SSRI Augmentation with Raloxifene for Partially Improved Depression

Director of Outpatient Services, Tisch Hospital’s Department of Psychiatry, New York University Medical Center

Introduction

As many as 45% of patients with major depression do not respond fully to treatment with single agents such as selective serotonin reuptake inhibitors (SSRIs). In some cases, persistent side effects prevent reaching or maintaining the dose required for robust benefit. Now comes a report in which addition of the selective estrogen receptor modulator (SERM) raloxifene, to a prior small dose of fluvoxamine, resulted in a remarkable improvement leading to complete remission of depressive symptoms.

The Case

A 75 year-old woman presented to a Japanese hospital in October 2005 with chief complaints of severe insomnia, loss of appetite, headache, and autonomic symptoms such as frequent elevations of blood pressure, tachycardia, and nocturnal sweating. Two of her 5 siblings had experienced depression and committed suicide. She had completely lost interest in flower arrangement, a hobby that she had previously enjoyed, and reported that her entire body felt lethargic. Diagnosed with major depression, she was started on paroxetine 10 mg/day.

A week after the first examination, she complained of nausea and severe dizziness. Paroxetine was discontinued and replaced by fluvoxamine 25 mg/day. In November 2005, two weeks after the initial examination, there were partial improvements in the patient’s symptoms of insomnia and decreased appetite. Fluvoxamine was increased to 50 mg/day. In February 2006, after 3 months of 50-mg/day fluvoxamine treatment, her insomnia and decreased appetite almost resolved. The patient was able to perform basic household chores and shopping. She refused any further increase in fluvoxamine dosage.

In May 2006, after 6 months of treatment with fluvoxamine 50 mg/day, there was demonstrable improvement in the patient’s facial expressions and manner of speech. She regained interest in flower arrangement and had come to enjoy her life. When asked about what had caused such improvement and whether there had been any changes in her life, the patient reported that 2 weeks prior (ie, April 2006) she had been diagnosed with osteoporosis and that she had begun taking 60 mg/day of raloxifene. Over the next 3 months, no symptoms of depression were evident, indicating a state of complete remission on the combination of fluvoxamine and raloxifene.

Conclusion

This appears to be the first published report suggesting a potential augmentation by raloxifene of an SSRI, in this case, fluvoxamine. It is believed that raloxifene acts as an agonist in the bone, the cardiovascular system, and the central nervous system, and as an antagonist in the uterus, ovary, and mammary gland. As to the question of whether estrogen may augment the antidepressant activity of SSRIs in depressed postmenopausal women, studies have yielded conflicting results. Viewed in the context of data indicating that raloxifene does not increase the risk of gynecological tumors or coronary heart disease, some are recommending raloxifene usage with SSRIs for depressed postmenopausal women. Double-blind, placebo-controlled trials are needed to more fully evaluate these effects.

Disclosure: Dr. Ginsberg is a speaker for AstraZeneca, Cyberonics, Forest, and GlaxoSmithKline; and has received research support from Cyberonics.