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When Antidepressants Fail, What Next?

By John M. Grohol, Psy.D.
June 27, 2007

Last month, we saw a flurry of new studies released related to the ground-breaking, large-scale depression study called STAR*D. STAR*D will likely provide data for researchers to continue to publish upon for many months to come.

Two of the studies dealt with what happens when an antidepressant treatment fails. What do people do next, and how much does the second treatment help them?

In the first study,

Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients’ willingness to accept different second-step treatment approaches.

The researchers found that, when patients are given a choice after failing with a first-step medication treatment — in this case, Celexa — only 29% would opt to add psychotherapy (cognitive therapy, to be precise) to the mix. 71% would have nothing to do with psychotherapy. What factors might influence a person’s decision to try psychotherapy to help with their depression?

Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram (Celexa) were more likely to accept a switch strategy as compared with an augmentation strategy.

In other words, well-educated people, people who saw their family doc, people who had nasty Celexa side effects, or found little anti-depressive benefits from the Celexa were all more willing to give psychotherapy a try. Those who had recurrent major depression or a drug abuse problem were less likely to do so.

Still, it’s a little depressing to read that so few people, when given the choice, choose not to try psychotherapy. I wish the researchers had asked the all-important question, “Why not?”

Meanwhile, Thase and his colleagues looked at what happens when people were assigned to either cognitive therapy or a different antidepressant, and whether both groups improve or not:

After an unsatisfactory response to citalopram (Celexa), patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.

Drugs work faster, psychotherapy works slower. Drugs have more side effects, while psychotherapy has few. Both were about equally as effective.

Which only goes to show you that (a) depression must not be as “biologically based” as some would have you believe (have you ever heard of psychotherapy doing much help in keeping blood sugar levels balanced in a diabetic?) and (b) psychotherapy is a very powerful treatment, working just as well as medications for most people.

Sources:
Wisniewski SR et. al. (2007). Acceptability of second-step treatments to depressed outpatients: a STAR*D report. Am J Psychiatry. 164(5):753-60.

Thase ME, et. al. (2007). Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 164(5):739-52.

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This entry was posted on Wednesday, June 27th, 2007 at 10:03 am and is filed under General, Brain and Behavior, Psychotherapy, Disorders, Depression, Treatment, Research. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

16 Responses to “When Antidepressants Fail, What Next?” (Pingbacks/trackbacks not shown below)

I’d add that people who get psychotherapy have lower rates of relapse.

There have been physical improvements noted from meditation. Jon Kabat-Zinn’s study on using guided meditation with psoriasis sufferers saw markedly faster physical healing.

I know this wasn’t your main point, but I feel that the physical can move the mental, but the mental can also move the physical. It’s all connected.

It tire of the “which is better, drugs or therapy” just as much as I tire of the “which therapy model is better” discussion. I prefer discussing the therapy models themselves.

Talking to myself for a moment: To clarify, I don’t see how we can distinguish between “biologically based” and some other basis. Biology is a huge part of what we are, albeit influenceable by therapy, meditation, drugs, music, exercise, etc. I don’t know how it helps to continue the “horse race” discussions about “my way is better than your way.” Tell me what’s been working for you and your clients lately. Let’s help each other help people. I would post a blog, but I do it so seldomly, it takes me an hour to figure out how to get back in every time.

Hi Greg, I agree 100% with your point, even if it wasn’t quite the point I was trying to make.

My sense in talking with many, many ordinary people over the years is (a) they don’t know what modern psychotherapy entails; (b) because they have older conceptions of psychotherapy, if any, they are often put off from even considering it; and (c) they don’t know it can be just as effective (or even more effective) than medications.

So my goal here with entries like this one isn’t to continue the “horse race” so much as to help improve people’s understanding of the potential of this type of treatment.

Perhaps if we talk about how modern psychotherapy can be brief, and how a lot can be accomplished in a few sessions. That clients no longer have to be in “analysis” for years…

That there are new therapy models that help people get a perspective on what is going on in their lives, and that help them learn new ways of relating to their thoughts and to other people in their lives.

