What effect do antidepressants have if you're not really depressed?

[WiseOne]

Are antidepressants like some other medications, where they only help you if you are depressed but actually make your performance poorer if you are not? (perhaps similar to caffeine where if you are tired, it makes you more functional, but if you are well-rested it may actually make you do more poorly)? Or do they help (or at least not negatively affect) everyone, in the way that adderall helps everyone whether or not they have ADHD?

Thank you. -not asking for medical advice. also if those analogies to caffeine and adderall make false claims about those drugs feel free to disregard them.

(post edited for purposes of clarity. The article posted by OldPsychDoc actually answers it quite well but looking for more observational, anecdotal answers also. Basically, what is the effect in people who meet criteria vs people who don't? Is it more like caffeine in my aforementioned analogy or more like adderall where people benefit even if they don't meet criteria for anything?)

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[NickNaylor]

What is SWIM?

I'm not really sure what the question is... the person is either depressed or they aren't in that they either meet criteria or they don't. If they don't - but let's say that have acute stressors and they're having some symptoms that you could attribute to a mood disturbance that aren't sufficient enough to meet criteria for a depressive episode - my first thought would be to encourage psychotherapy rather than medications.

In clinical trials, the efficacy of antidepressants is typically dependent on the fact that the intervention cohort actually has symptoms which meet criteria for a major depressive episode or some other proxy, e.g., meeting a threshold PHQ-9/MADRS/HAM-D/whatever score. I did a very brief search on outcomes in people with subclinical depressive symptoms and wasn't able to find much, but my guess is that the studies are out there.

On the whole antidepressants are fairly benign, so apart from the usual side effects associated with them I'm skeptical that an antidepressant would cause poorer functioning psychiatrically. But, again, the first question to me would be: is this person suffering from a major depressive episode? If yes, then an antidepressant may be indicated. If no, then you're going a bit off the beaten path and using a medication without much of an indication, which is something I would try and avoid since you're likely going to be causing side effects with an unclear benefit.

 

[WiseOne]

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[WiseOne]

What is SWIM?

I'm not really sure what the question is... the person is either depressed or they aren't in that they either meet criteria or they don't. If they don't - but let's say that have acute stressors and they're having some symptoms that you could attribute to a mood disturbance that aren't sufficient enough to meet criteria for a depressive episode - my first thought would be to encourage psychotherapy rather than medications.

In clinical trials, the efficacy of antidepressants is typically dependent on the fact that the intervention cohort actually has symptoms which meet criteria for a major depressive episode or some other proxy, e.g., meeting a threshold PHQ-9/MADRS/HAM-D/whatever score. I did a very brief search on outcomes in people with subclinical depressive symptoms and wasn't able to find much, but my guess is that the studies are out there.

On the whole antidepressants are fairly benign, so apart from the usual side effects associated with them I'm skeptical that an antidepressant would cause poorer functioning psychiatrically. But, again, the first question to me would be: is this person suffering from a major depressive episode? If yes, then an antidepressant may be indicated. If no, then you're going a bit off the beaten path and using a medication without much of an indication, which is something I would try and avoid since you're likely going to be causing side effects with an unclear benefit.

Thanks for the answer. I guess the concern is that he could meet the criteria but not "really" be depressed. So let's say for example he has some undiagnosed nutritional or endocrine problem, he meets the criteria, and he is given an SSRI despite the cause of his problems being nutritional or endocrine (or even obstructive sleep apnea lets say). What would the effect of an SSRI be in that situation? Would an SSRI still help or would it actually hurt given that the cause is from something else?

 

[NickNaylor]

Thanks for the answer. I guess the concern is that he could meet the criteria but not "really" be depressed. So let's say for example he has some undiagnosed nutritional or endocrine problem, he meets the criteria, and he is given an SSRI despite the cause of his problems being nutritional or endocrine (or even obstructive sleep apnea lets say). What would the effect of an SSRI be in that situation? Would an SSRI still help or would it actually hurt given that the cause is from something else?

