antidepressants in mild to moderate depression

[destinywon]

mild to moderate depression should not be treated with drugs.

So I'm a long time lurker, really just joined this because I saw splik's post in another thread and was somewhat befuddled and frustrated. I know splik is very knowledgeable but things like this do not really make sense to me. I simply don't see the evidence for splik's statement, and don't think this is line with the current evidence. It really frustrates me when people (even smart people) portray "truths" which are not backed in evidence. I'm sure folks have seen much of the data, but I don't understand how you can ignore it. I feel like you must at least qualify a response with - "Some psychiatrists would support meds in mild to moderate depression while others wouldn't." Would be happy to see evidence to the contrary of what I'm showing. I'll explain:

Guidelines
-Both APA and CANMAT suggest that pharmacological treatments can be used to treat mild to moderate depression (in certain situations for CANMAT).
-NICE does not recommend pharmacological treatment for mild depression (but does for moderate to severe depression)

Reviews
-Older trial-level reviews (e.g. by Kirsch) and the often cited review by Fournier 2010 (using six studies, with paxil and imipramine) are questioned by subsequent studies:

-Fountoulakis re-analyzed Kirsch's data with different results
Fountoulakis KN, Veroniki AA, Siamouli M, Möller H-J. No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis. Annals of General Psychiatry. 2013;12:26. doi:10.1186/1744-859X-12-26.

-Gibbons found no association with depression severity and fluoxetine/venlafaxine treatment effect
Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ. Benefits From Antidepressants: Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine. Arch Gen Psychiatry. 2012;69(6):572–579. doi:10.1001/archgenpsychiatry.2011.2044

-Locher found no effect of depression severity on treatment effect in late-life depression
Moderation of antidepressant and placebo outcomes by baseline severity in late-life depression: A systematic review and meta-analysis. Locher, Cosima et al. Journal of Affective Disorders , Volume 181 , 50 - 60

-A recent Japanese meta-analysis with Leucht found no effect of depression severity on patient-level data in six trials
Furukawa, T. A., Maruo, K., Noma, H., Tanaka, S., Imai, H., Shinohara, K., ... & Leucht, S. (2018). Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta‐analysis. Acta Psychiatrica Scandinavica, 137(6), 450-458.

-Furthermore, therapy in outpatient setting is well below typical academic research center CBT standards in terms of quality. Therapists don't use evidence-based CBT or other modalities of treatment, while drugs remain drugs (although obviously could be non-optimally dosed).
Shafran, Roz, et al. "Mind the gap: Improving the dissemination of CBT." Behaviour research and therapy 47.11 (2009): 902-909.

Sure, there are many limitations of the studies and guidelines I have presented (e.g. c/o industry sponsored trials, sample size, selection bias), but also of the points that splik brought up (SSRIs are generally well tolerated, HAMD/treatment scales aren't truly linear and don't capture full depression severity). But, I think it at least warrants a qualification that many clinicians may treat mild to moderate depression (more on the moderate side than mild on that mild to moderate continuum) reasonably with pharmacological treatments.

To answer that OPs question (what to use as tx for depression in primary care w/ delay in seeing psychiatrist):
Long answer - see prior responses.
Short answer - if no way to see psychiatrist for 6+ months, then I would trial 1 SSRIs, then trial another, augment with Wellbutrin/Remeron/Buspar if with partial response, or switch to Wellbutrin/Remeron/SNRI if without any response for other. Would make sure dose and duration are adequate - biggest problem I see. Also would look at family history and c/o bipolarity. But really this is a much more complicated question, as others have described.

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[erg923]

I would assume part of what Splik was getting at is that what we call "depression" in psychiatry (mild or moderate), and especially in primary care, per DSM, encompass a variety of causes and should not be assumed to be an actual "disorder" or "disease." And thus not something we treat with drugs unless we are sloppy, lazy, or colluding with pre-existing pathology and/or unrealistic expectation of life. Just because something "works" does not mean its the best solution in the overall scheme of things.

If you have a shoulder ache and I kick you in the nuts, your shoulder wont hurt much for while. Or at least you wont know it. That doesn't make it the most appropriate treatment for shoulder pain.

You should probably look up the history how "depression" was marketed as a disease after the discovery of the first MAOI. We are way past this thing we used to call 'endogenous depression."

 

[Merely]

So I'm a long time lurker, really just joined this because I saw splik's post in another thread and was somewhat befuddled and frustrated. I know splik is very knowledgeable but things like this do not really make sense to me. I simply don't see the evidence for splik's statement, and don't think this is line with the current evidence. It really frustrates me when people (even smart people) portray "truths" which are not backed in evidence. I'm sure folks have seen much of the data, but I don't understand how you can ignore it. I feel like you must at least qualify a response with - "Some psychiatrists would support meds in mild to moderate depression while others wouldn't." Would be happy to see evidence to the contrary of what I'm showing. I'll explain:

Guidelines
-Both APA and CANMAT suggest that pharmacological treatments can be used to treat mild to moderate depression (in certain situations for CANMAT).
-NICE does not recommend pharmacological treatment for mild depression (but does for moderate to severe depression)

Reviews
-Older trial-level reviews (e.g. by Kirsch) and the often cited review by Fournier 2010 (using six studies, with paxil and imipramine) are questioned by subsequent studies:

-Fountoulakis re-analyzed Kirsch's data with different results
Fountoulakis KN, Veroniki AA, Siamouli M, Möller H-J. No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis. Annals of General Psychiatry. 2013;12:26. doi:10.1186/1744-859X-12-26.

-Gibbons found no association with depression severity and fluoxetine/venlafaxine treatment effect
Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ. Benefits From Antidepressants: Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine. Arch Gen Psychiatry. 2012;69(6):572–579. doi:10.1001/archgenpsychiatry.2011.2044

-Locher found no effect of depression severity on treatment effect in late-life depression
Moderation of antidepressant and placebo outcomes by baseline severity in late-life depression: A systematic review and meta-analysis. Locher, Cosima et al. Journal of Affective Disorders , Volume 181 , 50 - 60

-A recent Japanese meta-analysis with Leucht found no effect of depression severity on patient-level data in six trials
Furukawa, T. A., Maruo, K., Noma, H., Tanaka, S., Imai, H., Shinohara, K., ... & Leucht, S. (2018). Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta‐analysis. Acta Psychiatrica Scandinavica, 137(6), 450-458.

-Furthermore, therapy in outpatient setting is well below typical academic research center CBT standards in terms of quality. Therapists don't use evidence-based CBT or other modalities of treatment, while drugs remain drugs (although obviously could be non-optimally dosed).
Shafran, Roz, et al. "Mind the gap: Improving the dissemination of CBT." Behaviour research and therapy 47.11 (2009): 902-909.

Sure, there are many limitations of the studies and guidelines I have presented (e.g. c/o industry sponsored trials, sample size, selection bias), but also of the points that splik brought up (SSRIs are generally well tolerated, HAMD/treatment scales aren't truly linear and don't capture full depression severity). But, I think it at least warrants a qualification that many clinicians may treat mild to moderate depression (more on the moderate side than mild on that mild to moderate continuum) reasonably with pharmacological treatments.

