I appreciate I might be a lucky exception, or it may be the placebo effect, or just coincidences, but because you're curious I'll tell you my story. Nearly ten years of depression that started when I was in my early 20s, after a very traumatic year during which my father nearly died, received a transplant, nearly died again, and then nearly died again, before he finally got better. Then harsh immigration laws forced me out of the life I had built for myself in the last five years and back into my home country, living with my grandma -- and found out she had alzheimer's and was not capable of handling herself anymore. Took care of her for a couple years while working on a project I truly believed in with a partner whom I trusted but ended up running away with all the credit and the money (I should have signed a contract).
Then I moved to yet another country, life was getting better but by then I was strongly under the grip of depression and it was difficult to find any joy. For years I pretended to smile, I was just barely hanging in there. For years I was lonely despite having many friends. Then came Covid, and I lost my job, and at the same time a child relative of mine who, I deeply care about developed a life-threatening rare disease. A friend of mine flew from across the world to help me through this and saved me. Then I started working on another project, with another partner I trusted, with another partner I did not sign a contract with, and I ended up losing $60k+ to that (all of the money I had saved up). While all of this was going on, I also broke up with a person whom I thought was the woman of my life. (I don't blame her, I was a sad mess).
One close friend who had been through depression told me that what I was experiencing was not normal (I had come to believe it was and in fact was seriously entertaining the delusion that every single person in the world was depressed and everybody was just pretending to be happy while deeply suffering inside), that I go get treated. I'd never wanted to get treated cause I never wanted to consider myself sick.
I was in quite a bad state at the time and I couldn't even get on the phone to call a psychiatrist. I had to have a friend do that for me, and I had to have another friend drive me to the appointment. After the appointment, the psychiatrist initially insisted on giving my prescription to my friend because he was afraid I'd take my own life -- despite not having mentioned any suicidal ideation, even though by that point the only reason I did not let myself die was because of other people in my life whom I could not give up on. I was given Lexapro, diagnosed with severe depressive disorder and general anxiety disorder.
Maybe it's the placebo effect. Maybe it's a complete coincidence. But within a month, I started feeling exponentially better. I still remember the first morning that sung again. I was in the shower and I heard somebody sing something in the street, and I thought - oh! life is sometimes so beautiful and graceful! A few months later, I had the energy and self-esteem and self-respect to tell the man who was exploiting me and my money to fuck off. Unfortunately, I had a close relative die and relapsed for a few months, isolating myself far away from the city where I live in. But even those times I "relapsed" I was still significantly better than I had been a year prior. Unlike before, I knew some measure of happiness was actually possible and I was confident it would come back. It took many months, it took exercise, and beyond that it took great support from my friends - but I am now NO LONGER DEPRESSED. I still have my difficulties and flaws, I still have a hard time waking up in the morning, but once I wake up, I go and get shit done, and at the end of the day, I go exercise, and after that I'm pretty happy with myself. There are many more things in my life I need to take care of, but they're getting taken care of, little by little. I have built a much more resilient life. I continue to meet difficulties and challenges but I confront them head on rather than run away from them or duck my head in the sand.
Lexapro and exercise were my only lifestyle changes in that period. Consequently, I credit them with getting better. And I started getting much, much better within a few months of taking them, with noticeable improvements from week 3 onward. I was actually surprised because I didn't think it was gonna work and I had previously been hostile to taking antidepressants. And as an avid reader of Scott Alexander's blog I know that despite his advocacy the data isn't strong.
Maybe all of that is a big coincidence, but my personal opinion is that it is not. I seriously went into this treatment believing it was not going to work. I am an intellectual person, I follow psychiatry, and I was not at all a proponent or follower of the serotonin theory of depression. I tried this because I felt I was out of options and today I'm still not a proponent/follower of the serotonin theory of depression, but I do believe in my particular case Lexapro had a decisive and very significant effect. I feel it got me my life back.
SSRIs did the heavy lifting (no pun intended), but lifting weights has definitely helped also. Now I'm at a point where I believe I'm ready to go off-meds; I won't do so brutally and without adequate supervision, but I think I have a strong enough life now that I can do without them and be fine -- knowing I can always go back to them if needed.
This is so perfectly expressed: "But within a month, I started feeling exponentially better. I still remember the first morning that sung again. I was in the shower and I heard somebody sing something in the street, and I thought - oh! life is sometimes so beautiful and graceful!"