Therapists can help identify negative patterns or “traps” and help clients come up with their own solutions about how to make small changes that will free them from these traps that we create for ourselves.

We can mention that most therapists won’t bea asking question about your childhood, but will ask what’s going on in the present that seems to be causing problems… Maybe if we talk about what therapy can be like, and how it can help, we can communicate your point (and mine!).

It doesn’t show that depression isn’t neuro biologically based. Personally, I think it is likely that therapy works by altering neuro biology (indeed there is some evidence for that) rather than working by… oh… I don’t know… creating changes in some immortal Cartesian soul…

The issue doesn’t seem to be the NATURE of depression (whether it is neuro biological or not) so much as the TREATEMENT of depression (where it might be the case that the best way to alter that neurology is to make social changes or psychological changes or neurological changes or physical changes…)

I would expect that the reason why people who had concurrent addiction were less likely to try therapy would be because it would be fairly ingrained in them that relief comes from a drug.

For those with recurrent depression it might be that they are more concerned about their depression not being perceived as being their fault. While this doesn’t follow (as I said above) it does seem to be the case that people often think that their disorder MUST be neuro-biological AND MUST be treated with medications because otherwise they must be responsible for their state of depression. That doesn’t follow exactly but since depression tends to be about helplessness and hopelessness my guess would be that it is that much easier (and people seem to view it as less stigmatising) for them to pop a pill for a disorder that has nothing to do with their psychology rather than to risk facing the possibility that their personality might be hopelessly flawed and / or defective in a way that they are responsible for.

“Personality hopelessly flawed or defective in a way they are responsible for”? Geee that’s enough to make me want some pills! What do you mean by that? I don’t know about you, but I don’t find the phrase you are “hopelessly flawed or defective” particularly useful in therapy sessions. If you truly believe that, it sounds like I might as well head for the heroin dealer and skip over the psych doc…

I agree that it would be helpful for many folks to take more responsibility for their life situations and mental states, but simply telling them so is not my idea of therapy. They tend to have plenty of people telling them stuff like that already. The idea is to work with them, asking them questions, helping them discover some of this stuff for themselves.

P.S. Nobody is hopeless. Some people may do better in institutional settings, etc. But nobody is hopeless. Everyone is an extension of, and connected to me. If there is anyone out there that is hopeless, I am hopeless.

I’ve been all over the map - in many ways - and have been granted lots of second chances. I’ve been respected when I deserved no respect. There were people who didn’t give up on me - lots of them. There is a human being inside of each body - somewhere in there, there is.

> “Personality hopelessly flawed or defective in a way they are responsible for”? Geee that’s enough to make me want some pills!

Why, yes. That was precisely my point.

> What do you mean by that?

It was my attempt (speculative to be sure) as to the thought processes (or unconscious fears) of someone who is willing to take medication yet is extremely resistent to and / or dismissive of psychological treatment.

> I don’t find the phrase you are “hopelessly flawed or defective” particularly useful in therapy sessions.

No. But sometimes the client comes up with it. Or sometimes you kinda have to drag it out of them before you get to beat them over the head with their ‘faulty cognition’ (gee I’m so hopeless I can’t even think rationally).

;-)

> The idea is to work with them, asking them questions, helping them discover some of this stuff for themselves.

Sometimes people discover stuff that is hurtful, though. Drugs on the one hand (wonderful mind-numbing drugs)… Therapy on the other (potentially hurtful process)…

Just trying to speculate about resistence to therapy…

I have bipolar disorder I (the worst kind) and I just started learning about cognitive therapy and some of the teachings of Buddism and Tao. Drugs help the brain part of the disease, but you have to be a willing participant in order to be well.

Great article…thanks for reiterating what I’ve been telling my mom for months! :)

Drugs are cheaper than opening a can of worms in psychotherapy by finding that you need long-term talk therapy.

