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February 9, 2022

Is It Time to Try Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Again?

Author Affiliations
  • 1Department of Psychiatry, Massachusetts General Hospital, Boston
  • 2Harvard Medical School, Boston, Massachusetts
JAMA Psychiatry. 2022;79(4):281-282. doi:10.1001/jamapsychiatry.2021.4281

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, initiated in 2001, was a landmark for psychiatry, one of the “big 3” effectiveness studies intended to better understand real-world clinical outcomes.1 It aimed to address the lack of head-to-head data regarding next-step treatment options in major depressive disorder, a clinical scenario that STAR*D itself demonstrated could affect up to two-thirds of individuals beginning antidepressant treatment.2

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2 Comments for this article
Predictors of resistance
Monica Kayo, MD, MSc | São Paulo, Brazil
I agree that we need to revisit STAR-D.
However, after 20 years, we still need to follow a sequence of treatments empirically. It would be quite nice if we knew when someone would not respond to SSRIs and nor to level 2 strategies.
When should we start with an antidepressant other than SSRI?
Some questions will remain.
STAR-D II: return of the hyphen
Eric Ross, MD | Massachusetts General Hospital
Drs. Perlis and Fava are to be commended for their thought-provoking proposal to update the landmark STAR*D study.(1) With the benefit of 20 years of hindsight, they offer a cogent assessment of the original trial’s strengths and weaknesses, and they provide a roadmap for incorporating the research methods and treatments developed over the past two decades into an equally impactful “STAR*D2”. Unfortunately, they have neglected to discuss a significant flaw of the original trial which has bedeviled clinicians and researchers ever since it was first published: the choice to use an asterisk in the trial’s name.

When searching citation
databases such as Google Scholar or Web of Science, an asterisk serves as a wildcard character, and hence the search term “STAR*D” will bring up any string of characters starting with “star” and ending with “d”. For example, a recent attempt to find articles about the STAR*D trial yielded papers on “starshaped hypersurfaces” and “Michelin-starred chefs” – and while this may have an unintended benefit of enhancing psychiatrists’ appreciation of geometry and gastronomy, it makes it quite challenging to find papers discussing the STAR*D trial. Indeed, how many STAR*D publications have been skipped over entirely when readers became distracted by “phosphate-starved plants” or “star-cross’d lovers” in their search results?

For solutions to this issue (and cautionary tales), we can look to the trials of the last 20 years. Following STAR*D’s lead, some have elected to push the envelope of typographic creativity. For example, the SUN(^_^)D trial one-upped STAR*D’s mere asterisk with a five-character smiling emoticon (or in some publications, an emoji ☺).(2) While this has the benefit of sparking joy in the reader, it produces only bewilderment in search engines: Web of Science, for example, renders it as “SUN((boolean AND)_(boolean AND)) D”. In contrast, the VAST-D trial returned to the humble hyphen;(3) though it unfortunately lacks the flair of its forebears, it is eminently searchable.

So how could the updated STAR*D trial maintain the panache of its name without confounding search engines? Recent trials have eschewed complex characters, instead generating excitement with only letters and numbers: a systematic review identified ILLUMINATE, CaRESS, and HI-5 as particularly compelling examples.(4) With all this in mind, I would suggest a slight name change that would honor the STAR*D trial's legacy of acronymic innovation, ensure easy searchability, and pay homage to a beloved diminutive droid: STAR2-D2.

1. Perlis RH, Fava M. Is it time to try Sequenced Treatment Alternatives to Relieve Depression (STAR*D) again? JAMA Psychiatry. Published online 2022:E1-E2.
2. Shimodera S, Kato T, Sato H, et al. The first 100 patients in the SUN(^_^)D trial (strategic use of new generation antidepressants for depression): Examination of feasibility and adherence during the pilot phase. Trials. 2012;13:1-11.
3. Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318(2):132-145.
4. Pottegård A, Haastrup MB, Stage TB, et al. SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names for Important Clinical trials (SCIENTIFIC): Qualitative and quantitative systematic study. BMJ (Online). 2014;349(December):1-11.