[See also mirtazapine research.]

Behnke K, Sogaard J, Martin S, Bauml J, Ravindran AV, Agren H, Vester-Blokland ED.
Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.
J Clin Psychopharmacol. 2003 Aug;23(4):358-64.
"This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient." [Abstract]

Benkert O, Szegedi A, Kohnen R.
Mirtazapine compared with paroxetine in major depression.
J Clin Psychiatry 2000 Sep;61(9):656-63
"BACKGROUND: The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine. METHOD: 275 outpatients with a diagnosis of major depressive episode (DSM-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (15-45 mg/day) or paroxetine (20-40 mg/day). Efficacy was assessed by the HAM-D-17, Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scales (Severity and Improvement), and analyses were performed on the intent-to-treat sample (127 mirtazapine-treated patients and 123 paroxetine-treated patients). RESULTS: Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine. Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out. Both drugs were equally effective in reducing symptoms of depression. At week 1, the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients (16.5 vs. 18.8, p = .0032). Similarly, significantly more mirtazapine-treated patients were HAM-D-17 responders (> or = 50% decrease from baseline) at weeks 1 (23.2% vs. 8.9%, p = .002) and 4 (58.3% vs. 44.5%, p = .04). Both treatments were equally effective in reducing anxiety. However, the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 (-5.1 vs. -3.5, p = .0435). Tolerability of both treatments was good, with more nausea, vomiting, tremor, and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group. CONCLUSION: Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated. A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression." [Abstract]

Wade A, Crawford GM, Angus M, Wilson R, Hamilton L.
A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care.
Int Clin Psychopharmacol. 2003 May;18(3):133-41.
"Primary care patients with a major depressive disorder and 17-item Hamilton Rating Scale for Depression (17-HAM-D) score >18 were randomized to 24 weeks of treatment with mirtazapine 30-45 mg/day (n=99) or paroxetine 20-30 mg/day (n=98). Both treatments were efficacious in improving depressive symptomatology, as assessed by group mean 17-HAM-D scores, percentages of HAM-D responders and remitters and Clinical Global Improvement responders. The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17-HAM-D scores at weeks 1, 2 and 4, and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4. Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment. Both treatments were well tolerated. The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue. Statistically significantly more paroxetine-treated patients complained of increased sweating, headache and nausea. The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care. An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine, and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors." [Abstract]

Schatzberg, Alan F., Kremer, Charlotte, Rodrigues, Heidi E., Murphy, Greer M., Jr., The Mirtazapine vs. Paroxetine Study Group
Double-Blind, Randomized Comparison of Mirtazapine and Paroxetine in Elderly Depressed Patients
Am. J. Geriatr. Psychiatry 2002 10: 541-550
"Of 255 patients randomized, 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis. Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D–17 score. Other significant differences were in the proportion of patients classified as responders (50% decrease from baseline Ham-D–17 scores) at Day 14 and in remission (Ham-D–17 score of 7 or less) at Day 42. The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group. The mirtazapine group also showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores. Efficacy of both drugs was maintained during the extension phase. Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events." [Abstract]

Murphy GM, Kremer C, Rodrigues H, Schatzberg AF; Mitrazapine versus paroxetine Study Group.
The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients.
Biol Psychiatry. 2003 Oct 1;54(7):665-73.
"BACKGROUND: Patients vary in response to antidepressant medications. Apolipoprotein E (APOE) genotype affects vulnerability to stress and risk for cognitive impairment. We sought to determine if the APOE epsilon4 allele influences response in geriatric depression to mirtazapine and paroxetine, two frequently prescribed antidepressants. We hypothesized that epsilon4 carriers would show impaired antidepressant response. METHODS: The study was a double-blind, randomized, 8-week trial with a 16-week extension phase involving 246 cognitively intact patients aged 65 years or older with major depression. Patients were treated with mirtazapine 15-45 mg (n = 124) or paroxetine 20-40 mg (n = 122). The outcome measures were the Hamilton Depression Rating Scale, the Geriatric Depression Scale, and the Clinical Global Impression Scale. APOE genotype was determined by restriction isotyping. RESULTS: Patients carrying the epsilon4 allele showed a rapid onset of mirtazapine action, whereas paroxetine-treated patients with the epsilon4 allele were slow to respond. This difference could not be attributed to dosage, compliance, severity of adverse events, ethnicity, baseline depression or cognition, gender, or age. CONCLUSIONS: The APOE epsilon4 allele may affect antidepressant treatment outcome, but the effect depends on the medication. Further studies should determine if this result applies to other samples and medications." [Abstract]