To answer that OPs question (what to use as tx for depression in primary care w/ delay in seeing psychiatrist):
Long answer - see prior responses.
Short answer - if no way to see psychiatrist for 6+ months, then I would trial 1 SSRIs, then trial another, augment with Wellbutrin/Remeron/Buspar if with partial response, or switch to Wellbutrin/Remeron/SNRI if without any response for other. Would make sure dose and duration are adequate - biggest problem I see. Also would look at family history and c/o bipolarity. But really this is a much more complicated question, as others have described.

You just gave us the response to that question typical of a person who might have read the literature but lacks the depth and experience/understanding to truly understand it. Splik not only is much more versed in the literature you’re quoting but has the range of experiences to have internalized and deconstructed that literature to really be able to apply it in the real world. I think that’s where the discrepancy in responses comes from.

 

[675015]

If you have a shoulder ache and I kick you in the nuts, your shoulder wont hurt much for while. Or at least you wont know it. That doesn't make it the most appropriate treatment for shoulder pain. "

If you want to be even more realistic/analogous you could just replace “kick in the nuts” with Percocet!

 

[erg923]

If you want to be even more realistic/analogous you could just replace “kick in the nuts” with Percocet!

I swear to God, I will rochambo you, MFer! 🙂

 

[NickNaylor]

I would assume part of what Splik was getting at is that what we call "depression" in psychiatry (mild or moderate), and especially in primary care, per DSM, encompass a variety of causes and should not be assumed to be an actual "disorder" or "disease." And thus not something we treat with drugs unless we are sloppy, lazy, or colluding with pre-existing pathology and/or unrealistic expectation of life. Just because something "works" does not mean its the best solution in the overall scheme of things.

If you have a shoulder ache and I kick you in the nuts, your shoulder wont hurt much for while. Or at least you wont know it. That doesn't make it the most appropriate treatment for shoulder pain.

You should probably look up the history how "depression" was marketed as a disease after the discovery of the first MAOI. We are way past this thing we used to call 'endogenous depression."

This was my interpretation as well. Despite our attempts to label what is really a very large number of distinct presentations that we call "depression," we are likely dealing with very different entities. I would make the argument that depression due to an acute stressor, depression that seemingly comes unprompted, and depression due to general life dissatisfaction (e.g., anger with their position in life due to a series of perceived disappointments/failings/whatever) are not the same thing even though they may symptomatically look similar and may all meet criteria for MDD. Scenario #2 may be most likely to respond to pharmacotherapy. Scenarios #1 and #3 would likely be more appropriate for individual psychotherapy rather than medications because there are very clear psychological factors contributing to the presentation. An SSRI is not going to help you cope with a stressor - for example, grieve a loss - nor will it cause you to feel better about your station in life. An SSRI may help correct a poorly-understood biological derangement that ultimately leads to the syndrome we call "depression."

Trying to get an understanding of how a person functions as an individual and their perception of their presenting problem can help you get a better sense of what kind of process may be contributing to their symptoms. This kind of consideration has no place in the DSM, yet, I would argue, it is very relevant when we talk to patients about treatment recommendations and what to expect from various options. But, of course, it requires more nuance, time, effort, and experience than the "checklist psychiatry" that many medical school behavioral sciences courses seem to teach.

 

[Attending1985]

This was my interpretation as well. Despite our attempts to label what is really a very large number of distinct presentations that we call "depression," we are likely dealing with very different entities. I would make the argument that depression due to an acute stressor, depression that seemingly comes unprompted, and depression due to general life dissatisfaction (e.g., anger with their position in life due to a series of perceived disappointments/failings/whatever) are not the same thing even though they may symptomatically look similar and may all meet criteria for MDD. Scenario #2 may be most likely to respond to pharmacotherapy. Scenarios #1 and #3 would likely be more appropriate for individual psychotherapy rather than medications because there are very clear psychological factors contributing to the presentation. An SSRI is not going to help you cope with a stressor - for example, grieve a loss - nor will it cause you to feel better about your station in life. An SSRI may help correct a poorly-understood biological derangement that ultimately leads to the syndrome we call "depression."

Trying to get an understanding of how a person functions as an individual and their perception of their presenting problem can help you get a better sense of what kind of process may be contributing to their symptoms. This kind of consideration has no place in the DSM, yet, I would argue, it is very relevant when we talk to patients about treatment recommendations and what to expect from various options. But, of course, it requires more nuance, time, effort, and experience than the "checklist psychiatry" that many medical school behavioral sciences courses seem to teach.

I don’t think I have ever seen scenario two

 

[destinywon]

I would assume part of what Splik was getting at is that what we call "depression" in psychiatry (mild or moderate), and especially in primary care, per DSM, encompass a variety of causes and should not be assumed to be an actual "disorder" or "disease." And thus not something we treat with drugs unless we are sloppy, lazy, or colluding with pre-existing pathology and/or unrealistic expectation of life. Just because something "works" does not mean its the best solution in the overall scheme of things.

If you have a shoulder ache and I kick you in the nuts, your shoulder wont hurt much for while. Or at least you wont know it. That doesn't make it the most appropriate treatment for shoulder pain.

You should probably look up the history how "depression" was marketed as a disease after the discovery of the first MAOI. We are way past this thing we used to call 'endogenous depression."

I'm not really sure how this shows why what splik said was inaccurate. Of course depression is heterogenous. Of course big pharma has a large role in antidepressant use. But also we don't understand things well enough to know what does and doesn't respond to SSRIs or other antidepressants. And I was not saying that mild to moderate depression should always be treated with meds, but that at least it could be a consideration. However, someone can have symptoms of depression that aren't severe without "pre-existing pathology and/or unrealistic expectation of life"

I don't really get your analogy. SSRIs don't cause more pain that results in the pain of whatever stressor from being relieved. I'm not saying SSRIs are the best treatment but that they may be a possible treatment.

You just gave us the response to that question typical of a person who might have read the literature but lacks the depth and experience/understanding to truly understand it. Splik not only is much more versed in the literature you’re quoting but has the range of experiences to have internalized and deconstructed that literature to really be able to apply it in the real world. I think that’s where the discrepancy in responses comes from.

I don't think the authors of those articles (who spend most of their careers doing mostly research) are less versed than splik in the literature. From what I understand, splik does clinical work. Similarly, psychiatrists agreed with those authors who are on the studies. I have worked with several senior attendings who directly contradict what splik has stated. Perhaps splik is more experienced than all of them combined (my guess would be no), but even one who is experienced can have numerous biases, e.g. confirmation bias.

 

[Liquid8]

The (non-psychiatrist) OP of that thread had described an issue with patients failing 2 trials of treatments, and then asked for an opinion regarding a “mild-moderate unipolar depression refractory to SSRIs.”

I think most people would have read the question in context and interpreted it as asking for what options could be used in a depressed patient where previous trials of treatments (at least 2) have been already tried. While the term “mild-moderate” was likely to have been incorrectly applied (and understandably so given the stated background of the OP), the intent of the question appeared clear. In the other thread I just thought splik was being a smartarse in only choosing to focus on the “Mild moderate” aspect in his first reply.

