Furious Seasons

January 10, 2008

The Politics Of Depression

There was a fascinating exchange of letters in this month's American Journal of Psychiatry concerning just how much depression doctors should accept in their patients and the implications of such decisions. What prompted the initial letter was the federally-funded STAR-D trial, which showed that current depression treatments--including some psychotherapies--are no where near as robust as doctors (and presumably patients) would like. What the trial showed, in short, was that various anti-depressants had anywhere from an 8 percent to 30 percent chance of success in remitting symptoms of depression.

That leaves a large subset of people who do not get relief using current therapies and that raises a host of practical issues for the mental health field. This situation affects millions of Americans.

Two other practical issue before I get to those: Both letter writers accept that STAR-D trialed drugs and therapies produced remission in 67 percent of people in the trial. That is wrong for two reasons: one, each arm of the trial was a discrete experiment, having no impact statistically on subsequent arms of STAR-D and to engage in additive probabilities the way these academics are is embarrassing. Two, the STAR-D trial, though the first long-term, real-world, independent study of depression treatment in this country, was still only a measure of how well people did in a snapshot in time. For instance, of the approximately 30 percent of people who took Celexa in the trial's first step and achieved remission of symptoms we have no idea how they are doing now, well after their comparatively short trial. Remission is hardly a static state because depression is simply too episodic a disorder. You can have no depressive symptoms for two years, say, on or off-meds and then suddenly have symptoms reappear later.

Those caveats aside, several psych researchers at Brown University wrote the AJP to offer commentary on an editorial by John Rush of the University of Texas. Rush's editorial on the STAR-D results appeared in the AJP last February. You can read it here.

What the researchers at Brown had issues with was the insistence of Rush and others that complete symptom remission is the appropriate goal of treatment. "It is not clear, however, that this recommendation is in the best interest of our patients," they write in their letter.

I've noted previously how obsessed the psych world is with complete symptom remission in all forms of mental illness and how useless such a goal is for patients. Yes, it's a laudable public health goal, but within the limits of current technologies and practices does not seem to be achievable for many patients. If complete symptom remission is your polestar, then that could spell all sorts of practical problems for patients, as I noted two years ago:

"I think there's a certain power to be gained from the admission that complete symptom remission is a false god and that what we really ought to be doing is getting symptom remission where we can and letting people live where we cannot instead of pounding them to death with meds and wasting billions in the process."

The trouble is that many psych docs have gotten in the habit of reasoning that if Prozac doesn't work, for example, and a patient doesn't have symptom remission on Celexa, then they need to put the patient on multiple anti-depressants (the argument goes that if you bomb the brain's serotonin receptors from slightly different "angles" then you'll cover the problem) or perhaps an anti-psychotic plus an anti-depressant (ick).

That's part of what the Brown researchers pick up on in their letter:

"Advocating for 'more complex regimens' even earlier in the treatment algorithm may cause more harm than good. Very few studies have assessed either the safety or the effectiveness of complex polypharmacy trials. Polypharmacy increases the likelihood of side effects, drug interactions, cost increases, and noncompliance. Polypharmacy, nonetheless, is becoming more commonly used in routine clinical practice, presumably in part because of the setting of remission as the goal of treatment. Focusing too much on symptom remission in treatment-resistant patients may aggravate an already difficult-to-manage illness. Patients may feel even more discouraged if they do not respond to complex treatment trials. Such discouragement may lead to noncompliance with treatment. The STAR*D trials reported substantial rates of attrition despite the extra staffing, attention, patient education, and free care usually associated with clinical trials."

Not only is the practice of polypharmacy a concern for the researchers, so is the idea that all symptoms must be remitted:

"There is ample evidence to show that patients who continue to experience residual symptoms of depression are at higher risk for multiple adverse outcomes. Such findings are used to justify the push for remission. The correlation of adverse outcomes with residual symptoms, however, does not prove causation. Persistence of depressive symptoms in spite of optimal treatment may be an indicator rather than a cause of a form of depression that is not likely to respond to treatments currently available. The idea that there are some patients with a form of depression that is not responsive to available treatments is consistent with our current nosology, which groups together many different types of depression."

I think it's safe to conclude that there are forms of bipolar disorder and schizophrenia, for example, that are unremittable and where doctors have got to start asking themselves why pound the patient to death with meds when we ought to be asking how they can live decent lives with what they've got. Those are perhaps trickier questions with those two disorders, but I'm sure most of you know what I am getting at.