If you've never known depression, and the anhedonia that comes with it, you don't get this. It's like that first day turning the corner from an awful flu; or when you wake up 3 weeks after a terrible back injury and realize that the searing pain down your leg has lightened up; but it's really better, and more important, because it's possible to feel physically terrible and appreciate being alive, but it's not possible when you're mired in depression.
In your particular case, after 10 years of depression, I can believe it was the lexapro (and probably a little bit of other things, too). Yours is that rare story where someone goes from depressed to fine. I wish lexapro had ever worked this well for any of my patients. But I'm glad you got to live a positive outlier experience!
A local clinician prescribed these to my wife after misdiagnosing her gluten intolerance as being all in her head.
She only took them a year (before they finally had her scoped and discovered she has celiac) and she had to be checked into a clinic to detox off of them for two weeks.
I have always believed that the sitcom Frasier was the most accurate representation of modern psychiatrists to date, and, that the whole industry took off when Ritalin became the 'wonder drug' to control unruly kids. Those kids are still taking meds.
I've learned the hard way to never even insinuate that a patient's suffering is "all in their head." It's usually not; but more importantly, if that's how I feel, they need another doctor.
Well, for what it's worth it was a military contracted doctor at a military clinic. Not to besmirch your profession, but I've always been well aware that docs are like mechanics - some are better than others.
Brilliant article. Good luck getting our corporate drug pushers (no better than the cartels) reined in, but at least you're providing evidence of their, and their congressional prostitutes, have done to this country.
I have one particular nightmare story in which a patient could never come off his Effexor. No taper was small enough, slow enough, to stop the awful electrical feeling. That's one of the best reasons to not jump into S/NRIs. Usually, patients do fine stopping, whether tapered or not. I do think that sort of story is quite rare, though; but I warn my patients of it every time I start an SSRI or SNRI prescription!
This sounds like a pt who needs to see a psychiatrist, for a different approach to discontinue med, or perhaps a different diagnosis. I think a better question is are we lumping people with difficulties in life which many Americans are not tolerating well, vs depression in it's truest sense.
With all due respect. Mr Cruise should stick to his all-american-man-of-action-scientology-witchcraft skit. Having had a number of family members that suffered from thiss affliction, I can reassure you that it's real and that the medication does work.
With all due respect. Mr Cruise should stick to his all-american-man-of-action-scientology-witchcraft skit. Having had a number of family members that suffered from thiss affliction, I can reassure you that it's real and that the medication does work.
Most comments seem very knowledgeable. Mine is speculation.
There seems to be some correlation between mood and metabolism. Over-eating and weight gain may be self medication against borderline depression since eating temporarily raises metabolism. Dieting makes any depression worse. I found that mega B vitamins improved my mood and diet results. If that is a placebo effect, I'll take it.
I am convinced that SSRI's are a factor in school shootings. Young men should not be artificially detached from their emotions during the very time they are meant to learn to deal with them. It's just another puberty blocker.
Again, in free range 60's and 70's we carried our own weapons to Junior High rifle clubs .. (and in 7th grade I shared a switchblade obtained in a family trip to Mexico at the back-to-school show and tell) .. The 70's often had high crime but it was actual purposeful crime .. not the inexplicable mass events that have occurred since schools replaced corporal punishment with a daily cattle call of pill dispension.
Does this controversy about SSRIs have any implication on tricyclics, MAOIs, Wellbutrin, Effexor, or other psychotropic treatments for depression that are not SSRIs? The FDA approves of using SSRIs for depression. Should the FDA rescind the approval of SSRI treatment for depression? I wonder if the next target of psychotropic treatment for mental illness will be antipsychotics? If not SSRI for treating depression then what? ECT? Pills that are not covered by FDA such as B6?
I steered clear of the medication alternatives to SSRIs for the sake of avoiding a 20 pg article. Irving Kirsch would say that they all lean heavily on placebo. I think most psychiatrists would say that the deeper/more atypical the depression, the more likely SSRIs won't suffice and the newer antipsychotics (and antiepileptics) might be needed. Then the "hard-resets" like ECT and ketamine for treatment-resistant cases. My daily practice is filled with algorithms like this (for all sorts of diseases) which are loosely "evidence-based"," though, and I've come to realize they are probably better at making doctors feel smart and well-prepared than actually optimizing medical care.