Um, no. If my personality is hopelessly flawed, then fixing that would be my goal. The truth is that I got tired (after years of it!) of hashing out what a lazy, hopeless person I was, and now I get relief with pharmaceuticals. Maybe there is better psychotherapy out there now, but 10 years ago it was all New Age crap. I get better results and end up much happier from going to Confession and taking my Lexapro. Some brains are wired a particular way, and drugs can fix that. Talking about your life doesn’t necessarily solve anything. Doing something about it does. Just my opinion as a consumer.

I am just curious to know among you who is a doctor and who is a patient - and who is neither.

I will address the first part mostly to the person who is clealy a doctor, Dr. Grohol. Is your suggestion that depression is not a biological process at all? Or that merely in some people it is not? I’d like to know if studies have been done on Parkinson’s and Alzheimer’s patients to determine whether their depression was concretely related to their “interpretation” of their own condition, or highly influenced by the disease process itself, wherein the mind has had some damage? I have been close to both patients as my father-in-law had Alzheimer’s and my grandfather had Parkinson’s. Both conditions are known to have depression as a symptom, likely as a result of being diagnosed with a terrible disease for one cause, but also, as far as I know, because the body’s own, physical, response is less than positive.

I would like to extend that argument to people who have never been diagnosed with a terminal illness, but may have other processes in place. Take, for example, thyroid disease. I am convinced - though I could be swayed by evidence, if evidence were given - that the process of thyroiditis causes both manic and depressive symptoms, and in fact, doctors will test for thyroid abnormalities to rule out that as a possible connection before prescribing lithium and calling the patient bipolar.

If I may be bold enough to extend my argument further, I would like to add that there may be other processes in the body that cause depression in an individual, but that are never rooted out by blood tests or MRIs. Scientists do not have the omniscience we attribute to them to pinpoint everything in the human body. I do not fault the doctors for this, but we must be careful not to put them too high on a pedestal, lest we give them power they would rather not have anyway.

Biology could still be a factor in my opinion. If it were not, then why is the percentage of women with depression higher than it is for men? Is this coincidence, chance? What is the commonality? Could it be hormonal imbalances? Clearly, for those women who have PMS, the men in their lives can attest to a marked shift in personality at that time - even the women might agree (but don’t ask them till it’s over, please). But, it is still debateable whether PMS is really a problem at all. Hormones are par for the course of being female, and I do not disagree. We are, as a society, far too eager to throw pills and syndromes at every discomfort. But, my argument is such that hormones can and probably do account for some levels of depression, even though some levels may be natural and okay. (Hormones are in men, as well, I know - but I am not a man, so I cannot speak to that).

But, since so many biological processes can cause a mental shift, then why is it so far-fetched to assume that depression is a biological or even neurological, not a purely spiritual or mental, abstraction?

I am not suggesting that it is wrong to pursue psychotherapy. In many cases, psychotherapy is a necessary treatment, particularly for those individuals who have suffered some disgrace in their childhoods (whether sexual or physical abuse) or may have lost a loved one (or ones) under dire and unusual circumstances, or seen horrible atrocities. Psychotherapy can prove to be useful in and of itself to help the patient wade through a lifetime of wreckage, and to potentially change some very poor patterns in thinking caused by a very bad upbringing. (Everyone suffers some degree of life’s consequences. Death and suffering are to be expected, and parents can only be blamed for so much. Bad events should be fairly traumatic, bordering or falling into the range of “abnormal.”)

Also, one must not be so quick to assume that an individual has never tried psychotherapy once or even many times without relief outside of this study. The article references only those people (I assume by the way it is presented here), that have never thought to try therapy or been in counseling prior to the study. Also, you do not make any mention of how long the benefits last, comparing the length of effectiveness of a medication with the length of effectiveness of therapy, and the consequent periods of relapse. How well does therapy work versus a different medication, when a patient has relapsed? It is my understanding that psychotherapy is intended for use in the short-term (up to 2 years?), while medication is intended as a life-long therapy. Very sick individuals are more concerned with the second bout of depression than the first, as it does get worse over time. [Studies have been done to prove that certain medications, such as lithium (among others) actually reduce shrinking of parts of the brain in individuals who are known to be bipolar, thereby stunting the progression of the disease.]

