Lydiatt, W.M., Denman, D., McNeilly, D.P., Puumula, S.E., & Burke, W.J. (2008). A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer. Archives of Otolaryngology, 134, 528–535.

To determine whether prophylactic treatment with the antidepressant citalopram hydrobromide can prevent major depression in patients undergoing treatment for head and neck cancer

The intervention consisted of 40 mg citalopram hydrobromide (a selective serotonin reuptake inhibitor). Medication began with 20 mg/day for week 1 and increased to 40 mg/day until week 12; after week 12, the dosage decreased to 20 mg/day for one week and then the drug therapy was stopped. Data were collected at baseline and at weeks 4, 8, 12, and 16 as well as at any time during the study.

• A total of 23 patients participated in the study (13 in the intervention group and 10 in the control group).
• Mean patient age was 61 years. The age range was 43–81 years.
• Eleven patients were female, and 12 were male.
• Patients were diagnosed with head and neck cancer only, mostly stage III or IV.
• No group differences existed in patients' age or sex, in tumor grade or type, in location of cancer, or in the number of treatment modalities.
• Patients began cancer treatment (surgery and/or radiation with or without chemotherapy) at baseline.

• Single site
• Outpatient
• Nebraska

Active treatment

Prospective, randomized, placebo-controlled trial with double blinding

• Hamilton Rating Scale for Depression (HRSD)
• Psychiatric interview using Mini-International Neuropsychiatric Interview I (MINI) for depression
• University of Washington disease-specific Quality-of-Life Questionnaire (UW-QOL)
• Clinician Global Impression-Severity (CGI-S) scale for global assessment of depression severity

During the 12 weeks of the study, 5 out of 10 taking the placebo and 2 out of 12 taking citalopram met the cutoff criteria for depression (measured by HRSD). However, the difference was statistically insignificant (Fisher exact test, p = 0.17). At the end of the study, of those receiving citalopram 15% were at least mildly ill in terms of global mood state as measured by the CGI-S scale; 60% of those in the control group were at least mildly ill as measured by the same means. Quality of life, measured by the UW-QOL, deteriorated in both groups from baseline to week 16, but less deterioration occurred in the citalopram group (p = 0.14).

Prophylactic treatment with citalopram hydrobromide may decrease the incidence and severity of depression during head and neck cancer therapy.

• The sample size was small, with fewer than 30 participants.
• Because of the small sample size and the inclusion of subjects from only one setting, the external validity and detection of intervention effect may be skewed.
• A priori sample estimation was set at N = 80, and the sample size of this study was much smaller. (Personnel factors led to early conclusion of the study.) As a result, researchers were unable to draw meaningful conclusions.

The risk of major depressive disorder can be very high in patients with head and neck cancer who are undergoing active treatment. Prevention of depression may be an attainable goal, although more research in this area is needed.