As far as treatment guidelines go, I like to look at exactly what has been written:

Australian RANZCP Guidelines (2016) (https://www.ranzcp.org/Files/Resources/Publications/CPG/Clinician/Mood-Disorders-CPG.aspx)
"In mild to moderate episodes of MDD, psychological management alone may be adequate, especially early in the course of illness. However, episodes of greater severity, and those that run a chronic course, are likely to require the addition of antidepressant medication, or some other combination of psychological and pharmacological treatment."

CANMAT Guidelines (2016) (Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments)
"Pharmacological treatments can be considered for mild depression in some situations, including patient preference, previous response to antidepressants, or lack of response to nonpharmacological interventions."

APA Guidelines (2010) (https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf)
"An antidepressant medication is recommended as an initial treatment choice for patients with mild to moderate major depressive disorder [1] and definitely should be provided for those with severe major depressive disorder unless ECT is planned [1]"
[1] = Recommended with substantial clinical confidence)

Even the UK NICE guidelines don’t exclude the use of antidepressants.

UK NICE Guidelines Depression in adults: recognition and management | Guidance and guidelines | NICE
"Do not use antidepressants routinely to treat persistent subthreshold depressive symptoms or mild depression because the risk–benefit ratio is poor, but consider them for people with:
-a past history of moderate or severe depression or
-initial presentation of subthreshold depressive symptoms that have been present for a long period (typically at least 2 years) or
-subthreshold depressive symptoms or mild depression that persist(s) after other interventions."

The APA guidelines appear to be the most aggressive in terms of prescribing antidepressants, and if followed slavishly would explain the angst about non-psychiatrist overprescribing psychotropic medications. The other guidelines are consistent with my own style of practice, allowing a reasonable degree of flexibility to use both psychotherapies, antidepressants or a combination as needed.

 

[clausewitz2]

I don’t think I have ever seen scenario two

That's really unfortunate. Classic melancholic or psychotic depression are very striking entities and are frequently a whole different animal from most of what gets called MDD. I would recommend reading some of the older descriptive psychopathology literature so you don't miss these things when you do encounter them, because it (probably) has a very different prognosis and is also likely going to require more than the 50 mg Zoloft qday you can write in your sleep.

 

[Evidence Based]

That's really unfortunate. Classic melancholic or psychotic depression are very striking entities and are frequently a whole different animal from most of what gets called MDD. I would recommend reading some of the older descriptive psychopathology literature so you don't miss these things when you do encounter them, because it (probably) has a very different prognosis and is also likely going to require more than the 50 mg Zoloft qday you can write in your sleep.

This is a quick aside, but as a trainee about to start residency, any good recs on classic descriptive psychopathology readings? Would love to have some interesting free time reading in this vein.

 

[tr]

This was my interpretation as well. Despite our attempts to label what is really a very large number of distinct presentations that we call "depression," we are likely dealing with very different entities. I would make the argument that depression due to an acute stressor, depression that seemingly comes unprompted, and depression due to general life dissatisfaction (e.g., anger with their position in life due to a series of perceived disappointments/failings/whatever) are not the same thing even though they may symptomatically look similar and may all meet criteria for MDD. Scenario #2 may be most likely to respond to pharmacotherapy. Scenarios #1 and #3 would likely be more appropriate for individual psychotherapy rather than medications because there are very clear psychological factors contributing to the presentation. An SSRI is not going to help you cope with a stressor - for example, grieve a loss - nor will it cause you to feel better about your station in life. An SSRI may help correct a poorly-understood biological derangement that ultimately leads to the syndrome we call "depression."

I think this sort of attempt to separate the 'biological' from the 'psychological' is nonsense and pretty much at odds with everything that modern neuroscience has to tell us.

There is not a 'unique biological derangement' that separates a 'biological MDD' from a 'psychosocial MDD.' There's been a ton of research guided by this sort of dualistic thinking and it has all come up empty-handed. No unique biomarker or genetic marker can separate 'biological MDD' from 'psychological MDD.' The idea that they are separable is wishful dualism in the face of a tsunami of evidence that the biological and the psychological are completely entwined. MDD is heterogeneous in causes and presentations but the bottom line is that all your mental processes are housed in your brain which is a physiological organ.

And in my experience SSRIs are actually quite helpful for people with MDD that occurs in the context of one or more major psychosocial stressors. And they do help people cope with the stressors. Patients commonly report that although they may still feel the effect of the stressor, they are more able to cope with it effectively and less prone to breaking down in tears at inappropriate times/places.

 

[Stagg737]

I think this sort of attempt to separate the 'biological' from the 'psychological' is nonsense and pretty much at odds with everything that modern neuroscience has to tell us.

There is not a 'unique biological derangement' that separates a 'biological MDD' from a 'psychosocial MDD.' There's been a ton of research guided by this sort of dualistic thinking and it has all come up empty-handed. No unique biomarker or genetic marker can separate 'biological MDD' from 'psychological MDD.' The idea that they are separable is wishful dualism in the face of a tsunami of evidence that the biological and the psychological are completely entwined. MDD is heterogeneous in causes and presentations but the bottom line is that all your mental processes are housed in your brain which is a physiological organ.

And in my experience SSRIs are actually quite helpful for people with MDD that occurs in the context of one or more major psychosocial stressors. And they do help people cope with the stressors. Patients commonly report that although they may still feel the effect of the stressor, they are more able to cope with it effectively and less prone to breaking down in tears at inappropriate times/places.

If we look at the biologic/psychological factors as a spectrum instead of cut and dry dualism though, wouldn't it make sense that patients whose dysfunction falls more heavily into the biological portion of the spectrum would have greater benefit from medication than those who fall more heavily into the psychosocial portion?

 

[Healer777]

Not a psychiatrist yet (med student), but...

What about patients whose depression was either sparked by or complicated by a major stressor, but is not merely a response to that stressor?

In my psych classes in undergrad I learned that chronically high levels of cortisol can change the functioning of the brain, even killing cells in the hippocampus leading to potential memory and cognitive problems. So let's say we have someone who loses their job. Their mind and body are constantly feeling the stress and tension of wondering how they are going to pay the rent, if they will ever get another job, if they are even worthy of having another job and contributing to society, because they believe they are a huge failure. Because of the neurohormonal effects of this severe stress, this person starts suffering a variety of physical and neurochemical effects, such as changes in sleep, appetite, and ability to concentrate. Maybe they start thinking about suicide, because they see no way out.

This person likely won't feel better just by getting another job, because by now the problem has become much more than just about that This person now is so beaten down that they cannot experience any pleasure at all, let alone think straight. They think they don't deserve to be a part of society.

How would we help this patient? They probably wouldn't make much progress in therapy if they believe that everything is doomed; they won't be motivated enough to try. They might show up, but they won't do the actual work needed to get better because they (rightly or wrongly) perceive themselves of being incapable of it.

They don't have endogenous depression; something triggered it. But can they get better without chemical help?

 

[Liquid8]

This is a quick aside, but as a trainee about to start residency, any good recs on classic descriptive psychopathology readings? Would love to have some interesting free time reading in this vein.