Gardner ME, Malone DC, Sey M, Babington MA.
Mirtazapine is associated with less anxiolytic use among elderly depressed patients in long-term care facilities.
J Am Med Dir Assoc. 2004 Mar-Apr;5(2):101-6.
"BACKGROUND: Depression is a common, treatable disorder among nursing facility residents. OBJECTIVE: The purpose of this study was to examine medication use and cost between two groups of patients: (1) persons treated with mirtazapine, as compared with (2) persons taking other antidepressants. DESIGN: This study was a retrospective chart review of long-term care patients. Consultant pharmacists collected data on patients who were receiving selective serotonin reuptake inhibitors (SSRIs), venlafaxine, nefazodone, or mirtazapine. SETTING: Nursing facilities that were geographically dispersed throughout the United States. PARTICIPANTS: We studied patients greater than 65 years of age with major depressive disorder or a depression-related diagnosis and receiving antidepressant treatment for at least 3 months. Patients with bipolar-induced depression were excluded as well as those receiving tricyclic antidepressants. RESULTS: The two groups were similar in terms of age, but those receiving mirtazapine had lower body weight and body mass index. Patients on mirtazapine were less likely to be taking a sedative/hypnotic (P = 0.006). This was primarily the result of fewer patients in the mirtazapine group taking lorazepam (P = 0.03). There was no difference between the two groups regarding their use of other psychotropic medications, including multiple antidepressants, antipsychotics, anticonvulsants, acetylcholinesterase inhibitors, or appetite stimulants. Monthly medication costs were less for those patients receiving mirtazapine ($82.83) as compared with other antidepressants ($97.03) (P <0.0001). CONCLUSIONS: The results of this study suggest that patients receiving mirtazapine are less likely to be on anxiolytic/hypnotic agents. The findings also suggest that medication costs are less when mirtazapine is used compared with other antidepressants." [Abstract]

Guelfi JD, Ansseau M, Timmerman L, Korsgaard S; Mirtazapine-Venlafaxine Study Group.
Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.
J Clin Psychopharmacol 2001 Aug;21(4):425-31
"The aim of this multicenter, randomized, double-blind, 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features. Patients with a baseline score of > or = 25 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to receive treatment with either mirtazapine (N = 78, 15-60 mg/day) or venlafaxine (N = 79, 75-375 mg/day, twice a day) in a rapid up-titration schedule. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Clinical Global Impression scale, and quality of life was assessed with the Quality of Life, Enjoyment, and Satisfaction Questionnaire and Quality of Life in Depression Scale. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Both drugs were effective in reducing overall symptoms of depression, showing substantial reductions in group mean MADRS scores (-20.1 for mirtazapine and -17.5 for venlafaxine) and HAM-D-17 scores (-17.1 for mirtazapine and -14.6 for venlafaxine) at the end of the treatment. Although not statistically significant, at all assessment times higher percentages of patients treated with mirtazapine were classified as responders (> or =50% reduction) on the HAM-D (at endpoint, 62% vs. 52%) and MADRS (at endpoint: 64% vs. 58%). Likewise were the percentages of remitters (HAM-D score < or =7; MADRS score < or =12) also higher in the mirtazapine group. A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points (p < or = 0.03). Both treatments were well tolerated. Although slightly more subjects treated with mirtazapine reported at least one adverse event, a statistically significantly higher percentage of patients treated with venlafaxine (15.3%) than mirtazapine (5.1%) dropped out because of adverse events (p = 0.037). Quality of life improved in both treatment groups. In this study, treatment with mirtazapine resulted in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events." [Abstract]

