He and his colleagues found several factors besides depression that contribute to treatment resistance. For example, some patients had bipolar disorder, attention-deficit/hyperactivity disorder (ADHD), substance abuse, or a parental history of depression, said Brent. He recommended determining whether these disorders precipitated the depression and then treating the patient for the more serious problem first. There may also be environmental factors at work—including a family history of trauma, abuse, or discord—that may require psychotherapy and medications. A medical illness such as thyroid disease or anemia should also be ruled out, suggested Brent. Early identification and treatment of patients with multiple problems often lead to less treatment resistance, said Brent.