• cancer;
  • depression;
  • insomnia;
  • mirtazapine;
  • nausea


  1. Top of page
  2. Abstract

Aims:  The purpose of the present paper was to evaluate the effectiveness of mirtazapine orally disintegrating tablets for nausea and sleep disturbance, which are common and distressing symptoms of cancer.

Methods:  This was a 4-week, prospective, open-labeled study of cancer patients. Assessments were performed at baseline and on days 1, 3, 5, 7, 14, and 28. Primary outcome measures were the Clinical Global Impression scale for nausea/vomiting and the Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire (C-LSEQ) including total amount of night sleep time. The secondary outcome measures consisted of pain items in the 36-item Short Form Health Survey, the Montgomery–Asberg Depression Rating Scale (MADRS), and the EuroQoL (EQ)-5D. Forty-two cancer patients were enrolled.

Results:  Those with nausea (n = 28) improved significantly from day 1. The total night sleep time and each item on the C-LSEQ improved from days 1–5. The scores on the MADRS and the depression/anxiety dimension and visual analog scale of EQ-5D improved significantly from the first week. Pain measures also improved from day 1. Exacerbation of sleepiness developed in approximately one-third of subjects during the initial few days, but disappeared gradually.

Conclusion:  In the present study mirtazapine rapidly improved nausea, sleep disturbance, pain and quality of life, as well as depression in cancer patients. Mirtazapine may be an effective treatment option in managing cancer patients with multiple distressing symptoms, including nausea and sleep disturbance.

NAUSEA, SLEEP DISTURBANCE, and depression are common and distressing symptoms in cancer patients,1 and the prevalence of depressive spectrum disorders in these patients is higher than in the general population, ranging up to 58%.2 Sleep disturbance has been reported to be one of the most frequent symptoms in cancer patients,1,3 and factors that are likely to precipitate sleep problems in these patients include not only psychiatric problems such as depression, anxiety, and emotional stress, but also pain and treatment side-effects such as nausea, vomiting, or urinary frequency.4

Selective serotonin re-uptake inhibitors (SSRI) and serotonin norepinephrine re-uptake inhibitors (SNRI) have been commonly used for the treatment of depression but they can induce sleep disturbance and nausea, associated with the pharmacologic stimulation of 5-HT2 and 5-HT3 receptors.5 Therefore, SSRI and SNRI are somewhat limited in their use for cancer patients who suffer from insomnia and nausea. In contrast, mirtazapine is a noradrenergic and specific serotonergic antidepressant with antagonistic effects on 5-HT2 and 5-HT3 receptors.6 Mirtazapine has been reported to be effective in controlling nausea and vomiting under various conditions7–10 and to facilitate sleep continuity.11 In addition, weight gain associated with increasing appetite, which is a common side-effect of mirtazapine, can be advantageous in patients with anorexia.

In clinical practice with cancer patients in consultation–liaison psychiatry, mirtazapine is often used as an antidepressant based on the aforementioned characteristics, but insufficient evidence exists to support its effectiveness in treating nausea, sleep disturbance, or depression in cancer patients. Specifically, to our knowledge, a study has not been performed with mirtazapine in a population of Asian cancer patients. We therefore evaluated the effectiveness of mirtazapine comprehensively on various cancer-related symptoms, including nausea and sleep disturbance.


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  2. Abstract


Eligible subjects were patients who had malignant cancer with nausea or insomnia. All subjects met DSM-IV diagnostic criteria for major depressive disorder, depressive disorder not otherwise specified (NOS), or adjustment disorder with depressed mood.12 Depressive disorder NOS included minor depressive disorder and cases in which the clinician had concluded that a depressive disorder was present but was unable to determine whether it was primary, due to a general medical condition, or substance induced.12 Subjects who were taking other antidepressants for controlling depressive symptoms were excluded. The subjects were recruited from patients who were referred from the Cancer Center of Chonnam National University Hwasun Hospital, Korea.

A total of 42 cancer patients were enrolled. The sample consisted of 23 men and 19 women, with a mean age of 57.5 ± 12.0 years (range 22–79 years). Twenty-six patients (62%) had stage IV cancer, and the lung was the most common lesion site (60%; Table 1). Thirty-seven subjects (88%) were inpatients.