For those individuals in the study that did not reap the rewards of therapy, what category do they get placed in after the study has concluded? Were additional studies done on those individuals? They are the people we should be interested in. Also, according to the study, only Celexa was tried on patients. It is accepted, I believe, that patients with a latent bipolar tendency, will fair poorly on SSRIs anyway, and that therapy may still be beneficial for those people, but that a mood stabilizer will be far more helpful and necessary, therefore reducing your argument. It would be interesting to see if the Celexa did not work, and the therapy worked to some degree, whether adding a mood stabilizer (if the situation warranted) might be the absolute best solution in the end anyway. I don’t think this study was conclusive in the least. Many pieces of information were missing from the overall argument.

To the rest of the crowd…

It is quite possible that the expectations that a patient brings with him into counseling could be dramatically different than what is actually achieved. And for this, it would be “nice” to have a discussion about what *can* be accomplished in a therapeutic setting, in layman’s terms.

Keep in mind, we are all members of this society, all subject to the general consensus, able to hear and see the same messages, in public, in schools, at work, knowing and unknowing all sorts of logic. So, what I may think incorrectly - my supposed distorted views, negativism, etc. - may not actually be all that different from a “healthy” individual with the capacity for rational thought. How can we know for sure what a healthy person thinks regularly, when healthy people rarely seek counseling to have these views challenged? Has there been a therapy study with an adequate “control group”? If anyone knows of one, please advise. In all sincerity, I would like to read it.

Also, in order to pursue treatment in the psychotherapy setting, one must be of apt mind to pursue something at all. A highly depressed individual is not likely to have the mental spirit to raise himself out of bed in the morning, let alone fix himself a coffee, take a shower, dress, and then chart a course to the psychologist’s office once every week, or more often if group therapy is involved, to be inundated with visual stimulation and personalities. He may find the stamina to do so after a great deal of positive self-talk (which depressed individuals often use, contrary to popular opinion), once or twice, but the gravity of the world around him is by far heavier than the gravity of other human beings who sail through the day with ease (it appears), and eventually it is all too easy to just quit treatment, particularly if the treatment is taking too long or doesn’t “make any sense” or just plain old doesn’t feel productive in the least. Who would waste their money and their time for 2 years of therapy, only to still be at square one? To have the optimism to overcome this possibility, one must not be depressed in the first place.

A depressed person, can, however, wait on God. Steadfast prayer is a possible route to success, and while it’s not always easy to read the bible (sometimes depression makes it hard to read anything), it’s that much easier than driving to the therapist’s office. The ideal route to success is via church, but like the group setting in therapy, it is not always the easiest. Social anxiety, even in a church full of well-meaning spiritual folk, can be crippling, and it is much easier to stay in bed on Sunday morning than fight with the demons of anxiety to exhaustion and confusion. If, however, I have the ability to manage it, church does tend to have a therapeutic benefit, and I am rewarded by having gone more so than having stayed in bed. That being said, I have had some success with my religion, but I am unable to maintain it to the level that I require for my ongoing well-being. I do, however, keep praying in the belief that someday, God will reward me with the much-needed mental stamina that successfully combats those forces that are against me, so that when I am sailing through life and come to that well-known complete halt, he will lift me up and save me from whatever it is that attempts so malevolently to chain me down. [Keep in mind that many people believe prayer also heals physical afflictions.]

So - Yes, popping a pill is the quick and easy solution for an illness that makes a person work through weight much heavier than the common crowd, a weight that defines our existence on a day-to-day, and not occasional, basis. (You can whisk away the doom and gloom, and in a moment, it is back. Again and again, it returns, without prompting or invitation.) Sometimes something is better than nothing, and when the challenge is so risky as to hint “suicide,” what would you choose in that moment?

