Treatment-Resistant Dimension of Depression Identified in New Study

There are numerous treatments designed to address the multiple facets of depression. They include medication, psychotherapy, exercise, mindfulness, breathing exercises, light therapy, sleep therapy, and behavioral therapy. However, not every individual with depression will respond equally to any or all of these treatments. Some individuals demonstrate treatment resistance and poorer outcomes than others. Understanding which mechanisms lead to negative outcomes could help clinicians target those symptoms specifically in depressed individuals. In an attempt to identify which factors lead to treatment resistance, Rudolf Uher of the MRC Social, Genetic, and Developmental Psychiatry Centre at King’s College Institute of Psychiatry in London conducted a study that examined nine specific depressive symptom dimensions in a sample of 811 participants with depression. All of the participants were receiving antidepressant medications and were evaluated for response and symptom severity. One of the goals of the study was to not only identify specific dimensions of depression, but to replicate the findings in a larger sample.

Uher discovered a unique dimension of depression that predicted treatment resistance in his participants. He found that those with the least amount of activity, interest, or enjoyment and with the highest levels of indecisiveness were the most resistant to antidepressants. Uher also discovered that this finding was consistent regardless of the level of symptom severity or type of antidepressant that the participants were given. Additionally, this same dimension was found to predict negative treatment outcomes in a larger sample of over 3,000 participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

The findings of Uher’s smaller study, and the replication of results on a broader scale, clearly demonstrate that these specific symptoms of depression create unique barriers to positive outcomes. This knowledge could help clinicians design treatments for individuals who have this dimension of depression. Rather than subjecting them to traditional therapy at the onset of treatment, mental health professionals may wish to try alternative approaches first. Uher said, “Although no evidence for such treatments in depression with loss of interest and decreased activity is available at present, indirect evidence suggests that several approaches may be effective.” Some such approaches that have been shown to be effective in treatment-resistant individuals are exercise, behavioral activation, and psychological therapeutic interventions.

Uher, R., Perlis, R. H., Henigsberg, N., Zobel, A., Rietschel, M. (2012). Depression symptom dimensions as predictors of antidepressant treatment outcome: Replicable evidence for interest-activity symptoms. Psychological Medicine, 42.5, 967-980.

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The preceding article was solely written by the author named above. Any views and opinions expressed are not necessarily shared by Questions or concerns about the preceding article can be directed to the author or posted as a comment below.

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  • Maria


    June 7th, 2012 at 5:15 PM

    “He found that those with the least amount of activity, interest, or enjoyment and with the highest levels of indecisiveness were the most resistant to antidepressants.”
    So basically those with the most difficult to treat symptoms were the most difficult to treat.
    It’s amazing how scientific literature often fails a logic test.

  • joe fern

    joe fern

    June 8th, 2012 at 4:26 AM

    So are these patients people who have some sort of genetic resistance to treatment or is it that they have their minds set against getting better?
    I have known someone like that in my life. She did not want help because I think that she thought that her suffering through depression made her some sort of martyr.
    I think that the one thing that she failed to see is that for a long time there were a lot of us who did feel pretty sorry for her and the things that she experienced.
    But after a while, when you have tried to give someone everything that they need to get better, and access to really anything that could help but she just wouldn’t try to take charge of anything, that just made a lot of us want to walk away.

  • Sara B

    Sara B

    June 8th, 2012 at 2:40 PM

    If someone wants to heal then they will, but you have to give them something to work toward. This is not going to happen automatically for everyone.

  • Brent B

    Brent B

    June 9th, 2012 at 6:57 AM

    No interest in anything, no activities to speak of, indecisive. . . yep, that for me sounds exactly like it will be the perfect recipe for antidepressants to do the job. I know that sometimes these sorts of pharmaceuticals can work as stand alones. They don’t need anything more than being taken correctly at the right time of day or the right amount of food or water to get the job done. But I would imagine that antidepressants, while alone can start to make a difference, have to largely depend on the patient making so e effort at recovery as well. Generally if someone is already in a lifestyle that supports being lazy or inactive, this is not going to be that go getter who is striving to do anything he can to better his life or situation. Just an observation.