Table 1.  Subject characteristics
Variablesn (%)
Age (years) (mean ± SD)57.6 ± 12.0
Sex (M : F)23:19 (45.2)
Psychiatric diagnosis
 Major depressive disorder3 (7.1)
 Depressive disorder, NOS35 (83.3)
 Adjustment disorder4 (9.5)
Region of cancer
 Lung25 (59.5)
 Breast5 (11.9)
 Gastrointestinal tract6 (14.3)
 Hepatobiliary tract3 (7.1)
 Other malignancy3 (7.1)
 I6 (14.3)
 II3 (7.1)
 III7 (16.7)
 IV26 (61.9)

Seventeen patients (41%) completed the 4-week study, and 26 patients (62%) finished assessment at 2 weeks. Several factors were involved in the failure to complete the study. The main reason for patients being dropped from the study was that they did not visit the psychiatric outpatient clinic for assessment on their scheduled date but continued to take mirtazapine (n = 9). The physical states of seven patients were too poor to continue the study. Four patients discontinued mirtazapine because of side-effects (two due to sedation and one each due to general weakness or constipation). Five patients were lost to follow up. The dropout group did not differ significantly from those who completed the study with regard to age, gender, and psychiatric characteristics (Montgomery–Asberg Depression Rating Scale [MADRS] score and sleep). However, the dropout rate of subjects with early stage cancer (I and II) was significantly lower (22%).

Study procedure

This was a 4-week, prospective, open-labeled study. Subjects were started on 15 mg mirtazapine orally disintegrating tablets, with a flexible dosage ranging between 15 and 45 mg based on clinical judgment. The mean treatment dose of mirtazapine at the last observation was 19.6 mg in the total population and 22.9 mg in the subjects who completed the study. Only 11 patients (26%) were administrated either 30 or 45 mg mirtazapine. Hypnotics, anti-emetics, and analgesics, which had been administered at stable dosages before starting mirtazapine, were permitted without increasing their dosages. The study was approved by the hospital's institutional review board and all subjects gave informed consent prior to participation in the study.

Outcome measures

Assessments were performed at baseline and at days 1, 3, 5, 7, 14, and 28. The primary outcome measures were the Clinical Global Impression (CGI) scale for nausea/vomiting (N/V) and the Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire (C-LSEQ) including the total amount of night sleep time. The secondary outcome measures consisted of two items (reduced sleep and reduced appetite) on the MADRS,13 two bodily pain items on the 36-item Short Form Health Survey (SF-36),14 the total MADRS score, and the EuroQoL (EQ)-5D.15 The full MADRS and EQ-5D were evaluated at baseline and on days 7, 14, and 28. Sleepiness/sedation and dizziness, which were expected to frequently develop with the use of mirtazapine, were assessed with the items of the Udvalg for Kliniske Undersogelser (UKU) scale,16 and all other side-effects were recorded at every visit. All the assessment ratings were performed by trained psychiatrists.

The severity of nausea and vomiting was graded using the CGI for N/V, a 7-point numeric analog rating scale modified from the Common Toxicity Criteria Grading Scale of the National Cancer Institute,17 which is a 5-point scale used to assess complications in patients participating in clinical trials. The CGI for N/V was operationally defined as follows: CGI 1, no N/V; CGI 2, borderline state; CGI 3, clear but mild and tolerable N/V; CGI 4, N/V with subjective discomfort not influencing the amount or pattern of oral intake; CGI 5, N/V causing decreased oral intake; CGI 6, N/V preventing the patient from eating solid food; CGI 7, N/V preventing the patient from eating anything.

The C-LSEQ was a modification of the LSEQ18 and was administered to assess sleep. It measures the subjective assessment of sleep factors, that is, ease of getting to sleep, quality of sleep, ease of awakening in the morning from sleep, and integrity of behavior following wakefulness. The original LSEQ is a 100-mm line visual analog scale (VAS), but was modified to a 5-point Likert scale because the VAS is somewhat vague in indicating each sleep dimension in older cancer patients. A lower score denotes better sleep conditions.

Pain was assessed using two bodily pain items on the SF-36, which is a commonly used health survey scale. The two items were pain magnitude (6-point Likert scale) and pain interference (5-point Likert scale). The sum of the two scores, ranging between 2 and 11, was used in the analysis. A higher score indicates severe pain.