What's deeply ironic about this challenge coming from researchers at Brown University is that the school is also home to Peter Kramer, the bestselling author of Listening to Prozac and Against Depression who is very much of the full symptom remission crowd. As the Brown researchers note, eschewing polypharmacy and complete symptom remission creates an obvious question:

"What should be the goals of antidepressant treatment? One goal should be to achieve the greatest symptomatic relief possible, with the recognition and acknowledgment that this may not mean remission for a significant minority of depressed patients. For these patients, in particular, more attainable goals may be to improve their quality of life and psychosocial functioning in spite of persisting depressive symptoms.
"There are ways to help patients manage their persistent illness more effectively. Disease-management programs for chronic and remitting/relapsing illnesses are available that help patients focus on improving their psychosocial functioning and quality of life in the face of persisting symptoms. Pharmacologic treatment and disease management are not mutually exclusive. Ongoing medication and psychosocial treatment trials should be pursued concurrently in order to engender hope, since some patients may benefit over time or take longer to achieve remission. Clinicians should also feel comfortable, however, to address with patients the reality that they are suffering from a chronic illness. We can do a great deal of good by facilitating more effective coping strategies rather than promising something that we cannot deliver."

While I'm not sure what role meds should have in what I'll call unremittable depression (I think that choice best rests with the patient), I admire the honesty of the researchers and their practicality. I'm not so sure I buy their argument that doctors have a huge role to play in helping patients achieve a reasonable level of psychosocial functioning. Isn't that what social workers and counselors are for? Isn't it something for the individual to work out on their own?

Quibbles aside, I think the initial letter opens up a huge can of worms for doctors who treat depression. Into the breach steps John Rush with his reply.

"Since STAR*D did not evaluate all available treatments for depression, we cannot conclude that the 33% who did not reach remission after four treatment steps would not have benefited from other medications, psychotherapies, or somatic treatments."

Oh, really? The differences between Celexa and Lexapro, for example, are so slim as to be almost meaningless, as they are between many SSRIs. Rush's bit of posturing is scientifically correct but in the real world is nonsense. So is another assertion of his.

"[T]he decision to scale back the goals of treatment to less than remission seems unwise until at least four treatment attempts. On the other hand, some patients may well be unable to reach and sustain remission. Clinicians must decide when to no longer pursue remission as the goal of treatment by making further treatment changes. However, patients who partially benefit from medication may further improve their well-being and quality of life when psychosocial interventions or other rehabilitative efforts are put in place. On the other hand, given the undisputed advantage of remission, both functionally and prognostically continued efforts may well be worthwhile in selected patients. The decision to switch from remission to improved quality of life should be a collaborative one between patient and doctor."

It's nice of Rush to admit that there are people who may have unremittable depression and that alternative strategies may be required. But why the emphasis on doctors--and by doctors Rush means psychiatrists--deciding when treatment has failed? Whose bodies and lives are we talking about here anyway? Who appointed doctors emperors of our lives and souls and depressions? No one. Would you trust someone to tell you how to live your life psychosocially whose offers of treatment have already proven to miserable failures? Not if you are smart.

Rush concludes his reply thus:

"Whether "more complex regimens" (i.e., medication combinations) are more burdensome, risky, or effective is an empirical question that deserves study. Many psychiatrists now use combination medications, but few controlled trials have actually evaluated this practice. Some studies do suggest better efficacy and little additional side-effect burden for selected combinations. Whole sale polypharmacy is not to be recommended. Carefully conducted randomized trials pitting monotherapy against drug combinations are needed to directly assess whether both acute and longer-term outcomes can be enhanced without undue patient burden."

Nice that he doesn't support wholesale polypharmacy, but his insistence upon further empirical trials to investigate medication combinations is a bit silly. We already have plenty of real world evidence that such polypharmacy is fraught with risk and offers few results.

I'm glad to see that some researchers are willing to be honest about the practical problems faced by a significant group of patients with depression. However, that does leave a big question on the table: how much depression is acceptable for a patient? Is there a scale that can properly measure this? Does one simply not shoot for as low a result on the Ham-D scale, for example?

