Watch for Depression in Long-term Tamoxifen Use

Roberta Friedman, PhD

May 19, 2003

May 19, 2003 (San Francisco) — Physicians who use tamoxifen to stop breast cancer should watch patients for depression in the months after treatment begins, according to findings presented here at the American Psychiatric Association 156th annual meeting. But the study failed to confirm previous studies that claimed a definite risk for depression if the drug is used.

While earlier studies have shown fairly rapid onset of depression with tamoxifen, the new study of nearly 3,000 women revealed that depression appeared on average eight months after starting the drug.

The researchers excluded women who had used antidepressants within six months of starting tamoxifen, and they also culled out women with risk factors such as use of other drugs that can cause depression (eg, interferon or methyldopa), or history of depression or alcohol abuse.

"We did this study because there is a lot of clinical and anecdotal experience" about tamoxifen's ability to instigate depression, Kelly Lee, PharmD, from the University of California at San Francisco, told Medscape in an interview. But, she said, to ensure that the drug itself is responsible, "we had to exclude lots of women because they had risk factors for depression." Ms. Lee presented the study at the meeting.

And these are the women "most vulnerable" to becoming depressed by tamoxifen, said National Institutes of Health researcher Jaskaran Singh, MD, who commented on the poster. Dr. Singh is researching the role of phosphokinase blockers in mania, so tamoxifen's ability to trigger depression, and also to block phosphokinase, "fits in well" with tamoxifen's link to depression. Dr. Singh was not involved in the study.

The study was a retrospective chart review of patients in northern California who were members of the Kaiser Permanente health plan. Depression was scored using ICD9 codes. Investigators did not delve into the actual patient records, due to Kaiser's privacy mandates, said Ms. Lee.

Investigators compared women with estrogen receptor-positive tumors who took tamoxifen to women with estrogen receptor-negative tumors and who therefore did not take tamoxifen.

Of the women with estrogen receptor-postive tumors who received tamoxifen, mean age was 62.7 years, and 84.1% were white. Of those who were estrogen receptor-negative and who did not take the agent, mean age was 56.6 years, and 75.1% were white. The majority of women in both groups had localized cancer.

Patients were diagnosed with breast cancer between 1997 and 2001.

Of the 771 patients diagnosed with depression and included for analysis, 78.6% used antidepressants, and 18.4% were diagnosed as outpatients.

Two thirds of women with estrogen receptor-negative tumors had chemotherapy compared with a quarter of those with estrogen receptor-positive tumors. Nearly all women in both groups had surgery.

"Chemotherapy is a known risk for depression, and we confirm this," Ms. Lee said. Radiation therapy did not show a link to depression.

A quarter of the women who received tamoxifen after diagnosis of cancer were diagnosed as depressed prior to beginning to take the drug.

Ms. Lee agreed that the study's strict exclusion removed women for whom tamoxifen might be a trigger. "It could be something underlying" in these women, Ms. Lee said, "so that tamoxifen adds to the increased risk.

"People need to be aggressive about screening or treating depression" in patients taking the agent, said Ms. Lee. "How much treatment they need is still an open question," she added. "It's up to the physician and the patient's profile."

The study was funded by the Kaiser Permanente Division of Research.

APA 156th Annual Meeting: Abstract NR19. Presented May 19, 2003.

Reviewed by Gary D. Vogin, MD


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