The MADRS is a 10-item objective rating scale commonly used to assess depression, and the EQ-5D is a commonly used health-related quality-of-life scale consisting of two components: descriptive systems and a VAS. In the descriptive systems a lower score indicates a better state of health. In the VAS representing the patient's overall state of health, a higher score denotes a better health status.

Statistical analysis

SPSS version 12.0 for Windows (SPSS, Chicago, IL, USA) was used for statistical analysis. Demographic and clinical characteristics were summarized. The changes in scores of the efficacy measures from baseline were analyzed using Wilcoxon signed-rank test for each time point. End-point analyses used a last observation carried forward (LOCF) approach; that is, the last available visit was used as the end-point. Analysis for nausea was performed only on subjects who suffered from nausea (n = 28). Subjects were divided into two groups according to chemotherapy for a post-hoc analysis; Wilcoxon signed-rank test was performed on each group, and changes in nausea between the two groups were compared using a Mann–Whitney U-test. The partial correlations among score changes for pain, CGI-nausea, total amount of night sleep time, quality of sleep in the C-LSEQ, EQ-5D VAS, and the MADRS from baseline to final evaluation were estimated after controlling the baseline score for pain and CGI-nausea. All changes in efficacy measures were compared according to cancer type (lung cancer and other malignancy) using a Mann–Whitney U-test and the relationships between the changes and cancer stage and age were analyzed using a partial correlation adjusting for the baseline scores. If hypnotics, anti-emetics, or analgesics were newly added or increased during the study period in subjects whose insomnia, nausea, or pain was intolerable with the use of only mirtazapine, the measure just before adding or increasing the medication was regarded as the final observation in the scale for sleep, nausea, or pain. Scores on the MADRS and EQ-5D and the reported side-effects were analyzed regardless of the use of additional medication. All statistical tests were two-tailed with a significance level of P = 0.05.


  1. Top of page
  2. Abstract

Table 2 lists the changes in scores on measures for nausea, sleep, pain, and quality of life over time.

Table 2.  Scores on measures for nausea, appetite, sleep, pain, and quality of life
 BaselineDay 1Day 3Day 5Day 7Day 14Day 28End-point
  • *

    P < 0.5;

  • **

    P < 0.01;

  • ***

    P < 0.001 by Wilcoxon singed-rank test for mean change from baseline.

  • Subscale of Chonnam National University Hospital-Leeds Sleep Evaluation Questionnaire.

  • Dimension of EuroQoL-5D.

  • CGI, Clinical Global Impression; MADRS, Montgomery–Asberg Depression Rating Scale; NA, not applicable; SF-36, 36 items of Short Form Health Survey.

CGI for nausea (n = 28)4.6 ± 1.33.6 ± 1.6***2.9 ± 1.7***3.0 ± 1.6***2.7 ± 1.8**2.9 ± 1.7**2.9 ± 2.2*2.6 ± 1.9***
Reduced appetite on MADRS (n = 42)3.7 ± 1.53.2 ± 1.5**2.7 ± 1.6**2.8 ± 1.5**2.8 ± 1.4**2.5 ± 1.6**2.3 ± 1.6**2.4 ± 1.5***
Amount of sleep (n = 39), hour3.6 ± 1.96.0 ± 2.8***6.2 ± 2.6***5.9 ± 2.4***5.9 ± 2.4***6.2 ± 2.6**6.9 ± 1.6**6.8 ± 2.5***
Ease of getting to sleep (n = 39)4.2 ± 1.02.9 ± 1.1***2.5 ± 1.0***2.4 ± 1.0***2.5 ± 0.9***2.3 ± 1.0***2.3 ± 0.9**2.4 ± 1.0***
Quality of sleep (n = 39)4.3 ± 0.92.8 ± 1.3***2.5 ± 1.1***2.6 ± 1.2***2.7 ± 1.2***2.7 ± 1.1***2.5 ± 1.0**2.6 ± 1.1***
Ease of waking in the morning (n = 39)3.2 ± 1.13.2 ± 1.02.8 ± 1.02.6 ± 0.9*2.4 ± 1.0**2.5 ± 1.0*2.2 ± 0.8*2.5 ± 1.0**
Behavior following wakefulness (n = 39)3.8 ± 0.93.4 ± 1.0**3.0 ± 1.1***3.1 ± 1.1**3.1 ± 1.0**2.9 ± 1.0**2.6 ± 1.0*2.9 ± 1.1***
Reduced sleep on MADRS (n = 39)4.3 ± 1.82.5 ± 2.3***1.9 ± 2.0***1.8 ± 2.0***1.8 ± 1.6***1.6 ± 1.7***1.3 ± 1.3**1.6 ± 1.6***
Pain items in SF-36 (n = 42)5.2 ± 2.84.5 ± 2.4**4.4 ± 2.4**4.3 ± 2.5***4.5 ± 2.4*4.4 ± 2.7*3.9 ± 2.6*4.1 ± 2.6**
Mobility (n = 42)2.0 ± 0.7NANANA1.9 ± 0.71.8 ± 0.51.9 ± 0.82.0 ± 0.7
Self-care (n = 42)1.8 ± 0.7NANANA1.9 ± 0.71.7 ± 0.71.6 ± 0.81.8 ± 0.7
Usual activities (n = 42)2.1 ± 0.6NANANA2.1 ± 0.61.9 ± 0.61.8 ± 0.72.0 ± 0.7
Pain/discomfort (n = 42)2.1 ± 0.7NANANA1.9 ± 0.6*1.9 ± 0.61.8 ± 0.61.9 ± 0.7*
Anxiety/depression (n = 42)2.3 ± 0.6NANANA1.9 ± 0.7**1.8 ± 0.5*1.6 ± 0.7**1.8 ± 0.7**