I can't speak to how you'd measure such a thing scientifically, but then I find most of the depression rating scales unreliable to begin with. What I do know is that this is another instance where doctors ought to begin listening very closely to their patients instead of arrogantly assuming that all symptoms must be destroyed. I don't think the latter approach is healthy for real people who are the ones who should be making these real decisions.

The trouble is that I fear whatever answers might be hammered out to this question will be driven not by science or patient input, but by the same politics and power dynamics that have always won arguments about mental health treatment in the past. And that means the pharma companies and doctors will be in charge and patting one another on the back at the end of the day because, at bottom, they know they don't have to listen to patients and consumers because we have so little power. They'll find a way to tip their hats to the notion that we should have some input and then find a way to undercut our interests because doctors are simply so much smarter and more well-intentioned than the rest of mankind. So are drug companies.

Can't you tell? That's why current depression treatments are working so well already.

Posted by Philip Dawdy at January 10, 2008 02:50 AM

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Comments

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Posted by: pd at January 7, 2008 11:48 PM

OK, here's a "what if," for you: what if people who have been denounced as mentally ill were actually some of the most excellent people on the planet, and those who would pen them in a box, whereby everything that they do is weird, or indicative of mental illness, abherrant behaviour, or something, were actually some of the most fucked up, damaged people in the world?

I can't help it! That's just the way I look at the world!

Matt

Posted by: Matthew Holford at January 10, 2008 04:21 AM

It seems to me that one significant problem here is the notion that meds are the solution and by implication, that depression is pretty much purely a medical disease. The whole disease model disposes toward this view.

What would "complete remission" look like? Would that be a state of steady happiness? Would there be normal ups and downs? How would anyone know what complete remission is as there is nothing to measure except via symptom checklist and surely these are greatly influenced by individual perception. Is my "off day" someone else's mild depression? We have no way to know. There is nothing to measure, no tests or indices to measure against so there is just theory.

And what about those people who are Eeyores -- gloomy, kind of depressed looking by virtue of their personality? Should they be medicated into happiness? How? To what end?

And what of the people who move out of depression by working in therapy? Oh right, we don't know about them because we don't study them.

Posted by: Cheryl Fuller at January 10, 2008 07:26 AM

What a thought provoking piece. I think one reason for the low rate of complete remission of all symtpoms of depression is that once you are diganosed as completely in remission of depressive symptoms, you meet another diagnostic criteria, hypomania...you don't have to look very far to see the tons of nonsensical writings on the idea that people who recover from depression, are really just getting sick in the other direction, i.e. hypomania, and thus have only begun to take pills.

Once you get a psych label, there is literally no such thing as returning to normal, there is no diagnostic criteria for normal. All states of emotion and consciousness are symptoms of mental illness.

Posted by: Sally at January 10, 2008 09:43 AM

Dear Philip,

In response to your posting I’ll address one of your last statements first:

“The trouble is that I fear whatever answers might be hammered out to this question will be driven not by science or patient input, but by the same politics and power dynamics that have always won arguments about mental health treatment in the past. And that means the pharma companies and doctors will be in charge and patting one another on the back at the end of the day because, at bottom, they know they don't have to listen to patients and consumers because we have so little power.” --- Philip Dawdy

As a long time support person and caregiver I am very well familiar with my spouse’s depressive illness or what I refer to as her MDD (Major Depressive Disorder) or TRD (Treatment Resistant Depression). Apparently you are either mislead or lacking in your knowledge or thinking that our current health care (mental health) “means the pharma companies and doctors will be in charge”. There are two entities in charge. One is government, CMS (Centers for Medicare & Medicaid Services) and the other is the health insurance industry. That is also not to say that I am naïve not to think that the pharmaceutical industry may attempt to influence government.

Apparently you are not aware that despite physician recommendation(s) and informed patient choice(s) treatment options are denied a very large percentage of depression patients simply by the fact that CMS or a health insurance carrier will and can refuse to pay for drug(s) and/or treatment(s). So while you’re advocating patient choice and decision making government in actuality is not only abrogating the patient’s right to choose but also denying the physician recommendations as well. In one of the largest write-ins to CMS regarding the VNS Therapy option numerous patients and over 200 of the leading researchers and psychiatric thought leaders as well as the approximately 36,000 membership of the APA and their recommendations for coverage of this therapy option were denied coverage by CMS and in turn the same decision by the health insurance industry. So regardless of your thinking “pharma companies and doctors will be in charge” in actually neither are. What you also seem to be missing or not addressing is the fact that the health insurance industry is practicing medicine.