I think the FDA has a low bar and SSRIs pass. I just think they are overprescribed.
"Siskind’s second point is also fair, namely that any SSRI trial will have responders and non-responders, including some whose depression scores might worsen during treatment". In any study using placebo, or just plain water as a treatement with an overall null effect you will find, if you look, a subgroup who imporoved, a and subgroup who deteriorated. This is just statistical noise and will be evident in any sample followed over time even without any pretence at treatment. Searching for and finding such subgroups is common in failed studies, and enhances the likelihood the studies will be accepted for publication. It would only mean something if the "improvers" can be somehow indentified and the effect validated in a new study.
Thank you very much for your commentaries. It's so good , and useful, to read appraisals on important medical issues that are clearly well informed, thoughtful, openminded and unbiasised, at a time when this seems to have become rather uncomoon. I think there are many who would be interested in your evaluations on Covid related topics where it is particularly difficut to get disinterested medical opinons, such as of the kind of early treatment protocols advocated by various independent medical groups, and the efficacy and safety of the Covid vaccines and new antivarial treatments.
Thank you; and I got into writing about medicine because of Covid, and because I found it so frustrating that the dialogue mostly consisted of Conventional Wisdom boosterism pitted vs overly cynical dismissal of anything supported by the former.
I agree that we are supposed to let statistical noise be noise. It's just that sometimes you see compelling examples of ppl getting better, genuinely better, with a treatment that did not quite reach statistical (or, in the case of SSRIs, clinical) significance. It's certainly possible that point of view leads to a great deal of sloppy medical practice and does more harm than good. But... it's also possible a smallish fraction of people can have a certain phenotype that makes them a legit candidate for a treatment approach that will fail the population at large. Medicine is hard.
Both publications post-date my involvement with psychiatry, which got me one year into a residency in Germany following med school, which I also did in Germany. Medicine is not a lucrative occupation in Germany, so I left the field altogether rather than take a year to learn English vocabulary and take the Boards, then compete in my late forties with 25 year olds for a slot in a residency.
I appreciate I might be a lucky exception, or it may be the placebo effect, or just coincidences, but because you're curious I'll tell you my story. Nearly ten years of depression that started when I was in my early 20s, after a very traumatic year during which my father nearly died, received a transplant, nearly died again, and then nearly died again, before he finally got better. Then harsh immigration laws forced me out of the life I had built for myself in the last five years and back into my home country, living with my grandma -- and found out she had alzheimer's and was not capable of handling herself anymore. Took care of her for a couple years while working on a project I truly believed in with a partner whom I trusted but ended up running away with all the credit and the money (I should have signed a contract).
Then I moved to yet another country, life was getting better but by then I was strongly under the grip of depression and it was difficult to find any joy. For years I pretended to smile, I was just barely hanging in there. For years I was lonely despite having many friends. Then came Covid, and I lost my job, and at the same time a child relative of mine who, I deeply care about developed a life-threatening rare disease. A friend of mine flew from across the world to help me through this and saved me. Then I started working on another project, with another partner I trusted, with another partner I did not sign a contract with, and I ended up losing $60k+ to that (all of the money I had saved up). While all of this was going on, I also broke up with a person whom I thought was the woman of my life. (I don't blame her, I was a sad mess).
One close friend who had been through depression told me that what I was experiencing was not normal (I had come to believe it was and in fact was seriously entertaining the delusion that every single person in the world was depressed and everybody was just pretending to be happy while deeply suffering inside), that I go get treated. I'd never wanted to get treated cause I never wanted to consider myself sick.
I was in quite a bad state at the time and I couldn't even get on the phone to call a psychiatrist. I had to have a friend do that for me, and I had to have another friend drive me to the appointment. After the appointment, the psychiatrist initially insisted on giving my prescription to my friend because he was afraid I'd take my own life -- despite not having mentioned any suicidal ideation, even though by that point the only reason I did not let myself die was because of other people in my life whom I could not give up on. I was given Lexapro, diagnosed with severe depressive disorder and general anxiety disorder.
