Carcinoid Tumor, Selective Serotonin Reuptake Inhibitors, and Diarrhea

To THE EDITOR: Selective serotonin reuptake inhibitor (SSRI) antidepressants are considered effective, easy to use, and well tolerated. Because of their fairly benign side effect profile and low degree of interaction with the metabolism of other medications, SSRIs are also frequently used in the treatment of depressive symptoms in patients with various physical illnesses.

Gastrointestinal symptoms, such as nausea and diarrhea, are relatively common side effects of SSRIs (e.g., diarrhea with citalopram1). Carcinoid tumors of the gastrointestinal tract are also frequently associated with diarrhea. Serotonin may play a role in the pathophysiology of diarrhea associated with both SSRIs and carcinoid tumors.

We report a case of an elderly woman with a carcinoid tumor who developed serious profuse diarrhea after starting treatment of depression with citalopram.

case Report

Ms. A was a 75-year-old retired clerk who was evaluated by her primary care physician for vague gastrointestinal complaints, namely, softer stools but no abdominal pain. Her appetite was good, and her weight was stable. A finding of occult blood in the stool was followed by a colonoscopy. Because of poor visualization caused by numerous diverticula, the colonoscopy was incomplete. A barium enema revealed suspicious polyps in the ascending colon. An abdominal computerized tomography and ultrasound confirmed a mass in the ascending colon and possible metastases in the liver. After a right hemicolectomy, the pathology revealed a tubulovillous adenocarcinoma. In addition, the foci of the carcinoid tumor were found in pericolonic adipose tissue; however, the primary carcinoid tumor was not found. Subsequent chemotherapy with raltitrexed (not available in the United States) was well tolerated. Ms. A had loose stools twice a day without abdominal pain. She lost about 13 Ib in 6 months.

Because of a depressed mood and anxiety that developed after the seventh course of chemotherapy, she was given citalopram, 20 mg/ day. She reported profuse diarrhea after the first dose of citalopram, with loose stools up to 14 times/day. She became dehydrated and had to be hospitalized. Infection or recurrence of her adenocarcinoma were ruled out. Results of her laboratory tests (a CBC, liver enzyme measures, a urinalysis) were within normal limits. Ms. A was rehydrated and released to home care. Without citalopram, she began having loose stools twice a day. 5- Hydroxyindoleacetic acid (5-HIAA) in her urine was not increased 1 month after discharge (no 5-HIAA level was obtained during hospitalization). No diarrhea developed during subsequent treatment with mirtazapine, 15 mg at night.

Discussion

SSRIs block the reuptake of serotonin by neurons and thus increase the amount of serotonin at the synapse. As noted, SSRIs may be associated with diarrhea. Carcinoid tumors of the gastrointestinal tract produce large amounts of serotonin at times and are associated with diarrhea. Serotonin has been implicated in diarrhea associated with both SSRIs and carcinoid tumor. We postulate that the additive effect of elevated serotonin associated with both SSRIs and carcinoid tumors played a role in the pathophysiology of profuse, severe diarrhea in this patient.

Depression associated with carcinoid tumors is relatively rare;2 nevertheless, it could develop, especially in rare cases of severe comorbidity with other illnesses, as in our patient. Our case suggests that SSRIs should be avoided in patients with carcinoid tumors because a severe dehydrating diarrhea may develop.

References

1. Muldoon C:The safety and tolerability of citalopram. lnt Clin Psychopharmacol 1996; ll(suppl 1):35-40

2. Larsson G, Sjoden PO, Oberg K, Eriksson B, von Essen L: Health- related quality of life, anxiety and depression in patients with midgut carcinoid tumours. Acta Oncol 2001; 40:825-831

Zdenk Simbera, M.D.

Chocerady, Czech Republic

Richard Balon, M.D.

Dtroit, Mich.

Copyright American Psychiatric Press, Inc. Jan/Feb 2005