Efficacy on nausea

Those with nausea (n = 28) improved significantly from day 1 after administration of mirtazapine, without increasing the dosage of prior anti-emetics or adding further anti-emetics. When subjects were divided into two groups, patients undergoing chemotherapy (n = 11) and those who were not (n = 17), nausea also significantly improved from day 1 in both groups, and the improvements were sustained to the end-point (the former, 4.6 ± 1.1–1.2 ± 0.4, z = 2.949, P = 0.003; and the latter, 4.6 ± 1.4–3.5 ± 1.9, z = 2.824, P = 0.005). However, changes in nausea in patients undergoing chemotherapy were significantly greater than those in patients not receiving chemotherapy (z = 3.617, P < 0.001). The relationship between the time of chemotherapy and commencement of mirtazapine in 11 patients was as follows: five patients received chemotherapy after starting mirtazapine, five patients started mirtazapine within 1 day after receiving chemotherapy, one patient started mirtazapine at 5 days after receiving chemotherapy, and one patient suffered from chronic nausea after receiving chemotherapy. Nausea almost completely improved in all of these patients and five (45%) were treated with mirtazapine only. In contrast, only three of 17 patients not receiving chemotherapy showed completely improved nausea, and 10 patients (59%) took only mirtazapine for nausea. Item 5 (reduced appetite) on the MADRS also improved significantly from day 1.

Efficacy on sleep disturbance

Eleven patients (26%) took hypnotics such as zolpidem or alprazolam with mirtazapine for sleep disturbance. Among these, three patients in whom hypnotics were newly started along with mirtazapine at baseline were excluded from the analysis on the effectiveness of mirtazapine for sleep disturbance. In two patients whose hypnotics were newly added in the middle of the study period because of uncontrolled insomnia with mirtazapine, the measures taken just before commencing the hypnotics were regarded as the final observation, and those rated after commencing the hypnotics were not entered into the analysis. In 39 subjects available for sleep measurement, the total night sleep time increased significantly from day 1 with the use of mirtazapine; the amount of sleep increased from 3.6 to 6.8 h/day at the last observation. Three items (ease of getting to sleep, quality of sleep, and behavior following wakefulness) on the C-LSEQ and item 4 (reduced sleep) on the MADRS also improved significantly from day 1. Ease of waking in the morning on the C-LSEQ improved significantly from day 5.

Efficacy on pain

Twenty-eight patients (67%) were given analgesics. Among these, 24 patients (57%) took opiates. In five patients whose opiates were newly commenced or increased in the middle of the study period, the measures taken just before adding or increasing the opiate dose were regarded as the final observation. Reduction of pain score was statistically significant from day 1.

Efficacy on quality of life and depression

In the five dimensions on the EQ-5D, the anxiety/depression dimension showed a significant improvement at every visit. The pain/discomfort dimension improved significantly on day 7 and at the final observation. However, mobility, self-care, and usual activities dimensions showed no significant changes over time.

