To the Editor:
This letter is in response to the article by Theobald et al., “An Open-Label, Cross-Over Trial of Mirtazapine (15 and 30 mg) in Cancer Patients With Pain and Other Distressing Symptoms.”1 The authors conclude that mirtazapine may be effective in the treatment of depression and several somatic symptoms in cancer patients. In support of their findings, we would like to present our results in short and to make some remarks concerning further research.
Data on treatment of depression with antidepressants in somatically ill patients are relatively scarce. The receptor profile of mirtazapine (antagonizing α-2-, 5HT2- and 5HT3-receptors, which may, among others, account for a reduction in nausea, agitation, and anxiety and an improvement in sleep quality) could indeed be beneficial in cancer patients with depressive complaints.
We performed an open-label pilot study with mirtazapine in 30 (22 women, 8 men, mean age 55.4 yrs) cancer patients with major depressive disorder (27), substance-induced mood disorder (1), or depressive disorder not otherwise specified (NOS) (2), according to the Diagnostic and Statistical Manual IV. All were outpatients and inpatients of a cancer clinic. Most depressions were rated as mild to moderate (90%). Of the individual symptoms, depressed mood, anhedonia, agitation, and anxiety were most frequently present and most intense. Typical cognitive depressive contents, such as self-reproach, suicidal ideation and guilt feelings, were scarce. The duration of the depressive episode was less than 1 month in 6 patients, 1–3 months in 14 patients, and more than 3 months in 10 patients. Sleep disturbance was present in 24 patients, mostly a combination of difficulties falling asleep and interrupted sleep.
Fourteen patients had metastatic disease, 2 localized disease, and 14 no evidence of disease. To our surprise, in 7 patients serious somatic comorbidity was present, such as chronic obstructive pulmonary disease, multiple sclerosis, systemic lupus erythematosus (SLE), and cardiomyopathy. Sixteen patients were on ongoing treatment for their cancer, mostly hormonal therapy for breast cancer.
Only 9 patients did not use any other drug. Nineteen patients were on benzodiazepines, mostly started before referral to our psychiatric service.
Mirtazapine was started at a dose of 30 mg, and could be raised to 45 or 60 mg. Prescription of mirtazapine was often combined with supportive psychotherapy and psychotherapy with cognitive behavioral elements. Treatment evaluation took place at 2 and 8 weeks.
Twenty patients completed the first 8 weeks, with CGI-improvement rated at 8 weeks as very good in 6, clear in 10, and fair in 4. Sixteen patients continued mirtazapine after 8 weeks. Drop-out was mostly related to sedation in the first two weeks of treatment. Of the drop-outs, 3 were not depressed anymore at the time of discontinuing the medication.
Our results support the conclusion of Theobald et al. that a controlled trial with mirtazapine is warranted. Mirtazapine appears safe and effective in an oncology population in open studies. It appears also to be safe when combined with other drugs. We would suggest that somatic comorbity, aside from the cancer, concomitant medication, and concomitant tumor treatment, be assessed in future research. Before our study, we did not fully realize that our patients had this much comorbidity and concomitant treatments. In case of sedation because of mirtazapine, the concomitant use of benzodiazepines (which was frequent in our sample) needs to be reconsidered. Furthermore, sample size merits attention: in concordance with the data from Theobald and coworkers, the depressions in our sample were mostly mild to moderate. In the case of relatively mild depression, because of a “floor effect,” larger sample size is needed to demonstrate an effect of an antidepressant. Finally, we would like to underscore the use by Theobald and coworkers of outcome variables other than depression rating scales. They incorporated separate measures for fatigue, pain, nausea, and loss of appetite. These measures are directly relevant for quality of life in oncology patients, maybe more so than scores on rating scales incorporating typical psychiatric symptoms as guilt feelings or self-reproach. Moreover, somatic complaints like pain, nausea, and loss of appetite have a negative influence on mood, on interest in others, and on the ability to experience pleasure, which would be ascribed to depression when using only depression rating scales.
RPII S0885-3924(02)00381-0
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