When I started training, for phenomenology I was recommended to read one of:
-Fish's Clinical Psychopathology
-Sim's Symptoms in the Mind
-Trzepacz & Baker - The Psychiatric Mental Status Examination Hardcover

I found Fish more readable than Sims. Can't comment on the last one.

Having a solid grasp of phenomenology is essential. A lot of my early work was with schizophrenia and borderline patients, so it was important to know the difference between a hallucination, pseudohallucination and an illusion. A lot of what is has been described is also rare and esoteric, although interesting things can come up from time to time. Last week I saw someone who described lexical gustatory synesthesia.

 

[WisNeuro]

Not a psychiatrist yet (med student), but...

What about patients whose depression was either sparked by or complicated by a major stressor, but is not merely a response to that stressor?

In my psych classes in undergrad I learned that chronically high levels of cortisol can change the functioning of the brain, even killing cells in the hippocampus leading to potential memory and cognitive problems. So let's say we have someone who loses their job. Their mind and body are constantly feeling the stress and tension of wondering how they are going to pay the rent, if they will ever get another job, if they are even worthy of having another job and contributing to society, because they believe they are a huge failure. Because of the neurohormonal effects of this severe stress, this person starts suffering a variety of physical and neurochemical effects, such as changes in sleep, appetite, and ability to concentrate. Maybe they start thinking about suicide, because they see no way out.

Ehhh, I'd look at this area of research with some caution. The data looked great in the animal models, not so clean in the human models. This was actually a part of my dissertation. Also, the PTSD/memory impairment literature should be viewed with extreme caution. It's 95% composed of VA samples that did not control for performance validity.

Sorry for the slight threadjack, just an area I get somewhat passionate about.

 

[thoffen]

There is some difficulty in evaluating the effectiveness of antidepressants for mild or moderate depression. This is a condition which does have significant placebo response, and baseline depressive scales are lower than more severe depression. Thus, if placebo is likely to go from a HAM-D 15 to a 10 and a 3-point difference is considered significant, then the treatment would have to go from a 15 to a 7 in order to show efficacy. That would likely be a very significant clinical difference for the patient and not too unreasonable, but expecting to show that difference across a whole pool of patients is challenging. One of the biggest issues is the duration of trials. A typical MDD study time may not be sufficient, and of course it's quite costly to run a large trial over a long period of time and requires doing something with increasing dropouts. Meta-analyses of dysthymia treatment suggest that effect sizes of antidpressants might actually be greater than for MDD, but again because the scores are lower to start with the absolute difference from placebo doesn't look impressive.

Generally, the hazard is not treating mild or moderate depression at all. I would say that psychotherapies might be reasonably the first-line treatment instead of antidepressants, but we have to do something with the whole slew of patients who aren't going to actually end up receiving high quality therapy or for whom the therapy isn't effective. In those cases, I do think antidepressants are indicated with perhaps greater attention to side effect burden.

 

[clausewitz2]

This is a quick aside, but as a trainee about to start residency, any good recs on classic descriptive psychopathology readings? Would love to have some interesting free time reading in this vein.

Well, to steelman the point I made earlier, Aubrey Lewis' 1931 "Melancholia: A Clinical Survey of Depressive States" lays out the strongest clinically-based argument against there being multiple types of depression. Actually reading Kraeplin is a good start as well, although I frankly skipped his lengthy digressions about measurement of muscle tension in manic depressive illness.

 

[NickNaylor]

I think this sort of attempt to separate the 'biological' from the 'psychological' is nonsense and pretty much at odds with everything that modern neuroscience has to tell us.

There is not a 'unique biological derangement' that separates a 'biological MDD' from a 'psychosocial MDD.' There's been a ton of research guided by this sort of dualistic thinking and it has all come up empty-handed. No unique biomarker or genetic marker can separate 'biological MDD' from 'psychological MDD.' The idea that they are separable is wishful dualism in the face of a tsunami of evidence that the biological and the psychological are completely entwined. MDD is heterogeneous in causes and presentations but the bottom line is that all your mental processes are housed in your brain which is a physiological organ.

And in my experience SSRIs are actually quite helpful for people with MDD that occurs in the context of one or more major psychosocial stressors. And they do help people cope with the stressors. Patients commonly report that although they may still feel the effect of the stressor, they are more able to cope with it effectively and less prone to breaking down in tears at inappropriate times/places.

I don't think they are inseparable, and I don't think they're two separate entities that must be considered separately. There is a mountain of evidence that psychosocial stressors result in biological changes that have downstream sequelae, both physical and psychiatric. I'm not sure where you got that idea from in my post. But the myopic, in my opinion, paradigm of "biological illness = biological treatment" - by which we mean medications, because, reasons - is hardly satisfying. I'm not convinced that we can simply give someone a yes/no checklist asking about MDD symptoms over the last 2 weeks and, if they endorse 5/9 symptoms, one of which must be anhedonia or low mood, and we sufficiently rule-out other diagnoses with a similar checklist, then we give them a script for the antidepressant of your choice and you're done. Otherwise, what's the whole purpose of doing a psychiatric interview? ****, I don't need to know anything about someone's social history or really even much of an HPI if that's the paradigm we're working under unless I have some concern about diagnostic clarity.

Psychotherapy also has biological effects - there are clear changes in brain structure that occur with psychotherapeutic treatment. Many of these changes are not dissimilar from those that occur following antidepressant treatment. But it's also likely that each has unique treatment effects; you can see this in differences in long-term data which generally show greater durability in treatment effects with psychotherapy vs. medications. They are obviously not 1:1 substitutes for one another. From a now-dated review looking at this issue:

The efficacy of ADM has been established in literally thousands of placebo-controlled clinical trials.15,16Approximately one-half of all patients will respond to any given ADM irrespective of its class, and many of the other half will respond to another ADM or to a combination of ADMs.17 However, ADMs seem to be symptom-suppressive rather than curative.18 That is, although ADM is effective in the treatment of the acute depressive episode and is preventive so long as its use is maintained, no published findings to date suggest that ADMs reduce future risk of depressive episodes once their use is terminated.19 This suggests that causal mechanisms of depression are unchanged by ADM treatment, and so patients are left with an elevated risk for subsequent episodes if they stop taking their medications. Because the risk is not absolute – not all patients experience a return of depression after they stop taking ADM – it is likely that these causal mechanisms take the form of stable diatheses that interact with negative life events to determine the onset of subsequent episodes. These causal diatheses might be represented by neural processes, and research that aims to specify these processes is ongoing.

...

CT is the best-known and most widely tested of a larger family of cognitive behavioural interventions. Like ADM, it is a safe and efficacious treatment for acute episodes of major depressive disorder. CT is based on the premise that inaccurate beliefs and maladaptive information processing (forming the bases for repetitive negative thinking) have a causal role in depression. This ‘cognitive model’ posits that when maladaptive thinking is corrected, both acute distress and the risk for subsequent symptom return will be reduced. Contrasting with the lack of evidence of enduring effects of ADMs is the substantiation of claims that CT provides protection against relapse and, possibly, recurrence.18

...