  • portia


    June 10th, 2012 at 8:37 AM

    Some of you guys posting here are so high and mighty and obviously have not ever dealt with depression on a personal level. You are on the outside looking in and being so judgemental. Just how easy do you think that it is to make decisions or to feel like going for a 5 mile run when you are clinically depressed? It’s not even easy to get out of bed in the mornings. It’s not that most of us make this conscious choice to either get better or to not, but for some of us it feels so daunting, like something that we can’t conquer. So please try to be a little more understanding about those challenges before deciding that we are just being lazt and don’t want to get better.

  • Betty


    June 11th, 2012 at 5:19 PM

    How is this enlightening at all? I mean, it does not take a rocket scientist to infer that if someone gets no meaning and joy out of life already, then they aren’t going to get anything out of therapeutic efforts, no matter how good they are. Am I right?

  • MaryAndrews


    June 12th, 2012 at 4:36 AM

    treatment resistant? more like pig headed. let them be and go help the people who want the help

  • Simon


    June 25th, 2012 at 9:15 AM

    In response to MaryAndrews – if you have a bad headache & the pain killer you take doesn’t work, is this because you really don’t want it to work & are just being pig headed ? Of course not. You’ve taken the pain killers to help but they are not working. They are not helping your medical condition. If the bad headache continues, then I’m sure you would want doctors to find a cure & the cause of this bad headache.
    You’re not ‘choosing’ to have a bad headache. Neither is someone with clinical depression CHOOSING to be depressed. I was diagnosed with major clinical depression in 1998 & thankfully for the majority of time since, I have had medication that has worked. Unfortunately (for some reason – I don’t know what), my depression has become ‘treatment resistant’. I’m not CHOOSING this resistance. Living is HUGELY better when a medication works. So if I had a choice, without hesitation, it would be that my symptoms of depression ceased.
    Pre diagnosis & post diagnosis I have always been employed, I have exercised etc etc. if you met me or passed me in the street you would not know I suffer from clinical depression. In my hypothetical, similarly if I met you or passed you in the street I wouldn’t know you had a headache.
    I realize that depression is very very difficult to understand/accept as a medical condition for those that have not experienced it. I think you may fall into that category. Geez, even for some that have/do experience depression it is difficult to understand/accept. When anti depressants stopped working for me & trying several different anti depressants still didn’t work, I tried & researched various methods. I increased my amount of exercise (not easy as a symptom is lethargy), etc etc. I also explored electric shock treatment (from memory I think called ECT). Being consulted for this it was revealed that it would require a couple of weeks in hospital, possible short term memory loss plus plus plus. I remember leaving that consultation thinking “right, bugger that !! I’ll up my exercise level again, I’ll……..etc etc” EVEN me, that has experienced depression, was at that instance not accepting that depression is a medical condition. So I do understand how our broader society has trouble accepting depression as a proper medical condition, and that ‘treatment resistant depression’ exists in reality & not because of pig headed choice.
    Most importantly to those suffering – the symptoms you’re suffering are temporary. I have suicidal thoughts every day, BUT keep reminding myself as you must, that these symptoms CAN be cured. My psychiatrist has identified the ‘treatment resistant’ & we are trying something new. Undoubtedly your symptoms can be cured (even ‘treatment resistant depression’). Seek out a professional – a psychiatrist. They WILL fix the condition you have.
    I know it all seems helpless & hopeless – that’s part of the medical condition. Its a medical condition that can be fixed. So seek out the expert.

  • Ann


    June 17th, 2012 at 11:10 AM

    It is naive to say that “those who want to be healed, will be.” Depression, like other mental & some physical illnesses, have multiple causes, including biological. Someone whose depression is primarily biological can not just choose to get well anymore than the person with ALS can choose to get well. And for the person who got frustrated with the woman who he believes chooses to be depressed for personal gain, there’s another name for that mental illness. Whatever it is, it’s not emotionally healthy behavior. IMHO.

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