Sunday, January 25, 2015

Do Antidepressants Increase Suicide Risk?

The subject of whether antidepressants increase or decrease suicide risk is a complicated one, and the literature on this subject remains conflicted. A study published in 2004, covering the period 1985 to 1999, found that U.S. suicides decreased 13.5% at a time when antidepressant use rose four-fold. The authors concluded, rather prematurely: "The decline in the national suicide rate (1985-1999) appears to be associated with greater use of non-tricyclic antidepressants." Those results have to be considered invalid, however, because from 1999 to today, suicides (and suicide rates) in the U.S. have increased every year, despite increasing use of antidepressants. The current rate (of 12.6 suicides per 100,000 Americans per year) is higher than before SSRIs were introduced. Are we to conlcude, now, that antidepressants are causing suicide rates to go up? That, too, would be premature.

We know suicide rates increase with age, and the U.S. population is growing older. Therefore, the ever-increasing suicide rate from 1999 to today reflects expected demographic trends.

In "Antidepressants and the risk of suicidal behaviors," JAMA 2004 Jul 21;292(3):338-43, Boston University School of Medicine researchers H. Jick H, J.A. Kaye, and S.S. Jick looked at suicide and suicidal behaviors in a population of 159,810 first-time users of four antidepressant drugs. They found a 4-fold increase in risk of suicidal behavior in antidepressant users in the first 9 days after starting a prescription. That's not the shocker. The shocker is that when they looked at risk of completed suicide in people who had started antidepressant drugs within 9 days, versus people who had been on drugs 90 days or more, there was a 38-fold increased risk for the former versus the latter. (The drugs in question were Elavil, Prozac, Paxil, and the tricyclic dothiepin, which has been sold in various countries as Prothiaden, Dothep, Thaden, or Dopress; it is not sold in the United States)

It's worth noting anecdotally that Robin Williams had started Seroquel just eight days before his death by suicide. He was also taking Remeron, an older serotonergic antidepressant. You can choose to look at his death as a fluke, if you want, or something that would have happened anyway, with or without drugs. We may never know for sure what really happened.

Why the increased risk in the first nine days of treatment? Various theories about this "rollback phenomenon" were discussed in a previous post. Accepted medical wisdom (going back at least 50 years) says that when severely depressed patients are "activated" by treatment, they go from avolitional to volitional and act out preexisting desires to inflict self-harm. This ancient theory needs to be reconsidered, however, as it was formulated back in the days when "clinical depression" was indeed severe and involved psychomotor retardation. Today's user of Paxil, Prozac, etc. is not that kind of patient. The overwhelming majority of "depressive" patients today suffer a less severe depression, often diagnosed by a family doctor rather than a psychiatrist.

"Activation" no doubt accounts for some (small) percentage of self-harm incidents. The other theories that need to be considered involve drug-induced worsening of depression, and/or severe akathisia reactions (which occur roughly 1% to 5% of the time), possibly also coupled with insomnia (which is known to bring a suicide risk in and of itself).

We can argue about the reasons, but the fact is, many people find that with antidepressants, they get worse before they get better. The drugs are no panacea. They work for about a third of users (This was the principle finding of the $35 million, 6-year STAR*D study, and it's also born out by clinical efficacy trials, especially those done in modern times.) In most antidepressant trials, a third of patients drop out of the trial rather than continue on the drug. This too is consistent with the fact that some people find the drugs immediately disagreeable.

If you're suffering, you should consider trying antidepressants, but only do so under close medical supevision; and be aware that many people get worse before they get better.

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