Figure 1 shows that scores on measures for depression and health related quality of life by visit and at end-point. Scores on the MADRS (33.2 ± 10.7–22.5 ± 12.5 at the end-point) and EQ-5D VAS (41.9 ± 20.9–54.1 ± 23.5 at the end-point) improved significantly from the end of the first week.


Figure 1. Scores on measures for health related quality of life and depression by visit and at end-point. (◆) Visual Analog Scale of EuroQoL-5D; (▪) Montgomery–Asberg Depression Rating Scale. *P < 0.5; **P < 0.01; ***P < 0.001.

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Relationship between changes in scores on outcome measures

Table 3 lists the correlations between changes in scores on measures for pain, nausea, sleep, quality of life, and depression. Changes in the pain score were significantly correlated with changes in sleep quality, nausea, and depression. Changes in the score on the MADRS were significantly correlated with changes in all other outcome measures analyzed for correlations, such as nausea, sleep quality, and quality of life. Cancer type, cancer stage, and age were not significantly correlated with changes in any outcome measures, except for the correlation between the item of behavior following wakefulness in C-LSEQ and age (r = −0.371, P = 0.022).

Table 3.  Partial correlation coefficients
 CGI-nauseaAmount of sleepQuality of sleepVAS of EQ-5DMADRS
  • *

    P < 0.5;

  • **

    P < 0.01;

  • ***

    P < 0.001.

  • Correlations were estimated after controlling the baseline score of pain and CGI-nausea.

  • CGI, Clinical Global Impression; MADRS, Montgomery–Asberg Depression Rating Scale; Quality of sleep, item from the Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire; VAS of EQ-5D, Visual Analog Scale of EuroQoL-5D.

CGI-nausea −0.1570.166−0.2400.349*
Amount of sleep  −0.521**0.248−0.386*
Quality of sleep   −0.3230.645***
VAS of EQ-5D    −0.549***


Sleepiness/sedation was reported in 20 subjects (48%) at baseline, even before starting mirtazapine. It was exacerbated in 36% of subjects following the administration of mirtazapine. Exacerbation of sleepiness/sedation decreased to 19% of subjects (n = 31) on day 7, 8% of subjects (n = 26) on day 14, and 0% of subjects (n = 17) on day 28. At the final observation (n = 42), sleepiness/sedation was exacerbated in only six patients (14%); in contrast, it improved compared to baseline in 60% of 20 patients who had suffered sleepiness at baseline. Dizziness was exacerbated in six patients (14%), but it also improved gradually. No patient experienced exacerbated dizziness after 2 weeks.


  1. Top of page
  2. Abstract

Mirtazapine has been recommended for use in cancer patients with nausea because of its unique characteristic of antagonizing 5-HT3 receptors, which is the same as that of ondansetron, a conventional anti-emetic frequently used in cancer patients.19 However, few data existed on the effectiveness of mirtazapine for nausea in cancer patients: a serial case report with positive results20 and a small open-label trial with negative results.21 In the present study mirtazapine was shown to be effective at improving nausea, and its effectiveness was greater for nausea related to chemotherapy than for that caused by other factors. Cautious interpretation is required because nausea induced by chemotherapy can be time-limited, usually persisting for approximately 7–10 days after chemotherapy. However, in the present study mirtazapine was immediately effective in ameliorating nausea, and in some patients the improvement was maintained at the next cycle of chemotherapy. These findings suggest that mirtazapine may be useful for controlling nausea or vomiting in cancer patients. Moreover, mirtazapine orally disintegrating tablets, which dissolve on the tongue, are helpful in patients who become nauseous when swallowing. In addition, mirtazapine, which is a potent blocker of the histamine H1 receptor and a 5-HT2C antagonist, also has potential as an appetite stimulant.

Few data are available concerning the effectiveness of mirtazapine for sleep disturbance in cancer patients.22 Our results suggest that mirtazapine may have an effect on sleep quality, as well as sleep quantity, in cancer patients. The mechanism of mirtazapine for promoting sleep seems to be related to its antihistaminic, α-adrenolytic, and 5-HT2 antagonistic actions.6 Compared to benzodiazepines, which are commonly used to induce sleep, mirtazapine does not have the potential for dependence, respiratory suppression, or disturbance of deep-stage sleep.