As shown in the figure, acutely depressed individuals could be characterized by decreased prefrontal function, possibly arising in part from increased amygdala reactivity. We propose that CT operates by bolstering prefrontal function whereas ADM operates more directly on the amygdala. These treatments might thus result in end states that are, in one important respect, similar; normalized amygdala and PFC activity might result from either ADM or CT. Further investigation of the differences in short-term responses will be crucial, then, for understanding why CT produces a sustained effect whereas ADM does not. If the amygdala is ‘the point of entry’ for environmental stressors, cessation of ADM treatment could leave a person at risk of having strong maladaptive reactions to new environmental insults. By contrast, if CT works by building skills that require the active operation of the PFC, the effects of CT on PFC activity and function might be relatively enduring.

I think you misunderstand my perspective. It is a priori obvious that psychiatric syndromes are due to pathology in the brain, thus I suppose it is appropriate to call them "biological." It must necessarily follow that treatments that improve psychiatric syndromes - including both medications and psychotherapy - must reverse that pathology, thus they are also "biological." My point is simply that I'm not convinced that we have definitively shown, one way or another, that there is no population for which psychotherapy may be more beneficial vs. medications or vice versa. We have shown at a 10,000-foot, population level that they are generally equivalent in mild-moderate cases. I'm not sure we have proved or disproved anything else, but maybe you have some studies that can educate me on the matter (and I really would be interested in seeing those if you do). I'm also not convinced that the two treatments can be directly substituted for each other and that medications are preferable simply because they require less resources. I don't think we have definitively proven that, mechanistically, all depression is the same irrespective of other contributing/mitigating factors. I think there is more nuance to this whole endeavor. I do think that these questions are answerable in the future once our level of understanding of the brain advances. I just don't think we've reached that point.

 

[DisorderedDoc417]

I don't think they are inseparable, and I don't think they're two separate entities that must be considered separately. There is a mountain of evidence that psychosocial stressors result in biological changes that have downstream sequelae, both physical and psychiatric. I'm not sure where you got that idea from in my post. But the myopic, in my opinion, paradigm of "biological illness = biological treatment" - by which we mean medications, because, reasons - is hardly satisfying. I'm not convinced that we can simply give someone a yes/no checklist asking about MDD symptoms over the last 2 weeks and, if they endorse 5/9 symptoms, one of which must be anhedonia or low mood, and we sufficiently rule-out other diagnoses with a similar checklist, then we give them a script for the antidepressant of your choice and you're done. Otherwise, what's the whole purpose of doing a psychiatric interview? ****, I don't need to know anything about someone's social history or really even much of an HPI if that's the paradigm we're working under unless I have some concern about diagnostic clarity.

Psychotherapy also has biological effects - there are clear changes in brain structure that occur with psychotherapeutic treatment. Many of these changes are not dissimilar from those that occur following antidepressant treatment. But it's also likely that each has unique treatment effects; you can see this in differences in long-term data which generally show greater durability in treatment effects with psychotherapy vs. medications. They are obviously not 1:1 substitutes for one another. From a now-dated review looking at this issue:



I think you misunderstand my perspective. It is a priori obvious that psychiatric syndromes are due to pathology in the brain, thus I suppose it is appropriate to call them "biological." It must necessarily follow that treatments that improve psychiatric syndromes - including both medications and psychotherapy - must reverse that pathology, thus they are also "biological." My point is simply that I'm not convinced that we have definitively shown, one way or another, that there is no population for which psychotherapy may be more beneficial vs. medications or vice versa. We have shown at a 10,000-foot, population level that they are generally equivalent in mild-moderate cases. I'm not sure we have proved or disproved anything else, but maybe you have some studies that can educate me on the matter (and I really would be interested in seeing those if you do). I'm also not convinced that the two treatments can be directly substituted for each other and that medications are preferable simply because they require less resources. I don't think we have definitively proven that, mechanistically, all depression is the same irrespective of other contributing/mitigating factors. I think there is more nuance to this whole endeavor. I do think that these questions are answerable in the future once our level of understanding of the brain advances. I just don't think we've reached that point.

Not to mention the PHQ9 is a tool made by pharma...

 

[Wilf]

Splik is a good psychiatrist but anyone who has read many of his posts will know he gets carried away at times. Medication absolutely has a place in the treatment of moderate depression and sometimes even mild, depending on the individual patient.

 

[tr]

I don't think they are inseparable, and I don't think they're two separate entities that must be considered separately. There is a mountain of evidence that psychosocial stressors result in biological changes that have downstream sequelae, both physical and psychiatric. I'm not sure where you got that idea from in my post. But the myopic, in my opinion, paradigm of "biological illness = biological treatment" - by which we mean medications, because, reasons - is hardly satisfying. I'm not convinced that we can simply give someone a yes/no checklist asking about MDD symptoms over the last 2 weeks and, if they endorse 5/9 symptoms, one of which must be anhedonia or low mood, and we sufficiently rule-out other diagnoses with a similar checklist, then we give them a script for the antidepressant of your choice and you're done. Otherwise, what's the whole purpose of doing a psychiatric interview? ****, I don't need to know anything about someone's social history or really even much of an HPI if that's the paradigm we're working under unless I have some concern about diagnostic clarity.

Psychotherapy also has biological effects - there are clear changes in brain structure that occur with psychotherapeutic treatment. Many of these changes are not dissimilar from those that occur following antidepressant treatment. But it's also likely that each has unique treatment effects; you can see this in differences in long-term data which generally show greater durability in treatment effects with psychotherapy vs. medications. They are obviously not 1:1 substitutes for one another. From a now-dated review looking at this issue:

I think you misunderstand my perspective. It is a priori obvious that psychiatric syndromes are due to pathology in the brain, thus I suppose it is appropriate to call them "biological." It must necessarily follow that treatments that improve psychiatric syndromes - including both medications and psychotherapy - must reverse that pathology, thus they are also "biological." My point is simply that I'm not convinced that we have definitively shown, one way or another, that there is no population for which psychotherapy may be more beneficial vs. medications or vice versa. We have shown at a 10,000-foot, population level that they are generally equivalent in mild-moderate cases. I'm not sure we have proved or disproved anything else, but maybe you have some studies that can educate me on the matter (and I really would be interested in seeing those if you do). I'm also not convinced that the two treatments can be directly substituted for each other and that medications are preferable simply because they require less resources. I don't think we have definitively proven that, mechanistically, all depression is the same irrespective of other contributing/mitigating factors. I think there is more nuance to this whole endeavor. I do think that these questions are answerable in the future once our level of understanding of the brain advances. I just don't think we've reached that point.

OK maybe I overinterpreted your post then. My apologies.

There has been some work on predicting better response to medicaton vs psychotherapy. My own read on this literature is very mixed, with results mostly showing that people with histories of childhood trauma or personality pathology are more resistant to treatments of all kinds, both pharmacological and psychotherapeutic. However I went and looked for a review and found this one

Psychiatry Online
Simon, G. E., & Perlis, R. H. (2010). Personalized medicine for depression: can we match patients with treatments?. American Journal of Psychiatry, 167(12), 1445-1455.

which reaches the conclusion that there is modest evidence that personality disorder suggests better response to pharmacotherapy, while childhood trauma and recent stressors both suggest better response to psychotherapy.
(I'm not even sure how to interpret this since the most common type of personality disorder among people seeking treatment seems to be Cluster B-type, which is itself highly associated with adverse childhood experiences, so where that leaves us I don't know.)

