Mirtazapine

Mirtazapine

PEP Topic 
Sleep-Wake Disturbances
Description 

Mirtazapine is in a class of medications called antidepressants. It also has been used as an antianxiety medication, antiemetic, and appetite stiumulant. It works by enhancing adrenergic and serotonergic neurotransmitter activity in the brain. Mirtazapine is also an antagonist of 5-HT3 and histamine receptors.  Mirtazapine is available as a tablet and an oral disintegrating tablet. As with other antidepressants, patients may not experience the full benefits of mirtazapine for several weeks and it may cause withdrawal symptoms on discontinuation. Mirtazapine has been evaluated for anorexia, chemotherapy-induced nausea and vomiting, depression, sleep-wake disturbances, and hot flashes.

Effectiveness Not Established

Research Evidence Summaries

Cankurtaran, E. S., Ozalp, E., Soygur, H., Akbiyik, D. I., Turhan, L., & Alkis, N. (2008). Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine. Supportive Care in Cancer, 16, 1291–1298.

doi: 10.1007/s00520-008-0425-1
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Study Purpose:

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.

Intervention Characteristics/Basic Study Process:

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.

Sample Characteristics:

  • 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.

Setting:

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

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

The study used a prospective, repeated measures design.

Measurement Instruments/Methods:

  • 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

Results:

  • 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. 

Conclusions:

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.

Limitations:

  • 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.

Nursing Implications:

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.

Kim, S. W., Shin, I. S., Kim, J. M., Kim, Y. C., Kim, K. S., Kim, K. M., . . . Yoon, J. S. (2008).  Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression. Psychiatry and Clinical Neurosciences, 62, 75–83.

doi: 10.1111/j.1440-1819.2007.01778.x
Print

Study Purpose:

To study the effectiveness of mirtazapine on various cancer-related symptoms, such as nausea, sleep disturbance, pain, and depression.

Intervention Characteristics/Basic Study Process:

Patients were treated at a starting dosage of 15 mg of mirtazapine in orally disintegrating tablets a day. The dosage was titrated between 15 and 45 mg per day based on clinical judgment. Mean treatment dosage was 19.6 mg per day in the total population and 22.9 mg in those who completed the study. Patients were administered serial assessments at baseline and on days 1, 3, 5, 7, 14, and 28.

Sample Characteristics:

  • The sample was comprised of 42 patients (55% males, 45% females).
  • Mean age was 57.5 years (standard deviation = 12 years; range 22–79 years).
  • Patients had mixed cancers, 59% of which were lung, breast, gastrointestinal, hepatobiliary tract, or other. Of the patients, 61% had stage IV cancer.
  • Patients had malignant cancer AND nausea or insomnia.

Setting:

  • Single site
  • Inpatient (88%)
  • Korea

Study Design:

The study used a prospective, open-label, repeated measure design.

Measurement Instruments/Methods:

  • Clinical Global Impression (CGI) scale for nausea/vomiting 
  • Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire (C-LSEQ)
  • Montgomery–Åsberg Depression Rating Scale (MADRS) (two items):  reduced sleep and reduced appetite 
  • MÅDRS total score:  10-item objective rating scale to assess depression
  • Short Form Health Survey 36 (SF-36) (two bodily pain items)
  • EuroQOL (EQ)-5D
  • Udvalg for KliniskeUndersogelser (UKU) scale for sleepiness/sedation and dizziness

Results:

Nausea improved significantly from day 1 after administration of mirtazapine (p < 0.001). Improvement was sustained throughout the treatment and seemed to work best for patients actively receiving chemotherapy. In addition, anorexia improved. All sleep measures improved, many as early as day 1, but at least one measure (ease of wakening) did not improve until day 5 (p < 0.001). Mirtazapine increased sleepiness in one of three patients, but this resolved after several days on therapy. Reduction in pain scores (p < 0.5), improvement in depression score (p < 0.01), and overall quality of life (QOL) (p < 0.01) were noted as well.

Conclusions:

Mirtazapine may be helpful in treating the cancer-related symptoms of nausea, sleep disturbance, anorexia, pain, and depression, as well as improving QOL.

Limitations:

  • The study had a small sample size, with less than 100 patients.
  • The mirtazapine dosage varied.
  • The study had a high drop-out rate.
  • The patients were a heterogeneous group as far as concomitant medications were concerned. These were not controlled for, and patients were allowed to continue preexisting medications for nausea, hypnotics, and analgesics.
  • The percentage of inpatients was high.

Nursing Implications:

Mirtazapine may be useful in treating chemotherapy-related symptoms, especially sleep disturbance and nausea, in patients with malignant cancers.


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