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Why is there an increased risk of suicidality when children and adolescents are initially placed on antidepressant therapy?
It's not clear that SSRIs increase suicidality in children or adolescents, for many reasons.
1) When you run a clinical trial and you start someone on an antidepressant, you start monitoring them closely for suicidality. If they are depressed, they have a good chance of being suicidal. They have a higher chance of being suicidal before their treatment is effective. If they are suicidal before the study, they wouldn't be in the study to begin with.
1a) In said studies, there was not a risk of suicidal acts, just suicidal thoughts. If you look for it, you might find it.
2) When the black box warnings came out, pediatricians stopped prescribing SSRIs. Suicide rates in adolescents went up.
3) Mechanistically, some wonder if early in treatment whether some of the neurovegetative symptoms (being sleepy, having no energy) abate before the existential angst and death wish do. If all the sudden you now have the get-up-and-go to kill yourself, you might think about it more.
4) We don't well understand suicide or suicidal behavior, and the way DSM deals with suicidality probably prevents some research questions from being addressed the way we might want to.
5) SSRIs themselves have side effects. One of those side effects is some level of akathisia. Feeling restless and agitated is a risk factor for suicidality.
3) Mechanistically, some wonder if early in treatment whether some of the neurovegetative symptoms (being sleepy, having no energy) abate before the existential angst and death wish do. If all the sudden you now have the get-up-and-go to kill yourself, you might think about it more.
4) We don't well understand suicide or suicidal behavior, and the way DSM deals with suicidality probably prevents some research questions from being addressed the way we might want to.
5) SSRIs themselves have side effects. One of those side effects is some level of akathisia. Feeling restless and agitated is a risk factor for suicidality.
I tend to put more money on these, with 3>5>4. No evidence for it though.
we just had a big grand rounds on this, and the conclusion was no. i dont have the presentation in front of me, so i can't give you the specifics, but the presenter went through all the recent/relevent studies, and was able to show how the research did not support this.
It's not clear that SSRIs increase suicidality in children or adolescents, for many reasons.
3) Mechanistically, some wonder if early in treatment whether some of the neurovegetative symptoms (being sleepy, having no energy) abate before the existential angst and death wish do. If all the sudden you now have the get-up-and-go to kill yourself, you might think about it more.
Yes, the most recent evidence suggests that an increase in SI with adolescents starting an anti-depressant is NOT the case. In fact, there was a study that concluded adolscents who take anti-depressants are a 1/3rd less likely to attempt suicide then those not treated with an anti-depressant. There is a big push to have the FDA remove that black box warning.
Not going to happen. They will immediately face a class-action suit of the families of kids who killed themselves after being taken off the antidepressants......There is a big push to have the FDA remove that black box warning.
In Paxil, mainly...Example: If you look for it, you'll find it; the kids are depressed and already at risk for suicide. Fair enough, but that does not explain why you would find it more than in those taking placebo. Remember, the black box warning is not b/c of more SI compared to pre-trial; it is for more (double) the rate of SI during the trial compared to placebo.
I'm a PGY1, and I don't feel comfortable yet even in diagnosing depression in the under 18 population. I mean, how do you tell the difference between a child who's acting out because of terrible parenting vs. a child who's "depressed"? How does one determine between healthy teenage angst/the struggle for establishing an independent identity and endogenous "depression" in an adolescent?
I CERTAINLY don't feel I'm able to reassure the parents of a child/adolescent that an SSRI would be "safe" for their child.
We see children & adolescents in the ED when we're on call, and I ALWAYS push psychotherapy with the parents, and then either admit the youngster or get them follow up with a C & A psych Fellow the next day.
Also, if I'm not mistaken, those studies that drove the black box warning showed an increase in suicidal ideation, not attempts.
I'm a PGY1, and I don't feel comfortable yet even in diagnosing depression in the under 18 population. I mean, how do you tell the difference between a child who's acting out because of terrible parenting vs. a child who's "depressed"? How does one determine between healthy teenage angst/the struggle for establishing an independent identity and endogenous "depression" in an adolescent?
I CERTAINLY don't feel I'm able to reassure the parents of a child/adolescent that an SSRI would be "safe" for their child.
We see children & adolescents in the ED when we're on call, and I ALWAYS push psychotherapy with the parents, and then either admit the youngster or get them follow up with a C & A psych Fellow the next day.
Example: Kugel, same goes for your explanation. It doesn't make sense that the kids taking placebo wouldn't experience the same phenomenon.
I've read data showing that the benefits of antidepressants to children is actually far less than that of adults. The studies I've seen gave me an impression that perhaps in children, depression is more situationally-based than it is for adults, and perhaps the depression, because it was not as long, may have not caused as much pharmacological changes in their brains.
If someone asks, I'll fish for the data. I generally try to put a link to this data, but as of right now I'm burned out!
Antidepressants should be considered, but the feeling I got from the studies were that psychosocial treatment was more important.
Anyone with C&A training please feel free to drop in and correct me if I'm wrong.
Hmm, Paroxetine is supposed to be decidedly non-noradrenergic. So now there is another proposed mechanism, one not dealing with reuptake inibition, but rather with enhancing the LC NE? Perhaps I am getting old and gray early, but I don't remember much about the SSRIs affecting NE other than as a rather delayed response? If we see SI in kids within weeks, can the LC and NE at all be involvedHow Do Antidepressants Increase Suicide Risk in the Young?
This animal study finds a possible answer in the locus ceruleus.
The small but real risk for suicide in youth taking selective serotonin reuptake inhibitors is well documented but still poorly understood. These researchers administered 1.25, 2.50, or 5.00 mg/kg/day of paroxetine for 2, 4, 8, and 14 days to adult and young rats and measured its ability to reduce activity in the locus ceruleus (LC), the main noradrenergic center. This reduction, observed in depressed humans treated with antidepressants, is thought to underlie their therapeutic effect.
A fourth dose (0.625 mg/kg/day) was also studied but showed no effect on any test. Adult rats showed the expected effects in the LC. However, in young rats, paradoxical LC activity increases occurred at days 2 and 4 at 1.25 and 2.50 mg/kg/day doses (but not at 5.00 mg/kg/day) and corresponded to increased depression-like behavior in the forced-swim test. Young rats had 2- to 10-fold lower paroxetine blood levels than adult rats on the same dose, even when LC activity was at its peak in the young rats (days 2 and 4).
Comment: In this study, an SSRI had counter-therapeutic effects in young rats (increased locus ceruleus activity), which seems to correspond with worsening "depression" in the swim test. The effects appear to occur only at lower doses and with low drug blood levels. Increased central noradrenergic activity has also been associated with increases in anxiety and agitation, which are thought to underlie suicidal risk. If these findings translate to humans, one possible strategy to prevent this effect might be to give higher SSRI doses, although this theory requires testing before anyone adopts such a recommendation.
Peter Roy-Byrne, MD
Published in Journal Watch Psychiatry August 2, 2010
CITATION(S):
West CHK et al. Paroxetine-induced increase in activity of locus coeruleus neurons in adolescent rats: Implication of a countertherapeutic effect of an antidepressant. Neuropsychopharmacology 2010 Jul; 35:1653.
cause they activate the suicide center in the brain....not just in kids...in everybody..
just like high dose dopaminergics activate the god/religon center in the brain...
doesn't get more technical than that