抗抑郁药与自杀风险：一位精神科医生谈 SSRIs 的临床观察与权衡

While most depressed and suicidal people who start an antidepressant experience a reduction in suicidality over the course of treatment as the depression improves, in some cases antidepressants such as SSRIs can lead to suicidal thoughts, suicide attempts, or suicide death. The signal for suicidal ideation is clearer for children and adolescents in clinical trials (hence the FDA black box warning), but the concern is not absent for adults.

SSRI-related suicide deaths in adults at the population level seem to be uncommon enough that observational studies of adults do not show a conclusive link. In RCTs and observational studies, to oversimplify a rather complicated and mixed body of literature, SSRIs seem to neither increase nor decrease suicide rates in adults overall—which could either mean that there is no substantial effect either way or that the two effects are roughly equal in magnitude and cancel out.

In my clinical work, I frequently encounter individuals who tell me that they have experienced suicidal thoughts on antidepressants. This experience is often restricted to a particular antidepressant, and a different one is tolerated well, but not always. In a small number of cases (usually with significant baseline mood dysregulation), all monoaminergic antidepressant medications seem to provoke suicidality.

The scenarios of SSRI-related suicidality I have observed and heard about from patients tend to fall into the following:

• Initiation of antidepressant leads to intense anxiety or dysphoria that produces (or exacerbates existing) suicidality

• Treatment with antidepressant leads to manic or mixed symptoms, which lead to suicidality

• Antidepressants make the person feel emotionally indifferent, and in the context of existing suicidal thoughts, it leads them to act on the suicidal thoughts because the usual emotional aversion to suicidal thoughts gets replaced by, “Eh, so what if I die?”

• Stopping an antidepressant abruptly (in someone who has been on them for a prolonged period) leads to a sudden exacerbation of mood and suicidality (withdrawal-related suicidality)

Such things make physicians uncomfortable, but I’ll restate it clearly: on starting an antidepressant (as well as going off them abruptly), some patients can experience worsening anxiety, agitation, restlessness, irritability, mood lability, or akathisia. These can subsequently induce or exacerbate suicidal thoughts, which in some cases can lead to suicide attempts and, rarely, suicide deaths. In my clinical experience of working with people with complicated mood and anxiety disorders, these issues with antidepressants are common enough that I try to see patients soon after starting an SSRI so that I can address early issues with tolerability. The idea of just starting an antidepressant and seeing them a month (or months) later worries me. As a psychiatrist, I get to see more complicated cases, and my experience doesn’t generalize to primary care, but I do think that even in primary care, it should be anticipated that a substantial number will struggle with SSRI-initiation and that a close follow-up after starting an SSRI is a useful general strategy.

SSRIs perform best, IMO, when the problem is chronic—generalized anxiety, dysthymia, adjustment disorder with high neuroticism—or sufficiently severe, e.g., major depression. Stress-related anxiety or depression that is mild and anticipated to be self-limiting is best addressed via supportive interventions or short-term use of quick-acting medications, such as sedatives. SSRIs can still be reasonable options in such situations, but the risk-benefit considerations are not quite straightforward.

We accept all kinds of risks in our lives. We drive cars on roads, we fly on planes, we drink alcohol socially, we use tobacco and cannabis, we invest our lifesavings in stocks, we undergo general anesthesia for surgical procedures, etc., etc. When my son was an infant, he loved being in a particular bouncer. We used it all the time. This is despite the fact that there was a warning prominently displayed on it. “Fall Hazard: Babies have suffered skull fractures falling while in and from bouncers.” Essentially, we accepted a very small risk of a catastrophic event because of the tremendous everyday convenience the bouncer offered us. Such considerations are ubiquitous in healthcare.

Every time a person uses an antidepressant (or any medication, for that matter), there is a small possibility that their experience may go very badly, sometimes in life-altering ways. Risk is ubiquitous in medicine and in life; the possibility of iatrogenic harm is unavoidable. This will not stop people from using antidepressants and other psychiatric medications. I have worked with many patients who experienced serious adverse effects with an antidepressant in the past but were still interested in trying others because they were desperate for relief.

But being transparent with the public about these risks accomplishes two things.

First, if patients and clinicians are aware of the possibility of harm, they can recognize the problem early and stop the medication before it progresses.

Second, it serves as a reminder that the condition being treated should be distressing enough or severe enough for the person or the benefit of the medication advantageous enough that they are willing to accept the possibility of uncommon but serious adverse events. The threshold for what counts as distressing enough or severe enough or advantageous enough will be different for different people, but what that threshold is in any particular situation for any particular person is worth giving some thought to.

This discussion was originally published as part of a post (Dec 2024) about Thomas Kingston’s death and has been edited to function as a standalone post.

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