It may help but the definitive treatment in that case would be identification and treatment of whatever underlying medical cause is thought to be causing the symptoms. Ideally treatment of the underlying cause would negate any need for treatment of his mood symptoms, though treating the depression in the meantime would probably be the appropriate (but not definitive) course of action.

 

[OldPsychDoc]

Antidepressants in healthy subjects: what are the psychotropic/psychological effects? - PubMed - NCBI

 

[tr]

In addition to the above, suicidal ideation may be more common among healthy volunteers given SSRIs vs those meeting criteria for depression. NNTH 16 in this review, which is definitely cause for worry.

Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. - PubMed - NCBI

 

[hamstergang]

Thanks for the answer. I guess the concern is that he could meet the criteria but not "really" be depressed.

What does it mean to "really" be depressed? What we treat in psychiatry are disorders, not diseases. A diagnosis of depression is made based on someone having a certain combination of symptoms without a known underlying etiology. The diagnosis says nothing about underlying brain processes. Different people with 'depression likely have different things going on.

We know that more people who have the right collection of symptoms get better when taking antidepressants than placebos.

 

[WiseOne]

Edited original post for clarity of what I intended to ask. The article posted by OldPsychDoc actually answers it quite well but looking for more observational, anecdotal answers also. Basically, what is the effect in people who meet criteria vs people who don't? Is it more like caffeine in my aforementioned analogy or more like adderall where people benefit even if they don't meet criteria for anything?

This article Mood and personality effects in healthy participants after chronic administration of sertraline. - PubMed - NCBI seems to suggest some generalizable effects

 

[WiseOne]

What does it mean to "really" be depressed? What we treat in psychiatry are disorders, not diseases. A diagnosis of depression is made based on someone having a certain combination of symptoms without a known underlying etiology. The diagnosis says nothing about underlying brain processes. Different people with 'depression likely have different things going on.

We know that more people who have the right collection of symptoms get better when taking antidepressants than placebos.

Thank you. I accidentally ended up asking a different question in response to NickNaylor that was not my original intended question. Nonetheless, your response is enlightening, as I think the general public believes that antidepressants are used to correct an "imbalance" whereas (from what you indicate) are just used for anyone who meets criteria with no claims made as to the cause of those symptoms.

 

[SmallBird]

What does it mean to "really" be depressed? What we treat in psychiatry are disorders, not diseases. A diagnosis of depression is made based on someone having a certain combination of symptoms without a known underlying etiology. The diagnosis says nothing about underlying brain processes. Different people with 'depression likely have different things going on.

We know that more people who have the right collection of symptoms get better when taking antidepressants than placebos.

This is really the crux of it and highlights how pseudoneurscientific thinking that tries to apply specific antidepressants based on inferences about the underlying brain issue is ridiculous.

As a caveat, figuring out the determinants of someones mood (or any symptoms) is nevertheless a critically important task and may particularly inform the best psychosocial interventions to apply. But when it comes to meds, the data we have is simply on people who had specific symptoms.

 

[birchswing]

They make sex so unenjoyable that you get depressed and need a . . . oh, oops.

 

[tr]

Edited original post for clarity of what I intended to ask. The article posted by OldPsychDoc actually answers it quite well but looking for more observational, anecdotal answers also. Basically, what is the effect in people who meet criteria vs people who don't? Is it more like caffeine in my aforementioned analogy or more like adderall where people benefit even if they don't meet criteria for anything?

Not sure if this is what you are asking but I have given antidepressants (all SSRI I think) to a small number of people who came to me for symptoms that were clearly precipitated by a stressful situation (like a bad boss situation at work or an ill child), but who did not meet criteria for a depressive episode or for generalized anxiety disorder, and who didn't have any previous history of mental illness. Basically people who were having an appropriately upset reaction to an upsetting situation.