In your constant dialog relating to the evils of drugs and the pharmaceutical industry and your thoughts of patient choice and other approaches toward achieving wellness I wrote to you a while ago about a different avenue that my spouse took and at the time you indicated you knew nothing about VNS Therapy. It is a non-drug approach. It was approved by the FDA. Payment has been denied by CMS and the health insurance industry despite the fact that some 17,000 relatively informed patients in conjunction with their attending physicians have made a decision to try this alternative and/or adjunctive therapy but are unable to obtain the therapy for lack of reimburse or inability to pay out of pocket. My spouse has been almost continuously depression free and in remission for approximately 8 years, three of which were without the use of any psychotropic medications, after some 36 years of pain, suffering and anguish from severe depression has nothing to do with drugs but all to do with the aid of her physicians, a new and unique therapy option and her own uniqueness and internal dynamics. Now this therapy option has nothing to do with drugs and all to do with government and the health insurance industry and the inability of patients to make informed choices toward their wellness.

Someone in a previous posting I recall referred to you an “ideologue.” So why is it now wrong in your opinion to have an ideal of “complete symptom remission”? In my opinion there is nothing wrong to establish an ideal in mind as a potential goal. In the real world I believe we both can agree as to the difficulty and/or impossibility of achieving such lofty ideals as it relates to depression but then again, I also know of individuals with whom I collaborate and have also utilized this therapy that have also obtained long periods of remission and most importantly reasonably improved the quality of their lives. What is unique about the VNS Therapy is that you have discussed in your dialog that while a drug(s) may exhibit response in the short run and peter out this particular therapy has tended to illustrate increasing responses over time and increasing longer-term remissions.

My purpose of citing my spouse’s case history and the VNS Therapy is not to promote and/or suggest any therapy or one therapy over another but to advocate for patient education and awareness that there are alternative treatment options to be investigated and pursued in collaboration with one’s trusted, compassionate, knowledgeable and licensed health care physician and to encourage hope and persistence. I’ve come to learn that each individual is truly unique and so too their response to treatments. With this in mind while you rail against drugs I am also aware of informed individuals that benefit and despite your belittling this therapy approach and because of the uniqueness of these individuals and their individual unique response(s) I personally object to your generalizing.

"I think there's a certain power to be gained from the admission that complete symptom remission is a false god and that what we really ought to be doing is getting symptom remission where we can and letting people live where we cannot instead of pounding them to death with meds and wasting billions in the process." --- Philip Dawdy

Do you know for certain there is a god? Is your statement to mean that one’s symptom of anxiety may be overcome and that there should be no need to also overcome the accompanying depressive symptoms or vice-versa? I personally think it is incumbent upon the individual patient to determine what it is best for the individual and what one is comfortable and able to live with and if that entails “complete symptom remission” so be it. I know from our experiences that most all of my spouse’s attending physicians were compassionately interested in her wellbeing by offering and educating us to those treatment options and alternatives that they believed would help control, stabilize and obtain long-term remissions. Your writing seems to me to indicate that the patients are powerless, lacking choices and decision making abilities. I cannot speak for others but I can tell you we listened, became informed and made our own decisions and treatment choices although in my opinion the choices are limited for those who suffer MDD/TRD. My spouse having had refractory experiences to many treatment options over a period of some 36 years opted to enter a unique neuromodulation study (VNS Therapy) simply because she was still tormented and experiencing suicidal ideations and we felt anything was worth a try. In her case the results have been nothing short of remarkable and we owe much to her then attending physician who agreed it too was worth a try and assisted my spouse in becoming a study subject.

Unlike your inclination based upon your writings and my experiences I do not see a number of physicians who caringly do the best they can with what they have available as evil but truly caring health care practitioners challenged by another of a number of neurological disorders without definitive and quantitative diagnostic means dealing with disorders diagnosable only through symptomology. I strongly believe Dr. Rush and many of his colleagues in the best interests of their patients are doing the best they can even when CMS and the health insurance industry go against their educated recommendations and your general bias against drugs.

Warmly,
Herb
VNSdepression.com

Posted by: herb at January 10, 2008 09:50 AM

What Herb? Cybertronics can't get the VNS device approved for children?

Posted by: Jane at January 10, 2008 10:23 AM

I really appreciate the thoughtfullness of this post---Thanks, PD!

