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Goserelin-Induced New-Onset Depressive Disorder

TO THE EDITOR: We report a case of new-onset depressive disorder in a patient with a documented history of prostate cancer treated with goserelin and no previous formal psychiatric history. This case raises the possibility of a link between goserelin and depression. The case also highlights the need to screen patients treated with goserelin for depression and to treat them as needed.

Case Report

This 73-year-old man with no past psychiatric history and a recent diagnosis of prostate cancer presented to the geriatric psychiatry clinic with new-onset symptoms of depression meeting criteria for a major depressive episode. The patient had been diagnosed with prostate cancer 2 months before his clinic visit. He was started by his urologist on goserelin injections and received two injections over the course of 4 weeks. Before the initiation of the goserelin treatment, the patient had been in his usual state of mental well-being, with no depressive symptoms. Two weeks after the first injection, he began to complain of feeling "down." He also complained about having poor concentration, being unmotivated, and not enjoying his old activities and hobbies. He showed psychomotor retardation, with feelings of hopelessness and worthlessness. A medical work-up for depression was unremarkable. Two weeks after his first injection, his internist started him on sertraline 25 mg in the morning to treat these new symptoms of depression. However, the patient and his wife stated that his symptoms continued to worsen after he received a second injection of goserelin, and the patient was referred for psychiatric evaluation.

Discussion

Gonadotropin-releasing hormone (GnRH)-agonists are synthetic derivatives of the natural decapeptides produced by the hypothalamus. These agents, such as goserelin (Zoladex®), cause a reversible suppression of the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland. As a result, GnRH-agonists significantly reduce plasma concentrations of androgens and estrogens. They are used to effectively treat disorders aggravated by estrogen or testosterone, such as prostate cancer, endometriosis, precocious puberty, and uterine leiomyomata.¹

Because of their effects on estrogen and androgens, these agents are associated with physical and psychiatric side effects. Some of the reported psychiatric symptoms linked to GnRH-agonists include depression, emotional lability, poor concentration, fatigue, low energy, and decreased libido.² The initial drug company study for FDA approval was 411 women treated with goserelin for endometriosis, and it showed a depression rate of 54% in the active-agent group.³ There were several other studies that described higher rates of depression with goserelin in women treated for endometriosis.^4,5

This case report suggests a possible link between the onset of depressive symptoms and treatment with a GnRH-agonist in a patient with prostate cancer. In this case, there was a temporal relationship between the beginning of therapy and the onset of symptoms in a 73-year-old patient with no formal psychiatric history. A literature search revealed no case reports or studies regarding new depressive symptoms in men treated with GnRH-analogues for prostate cancer. Further investigation is required to confirm this relationship.

REFERENCES

1. Conn PM, Crowley WF: Gonadotropin-releasing hormone and its analogs. Annu Rev Med 1994; 45:391–405[CrossRef][Medline]
2. Warnock JK, Bundren JC, Morris DW: Depressive symptoms associated with gonadotropin-releasing hormone-agonists. Depress Anxiety 1998; 7:171–177[CrossRef][Medline]
3. Zeneca Pharmazeuticals: Gosrelin Acetate Package Insert and Professional Product Brochure, 1995 (rev)
4. Steingold KA, Cedars M, Lu JK, et al: Treatment of endometriosis with a long-acting gonadotropin-releasing hormone-agonist. Obstet Gynecol 1987; 69:403–411[Abstract]
5. Warnock JK, Bundren JC: Anxiety and mood disorders associated with gonadotropin-releasing hormone-agonist therapy. Psychopharmacol Bull 1997; 33:311–316[Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Kohen, I. Articles by Koppel, J. Search for Related Content PubMed Citation Articles by Kohen, I. Articles by Koppel, J. Depression Other Somatic Therapy

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