Leinonen E, Skarstein J, Behnke K, Agren H, Helsdingen JT.
Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group.
Int Clin Psychopharmacol 1999 Nov;14(6):329-37
"We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomized, double-blind, multicentre, 8-week study. Patients with a Major Depressive Episode (DSM-IV) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopram (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton Anxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group mean MADRS scores was large in both groups, reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of responders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM-A and CGI-Severity of illness and Quality of life scores. A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinically relevant superiority between two proven antidepressants. Mirtazapine treatment was also related to faster improvement of sleep, quality of sleep and improved alertness following awakening, as shown by statistically significant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Both drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group. There were no clinically relevant changes in laboratory parameters and vital sign variables with either treatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI Severity of illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of efficacy of mirtazapine over citalopram." [Abstract]

Wheatley DP, van Moffaert M, Timmerman L, Kremer CM.
Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.
J Clin Psychiatry 1998 Jun;59(6):306-12
"OBJECTIVE: To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients. METHOD: Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method. RESULTS: Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group. CONCLUSION: We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy." [Abstract]

Hong CJ, Hu WH, Chen CC, Hsiao CC, Tsai SJ, Ruwe FJ.
A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients.
J Clin Psychiatry. 2003 Aug;64(8):921-6.
"AIM: To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression. METHOD: 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group. RESULTS: Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog. CONCLUSION: Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study." [Abstract]

Wan DD, Kundhur D, Solomons K, Yatham LN, Lam RW.
Mirtazapine for treatment-resistant depression: a preliminary report.
J Psychiatry Neurosci. 2003 Jan;28(1):55-9.
"OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression." [Abstract]

Schule C, Zwanzger P, Baghai T, Mikhaiel P, Thoma H, Moller HJ, Rupprecht R, Padberg F.
Effects of antidepressant pharmacotherapy after repetitive transcranial magnetic stimulation in major depression: an open follow-up study.
J Psychiatr Res. 2003 Mar-Apr;37(2):145-53.
"An increasing number of clinical studies demonstrates antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, limited data are available so far concerning the stability of these effects and the efficacy of subsequent maintenance therapy. Therefore, we examined whether antidepressant pharmacotherapy can stabilize clinical improvement after rTMS monotherapy. Twenty-six drug-free patients suffering from a major depressive episode (DSM-IV criteria) participated in an open rTMS trial over two weeks (10-13 sessions, 10 Hz, left prefrontal stimulation at 100% motor threshold intensity). Subsequently, the patients were followed up during standardized antidepressant pharmacotherapy with mirtazapine for a further 4 weeks. The interval between the last rTMS and the first day of pharmacotherapy varied between one and five days. After two weeks of rTMS monotherapy 39% of the patients responded to rTMS by at least 50% reduction in their Hamilton Rating Scale for Depression (HRSD) scores. Treatment interruption after rTMS resulted in a significant increase in the HRSD score of rTMS responders. The degree of the deterioration was dependent on the length of interval without treatment. However, this deterioration was reverted and the further clinical course stabilized by subsequent mirtazapine treatment. The overall response rate after rTMS and mirtazapine treatment (alone or in combination) was 77%. Our results suggest that (1) antidepressant pharmacotherapy is able to further improve the clinical response to rTMS and (2) that responders to rTMS monotherapy should receive subsequent psychopharmalogical treatment without interruption in order to avoid a deterioration of symptoms." [Abstract]

van Moffaert M, de Wilde J, Vereecken A, Dierick M, Evrard JL, Wilmotte J, Mendlewicz J.
Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression.
Int Clin Psychopharmacol 1995 Mar;10(1):3-9
"Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were randomized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial. The dosages were 24-72 mg/day for mirtazapine and 150-450 mg/day for trazodone. The improvement on all depression rating scales used was generally greater for mirtazapine, with statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores (the Bech melancholia factor and retardation factor), the Brief Psychiatric Rating Scale total score, the General Psychiatric Impression Global Assessment Scale, the Beck score and responder rates. Mirtazapine was well tolerated, while the trazodone-treated patients experienced somnolence more frequently, particularly during the first 2 weeks of treatment. Furthermore, postural symptoms were a clinical problem in 6% of the trazodone-treated patients. In this trial, mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability."
[Abstract]