In each case I explained to them that they didn't meet criteria, this wasn't an orthodox approach and their best bet would be to either resolve the situation (like, quit the job) or, failing that, engage in targeted psychotherapy to help them manage their stressors more effectively. After that discussion there have been several people who were still like "Just give me the pill." I didn't expect much but to the best of my recollection all of them actually benefited from the medication.

 

[WiseOne]

Not sure if this is what you are asking but I have given antidepressants (all SSRI I think) to a small number of people who came to me for symptoms that were clearly precipitated by a stressful situation (like a bad boss situation at work or an ill child), but who did not meet criteria for a depressive episode or for generalized anxiety disorder, and who didn't have any previous history of mental illness. Basically people who were having an appropriately upset reaction to an upsetting situation.

In each case I explained to them that they didn't meet criteria, this wasn't an orthodox approach and their best bet would be to either resolve the situation (like, quit the job) or, failing that, engage in targeted psychotherapy to help them manage their stressors more effectively. After that discussion there have been several people who were still like "Just give me the pill." I didn't expect much but to the best of my recollection all of them actually benefited from the medication.

thank you for sharing that. there is so much clinical wisdom like this out there which you just can't find through a literature search.

 

[okokok]

thank you for sharing that. there is so much clinical wisdom like this out there which you just can't find through a literature search.

To state an obvious observation, the benefit from people taking SSRIs to deal with acute stressors rather than MDD could just as well be due to a placebo effect as to mechanism of the drug. (Not that that necessarily makes the effect any less real for those specific individuals who experienced a benefit, but perhaps less generalizable to the population at large.)

 

[HarryMTieboutMD]

In addition to the above, suicidal ideation may be more common among healthy volunteers given SSRIs vs those meeting criteria for depression. NNTH 16 in this review, which is definitely cause for worry.

Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. - PubMed - NCBI

This "study" got more publicity than it was worth, but note that it's in J Royal Society Medicine- a far cry from BMJ or Lancet. If you read it there is a design flaw at virtually every level of the meta analysis, and note that SI/suicidal behaviors were not increased, just activation symptoms and other SEs that are epidemiologically associated with suicide. So... much ado about nothing

That said the line between trait anxiety (harm avoidance, neuroticism, etc) and what we call GAD (which as a "natural kind" is debated among the experts) is pretty blurred, and sometimes SRIs can be helpful for these patients not meeting explicit axis one criteria for anything (even if it is the placebo effect)

 

[tr]

To state an obvious observation, the benefit from people taking SSRIs to deal with acute stressors rather than MDD could just as well be due to a placebo effect as to mechanism of the drug. (Not that that necessarily makes the effect any less real for those specific individuals who experienced a benefit, but perhaps less generalizable to the population at large.)

Sure. Available evidence suggests that about half the benefit of antidepressant pharmacotherapy is ascribable to placebo effects. Not sure why this is relevant or why it should alter generalizability (which is near zero to begin with as I'm merely offering clinical anecdotes).

 

[splik]

Not half - the vast majority of the effect is placebo and is massively dwarfed by any effect of the drug

 

[tr]

This "study" got more publicity than it was worth, but note that it's in J Royal Society Medicine- a far cry from BMJ or Lancet. If you read it there is a design flaw at virtually every level of the meta analysis, and note that SI/suicidal behaviors were not increased, just activation symptoms and other SEs that are epidemiologically associated with suicide. So... much ado about nothing

Suicide itself is a rare event, more so among healthy volunteers, and thus very difficult to study prospectively. If you read the discussion, the authors had to exclude the few instances of completed suicide by healthy volunteers because the parent studies didn't meet the requirements of the meta-analysis (or were suppressed by Eli Lilly). Nonetheless even one such event would be concerning.

 

[tr]

Not half - the vast majority of the effect is placebo and is massively dwarfed by any effect of the drug

Don't be silly. Irving Kirsch, the king of antidepressant skeptics, puts active drug at 30% more effective than placebo over all subjects, and twice as effective in the most severely depressed.

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration