Distinguishing between regular depression and bipolar depression can be a tough call for physicians. The symptoms are similar, but medications that ease depression can make bipolar patients worse by triggering mania episodes.

The dilemma is fueling new research efforts to understand how the two conditions differ and how to predict which patients will respond to which drugs. Scientists at the Mayo Clinic, which treats some 3,000 patients a year with bipolar disorder, are collecting DNA samples, blood tests, brain scans and clinical information in hopes of identifying genetic risk factors, or biomarkers, that can lead to earlier diagnoses and individualized treatments. Researchers at the University of Pittsburgh Medical Center and other centers are using neuro-imaging studies to understand how depression differs in the brains of patients with and without bipolar disorder.

Depression in bipolar disorder can look like regular depression, known as unipolar depression. Patients might feel helpless, sluggish, irritable and have thoughts of suicide. The manic side of bipolar disorder includes periods of frenzied energy; racing, irrational thoughts and sometimes dangerous behavior. These might not appear for years, or patients might not recognize the symptoms, leading to delayed diagnoses.

Even when patients are diagnosed with bipolar disorder, as many as 50% of them are treated with antidepressants.

“We don’t have a lot of treatment options for the depression phase of bipolar disorder, which is very troubling from a public-health standpoint,” says Mark Frye, chairman of psychiatry at the Mayo Clinic. “That’s why clinicians still reach for those antidepressants.”

Fran O’Loughlin, 48, of Green Bay, Wis., says she has had bouts of depression since high school and was finally diagnosed with bipolar disorder about 5 years ago. She has been on more than a dozen medications that provided relief only temporarily, often making her feel manic and then crash even lower. “My doctor and I have both been very aware and very cautious about introducing an antidepressant into the mix. I just can’t find happiness and we keep hoping the antidepressants will bring that to me,” she says.

Scientists aren’t sure how antidepressants can bring on a manic episode, called mood-switching, in some bipolar patients. The disorder is believed to involve dysfunction in neurotransmitters, the chemical messengers in the brain. Many antidepressants target those same neurotransmitters, and may overcompensate, some experts suggest. Studies show mood-switching occurs in 10% to 25% of patients, more often in young people than adults.

Mood stabilizers such as lithium are usually the first medications clinicians prescribe when bipolar disorder is diagnosed. Anticonvulsant drugs such as Lamictal or antipsychotic drugs such as Zyprexa can also help slow racing thoughts. But most of these drugs have significant side effects and are only marginally effective at controlling depressive symptoms. So some physicians say they cautiously add antidepressants as well.

Mayo Clinic scientists have identified a gene variation that may protect bipolar patients from developing manic symptoms while taking antidepressants. “Our hope is that further studies like that can help clinicians understand for which bipolar patients antidepressants might be helpful, not helpful or even harmful,” says Dr. Frye.

Therese Borchard says her bipolar disorder involves far more depression than mania. “I love being manic, to a certain extent. You feel alive – but then you crash afterward,” she says. She has founded an online community called Project Beyond Blue for people with intractable depression. “What’s difficult is finding the right amount so you are lifted from the depression but don’t have cycles of mania,” Ms. Borchard says.

She recommends some lifestyle steps to help keep people with bipolar disorder on an even keel. These steps include aerobic workouts at least 3 times a week, which can keep runaway thoughts and emotions in check. And getting at least 8 hours of sleep a night. “Mania feeds on insomnia,” she says.

wsjhealth.com    July 6, 2015