A tuberculosis drug that lifted mood
Iproniazid was a tuberculosis treatment. Ward staff noticed patients cheering up, and by 1957 it was being evaluated as an antidepressant.
We have not finished checking this source. No judgement either way. how we score evidence
Caveat on this rating: This stop deliberately breaks its own trail's pattern, because the record does. Zeller and colleagues published monoamine-oxidase inhibition by these compounds in 1952 (Experientia 8:349-350, doi 10.1007/bf02174413); Loomer, Saunders and Kline published the antidepressant evaluation in 1957 (Psychiatric Research Reports 8:129-141, PMID 13542681). So the mechanism preceded the psychiatric indication by five years, and iproniazid is NOT an example of a mechanism found after the fact. What was built backward is the inference from the drug's action to the cause of the illness, which is what the body says. No synthesis year is stated: two peer-reviewed sources disagree (1953 versus clinical use in 1952) and the conflict is unresolved.
The first antidepressants came out of tuberculosis wards. Iproniazid was a TB drug, and staff noticed that patients taking it became more cheerful.
Significant findings
By 1957 Nathan Kline and colleagues had published a clinical evaluation of iproniazid as what they called a psychic energizer. The observation came from the ward, not from a theory of depression.
A tuberculosis drug, redirected on a bedside observation.
This one carries an honest twist that cuts against the easy version of the story. The chemistry was known first here. In 1952 Zeller and colleagues showed these compounds block monoamine oxidase, an enzyme that breaks down brain messenger chemicals.
So the mechanism sat on the shelf five years before the mood finding. What got built backward was the step after it. If blocking that enzyme lifts mood, the reasoning went, low levels of those chemicals must cause depression.
Worth asking
That inference is the whole subject of the next stop.
Notice how often a treatment gets explained by what the drug does, rather than by anything measured in the person.
Source
Role of serendipity in the discovery of classical antidepressant drugs: Applying operational criteria and patterns of discovery — Lopez-Munoz F, D'Ocon P, Romero A, Guerra JA, Alamo C (2022)
Read the source: https://doi.org/10.5498/wjp.v12.i4.588
DOI: 10.5498/wjp.v12.i4.588
How this was scored
- Study design
- not recorded
- Funding
- not recorded
- Published in
- not recorded
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
We have not finished checking this source, so there is no scoring to show yet. “We have not checked this yet” and “this is disputed” are different statements, so no scored band is shown rather than a low one.
Read the full scoring rubric, including what it can't tell you.
Published August 31, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "not yet assessed". We have not finished checking this source. No judgement either way. One caveat travels with that badge: This stop deliberately breaks its own trail's pattern, because the record does. Zeller and colleagues published monoamine-oxidase inhibition by these compounds in 1952 (Experientia 8:349-350, doi 10.1007/bf02174413); Loomer, Saunders and Kline published the antidepressant evaluation in 1957 (Psychiatric Research Reports 8:129-141, PMID 13542681). So the mechanism preceded the psychiatric indication by five years, and iproniazid is NOT an example of a mechanism found after the fact. What was built backward is the inference from the drug's action to the cause of the illness, which is what the body says. No synthesis year is stated: two peer-reviewed sources disagree (1953 versus clinical use in 1952) and the conflict is unresolved. 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?
Role of serendipity in the discovery of classical antidepressant drugs: Applying operational criteria and patterns of discovery — Lopez-Munoz F, D'Ocon P, Romero A, Guerra JA, Alamo C (2022). DOI: 10.5498/wjp.v12.i4.588. The full source is linked on this page so you can read it yourself.
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.