In a 20-year NIMH cohort, depression returned during 25% of maintenance treatment periods
103 people with unipolar depression, followed up to 20 years. Of 171 stretches of maintenance medication after recovery, symptoms returned in 43 (25%), at a median of 20 weeks. The melancholic subtype raised the risk.
Suggestive but preliminary. Not settled. how we score evidence
Caveat on this rating: Observational: nobody controlled the treatment, and the drugs in use were those of 1978 to the 1990s. The unit is the maintenance interval, not the person, and the 103 people were selected as medication responders. The word tachyphylaxis names the event, not a proven mechanism.
The cleanest single number on how often an antidepressant that worked stops holding, from a cohort watched for two decades.
Significant findings
Solomon and colleagues used the NIMH Collaborative Depression Study, a multicentre observational study of mood disorders. Their sample was 103 people with unipolar major depression enrolled from 1978 to 1981 and followed for up to 20 years. Each had been treated with an antidepressant for an episode, recovered, and then stayed on maintenance medication. Some did this more than once, so the unit of analysis is the maintenance interval, not the person.
"For the 103 subjects, there were 171 maintenance treatment intervals." The median maintenance period was 20 weeks. "Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals."
One predictor stood out: "The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval."
The conclusion: "Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence."
The other direction
Seventy-five percent of the maintenance periods did not see symptoms return. The study is observational: "treatment was recorded but not controlled by anyone connected with the study," so the drugs, doses and the reasons for any changes were whatever ordinary care produced between 1978 and the 1990s, before most of the drugs prescribed today existed. The 103 people were selected because they had recovered on medication and then stayed on it, which is not everyone.
What this does not show
It cannot say whether the 25% is the drug losing its effect or the illness recurring through it; the authors use the word tachyphylaxis for the event, not for a mechanism. It does not test any response to the event. It gives no one a reason to change a prescription.
Worth asking
Do I have the melancholic pattern, and does that change how closely we watch this?
Source
Tachyphylaxis in unipolar major depressive disorder — Solomon DA, Leon AC, Mueller TI, Coryell W, Teres JJ, Posternak MA, Judd LL, Endicott J, Keller MB (2005)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.4088/jcp.v66n0302
DOI: 10.4088/jcp.v66n0302
How this was scored
- Study design
- Cohort study
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 103
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 29, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "early signal". Suggestive but preliminary. Not settled. It scores 49 out of 100 on our published rubric. One caveat travels with that badge: Observational: nobody controlled the treatment, and the drugs in use were those of 1978 to the 1990s. The unit is the maintenance interval, not the person, and the 103 people were selected as medication responders. The word tachyphylaxis names the event, not a proven mechanism. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Tachyphylaxis in unipolar major depressive disorder — Solomon DA, Leon AC, Mueller TI, Coryell W, Teres JJ, Posternak MA, Judd LL, Endicott J, Keller MB (2005). Published in: Reputable peer-reviewed journal. DOI: 10.4088/jcp.v66n0302. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cohort study. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.