Unexpected links found between antidepressants, mood stabilizers, and mood swings

—A large study finds that patients with bipolar disorder face more frequent mania when first diagnosed early, with mixed initial episodes, substance use, fewer years of schooling or lacking mood stabilizers — and more depression among men, those using stabilizers, and those with bipolar II.

The findings, published May 20, 2025, in BMC Psychiatry, draws on data from 520 bipolar patients treated at hospitals across China. Conducted by researchers at Capital Medical University and other institutions, it sheds new light on factors tied to how often mood episodes strike.

Researchers analyzed clinical and social information — including education level, age at diagnosis, substance use, symptom type, and medication — for adult bipolar patients across seven hospitals. They used a statistical method called Poisson regression to identify which factors increase the number of manic or depressive episodes.

Key triggers for more frequent mood episodes in bipolar disorder

Manic episodes

• Fewer years of schooling
• First episode with mixed polarity (both manic and depressive symptoms)
• Younger age at diagnosis
• Substance use disorders
• Psychotic symptoms
• Use of antidepressants
• Not using mood stabilizers

Depressive episodes

• Male gender
• Use of mood stabilizers
• Bipolar II diagnosis (vs. bipolar I)

For manic episodes, the study found that patients with fewer years of schooling had slightly higher odds. Those whose first episode showed both manic and depressive symptoms — known as “mixed polarity” — were more than twice as likely to have more mania compared with those who began with mania alone, and nearly twice as likely compared with those who began with depression. An earlier age at diagnosis also raised the odds.

Substance use disorders, psychotic symptoms, use of antidepressants, and not using mood stabilizers were all linked to more frequent manic episodes.

When it came to depressive episodes, the study noted that being male increased the likelihood of having more depressive episodes. Use of mood stabilizers also raised odds, as did a diagnosis of bipolar II disorder compared with bipolar I.

The research is among the first large-scale investigations conducted at several hospitals and facilities of episode frequency in mainland China. It highlights the unexpected link between antidepressant use — but not mood stabilizers — and more mania, and the finding that mood stabilizer use correlates with more depression.

The authors write, “Addressing these factors may improve long-term outcomes for individuals with bipolar disorder.”

The findings may prompt a closer look at how treatment decisions shape episode patterns. They also suggest that tracking early warning signs — such as mixed episodes or substance use — could help clinicians reduce recurrence and tailor treatment more effectively.

Future studies could explore whether modifying these factors can help slow mood swings, improve stability, and enhance quality of life for those living with bipolar disorder.

Source: “Factors associated with the frequency of manic and depressive episodes in bipolar disorder: a multicenter study in China,” BMC Psychiatry, May 20, 2025.

Comment from a reader: As someone who experienced their first manic episode and depressive phase later in life, this give me some hope that future biopolar disorder problems might be rare for me. I will stick with my psychiatrist, medication, and therapy. The research also shows how important it is for parents and teachers too look for the symptoms in young people so they may have earlier interventions.