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. 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 that measure response (i.e. a ≥50% reduction in symptom rating scale scores). Remission rates can be substantially lower than response rates; however, they’re useful, as there are better long-term outcomes for people who do achieve full remission.
Note: For more on the research terminology used in this post, see this post on research literacy.
STAR*D Treatment levels
Level 1 treatment consisted of the selective serotonin reuptake inhibitor (SSRI) citalopram (Celexa), 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.
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 (bupropion or buspirone).
Among level 2 patients who switched to another medication, remission rates were:
- 21.3% for bupropion (Wellbutrin), a norepinephrine and dopamine reuptake inhibitor (NDRI)
- 17.6% for sertraline (Zoloft), an SSRI
- 24.8% for venlafaxine (Effexor), a serotonin and norepinephrine reuptake inhibitor (SNRI)
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.
In level 3, patients either switched medication or received an additional medication for augmentation. Patients who switched were randomly assigned to mirtazapine (Remeron, an atypical antidepressant) or nortriptyline (Aventyl, a tricyclic antidepressant).
Patients who received augmentation were randomly assigned to lithium or the T3 form of thyroid hormone (liothyronine, or Cytomel).
Remission rates were 12.3% for mirtazapine, 19.8% for nortriptyline, 15.9% for lithium, and 24.7% for thyroid hormone.
In level 4, patients were randomly assigned to switch to either the monoamine oxidase inhibitor (MAOI) tranylcypromine (Parnate) or the combination of 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. STAR*D 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.
Where we go now
Personally, I found the take-home message from the STAR*D 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.
Yes, antidepressants work better than placebo. Still, 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 somatic treatments such as electroconvulsive therapy (ECT) aren’t included, and psychotherapy plays a limited part. Still, we deserve better. A lot better.