Perimenopausal depression

Ms. A was a 48-year-old Caucasian woman who, like her mother, had first suffered a psychiatric disorder when she had a major depressive disorder with postpartum onset. At age 26, within a month after the birth of her first child, Ms. A developed rapid mood shifts, anxiety, agitation, somatic symptoms, and transient paranoid delusions that did not progress to psychosis; there were no episodes of mania. She was treated effectively with a combination of pharmacotherapy (monotherapy with 20 mg fluoxetine daily) and psychotherapy. The same treatment prevented relapses when it was instituted after the births of her second and third children and maintained for 6 months. During perimenopause, when Ms. A's menstrual cycles started becoming irregular, she again developed a major depressive disorder, with symptoms similar to those she had experienced postpartum but without the transient paranoid ideation and agitation. She was started on fluoxetine, but she remained unresponsive after several weeks of treatment. Ms. A had also developed perimenopausal hot flashes, which became particularly bothersome at night. Because she had experienced problematic side effects in the past when taking larger doses of fluoxetine, including flushing, sweating, headaches, and anorgasmia, she was reluctant to increase her antidepressant dosage. What is the role of estrogen replacement therapy, with or without progesterone, in such a patient? What other factors should be taken into account in the decision on whether to institute hormone replacement therapy?.