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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Buckeye Fan on July 21, 2004, at 13:46:04
Study Backs Antidepressant-Suicide Link
By LINDSEY TANNER, APCHICAGO (July 20) - A study of nearly 2,800 British adults and children bolsters the evidence that patients are prone to suicidal impulses when they are first put on antidepressants. But it found no difference in risk between newer and older drugs.
The study looked at four drugs and found that suicidal thoughts or attempts were four times more likely during the first 10 days of treatment than they were after three months. Suicide was almost 40 times more common early on than later in treatment, though there were only 17 suicides, all in patients older than 19.
But the study is unlikely to resolve the debate over whether the drugs themselves increase the suicide risk.
And it may not soothe skeptics who maintain that newer drugs such as Paxil and Prozac that increase brain activity of the mood-regulating chemical serotonin are particularly risky for children. The study found no clear-cut evidence to support that idea, and the researchers did not specifically compare children on antidepressants with those not taking medication.
Some doctors argue that patients just starting on antidepressants are usually in the deepest throes of depression - which itself can cause suicidal behavior - and that the risks subside as the drugs take hold. Others say a medication-induced mood boost may give a profoundly depressed person just enough energy to act on suicidal thoughts.
But some relatives of people who have committed suicide blame the drugs themselves, and British health authorities have said that most serotonin-affecting antidepressants are unsuitable for children. GlaxoSmithKline, the maker of Paxil, has been hit with a lawsuit accusing it of suppressing studies indicating the drug might increase suicidal tendencies in children.
The U.S. Food and Drug Administration is investigating and earlier this year issued a public health advisory asking makers of 10 drugs to add or strengthen suicide-related warnings on their labels. Doctors were warned to watch patients on antidepressants carefully, especially when they first start taking the drugs.
The FDA advisory includes Paxil and Prozac but not the two other drugs studied - amitriptyline and dothiepin, older medications that work differently. The newer drugs have gained favor in part because they have fewer side effects.
The study, by Drs. Herschel and Susan Jick and James Kaye at Boston University, appears in Wednesday's Journal of the American Medical Association. It was funded by the Boston Collaborative Drug Surveillance Program, which received consultation fees from Glaxo in connection with other research. The authors said Glaxo had no role in the current study's design.
The data "simply means that antidepressants are being prescribed for the right indication, and that they do not immediately eliminate suicide risk," Drs. Simon Wessely and Robert Kerwin of London's Institute of Psychiatry said in a JAMA editorial. Still, careful monitoring of youngsters is essential, they said. Wessely has received funding from pharmaceutical companies including Prozac maker Eli Lilly and Co.
The researchers looked at 2,791 first-time users ages 10 to 69 of any of the four drugs from 1993 to 1999.
Suicidal tendencies were 29 percent more common among Paxil users than among dothiepin users studied. Kaye said that finding was statistically insignificant and could reflect doctors' tendency to prescribe the newest drug for more serious cases. Still, he said it "doesn't exclude the possibility" that Paxil is more risky.
Dr. David Fassler, a Vermont psychiatrist not involved in the research, said the study leaves key questions unresolved: "This study isn't specific to children and adolescents, and that's been the area of most recent concern."
Posted by Wildman on July 21, 2004, at 13:50:22
In reply to Opinions??????????????, posted by Buckeye Fan on July 21, 2004, at 13:46:04
....Others say a medication-induced mood boost may give a profoundly depressed person just enough energy to act on suicidal thoughts....
I've never been suicidal, but this statement makes sense to me. It's the medication at work, doing what it's supposed to do. Perhaps folks with suicidal tendencies should be supervised during the first couple of weeks on meds...
Wildman
Posted by linkadge on July 21, 2004, at 13:59:52
In reply to Re: Opinions??????????????, posted by Wildman on July 21, 2004, at 13:50:22
I would say that SSRi's have made me more suicidal. This does not mean I don't feel better on them :)!! (kind of paradoxical)
They provide relief but they also leave me disinhibited a little. I feel more liberated to take my own life if I want to. But if you ask me if I'd rather be on them or off them. On them hands down, but yes I can agree with what the study is saying.
Linkadge
Posted by SLS on July 21, 2004, at 14:36:39
In reply to Re: Opinions??????????????, posted by Wildman on July 21, 2004, at 13:50:22
> Perhaps folks with suicidal tendencies should be supervised during the first couple of weeks on meds...
I think everyone should be supervised. That's only good medicine. I also think they should be educated in advance regarding the possibility that they might feel worse before they feel better.
- Scott
Posted by retrojen on July 21, 2004, at 17:31:59
In reply to Re: Opinions??????????????, posted by SLS on July 21, 2004, at 14:36:39
I've heard that ssri's in particular are not good for some people because not all depressions are serotonin based. If that's the case, then there's a surge in the wrong neurotransmitter system, resulting in disinhibition, impulsivity, anger, suicidality....Some people respond better to tricyclics, or Norep/dop antidepressants, because it doesn't selectively blast one system
I also in general agree that the quick acting antidepressants give the person the oomph necessary to off themselves. It takes time to to restructure the depressive thinking- another good reason for combo meds&therapy....
> > Perhaps folks with suicidal tendencies should be supervised during the first couple of weeks on meds...
>
> I think everyone should be supervised. That's only good medicine. I also think they should be educated in advance regarding the possibility that they might feel worse before they feel better.
>
>
> - Scott
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
Posted by CindyLou on July 23, 2004, at 16:49:11
In reply to Opinions??????????????, posted by Buckeye Fan on July 21, 2004, at 13:46:04
This is very interesting. I have been on several medications over the past 15 years. Almost every time I start an SSRI, the depression gets WORSE before it gets better! My pdocs never seemed to believe me. Now, whenever I start a new SSRI, I start at a VERY low dose (e.g., 2.5 mg. Prozac) and work my way up. I can see how suicidal rates go up when someone first starts an SSRI.
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