Interestingly, the strongest effect they uncovered was patient preference: people who had a strong preference for psychotherapy over pharmacotherapy or vice versa clearly did best when assigned to their preferred treatment. However this was investigated only in a small number of individuals within a single trial.

 

[deleted736562]

Anyone else feels that this thread is like a witch hunt? I mean, really, this discussion could have been easily carried in the original thread since it's the same topic. Maybe they should be merged.

 

[DisorderedDoc417]

Is it not hilarious that specialists can’t agree on how to treat the mild form of their most common problem? Good riddance.

 

[Drrrrrr. Celty]

Is it not hilarious that specialists can’t agree on how to treat the mild form of their most common problem? Good riddance.

Specialists on this forum*

Also this and the last thread are so quazi cerebral that we still haven't defined what mild even means.

 

[DisorderedDoc417]

Specialists on this forum*

Also this and the last thread are so quazi cerebral that we still haven't defined what mild even means.

An important distinction, I agree. I was not facetious to the degree necessary to make my point.

 

[Drrrrrr. Celty]

An important distinction, I agree. I was not facetious to the degree necessary to make my point.

I feel like and this is my impression just based off of the people who I rotated with, at a single in-patient residency program is that if you have even mild-moderate depression +/- some evidence that your life isn't going to spontaneously improve then you get an SSRI and we can talk about removing or tapering when things get better or therapy starts getting you out through crap.

No one in this thread or the last really seems to want to talk about how essentially this is akin kind of to obesity related metabolic disorders. People generally don't actually change their life style despite their doctor telling them to do so. What percent are actually interested in therapy or go to it?

So in the end you're kind of telling someone go to therapy, they don't go to therapy, then they get worse, potentially end up hurting themselves or baker acted and then need something stronger on board to keep them afloat, ex abilify.

 

[FlowRate]

Also this and the last thread are so quazi cerebral that we still haven't defined what mild even means.

There have been ample references to that exact topic.

 

[FrasierMD]

Antidepressants Work! Not so Fast

Curious what others think of Ghaemi's perspective here? I find it fairly compelling.

 

[Attending1985]

I feel like and this is my impression just based off of the people who I rotated with, at a single in-patient residency program is that if you have even mild-moderate depression +/- some evidence that your life isn't going to spontaneously improve then you get an SSRI and we can talk about removing or tapering when things get better or therapy starts getting you out through crap.

No one in this thread or the last really seems to want to talk about how essentially this is akin kind of to obesity related metabolic disorders. People generally don't actually change their life style despite their doctor telling them to do so. What percent are actually interested in therapy or go to it?

So in the end you're kind of telling someone go to therapy, they don't go to therapy, then they get worse, potentially end up hurting themselves or baker acted and then need something stronger on board to keep them afloat, ex abilify.

On the flip side people who are extremely depressed and anxious tend to make poor decisions like quitting their job, not showing up for work, abandoning relationships, ect. If an AD causes them some symptom relief which allows them to make better decisions that’s important. Patients should understand that. If the AD numbs them out just enough to continue making terrible decisions perpetuating their misery this need to be confronted with a reality check. If this doesn’t happen and more medications are utilized you’re right it’s a chronic model. This is where saying no, setting limits and using common sense become very important.

 

[Attending1985]

Antidepressants Work! Not so Fast

Curious what others think of Ghaemi's perspective here? I find it fairly compelling.

I agree with his point that we’ve gotten mdd wrong. I think ADs do “work” for a good portion in clinical practice but diagnosing mdd with checklist doesn’t work and you include at least half people who have something else. That being said the way we use ADs ubiquitously and chronically for “depression” doesn’t work which this article supports.

 

[Drrrrrr. Celty]

On the flip side people who are extremely depressed and anxious tend to make poor decisions like quitting their job, not showing up for work, abandoning relationships, ect. If an AD causes them some symptom relief which allows them to make better decisions that’s important. Patients should understand that. If the AD numbs them out just enough to continue making terrible decisions perpetuating their misery this need to be confronted with a reality check. If this doesn’t happen and more medications are utilized you’re right it’s a chronic model. This is where saying no, setting limits and using common sense become very important.

True.

 

[thoffen]

Antidepressants consistently beat placebo by a small amount. Placebo beats the course of untreated depression by leaps and bounds. Placebo is good medicine. It's a provider showing interest in, understanding of, and belief in deliverance from a person's darkest suffering over time. It's almost.... Psychotherapy... It's not nothing. And adding some extra serotonin and/or norepinephrine in there usually helps more.

And there's no question that those monoamine effects are what is responsible for the difference. Every antidepressant has them in some fashion (you might argue lithium as an exception, antipsychotics with some evidence although also possessing monoamine actions). Most remarkably, antidepressants share this action which were developed (first by accident) before any knowledge of that mechanism ever existed.

 

[tr]

Antidepressants Work! Not so Fast

Curious what others think of Ghaemi's perspective here? I find it fairly compelling.

I think it's funny that anybody is still arguing over this since multiple meta-analytic reviews have found the same thing.

Yes antidepressants are effective in RCTs over placebo. No the effect is not large, it's about 0.33, and generally scales with depression severity.

These are the basic facts, and they are agreed upon, but then people go and have enormous tiffs about whether 0.33 is a meaningfully sized difference, which is obviously a matter of opinion. Effect size of antidepressants for depression is more than twice the size of the effect of statins for lowering cholesterol or of aspirin for prevention of vascular disease (How effective are common medications: a perspective based on meta-analyses of major drugs), but I don't see anyone having huge epistemic battles over whether those effects are 'real' or 'meaningful.' I can't help but think this has something to do with the still! ongoing! stigma against mental disorders that is prevalent not only among the general population but also, apparently, among providers of mental health care as well.

 

[clausewitz2]

' I can't help but think this has something to do with the still! ongoing! stigma against mental disorders that is prevalent not only among the general population but also, apparently, among providers of mental health care as well.

I think if you are going to make a statement suggesting that saying "I think a treatment other than SSRIs is better for this particular condition" is the same as hating your patients on some level, you really ought to justify this a bit more explicitly.

 

[omnirom]

I've struggled with this question over the last year in the outpatient clinic. What is the appropriate way to diagnose the severity of depression ie: mild, moderate, or severe? Is the gold standard the psychiatrist's interpretation of severity of occupational/social/relationship functioning? Or is it from having ~2-3 associated symptoms for mild depression and >4 for moderate/severe? Or is it based off of PHQ9 or BDI scores? I've had several patient's who've scored in the severe range on PHQ9 or BDI but functionally are much more in the moderate severity range.

 

[tr]

I think if you are going to make a statement suggesting that saying "I think a treatment other than SSRIs is better for this particular condition" is the same as hating your patients on some level, you really ought to justify this a bit more explicitly.

Hm. I think the above bears pretty much no relationship to what I actually said.

But I'll bite: What's your explanation for why physicians have no problem accepting an effect size of 0.15 for aspirin and vascular disease prevention, but are so mistrustful of an effect size of 0.33 for SSRIs and depression?

