What the STAR*D study means for depression treatment

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The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial studied 2876 people with major depressive disorder to evaluate their response to depression treatment in a real-world setting.  Unlike the randomized controlled trials that are often used to evaluate a drug’s efficacy, there were few exclusion criteria, the patient and their physician knew which drug they were taking, and patient choice was incorporated.

Four sequential levels of treatment were established, and if a patient failed to achieve remission after 12-14 weeks, they would be moved to the next level.  The target was full remission, unlike many other studies which measure response (i.e. a ≥50% reduction in symptom rating scale scores).  Remission rates can be substantially lower than response rates, but are useful because there are better long-term outcomes for people who do achieve full remission.

Level 1

Level 1 treatment consisted of citalopram, and 28% of patients achieved remission based on the Hamilton Rating Scale for Depression (HAM-D).  Certain factors were identified, such as other comorbid mental illnesses, that were associated with lower or higher remission rates.

Level 2

In level 2, patients were offered cognitive psychotherapy, a switch to another antidepressant (randomly selected), or the addition of another medication to augment the treatment.  Among level 2 patients who switched to another medication, remission rates were 21.3% for bupropion, 17.6% for sertraline, 24.8% for venlafaxine.  Rates were similar among those patients who switched to cognitive psychotherapy.  Among the patients who received augmentation treatment, the remission rates were approximately 30% for both bupropion and buspirone.  Augmentation with medication produced more rapid remission than augmentation with cognitive psychotherapy.

Level 3

In level 3, patients who switched medication were randomly assigned to mirtazapine or nortriptyline, and patients who received an medication for augmentation were randomly assigned to lithium or the T3 form of thyroid hormone (liothyronine).  Remission rates were 12.3% for mirtazapine, 19.8% for nortriptyline, 15.9% for lithium, and 24.7% for thyroid hormone.

Level 4

In level 4, patients were randomly assigned to switch to either tranylcypromine (an MAOI antidepressant) or venlafaxine plus mirtazapine.  Remission rates were 6.9% for tranylcypromine and 13.7% for venlafaxine plus mirtazapine.


Altogether, 67% of patients were able to achieve remission.  The study found that people may still remit by 12 weeks even if there’s only a modest symptom reduction at 6 weeks.  However, the more treatment steps that are required, the lower the chance of a patient achieving remission and the higher the chance of intolerable side effects and relapse.

Personally I found the take-home message from this study rather discouraging.  During my last hospitalization I argued that my suicide attempt was supported by the STAR*D’s not so subtle hint that I was shit outta luck.  I think it’s crucial that we find new kinds of treatment that will help that 33% of people who are treatment-resistant and just aren’t achieving remission with many currently available antidepressant medications.  This study doesn’t consider all potential treatments; for example, atypical antipsychotics, ketamine, and ECT aren’ included, and psychotherapy plays a limited part.  Still, we deserve better.  A lot better.


For more info on the research terminology I’ve used in this post, see my post on research literacy.


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37 thoughts on “What the STAR*D study means for depression treatment

  1. Karen says:

    When I first accessed psychology, I was told that medication worked for a third of people on the first one they tried and another third on an alternative. Leaving 33% where medication didn’t work… very similar stats to what you’ve quoted above.
    I’m interested that there is an expectation to achieve remission within 12-14 weeks, knowing that I should have switched meds/augmented way earlier than I did. I was on mirtazapine for over a year before any changes were made.

    Great post x

  2. Raina says:

    RTMS…repetitive Transmagnetic stimulus has helped a lot with my severe depression and anxiety…and therefore helped me better cope with my BPD symptoms.
    Is this option available?

      • Raina says:

        Just come here….Grrr

        I was on various combination of meds for depression n BPD. It’s the intensity of depression that makes it impossible to see the BPD or gaslighting or ANYTHING.
        I was rated 2.5 on a 0 to 10 scale exactly a year and 1 month ago. I would stand on the side of the road and just wanna walk into the traffic…
        After rTMS…my depressive state is not so depressive. I see it and can fight with it.
        My love n hugs

  3. marandarussell says:

    I often wonder how much my medications really help me. I don’t notice that much of a difference seemingly, but then I do find myself getting kind of addicted to the meds anyhow. For instance, I’m not sure if the Seroquel is really helping my mood swings much, but now I can’t sleep without it. And I’m not sure if the Prozac really helps my depression much, but I am almost afraid to stop taking it after so many years.

  4. Luftmentsch says:

    I think I’m also outta luck. Meds and therapy help a little, but it’s maintaining a level of bearable awfulness rather than the normality other people get to experience – and even then, there’s so much of my life that I’m just not living (not taking much exercise, not living the type of religious life I would want, not working full time (which led to my girlfriend just breaking up with me…)). Outta luck indeed.

  5. Meg says:

    Yeah, it can be frustrating when there are no options!! Other medicine options might be atypical antipsychotics, as you pointed out. Also, alertness aids, like the Provigil I take–who knows? Maybe what people need is good psychiatry. I have the greatest psychiatrist ever, Dr. Phlegm, who has spent years getting my meds adjusted properly for me. He’s not perfect–he just has a great attitude. (None of that “I’m a walking ego who can diagnose you in five minutes, after which you must bow down and worship me” crap that so many psychiatrists exude.)

    He’s also open-minded if I want to try a drug. It took me years to discover Provigil, which I stumbled upon online while researching fatigue. (Prior, I had tried supplements, caffeine pills, you name it.) I marched into his office and said I was sick of needing 11 to 13 hours of sleep at night, that there are things I’d like to be doing every day (so I knew it wasn’t depression), and I swear, he got this look on his face like, “Yikes! I should have thought of it!” (It was at that moment that i noticed his Provigil notepad…. hello.) Anyway, I guess my long-winded point is that you’ve got to keep trying and leave no stone unturned, or whatev. I’d like to hope there are answers to be found for every problem! 🙂

  6. Autistickish says:

    Very clear and useful explanation of the article, but I’m sorry that you feel trapped in that 33%. For whatever it may be worth, here’s a smiley:


  7. Ayahuasca says:

    Immuno-suppressant therapy was the effective treatment for me, nothing else worked, I just wanted to die. I am still alive now, thanks to intra-venous steroids and othetr anti-inflammatory treatment. My case is depression due to autoimmune disease, so I advise anyone with depression getting tested!

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