Maybe it's the placebo effect. Maybe it's a complete coincidence. But within a month, I started feeling exponentially better. I still remember the first morning that sung again. I was in the shower and I heard somebody sing something in the street, and I thought - oh! life is sometimes so beautiful and graceful! A few months later, I had the energy and self-esteem and self-respect to tell the man who was exploiting me and my money to fuck off. Unfortunately, I had a close relative die and relapsed for a few months, isolating myself far away from the city where I live in. But even those times I "relapsed" I was still significantly better than I had been a year prior. Unlike before, I knew some measure of happiness was actually possible and I was confident it would come back. It took many months, it took exercise, and beyond that it took great support from my friends - but I am now NO LONGER DEPRESSED. I still have my difficulties and flaws, I still have a hard time waking up in the morning, but once I wake up, I go and get shit done, and at the end of the day, I go exercise, and after that I'm pretty happy with myself. There are many more things in my life I need to take care of, but they're getting taken care of, little by little. I have built a much more resilient life. I continue to meet difficulties and challenges but I confront them head on rather than run away from them or duck my head in the sand.
Lexapro and exercise were my only lifestyle changes in that period. Consequently, I credit them with getting better. And I started getting much, much better within a few months of taking them, with noticeable improvements from week 3 onward. I was actually surprised because I didn't think it was gonna work and I had previously been hostile to taking antidepressants. And as an avid reader of Scott Alexander's blog I know that despite his advocacy the data isn't strong.
Maybe all of that is a big coincidence, but my personal opinion is that it is not. I seriously went into this treatment believing it was not going to work. I am an intellectual person, I follow psychiatry, and I was not at all a proponent or follower of the serotonin theory of depression. I tried this because I felt I was out of options and today I'm still not a proponent/follower of the serotonin theory of depression, but I do believe in my particular case Lexapro had a decisive and very significant effect. I feel it got me my life back.
SSRIs did the heavy lifting (no pun intended), but lifting weights has definitely helped also. Now I'm at a point where I believe I'm ready to go off-meds; I won't do so brutally and without adequate supervision, but I think I have a strong enough life now that I can do without them and be fine -- knowing I can always go back to them if needed.
This is so perfectly expressed: "But within a month, I started feeling exponentially better. I still remember the first morning that sung again. I was in the shower and I heard somebody sing something in the street, and I thought - oh! life is sometimes so beautiful and graceful!"
If you've never known depression, and the anhedonia that comes with it, you don't get this. It's like that first day turning the corner from an awful flu; or when you wake up 3 weeks after a terrible back injury and realize that the searing pain down your leg has lightened up; but it's really better, and more important, because it's possible to feel physically terrible and appreciate being alive, but it's not possible when you're mired in depression.
In your particular case, after 10 years of depression, I can believe it was the lexapro (and probably a little bit of other things, too). Yours is that rare story where someone goes from depressed to fine. I wish lexapro had ever worked this well for any of my patients. But I'm glad you got to live a positive outlier experience!
A local clinician prescribed these to my wife after misdiagnosing her gluten intolerance as being all in her head.
She only took them a year (before they finally had her scoped and discovered she has celiac) and she had to be checked into a clinic to detox off of them for two weeks.
I have always believed that the sitcom Frasier was the most accurate representation of modern psychiatrists to date, and, that the whole industry took off when Ritalin became the 'wonder drug' to control unruly kids. Those kids are still taking meds.
That... is a terrible story.
I've learned the hard way to never even insinuate that a patient's suffering is "all in their head." It's usually not; but more importantly, if that's how I feel, they need another doctor.
Well, for what it's worth it was a military contracted doctor at a military clinic. Not to besmirch your profession, but I've always been well aware that docs are like mechanics - some are better than others.
Brilliant article. Good luck getting our corporate drug pushers (no better than the cartels) reined in, but at least you're providing evidence of their, and their congressional prostitutes, have done to this country.
Getting people off these meds is no joke. One patient recently told me: "whoever made these things should be lined up and shot"
I have one particular nightmare story in which a patient could never come off his Effexor. No taper was small enough, slow enough, to stop the awful electrical feeling. That's one of the best reasons to not jump into S/NRIs. Usually, patients do fine stopping, whether tapered or not. I do think that sort of story is quite rare, though; but I warn my patients of it every time I start an SSRI or SNRI prescription!
This sounds like a pt who needs to see a psychiatrist, for a different approach to discontinue med, or perhaps a different diagnosis. I think a better question is are we lumping people with difficulties in life which many Americans are not tolerating well, vs depression in it's truest sense.
With all due respect. Mr Cruise should stick to his all-american-man-of-action-scientology-witchcraft skit. Having had a number of family members that suffered from thiss affliction, I can reassure you that it's real and that the medication does work.