 

[clausewitz2]

Hm. I think the above bears pretty much no relationship to what I actually said.

But I'll bite: What's your explanation for why physicians have no problem accepting an effect size of 0.15 for aspirin and vascular disease prevention, but are so mistrustful of an effect size of 0.33 for SSRIs and depression?

The relationship to what you said is that you quite literally said that stigma against mental health disorders is the only or major reason why a psychiatrist might be leery of prescribing an SSRI. This is an assertion that it is not a considered stance perhaps based on clinical experience or judgment based on assessment of available clinical evidence, but rather because of discriminatory bias against people with mental health disorders, i.e. our patients. Hate is a strong word to be fair, so I'll grant that, but "stigma" inherently suggests a negative valuation of the persons/conditions being stigmatized. If it is not an unfounded negative valuation, but is actually founded, then it is an "accurate assessment", not "stigma." Saying that reluctance to prescribe antidepressants in mild depression is due chiefly to stigma against mental health disorders is functionally equivalent to saying that psychiatrists reluctant to do this irrationally dislike something about their patients.

As to what I think is going on: I think much of the reluctance to taking these effect sizes at face value is due to a lack of clarity about the entities in question and what those effect sizes actually mean. It is not hard to come up with a relatively robust consensus definition of an MI or a stroke, and so everyone can understand what is being prevented or staved off by aspirin, even if the NNT is relatively high. While I understand that if you apply the SCIC you have a relatively reliable definition of major depression, I hope that you will also acknowledge that this is not the means of diagnosing >99% of cases of major depression in clinical practice. We are talking about an entity/entities that are much, much less concrete and directly observable. I am not doubting the effect size defined over MDD-as-rigorously-diagnosed-through-structured-interview, but reasoning that things that are true about this entity/entities to the much broader diagnostic congeries often treated as depression is a bit like reasoning from "things that are true about thoroughbred Arabian stallions" to "things that are true about everything that looks like a horse."

Have you considered that the skepticism you are seeing here might reflect actual clinical experience that is predicated on this broader definition? Yes, yes, we should all be more rigorous about everything, but that is a side question to whether there is possibly a reason people might come to the opinion you mention above without it necessarily being motivated by simply disliking mental health conditions and the people who struggle with them.

 

[WisNeuro]

I've struggled with this question over the last year in the outpatient clinic. What is the appropriate way to diagnose the severity of depression ie: mild, moderate, or severe? Is the gold standard the psychiatrist's interpretation of severity of occupational/social/relationship functioning? Or is it from having ~2-3 associated symptoms for mild depression and >4 for moderate/severe? Or is it based off of PHQ9 or BDI scores? I've had several patient's who've scored in the severe range on PHQ9 or BDI but functionally are much more in the moderate severity range.

It depends on who wants the diagnosis, really. But, you should really be looking at it from an overall point of view. Symptom count can be a good way to identify targets in therapy, but I don't think it should be the main marker for severity. Someone can have 7-8 of the DSM symptoms of depression, but they are mild enough that the person is still working full-time and maintaining household responsibilities, while someone else can have 6 reported symptoms and essentially be avolitional and relatively bedbound. Definitely need to look at the impairment of applicable areas as a big marker. However, in healthcare, it's usually just a cutoff point on a questionnaire. And I usually never see any further exploration by other providers other than to just report the score and the associated severity label.

 

[NickNaylor]

I've struggled with this question over the last year in the outpatient clinic. What is the appropriate way to diagnose the severity of depression ie: mild, moderate, or severe? Is the gold standard the psychiatrist's interpretation of severity of occupational/social/relationship functioning? Or is it from having ~2-3 associated symptoms for mild depression and >4 for moderate/severe? Or is it based off of PHQ9 or BDI scores? I've had several patient's who've scored in the severe range on PHQ9 or BDI but functionally are much more in the moderate severity range.

The DSM actually breaks down criteria for the MDD severity specifier. I believe the full DSM has more specific criteria with respect to number of symptoms. The desk reference states:

Mild: "Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning."

Moderate: "The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for 'mild' and 'severe.'"

Severe: "The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning."

For whatever that's worth.

 

[clozareal]

I don't have much to add to this thread, but came to say that I really appreciate the community on this forum because of thoughtful discussions like this!

 

[tr]

The relationship to what you said is that you quite literally said that stigma against mental health disorders is the only or major reason why a psychiatrist might be leery of prescribing an SSRI.

Indeed not. I said that stigma seemed a likely/obvious explanation for why physicians are more mistrustful of a given effect size for an SSRI than for the same or smaller effect size for a nonpsychiatric medication. Not for why a psychiatrist might choose not to prescribe an SSRI. Presumably it doesn't need to be stated explicitly that SSRIs are not the universal answer to any clinical scenario. Obviously there are many cases when SSRIs are not indicated. It's the skepticism over the large and solid body of research on SSRI efficacy in general that raises my eyebrow.

Have you considered that the skepticism you are seeing here might reflect actual clinical experience that is predicated on this broader definition? Yes, yes, we should all be more rigorous about everything, but that is a side question to whether there is possibly a reason people might come to the opinion you mention above without it necessarily being motivated by simply disliking mental health conditions and the people who struggle with them.

Hm. This is quite separate from the effect size issue, but here it sort of sounds like you are saying that many or most psychiatrists do not rigorously apply standard diagnostic criteria, and that they then observe that SSRIs are often not useful in their treatment population, and that they then conclude that SSRIs are not effective. Is that what you are actually saying? It seems... not very well thought out. If I misinterpret, please do clarify.

 

[clausewitz2]

Indeed not. I said that stigma seemed a likely/obvious explanation for why physicians are more mistrustful of a given effect size for an SSRI than for the same or smaller effect size for a nonpsychiatric medication. Not for why a psychiatrist might choose not to prescribe an SSRI. Presumably it doesn't need to be stated explicitly that SSRIs are not the universal answer to any clinical scenario. Obviously there are many cases when SSRIs are not indicated. It's the skepticism over the large and solid body of research on SSRI efficacy in general that raises my eyebrow. .

Appreciate the clarification. This was not obvious from your statement. I think my point about the outcome still being a different sort of entity between the two situations stands, i.e. stroke v. reduction in a depression rating scale. I do not doubt the formal psychometric properties of any of these scales when applied appropriately to the groups they were normed on, but I do get the sense that many clinicians are unpersuaded of the relevance of these scales to the outcomes that they or most of their patients care at all about. This may be a perceptual confusion on their part and if they only thought more carefully about what depression means and had an understanding more in line with the research they would not fall into this trap, but I think it breeds suspicion of claims of efficacy. Why believe this when they have the apparent frequent experience of SSRIs not accomplishing very much in treating ostensibly "depressed" people?

Less careful PCPs handing them out like candy or to anyone who cries obviously does not help the situation.

Hm. This is quite separate from the effect size issue, but here it sort of sounds like you are saying that many or most psychiatrists do not rigorously apply standard diagnostic criteria, and that they then observe that SSRIs are often not useful in their treatment population, and that they then conclude that SSRIs are not effective. Is that what you are actually saying? It seems... not very well thought out. If I misinterpret, please do clarify.