Posted by: lizzie simon at January 10, 2008 12:38 PM

I just have a lot of problems with what criteria we are really using to define "depression" and "symptom remission". They are highly subjective and therefore throw all this "research" into question in my view. As Cheryl Fuller says one person's "off day" might be another's "depression". I guess the DSM tries to define it as whether someone's functioning is impaired or not and maybe that has some more objective ways of being measured than unhappiness itself does, but even then if someone can't sleep, can't get a job, can't eat -- aren't these the things that should be specifically addressed rather than the person's "chemical imbalance"? "Full remission" sounds like some really weird state that just isn't consistent with living a full feeling life. Full remission from all of life's ups and downs? Why would that even be a goal worth attaining? How do you measure that over any significant period of time?

Posted by: Sara at January 10, 2008 04:20 PM

i bet you ask ten people what the term depression means you get ten different answers. the term is so general it is meaningless, and assuming two people talking about depression are actually talking about the same phenomena (feeling, symptoms, disease, mood)is risky.

also periodic malaise is a human condition.

also complete remission is impossible because nothing is static. cycles, ups and downs, bad days good days, interpersonal relationships, politics, ad nauseum. understand my point. nothing is forever, this too will pass.

Posted by: jenna at January 10, 2008 06:19 PM

I understand what you are saying and to some extent why, but I think you are oversimplifying the situation and putting too negative a spin on doctors and drugs. I have MDD with psychotic features and have been somewhat treatment-resistant. Polypharmacy has helped me because to get to the point on one medication that I can consistently make it to work and act like a "normal" person I find the side effects terrible. By reducing the dosage of one drug and adding one with a different delivery method, also at a lower dose than would be required alone, I am able to work without unceasing tics/really noticeable tremors.

Drugs are not a panacea. Doctors - like my current ones, to be honest - who want people with MDD to be a 10 on a 1-10 scale of mood (however that is supposed to be calculated) need to chill out. I don't know that I have ever met a person with responsibilities over the age of about 17 who could qualify as a 10. Life is just not that easy, even without a chronic MI. That said, drugs and doctors can help, and patients who have been through the process can find themselves listened to, particularly with PCPs. I have been forceful, when needed, about what I am and what I am not willing to take, and it has worked. I just reduced - on my own - my dosage of Wellbutrin because the side effects were just too bad. I told the doctor I'd done it, and he had no choice but to accept it. That kind of collaboration, for lack of a better term, can be done and can work.

Also, the difference between Celexa and Lexapro on paper might not be that different, but I'm allergic to Celexa and not to Lexapro so for some of us the little differences are important.

Posted by: anne at January 11, 2008 10:31 AM

anne, your point about celexa vs. lexapro is well taken. i've experienced vastly different side effects on chemically very similar drugs.

Posted by: jenna at January 11, 2008 03:07 PM

From a European standpoint treatment in the US for depression is characterized by new is always better than old and more is better than less. By this I mean that very good antidepressants are considered obsolete in the US. I am referring to tricyclic antidepressants (TCAs). In a review by Anderson as well as in studies conducted by the DUAG group TCAs are more efficacious with severe depressed inpatients. Another advantage is plasma controlled dosing of TCAs. Recently it is modern to use different antidepressants together. It is a sort of alchemy. Psychiatrists combine different antidepressants without scientific evidence.
Nevertheless I agree we have to accept that depression is a is a heterogeneous disorder, as the other major psychiatric disorders, with a highly variable course, an inconsistent response to treatment, and no established mechanism.
Treating depression is a science, helping depressed patients is an art of which not everyone is capable or inclined to try.

Posted by: Dr Shock at January 12, 2008 08:32 AM

HI i am from the uk. Sorry guys it is not any better over this side of the pond. Even though our healthcare is free you still do not get to choose your meds of course it is about politics and money sorry did you think it was not just because you pay for your healthcare?:-)

Sorry have had depression for 7 years my life ended that day and I have never been the same since, i agree if I had been told in the begining by medics there was no hope of remission of the complete variety I could have spent the last 7 years differently rather than being a guinea pig for a range of treatment options which have not done anything.

But if you are left with nothing where are you supposed to go or do you just end it and get it over with I certainly cannot live the rest of my life like this ?

Posted by: kristina Hurst at January 16, 2009 10:52 PM