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Re: Opinions?????????????? Buckeye Fan

Posted by Larry Hoover on July 22, 2004, at 7:25:33

In reply to Opinions??????????????, posted by Buckeye Fan on July 21, 2004, at 13:46:04

This wasn't on Pubmed yesterday, so I couldn't comment.

JAMA. 2004 Jul 21;292(3):338-43.

Antidepressants and the risk of suicidal behaviors.

Jick H, Kaye JA, Jick SS.

Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Mass 02421, USA. hjick@bu.edu

CONTEXT: The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. OBJECTIVE: To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. DESIGN AND SETTING: Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. PARTICIPANTS: The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). MAIN OUTCOME MEASURES: Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. RESULTS: After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide. CONCLUSIONS: The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.


"OBJECTIVE: To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin."

Antidepressant treatment was compared to antidepressant treatment. There was no control (untreated depressive) group.

"The base population included 159,810 users of the 4 antidepressant drugs."

Good sized N (sample population), making it more likely that the results of the statistical analysis will be generalizable to the population as a whole.

"MAIN OUTCOME MEASURES: Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior."

This is a within-groups comparison, not a comparison to untreated subjects. <for emphasis>

"After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls..."

They picked a subset to make sure they were comparing people with similar characteristics.

"newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin."

All confidence intervals include the value 1.0. That means there were no significant differences between any of the comparator drugs against the index drug, dothiepin. In other words, SSRIs (two of them) are no different than tricyclics. So, what we knew fifty years ago, with respect to tricyclics, is still true today, with more modern antidepressants.......early treatment phase is a period of substantially increased risk for suicide. Why anyone would ever have thought otherwise is quite beyond comprehension, given our prior experience with tricyclics and MAOIs.

"The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date."

Suicidal behaviour is significantly increased in the first nine days. We knew that.

"Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide."

Interesting that this (38-fold increased risk) was the only statistic mentioned in the lay press. Note also that the confidence interval was *not* reported. The true value might lie near 6-fold. You just can't say. The CI is also very broad, indicating that the data upon which the statistic depends are not very consistent, or perhaps very sparse. Oh, that's it, they were very sparse. There were only 17 suicides recorded, and not one in subjects under 19 years of age.

"Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs."

In other words, they tested the interaction statistically, and found that there was no relationship.

"There were no significant associations between the use of a particular study antidepressant and the risk of suicide."

Prozac and Paxil were no worse than Elavil, an old tricyclic. The truth is out.

"A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression."

In other words, even if you wanted to say Paxil was worse than the others, there is no basis for that argument.

"Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years."

No evidence of pediatric risk, based on a naturalistic study.

This study also tells us nothing about the relative risk of treated versus untreated depression. You can draw no conclusions about that from the data presented here.

As I have argued, the suicide risk upon initiation of antidepressant therapy is a medical management issue. For fifty years, we have known of the risk, and it remains the same, even with newer drugs. The question is not whether the drugs are safe, but why people behave so irrationally when initiating use of these meds. Why is that risk not better managed?

Lar

 

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poster:Larry Hoover thread:368648
URL: http://www.dr-bob.org/babble/20040719/msgs/368871.html