Mirtazapine exacerbated sleepiness in more than one-third of the present patients during the initial few days, and two patients were not able to tolerate mirtazapine due to excessive sedation. Among items on the C-LSEQ, ease of waking improved last. However, sleepiness was not caused by mirtazapine alone. Sleepiness was reported in nearly half of the present subjects, even before starting mirtazapine. This sleepiness was assumed to be related to the poor quality of night-time sleep, physical condition, and other medication used, including opiates.23 Exacerbation of sleepiness by mirtazapine disappeared gradually. Moreover, mirtazapine ameliorated sleepiness in 60% of the subjects who suffered from it at baseline. Previous studies have also reported that daytime sedation by mirtazapine, which has a half-life of 20–40 h, is prominent during the first week of treatment but appears to diminish after a few days.24 Therefore, information about sleepiness related to the use of mirtazapine, which can develop initially but becomes tolerable within a few days, should be given to patients. In particular, the concomitant use of benzodiazepines with mirtazapine needs to be avoided to prevent over-sedation.25

Antidepressant agents have been used extensively to treat pain.26 Several studies have examined the effect of mirtazapine on pain under various conditions, such as tension headache, fibromyalgia, and chronic pain syndrome,27–29 but the effect of mirtazapine on cancer pain had not been sufficiently studied.21 In the present study the reduction in pain score, including pain magnitude and its interference with daily activities, was statistically significant from day 1. One of the reasons for rapid improvement in pain and pain behavior seemed to be an indirect result of an improvement in sleep and mood. Pain is usually exacerbated at night when sensory stimuli decrease, and depression worsens pain by lowering the pain threshold, while pain also can worsen sleep disturbance and depression.3,30–32 The correlation between pain reduction and improvement in the quality of sleep and depression was significant in the present study.

The mean dose of mirtazapine used in the present study was around 20 mg. However, previous studies performed in Western countries have reported a dosage of ≥30 mg in the treatment of cancer patients.20,25 The pharmacokinetic difference between Caucasian and Asian patients possibly contributed to a lower dose being used in the present study compared to past studies.33 Another study with mirtazapine performed on Korean alcoholic patients reported that low doses of mirtazapine (mean 23 mg/day) were effective.34 Moreover, the effective dose of mirtazapine for sleep disturbance and nausea has been reported to be relatively low (≤30 mg).7–11,24 Finally, the dosage used in the present study might have been influenced by the patients' physical condition because most had advanced cancer.

We acknowledge several limitations of the present study. A possibility exists that the placebo effect influenced the results because this was not a controlled trial. The sample was relatively small in relation to the large number of outcome variables. Furthermore, some confounding factors were present, including concomitant medical treatments, which were not strictly controlled. However, strict prohibition of concomitant medication in patients with advanced cancer would have produced ethical conflicts. To avoid confounding effects, we tried not to increase or add anti-emetics, hypnotics, or analgesics, and in the analysis did not include symptom measures that were taken after commencing or altering the dosages of these drugs. In addition, the dropout rate was high. The physical status of the subjects and the study design requiring frequent assessment seemed to influence the dropout rate. It was difficult to follow up patients with advanced-stage cancer who were discharged from the oncology unit or transferred to another hospital for supportive care. To overcome this limitation, measurements in subjects who dropped out were analyzed using end-point analysis. Although the follow-up period was relatively short for the evaluation of depression, we performed more frequent assessments than previous studies on changes in sleep and nausea, which were primary outcomes of the study. This was one of the strengths of the present study. Finally, all of the present subjects were depressed; therefore, the improvement in nausea, anorexia, insomnia, and pain might have been related to an improvement in depression. Further research is warranted, and studies that include non-depressed patients using a randomized controlled design in a large sample, while focusing on specific symptoms, are needed.

In the present study, nausea, anorexia, sleep disturbance, pain, depression, and quality of life rapidly improved in cancer patients with the use of mirtazapine. The present results suggest that mirtazapine may be an effective treatment option for managing cancer patients with multiple distressing symptoms. A controlled trial is needed to confirm the study results.


  1. Top of page
  2. Abstract

This study was supported in part by an investigator-initiated grant from Organon Pharmaceuticals, a grant (CUHRICM-U-200626) from Chonnam National University Hospital Research Institute of Clinical Medicine, and grants (A050047 and A050174) from the Korea Health 21 R & D Project, Ministry of Health and Welfare, Korea.


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  2. Abstract
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