem to trifle with psychoanalytic nonsense. There was steady, linear increase in teenage suicide rates for more than half a century during heydays of psychoanalysis in absence of other viable treatments until 1990, when (as some might remember) SSRI’s was introduced. Then, there was a 15 years of suicide decline (first time in recorded history). The decline reversed when first reports of suicidal thoughts related to SSRI treatment initiation emerged in the literature accompanied by sharp decrease in prescriptions

http://www.emaxhealth.com/1/22/24448.html
http://www.sciencedaily.com/releases/2007/09/070907221530.htm
http://www.infoplease.com/ipa/A0779940.html
http://teenadvice.about.com/b/2008/09/05/teen-suicide-rates-growing-in-us.htm
http://www.afsp.org/index.cfm?fuseaction=home.viewpage&page_id=050fea9f-b064-4092-b1135c3a70de1fda

We ought to talk about suicidality (i.e. suicidal thoughts) only in conjunction with discussion about protective role of medications contrasted with measurable (!) impact of other treatment modalities on suicide. Otherwise the discussion turns into fear mongering and emotional plea for "healthy doubt".

Me: No dogmas in biological psychiatry? How about every difference found between diagnostic groups and normals on an fMRI [a brain scan] being automatically labeled as an abnormality when it might instead be a conditioned response or even an adaptation? London taxi drivers have more grey matter in their posterior hypothalamus [part of the more primitive section of the brain] than controls. I suppose that driving a taxi is a disease?

How about the complete ignorance by biological psychiatrists of the vast literature in social psychology, which shows that, given the right environmental context, most people can be induced to do almost anything?

The effect of trauma on the hypothalamic-pituitary axis [the part of the brain that is responsible for regulating the release of stress hormone in the body] not specific or replicable? That's factually incorrect.

I agree that antidepressants, properly prescribed and in patients who are closely followed for the emergence of side effects, do reduce the suicide rate in some patients. Unfortunately they don't work for a significant number of suicidal patients.

Following epidemiological trends is suggestive but proves nothing, however. There are unfortunately almost no drug OR psychotherapy outcome studies that directly involve suicidal patients (for obvious ethical and practical reasons), so I think making overly broad statements about which treatments are most effective in preventing suicide (without regard to the evaluation of the individual patient) is both naive and extremely premature.

MD #2: Let's sort out confusions and contradictions. First paragraph is critical of "every difference found ... on an fMRI being automatically labeled as an abnormality when it might instead be a conditioned response or even an adaptation."

Third paragraph categorically refutes any suggestion that "the effect of trauma on the hippothalamic-pituitary axis" is not specific and replicable.

When a biopsychiatrist finds correlation then it is fatuous, unless it's convenient finding. Then it's alright.

The studies, BTW, found certain degree of ASSOCIATION - not cause-effect relationship, as implied, - between trauma and "dysregulation" (!) of HPA (blunted HPA-axis reactivity ) which was neither indicative nor specific for the type of trauma or associated diagnoses. Similar "dysregulations" were found in physical trauma, chronic disease, maternal undernutrition, substance abuse, and every mental disorder in DSM). It is a nonspecific finding in medicine, akin elevated sed rate, that don't demonstrate, less so proof, anything. There might be confusion btwn HPA studies and hippocampal volume decrease (cell death and cell atrophy )and corresponding increase in amygdala size and activation associated with chronic abbuse (http://www.isps-us.org/koehler/trauma_brain.html)

These studies indeed demonstrated that CHRONIC repetitive trauma in certain (not all) vulnerable individuals might produce anatomical and physiological changes. But these do not explain psychiatric disorders in children who were never abused and lack of mental disorders in many chronically abused.

Some biopsychiatrists my not be familiar, as was suggested, with "vast literature in social psychology" (this particular biopsychiatrist is an exception) but why should they if this literature, as interesting as it might be, has little to do with diagnosis and treatment of debilitating mental disorders. From social psychology viewpoint, hypothalamus and hippocampus are just two Greek words. Biopsychiatrists would disagree.

Another quote: "...given the right environmental context, most people can be induced to do almost anything". Not to develop a psychiatric disorder, they don't.

Now, back to our suicidal patients. It is irresponsible, IMO, not to consider the role of medications in suicide prevention. We may not know to what extent if any medications protect from suicide, but we can convincingly assume that psychoanalysis is as good as useless in these cases.

Me: Good point about my inconsistency on the hypothalamic-pituitary axis example. What I should have said was that this finding was found frequently in, as you say, chronic repetitive trauma, and of course not everyone is genetically susceptible. My bad. This finding has been replicated, however.

There are NO necessary or sufficient "causes" for almost any psychiatric diagnoses, only risk factors. No matter what biological, psychological, or social risk factor you look at, there will always be a lot of people who have a lot of it but don't develop any disorder, and a lot of people who have very little of it that do develop a disorder. And almost all risk factors like child abuse or the short allele of the MAOI [An enzyme that degrades chemicals in the brain] gene are risk factors for any number of different disorders. Totally non-specific.

Looking for necessary or sufficient causes in psychiatry is for the most part a fool's errand, and as statisticians (e.g. Cook & Campbell) will tell you, any study results that suggest otherwise are in most cases presenting a statistical artifact generated by where continuous variables were dichotomized [coded as present or absent].

I would also fault social psychologists who are not aware of biology. If one is going to truly understand human psychology, one needs to include ALL sources of information. Yes, there were horrendous historical mistakes made by the analysts with schizophrenia and autism. There were also horrendous historical mistakes made by the biological psychiatrists - i.e., eugenics [the theory that weaker members of society should be prevented from reproducing or even eliminated to improve the human gene pool]. Brainlessness versus mindlessness, as Eisenberg pointed out.

Not all psychiatric diagnoses are created equal - and many of them are probably not brain diseases in the way schizophrenia is. (and yes, even that dichotomy is simplistic).

I agreed with you, by the way, that NOT considering the role of medication in suicide IS irresponsible.

And please, everyone, quit conflating all psychotherapy with orthodox psychoanalysis. I personally think DBT [dialectical behavior therapy, a type of psychotherapy that does not directly involve psychoanalytic theory or technique] is an incomplete treatment for borderline personality disorder, but replicated randomized controlled studies do show it is quite effective for reducing suicidal and parasuicidal behavior in that population, at least for the first year after therapy. That's more than I can say for almost any drug study you care to look at.

[I did not mean to give myself the last word on purpose; MD #2 never responded to my last post, and it's been over a week].