With all due respect. Mr Cruise should stick to his all-american-man-of-action-scientology-witchcraft skit. Having had a number of family members that suffered from thiss affliction, I can reassure you that it's real and that the medication does work.
Most comments seem very knowledgeable. Mine is speculation.
There seems to be some correlation between mood and metabolism. Over-eating and weight gain may be self medication against borderline depression since eating temporarily raises metabolism. Dieting makes any depression worse. I found that mega B vitamins improved my mood and diet results. If that is a placebo effect, I'll take it.
I am convinced that SSRI's are a factor in school shootings. Young men should not be artificially detached from their emotions during the very time they are meant to learn to deal with them. It's just another puberty blocker.
Again, in free range 60's and 70's we carried our own weapons to Junior High rifle clubs .. (and in 7th grade I shared a switchblade obtained in a family trip to Mexico at the back-to-school show and tell) .. The 70's often had high crime but it was actual purposeful crime .. not the inexplicable mass events that have occurred since schools replaced corporal punishment with a daily cattle call of pill dispension.
Does this controversy about SSRIs have any implication on tricyclics, MAOIs, Wellbutrin, Effexor, or other psychotropic treatments for depression that are not SSRIs? The FDA approves of using SSRIs for depression. Should the FDA rescind the approval of SSRI treatment for depression? I wonder if the next target of psychotropic treatment for mental illness will be antipsychotics? If not SSRI for treating depression then what? ECT? Pills that are not covered by FDA such as B6?
I steered clear of the medication alternatives to SSRIs for the sake of avoiding a 20 pg article. Irving Kirsch would say that they all lean heavily on placebo. I think most psychiatrists would say that the deeper/more atypical the depression, the more likely SSRIs won't suffice and the newer antipsychotics (and antiepileptics) might be needed. Then the "hard-resets" like ECT and ketamine for treatment-resistant cases. My daily practice is filled with algorithms like this (for all sorts of diseases) which are loosely "evidence-based"," though, and I've come to realize they are probably better at making doctors feel smart and well-prepared than actually optimizing medical care.
I think the FDA has a low bar and SSRIs pass. I just think they are overprescribed.
"Siskind’s second point is also fair, namely that any SSRI trial will have responders and non-responders, including some whose depression scores might worsen during treatment". In any study using placebo, or just plain water as a treatement with an overall null effect you will find, if you look, a subgroup who imporoved, a and subgroup who deteriorated. This is just statistical noise and will be evident in any sample followed over time even without any pretence at treatment. Searching for and finding such subgroups is common in failed studies, and enhances the likelihood the studies will be accepted for publication. It would only mean something if the "improvers" can be somehow indentified and the effect validated in a new study.
Thank you very much for your commentaries. It's so good , and useful, to read appraisals on important medical issues that are clearly well informed, thoughtful, openminded and unbiasised, at a time when this seems to have become rather uncomoon. I think there are many who would be interested in your evaluations on Covid related topics where it is particularly difficut to get disinterested medical opinons, such as of the kind of early treatment protocols advocated by various independent medical groups, and the efficacy and safety of the Covid vaccines and new antivarial treatments.
Thank you; and I got into writing about medicine because of Covid, and because I found it so frustrating that the dialogue mostly consisted of Conventional Wisdom boosterism pitted vs overly cynical dismissal of anything supported by the former.
I agree that we are supposed to let statistical noise be noise. It's just that sometimes you see compelling examples of ppl getting better, genuinely better, with a treatment that did not quite reach statistical (or, in the case of SSRIs, clinical) significance. It's certainly possible that point of view leads to a great deal of sloppy medical practice and does more harm than good. But... it's also possible a smallish fraction of people can have a certain phenotype that makes them a legit candidate for a treatment approach that will fail the population at large. Medicine is hard.
There are other issues as well. One is with SNRIs, which act on norepinepherine as well as serotonin. See
https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20044.
The other is with an unexplained delay in effect of all antidepressants. See
https://pubmed.ncbi.nlm.nih.gov/11229783/
Both publications post-date my involvement with psychiatry, which got me one year into a residency in Germany following med school, which I also did in Germany. Medicine is not a lucrative occupation in Germany, so I left the field altogether rather than take a year to learn English vocabulary and take the Boards, then compete in my late forties with 25 year olds for a slot in a residency.