Marttila M, Jaaskelainen J, Jarvi R, Romanov M, Miettinen E, Sorri P, Ahlfors U, Zivkov M.
A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression.
Eur Neuropsychopharmacol 1995 Dec;5(4):441-6
"One hundred and sixty-three patients with major depression were randomly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial. Initially, patients received mirtazapine 20 mg/day or doxepin 75 mg/day; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day, respectively. Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups. In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences, as compared to six in the doxepin-treated group. Moreover, doxepin-treated patients complained more frequently of dry mouth and movement disorders. In conclusion, mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin." [Abstract]

Montgomery SA, Reimitz PE, Zivkov M.
Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study.
Int Clin Psychopharmacol 1998 Mar;13(2):63-73
"Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage compared with amitriptyline, coupled with its improved side-effect profile, commends this antidepressant for the long-term treatment of depression." [Abstract]

Kasper S, Zivkov M, Roes KC, Pols AG.
Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline.
Eur Neuropsychopharmacol 1997 May;7(2):115-24
"Efficacy data were available from 405 severely depressed patients (baseline 17-item Hamilton Rating Scale for Depression-HAMD scores > or = 25) participating in randomized, double-blind, amitriptyline-controlled studies of mirtazapine. Main efficacy variable were changes from baseline in the group mean 17-item HAMD scores and responder rates. Secondary efficacy variables were changes in depressed mood item on the HAMD and in factors derived from the 17-item HAMD scale. Treatment with either mirtazapine or amitriptyline resulted in robust reductions of baseline HAMD scores and in similar and high percentages of responders. Both drugs produced favourable effects on depressed mood and on symptoms commonly associated with depression, such as anxiety, sleep and vegetative disturbances. There were neither statistically significant nor clinically relevant differences between mirtazapine and amitriptyline at any assessment point nor at endpoint. The results demonstrate that the new antidepressant mirtazapine and the tricyclic antidepressant amitriptyline are equally effective in the treatment of severely depressed patients." [Abstract]

Bremner JD.
A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.
J Clin Psychiatry 1995 Nov;56(11):519-25
"BACKGROUND: A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo. METHOD: One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo. RESULTS: At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo. CONCLUSION: In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety." [Abstract]

Smith WT, Glaudin V, Panagides J, Gilvary E.
Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.
Psychopharmacol Bull 1990;26(2):191-6
"Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects." [Abstract]

Zoccali R, Muscatello MR, Cedro C, Neri P, La Torre D, Spina E, Di Rosa AE, Meduri M.
The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study.
Int Clin Psychopharmacol. 2004 Mar;19(2):71-6.
"The development of therapeutic strategies to effectively treat negative symptoms remains one of the primary goals in the treatment of schizophrenia. Mirtazapine is the first of a new class of dual action compounds, the noradrenergic and specific serotonergic antidepressants (NaSSa), whose activity is related to the enhancement of noradrenergic and serotonergic transmission by a presynaptic alpha2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism, respectively. This study was a 8-week double-blind, randomized, placebo-controlled trial of 30 mg adjunctive mirtazapine to clozapine therapy in 24 patients with DSM-IV schizophrenia. The main finding at the end of the trial was a significant reduction on the Scale for the Assessment of Negative Symptoms (SANS) total scores in the mirtazapine group compared to placebo (P<0.01) with a significant improvement on the SANS subscales avolition/apathy and anhedonia/asociality. The Brief Psychiatric Rating Scale total score at week 8 showed superiority of mirtazapine over placebo. These findings suggest a potential role for mirtazapine as an augmentation strategy in the treatment of negative symptoms of schizophrenia." [Abstract]

Berk M, Ichim C, Brook S.
Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study.
Int Clin Psychopharmacol 2001 Mar;16(2):87-92
"The negative symptoms of schizophrenia remain a major clinical challenge. Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of efficacy in schizophrenia. This study was a 6-week randomized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo. There was no difference between the groups on the Hamilton depression scale at endpoint, suggesting that the improvement in negative symptoms was not an artifact of mood improvement. These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia." [Abstract]

