Antidepressants

To compare the effectiveness of two psychotropic medications, mirtazapine and imipramine, on distressing somatic symptoms (i.e., pain, nausea, vomiting, decreased appetite, and sleep disturbance) of cancer as well as symptoms of depression and anxiety.

Patients self-selected to receive psychotropic medication and supportive psychotherapy (intervention group) or supportive psychotherapy only. Those who elected to take medication were randomly enrolled to receive mirtazapine or imipramine. Mean dosage of mirtazapine ranged from 5 to 30 mg/day, depending on the visit. Mean dosage of imipramine ranged from 5 to 100 mg/day, depending on the visit. Each group was then assessed at three visits:  baseline and three and six weeks after therapy had begun.

• The sample was comprised of 53 patients with cancer (35%–38.5% male, 61.5%–65% female).
• Median age was 43 to 47.5 years (range 26–56).
• All cancer types were included; no information about cancer stage was provided. 
• In each group, median time since diagnosis ranged from 6.5 to 8 months.
• All patients had an additional psychiatric diagnosis. All had cancer; were undergoing chemotherapy; and had been diagnosed with major depressive disorder, adjustment disorder, and/or anxiety disorder.

• Single site
• Outpatient
• Large oncology research and training hospital in Turkey

Patients were undergoing the active treatment phase of care.

The study used a prospective, repeated measures design.

• Patient sociodemographic information    
• Pain, nausea, and vomiting (evaluated by single-symptom scale)
• Weight
• Appetite (evaluated by single item)
• Hamilton Rating Scale for Depression (HRSD) (three items to assess sleep disturbance)
• Hospital Anxiety and Depression Scale (HADS), Turkish version

• Among the three visits, no significant differences were observed with regard to the degree of pain, nausea, vomiting, or appetite in the mirtazapine, imipramine, and control groups, and nor did differences exist in terms of the scores relating to the degree of pain, nausea, vomiting, appetite, weight, or insomnia, among the mirtazapine, imipramine, and control groups.
• In the mirtazapine group, the initial, middle, and late insomnia scores improved between the first and second and first and third visits. In the control and imipramine groups, no significant change occurred in insomnia scores between visits.
• In the imipramine group, a significant difference was seen in weight at the three visits. Median weight decreased from the second to third visit.
• In the mirtazapine group, statistically significant differences were noted in the mean total, anxiety, and depression HADS scores at each visit. Especially notable were score changes between the first and second visit. In the imipramine and control groups, no differences were found in the total, anxiety, and depression HADS scores across visits. 

Mirtazapine is effective in resolving insomnia and in reducing the symptoms of anxiety and depression in patients with cancer who have depression, anxiety, or adjustment disorders.

• The study had a small, heterogeneous sample, with less than 100 patients.
• The study had a high drop-out rate; by six weeks, 10 of 20 patients had dropped out of the control group, 4 of 20 had dropped out of the mirtazapine group, and 4 of 13 had dropped out of the imipramine group.
• The study had no control group or random assignment and presented no information about confounding factors. 
• Patients were not controlled for use of concomitant medications to treat the somatic symptoms being evaluated.

Mirtazapine may be useful in treating anxiety, depression, and insomnia in patients undergoing chemotherapy for cancer who have clinically relevant anxiety or depression. More systematic research, such as placebo-controlled studies, is required.

To investigate the safety and efficacy of fluvoxamine to treat anxiety and depression in patients with gynecologic cancer

For eight weeks patients were treated with escalating doses:

• Week 1: 25 mg once daily
• Week 2: 50 mg once daily
• Week 3: 50 mg twice daily
• Week 4: 50 mg three times daily
• Week 5 and onward: Dosing varied according to each patient's condition. 

Subjects were evaluated at two, four, six, and eight weeks.

• The study reported on a sample of 10 female patients.
• Median patient age was 53 years, with a range of 33–66 years.
• All patients had gynecologic cancers and were diagnosed at least two weeks prior to study entry.
• All patients had a HADS score of at least 11, indicating clinically relevant conditions. Mean HADS score was 19.
• Five patients had a diagnosed adjustment disorder, and five patients had major depression.

• Single site
• Setting not specified
• Japan

Patients were undergoing active antitumor treatment.

Prospective trial design 

• Hospital Anxiety and Depression Score (HADS)
• Short Form 36 Health Survey (SF-36)

Compared to HADS anxiety and depression scores at baseline, the scores were significantly lower after four weeks of treatment (p < 0.05) and remained significantly lower. After eight weeks, researchers noted significant improvements in SF-36 scores for vitality, mental health, and emotional role functioning (p < 0.05). No adverse effects of treatment were reported.

Fluvoxamine treatment of patients with gynecologic cancer who had clinically relevant anxiety and depression appears to reduce anxiety and depression. The small study sample precludes firm conclusions.

• The sample size was small, with fewer than 30 participants.
• The study had risks of bias because it had no control group, no blinding, and no random assignment.
• All patients had, at baseline, significant depression and anxiety, so findings cannot be generalized to patients with levels of these symptoms that are not clinically relevant. The follow-up period was only eight weeks; longer-term safety and efficacy are unknown.

Fluvoxamine as provided appeared to be effective in management of clinically relevant anxiety and depression in women with gynecologic cancer. Studies of anxiety and depression are often done with patients who do not have clinically significant problems in these areas at baseline, often making findings nonsignificant. This study provided some support for effective use of medication in patients with clinically relevant levels of anxiety and depression. The sample was very small, and the study design had multiple risks of bias. To determine which groups of patients can benefit from treatment, larger, well-designed trials are warranted.

To investigate the efficacy and tolerability of duloxetine in patients with cancer with mood disorder

Consecutive patients with diagnosed mood disorder started a regimen of duloxetine. They received an initial dose of 30 mg/day for one week, then 60 mg daily. If response was poor after one month, the dose was increased to 120 mg. Benzodiazepines were allowed as needed during the first two weeks. Study assessments were done at baseline, week 4, and week 12. Analysis compared results pertaining to those who had cancer and to those who did not.

• The study reported on a sample of 37 patients, 23 with cancer.
• Mean patient age was 63.6 years (SD = 10.9 years).
• The sample was 44.7% male and 45.3% female.
• Cancer types were not reported.

• Single site
• Outpatient setting
• Italy

Prospective observational design

• Hospital Anxiety and Depression Scale (HADS)
• State-Trait Anxiety Inventory
• EORTC questionnaire

Overall, 20% of patients dropped out of the study. Of the patients with cancer, 15% dropped out due to agitation, insomnia, or tachycardia. Analysis showed similar response over time of those with and without cancer diagnoses. Depression and anxiety by all measures declined at all follow-up times (p < 0.001).

Duloxetine was effective in reducing anxiety and depression in patients with and without cancer. The majority of patients tolerated the medication well.

• The study had small sample sizes, with samples of fewer than 30 and fewer than 100, respectively.
• The study had risks of bias due to no control group, no blinding, and no random assignment.
• Participant withdrawals were ≥ 10%.

Findings suggest that antidepressant use by patients with cancer who also have clinically relevant mood disorders can improve symptoms of anxiety and depression. Note: Most antidepressant studies that show a positive impact involve use by patients who have clinically relevant mood disorders at baseline.