In bipolar disorder, an antidepressant alone nearly tripled the rate of mania; with a mood stabilizer it did not
Swedish registers, 3,240 patients, each compared with themselves: mania in the three months after starting an antidepressant alone, hazard ratio 2.83. With a mood stabilizer, 0.79.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Mania identified from register diagnoses, so milder hypomania is missed. The monotherapy estimate has a wide interval (1.12 to 7.19). People given monotherapy may differ in ways a within-person design does not capture, such as a recent change in illness course.
This is the clearest case where starting a psychiatric drug can itself lead to a hospital bed. Mania is a common reason for admission, and an antidepressant can set it off.
Significant findings
Viktorin and colleagues (American Journal of Psychiatry, 2014) "identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year." "A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors."
"Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79", "and a decreased risk was observed during the period 3-9 months after treatment initiation (hazard ratio=0.63".
The authors: "The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder."
Worth asking
Every patient here had a known bipolar diagnosis, and a third were still given an antidepressant alone. The larger problem is the people whose bipolar disorder has not been recognized yet, because the first episode is often depression and the first prescription is often an antidepressant from a primary care visit. If you have ever had a period of days with little sleep, racing thoughts and unusual energy, or a close relative has bipolar disorder, say so before starting an antidepressant. Never stop one on your own.
Source
The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer — Viktorin A, Lichtenstein P, Thase ME, Larsson H, Lundholm C, Magnusson PK, Landen M (2014)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1176/appi.ajp.2014.13111501
DOI: 10.1176/appi.ajp.2014.13111501
How this was scored
- Study design
- Cohort study
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 3,240
- 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 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 56 out of 100 on our published rubric. One caveat travels with that badge: Mania identified from register diagnoses, so milder hypomania is missed. The monotherapy estimate has a wide interval (1.12 to 7.19). People given monotherapy may differ in ways a within-person design does not capture, such as a recent change in illness course. 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?
The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer — Viktorin A, Lichtenstein P, Thase ME, Larsson H, Lundholm C, Magnusson PK, Landen M (2014). Published in: Top-tier peer-reviewed journal. DOI: 10.1176/appi.ajp.2014.13111501. 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.