Can an SSRI trigger mania in someone with undiagnosed bipolar disorder?

Yes — and the risk is high enough that every psychiatrist learns to ask about it before prescribing.

Antidepressant-induced mania (sometimes called AIM or “treatment-emergent affective switch”) is a well-documented phenomenon where a patient being treated for depression flips into a manic or hypomanic episode after starting or increasing an antidepressant. The risk concentrates in people who actually have bipolar disorder but have been misdiagnosed as having unipolar depression — which is common, because the depressive phase of bipolar is the phase that drives most people to a doctor in the first place. The manic phase often comes years later, or never surfaces unless something tips the chemistry.

The numbers are specific. A 2004 systematic review by Hannah Gijsman and colleagues, published in the American Journal of Psychiatry, looked at 12 randomized controlled trials of antidepressants for bipolar depression and found that switches into mania were significantly more common on antidepressants than on placebo. A 2007 study by Chris Truman and Joseph Goldberg, published in the Journal of Clinical Psychiatry, surveyed patients with confirmed bipolar disorder and found roughly 20–40% reported a manic or hypomanic switch after antidepressant exposure, particularly when no mood stabilizer was being co-prescribed. The risk varies by drug — older tricyclics carry higher switch rates than SSRIs, but SSRIs are not risk-free.

Why SSRIs specifically can trigger the switch. SSRIs (selective serotonin reuptake inhibitors — fluoxetine, sertraline, escitalopram, paroxetine, and others) work by increasing serotonin availability in the synapse. In a unipolar depressed brain, that pushes mood up. In a bipolar brain, serotonin increase can destabilize the regulatory system that normally keeps mood cycling between two poles, and the result is the upper pole flipping up further than intended. The clinical sign that this is happening isn’t “feeling a bit better” — it’s a sudden, abnormal elevation: euphoria, racing thoughts, decreased need for sleep, hypersexuality, impulsive spending, or agitation. In severe cases, the manic episode includes psychotic features — hallucinations or delusions — because the brain is firing in a pattern it doesn’t normally reach.

The current high-profile example. The mechanism got mainstream attention through the Lindsay Clancy case, which became publicly visible in 2024 and went to trial in 2025–2026. Clancy, a Massachusetts nurse with a documented psychiatric history, was prescribed multiple medications — including an SSRI — by seven different providers. In her case, the standard psychiatric protocol for postpartum depression was followed; the SSRI was reasonable on its face. But if Clancy had undiagnosed bipolar disorder (which her psychiatric history is consistent with), the SSRI could have acted as a destabilizer rather than a treatment. Psychiatrists interviewed in coverage of the case, including Dr. Alok Kanojia (Dr K) on Modern Wisdom #1151 in September 2026, emphasized that this is the exact mechanism by which SSRI prescriptions can backfire in undiagnosed bipolar patients — the SSRI doesn’t cause bipolar, but it can trigger the manic pole in someone who already has the underlying condition.

What clinicians do about it. The standard of care has been updated precisely because of this risk. The most common prevention is to start a mood stabilizer (lithium, valproate, or an atypical antipsychotic such as quetiapine or lamotrigine) before or alongside any antidepressant in anyone with possible bipolar features. The US National Institute of Mental Health’s public information page on bipolar disorder flags this directly. The diagnostic question clinicians are trained to ask before prescribing an SSRI for depression includes: any history of periods of high energy, decreased need for sleep, racing thoughts, or impulsive behavior? Any family history of bipolar disorder? Any postpartum episode? Any antidepressant that “didn’t work” or made the patient feel worse in a strange way? Each of those is a flag to slow down and rule out bipolar before reaching for the SSRI pad.

The practical takeaway. If you or someone you know is being treated for depression with an SSRI and starts experiencing a sudden, abnormal elevation in mood, energy, or impulsivity — especially if it feels qualitatively different from normal happiness — that’s a clinical emergency signal. Call the prescriber the same day. SSRI-induced mania in someone with undiagnosed bipolar is reversible if caught early, but the window is short and the consequences of missing it (psychosis, hospitalization, dangerous decisions) can be severe. The risk is small in absolute terms — millions of people take SSRIs without incident — but it is real, it is documented, and it is the reason every responsible prescriber asks those questions before writing the first prescription.