I mean, as a positive rather than normative observation, this is absolutely true and I think accounts for the attitude I am talking about. Put aside for one moment more principled debates such as whether MDD being treated as a unitary entity obscures important endophenotypical differences. It is certainly the case that the patients identified for trials generating these positive effect sizes have satisfied numerous inclusion and exclusion criteria that make them look entirely different from the general population presenting to a psychiatric clinic. Add to that the fact that it does not seem to be the case that most people in practice are sitting down with careful timelines of illness and checking off criteria one by one before arriving at the billable diagnosis they choose to chart and you have the means by which clinical experience becomes highly divorced from the findings of research. And then the doubt sets in.

I'm not trying to defend a lack of rigor, although I am not convinced that slavishly following the DSM is enormously helpful. I'm just trying to point out a more realistic means by which the skepticism you were expressing surprise at comes about. It is also a route to doubt that does not go through "well they must just be laboring under stupid prejudices about mental illness that We Enlightened Ones have transcended." Bias against mental illness and the mentally ill is without a doubt a real and pernicious thing, but I think more progress can be made ascribing disagreement to conceptual confusion than wrongthink.

 

[tr]

Appreciate the clarification. This was not obvious from your statement. I think my point about the outcome still being a different sort of entity between the two situations stands, i.e. stroke v. reduction in a depression rating scale. I do not doubt the formal psychometric properties of any of these scales when applied appropriately to the groups they were normed on, but I do get the sense that many clinicians are unpersuaded of the relevance of these scales to the outcomes that they or most of their patients care at all about. This may be a perceptual confusion on their part and if they only thought more carefully about what depression means and had an understanding more in line with the research they would not fall into this trap, but I think it breeds suspicion of claims of efficacy. Why believe this when they have the apparent frequent experience of SSRIs not accomplishing very much in treating ostensibly "depressed" people?

Less careful PCPs handing them out like candy or to anyone who cries obviously does not help the situation.

I mean, as a positive rather than normative observation, this is absolutely true and I think accounts for the attitude I am talking about. Put aside for one moment more principled debates such as whether MDD being treated as a unitary entity obscures important endophenotypical differences. It is certainly the case that the patients identified for trials generating these positive effect sizes have satisfied numerous inclusion and exclusion criteria that make them look entirely different from the general population presenting to a psychiatric clinic. Add to that the fact that it does not seem to be the case that most people in practice are sitting down with careful timelines of illness and checking off criteria one by one before arriving at the billable diagnosis they choose to chart and you have the means by which clinical experience becomes highly divorced from the findings of research. And then the doubt sets in.

But you'll forgive me if I don't find this argument very compelling. You're basically saying that psychiatrists who are skeptical of SSRI efficacy do a bad job of diagnosis and consequently find SSRIs ineffective because, presumably, they are giving them to people who aren't 'really' depressed (whatever that means).

Another reason I'm having trouble following it is that is so intensely divorced from my own clinical experience. I'd say that a good 80-90% of the people I treat with SSRIs for depression or anxiety report positive benefit from the first or second drug they try. A small proportion, maybe 10-20%, have to try a larger number of medications and/or ultimately report no benefit from any of the pharmacological interventions we try. I'd say my clinical experience supports a much greater efficacy than is demonstrated by rigorous clinical trials. (Presumably this is mostly due to placebo/therapeutic milieu effects.) I'm finding it a bit hard to believe that there are large numbers of psychiatrists out there who routinely observe failure of SSRIs to provide benefit in anxiety/depression. I'd guess this is routinely seen only in large tertiary care centers that see a lot of treatment-resistant patients who have already failed community treatment. That's another reason I doubt that skepticism over research findings is fed by clinical observation. If anything, clinical experience typically *overstates* the SSRI benefit.

although I am not convinced that slavishly following the DSM is enormously helpful.

Completely agreed

I'm just trying to point out a more realistic means by which the skepticism you were expressing surprise at comes about. It is also a route to doubt that does not go through "well they must just be laboring under stupid prejudices about mental illness that We Enlightened Ones have transcended."

But it instead goes through "well they are incompetent diagnosticians whose perception of treatment efficacy is altered by their poor diagnostic skills." Is that better?

 

[Trismegistus4]

@destinywon, please loosen your profile security. I'd like to send you a PM.

 

[clausewitz2]

But you'll forgive me if I don't find this argument very compelling. You're basically saying that psychiatrists who are skeptical of SSRI efficacy do a bad job of diagnosis and consequently find SSRIs ineffective because, presumably, they are giving them to people who aren't 'really' depressed (whatever that means).

Another reason I'm having trouble following it is that is so intensely divorced from my own clinical experience. I'd say that a good 80-90% of the people I treat with SSRIs for depression or anxiety report positive benefit from the first or second drug they try. A small proportion, maybe 10-20%, have to try a larger number of medications and/or ultimately report no benefit from any of the pharmacological interventions we try. I'd say my clinical experience supports a much greater efficacy than is demonstrated by rigorous clinical trials. (Presumably this is mostly due to placebo/therapeutic milieu effects.) I'm finding it a bit hard to believe that there are large numbers of psychiatrists out there who routinely observe failure of SSRIs to provide benefit in anxiety/depression. I'd guess this is routinely seen only in large tertiary care centers that see a lot of treatment-resistant patients who have already failed community treatment. That's another reason I doubt that skepticism over research findings is fed by clinical observation. If anything, clinical experience typically *overstates* the SSRI benefit.

I will allow that I do work in one of those tertiary care centers and so I constantly see people who have failed SSRIs. This is of course the major drawback of clinical experience as a guide to practice, it is so heavily influenced by the local and idiosyncratic conditions of wherever the experience was obtained, not to mention the random chance of who happens to walk in through the door while one is working there.



But it instead goes through "well they are incompetent diagnosticians whose perception of treatment efficacy is altered by their poor diagnostic skills." Is that better?[/QUOTE]

It's much better. Ignorance can be corrected. Plain and simple prejudice is much harder to correct. For all that we stress psychoeducation, there is not especially good evidence that any of the metaphors we use for how mental illness should be understood especially reduces stigma.

 

[Liquid8]

Another reason I'm having trouble following it is that is so intensely divorced from my own clinical experience. I'd say that a good 80-90% of the people I treat with SSRIs for depression or anxiety report positive benefit from the first or second drug they try. A small proportion, maybe 10-20%, have to try a larger number of medications and/or ultimately report no benefit from any of the pharmacological interventions we try.

I've also had a similar experience and positive results with treatment, although as all my patients are referred to me by GPs, there is also a large proportion where what has been considered "antidepressant failure" was due to being on an inadequate dose or duration.

I'm finding it a bit hard to believe that there are large numbers of psychiatrists out there who routinely observe failure of SSRIs to provide benefit in anxiety/depression. I'd guess this is routinely seen only in large tertiary care centers that see a lot of treatment-resistant patients who have already failed community treatment.

For the most part, most of the depressed patients who are referred to me are ones that have not responded to initial treatments, both pharmacological and psychological. Due to the referral method I work under (which is also the case for all psychiatrist in Australia), there would also be many depressed patients that GPs do not refer on due to responding well on an initial antidepressant.