In the FDA file for a home-use depression headset, scores in the sham arm fell by 6.01 points
- On December 31, 2025, the U.S. FDA approved Proliv Rx, a prescription headset for use at home or in clinic that stimulates the trigeminal and greater occipital nerve branches, as an adjunctive treatment for major depressive disorder in adults who did not improve enough on at least one antidepressant.
- The pivotal MOOD trial was double-blind and sham-controlled, at 13 sites (12 in the US, one in Israel): 126 people were randomized, and the main analysis (modified intent-to-treat) covered 97, 47 on active and 50 on sham stimulation. All stayed on a stable antidepressant dose.
- At week 8 the adjusted mean reduction in the 17-item Hamilton Depression Rating Scale (HDRS17) was 8.62 points with active stimulation and 6.01 with sham, a difference of 2.61 (p = 0.0196). On the MADRS the changes were -10.3 and -8.3.
- In the next 8 weeks everyone received active stimulation; 93 of 97 continued (45 of 47 from the active group, 48 of 50 from the sham group).
Clients on an antidepressant may ask about a device they can use at home alongside it. The FDA's approval summary for Proliv Rx describes the trial behind the decision, including what happened in the sham arm.
Design of the MOOD trial
Participants were adults with unipolar major depressive disorder who had not improved enough on one to four antidepressant trials and were taking an antidepressant at a dose stable for at least 28 days. They were randomized 1:1 to active or sham stimulation for 8 weeks, 60 minutes a day (plus or minus 20), 5 to 7 days a week. The sham used reduced parameters, such as lower intensity and a pulse frequency of 0.33 Hz, to mimic active stimulation without a therapeutic effect.
Week 8 in numbers
On the HDRS17, adjusted mean change was -8.62 with active stimulation and -6.01 with sham. A reduction of at least 7 points occurred in 29 of 47 (61.7%) against 16 of 50 (32.0%). Participants were asked to guess their assignment once, after the training session at the baseline visit: 15% of the active group and 6% of the sham group guessed correctly.
The six points in the sham arm
My reading: a person in the sham arm wore the headset daily, followed the routine and took an antidepressant, and the HDRS17 still fell by 6.01 points over eight weeks. I take that figure as a reminder of how much a client may receive from the fact of being treated with a device. I do not claim a mechanism for it.
When a client on a stable antidepressant starts an add-on device, rate depression with the same scale at baseline and again at weeks 4 and 8, and ask before the first session what the client expects the device to do. A drop of several points over eight weeks is the range the sham arm produced.
The sham arm lost 6.01 HDRS17 points in eight weeks – a figure to keep in mind when a client says the device is working.
The summary reports one pivotal trial with an 8-week controlled phase; from week 9 all participants received active stimulation, so there is no controlled comparison for weeks 9 to 16. The main analysis covers 97 of 126 randomized participants, those who completed the minimum stimulation time. The sham-arm change occurred alongside continued antidepressant treatment, and the comment on it is the author's reading, not a trial result.