I want to add - often, depression will lift on its own, without any intervention whatsoever. And often, after a period of normalcy, depression will settle like a brick - unexpected and unprovoked. Try as you might to conjure up the cause, no cause is found. No one died. No one caused you pain. The house didn’t blow away, and the bank accounts didn’t dry up. Life can be exciting and full of hope at the very moment your will can disappear, vanishing like a forgotten whisper. What factors cause this?

It is my contention then, that certain persons who have offered insight into this discussion are not, or have never met, a mentally ill individual, or who keep themselves at quite an arm’s length for fear of “catching it,” doctors included. I would like to add that by our very human, un-divine natures, we are all flawed in some way. Some are flawed by our biology, some by our ignorance. And by that, I am referring to those who feel compelled to offer opinions on a subject with the frame of mind that we who suffer from depression have not thought of all of this in the rounds, a million times over, have suffered for hope of some kind of relief, and would have tried anything - anything at all - taken pills, talked to therapists, read books, wrote books, been baptized, listened to anyone and everyone. We are not ignorant or lazy. On the contrary… Being depressed does not equate a person to lacking in intelligence. Anne Sexton, an amazing poet, went through years of counseling and psychotherapy - before adequate medication. She still managed to suffocate on carbon monoxide with intent. It was too much weight for her to bear, and I would not dare call her a coward for she lived longer than many with the illness she had. I suppose if you have never experienced this weight that I refer to, then maybe you could never understand it? But, Ms. Sexton is just one artist and intellectual in a long, long line who have understood too well.

Depression may appear as laziness on the surface, but under normal conditions when the beast has lifted, I am just as active as my peers and sometimes more so, hiking, kayaking, traveling, cleaning, paying my bills, loving my family… So, with this, I am comforted by the idea that I am not a lazy individual. I must believe this for my sobriety. If I were lazy or believed it, could I ever hope to be cured? What hope would there be for me? I must counter the depression with the perception of wellness in order to see a difference and get well again. One must be in contrast to the other.

I can say that, despite feeling myself hopelessly despaired and at odds with the world, ready to jump at a moments notice, that there has never been a time where I didn’t hunger to feel better, and where I didn’t try something, including therapy. None of it - the drugs, the therapy, the well-meaning churches - are not all they are cracked up to be as independent entities. You need them all to get through it - not one to the exclusion of another - even though they do not work all that well. And you need to keep changing and trying new things or else, why not quit on life altogether? This illness is a practice in living so intricate that to know it, you have to feel it yourself.

It would be nice just once to hear someone say it’s okay that I’m flawed and different. It’s okay - and I still accept you as you are, even when you can’t accept yourself - because, I too, am flawed - although I am not ready or able to admit to you in what way. I would for once like to hear how amazing I am that I opened myself up to the criticism by admitting my mental differences, was willing to take a chance with all these different treatments like a guinea pig, was strong enough to get this far even though every day was akin to walking through bogs of mud while watching the rest of the world on roller skates. And mostly, I would love to hear how courageous I am that I didn’t quit when I most wanted to because of how much I loved my family, even when I didn’t necessarily love myself.

I know - I won’t hold my breath. I will say it to myself at least.

To Depressed Person,
I thought your contribution here was exceptional and beautifully written. I wonder if you have ever looked at the work of Marsha Linehan, the originator of Dialectical Behavior Therapy, who does tell you, in essence, “you’re perfect” and then helps you to change.

I can tell you $20,000 dollars of therapy later two things. Yes, it seems to help and two, you will be arguing with your insurance company about billing for the rest of your life!!!! Makes drugs seems so much easier.

ACSA/ACOA

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Last reviewed:
  On June 27, 2007
  By John M. Grohol, Psy.D.



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Hope is the thing with feathers that perches in the soul.
-- Emily Dickinson