Poyurovsky M, Epshtein S, Fuchs C, Schneidman M, Weizman R, Weizman A.
Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study.
J Clin Psychopharmacol. 2003 Jun;23(3):305-8.
"The nonselective serotonin (5-HT)-2A antagonists ritanserin, mianserin, and cyproheptadine were found efficacious in neuroleptic-induced akathisia (NIA). Mirtazapine is structurally and pharmacologically similar to mianserin, and the authors sought to determine its anti-NIA activity. Twenty-six neuroleptic-treated schizophrenic patients with DSM-IV diagnosis of NIA received add-on mirtazapine (15 mg/day) or placebo for 5 days in a double-blind design. Patients were assessed at baseline and days 3 and 5 with the Barnes Akathisia Scale (BAS), Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, and Simpson-Angus Scale for parkinsonism. Analysis of covariance with repeated measurements revealed significant group x time effects in favor of the mirtazapine group in both completers (n = 10 in each group) and intent-to-treat analysis (n = 13 in each group) for the BAS global subscale (F [1, 17] = 14.87, p = 0.001, and F [1, 23] = 13.24, p = 0.01, respectively) and objective subscale (F [1, 17] = 8.25, p = 0.011, and F [1, 23] = 7.35, p = 0.012, respectively) and borderline significant superiority for the BAS subjective subscale (F [1, 17] = 4.39, p = 0.051, and F [1, 23] = 4.12, p = 0.054, respectively) and distress subscale (F [1, 17] = 4.21, p = 0.056, and F [1, 23] = 3.80, p = 0.064, respectively). Significantly more mirtazapine-than placebo-treated patients (53.8% [7/13] vs. 7.7% [1/13], respectively; chi2 = 8.3, p = 0.004) met operational response criterion, a reduction of at least two points on the BAS global subscale. Mirtazapine treatment was associated with modest improvement of psychotic and parkinsonian symptoms. Mild sedation was the only side effect. Our study demonstrated that mirtazapine (15 mg/day) is an efficacious and well-tolerated therapeutic option in NIA. Marked 5HT2A/2C antagonistic activity of mirtazapine apparently accounts for its anti-NIA activity. The role of mirtazapine in the treatment of akathisia induced by atypical antipsychotic agents merits further investigation." [Abstract]

Pahwa R, Lyons KE.
Mirtazapine in essential tremor: A double-blind, placebo-controlled pilot study.
Mov Disord. 2003 May;18(5):584-7.
"We conclude that the majority of the ET patients do not benefit from mirtazapine." [Abstract]

Posey DJ, Guenin KD, Kohn AE, Swiezy NB, McDougle CJ.
A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders.
J Child Adolesc Psychopharmacol 2001 Fall;11(3):267-77
"Mirtazapine was well tolerated but showed only modest effectiveness for treating the associated symptoms of autistic disorder and other PDDs." [Abstract]

Nierenberg AA, Quitkin FM, Kremer C, Keller MB, Thase ME.
Placebo-controlled continuation treatment with mirtazapine: acute pattern of response predicts relapse.
Neuropsychopharmacology. 2004 May;29(5):1012-8.
"Pattern of response to antidepressants has been proposed as a method to identify patients whose improvement is more likely due to drug vs those whose improvement on drug is more likely to be a placebo effect. It is hypothesized that those with 'true-drug initial response pattern' are most likely to benefit from continuation treatment. The relationship between acute patterns of response and subsequent placebo-controlled continuation treatment with the antidepressant mirtazapine is examined. A total of 410 outpatients were treated openly with mirtazapine for 8-12 weeks. Patients who remitted in the acute phase were randomized to continue the same dose of mirtazapine or switched to placebo. Acute phase responders were classified as 'placebo initial response pattern' (early responders and nonpersistent responders) and 'true-drug initial response pattern' (delayed and persistent responders). Of those with a 'true-drug initial response pattern,' 10/40 (25.0%) relapsed with continuation mirtazapine, and 23/41 (56.1%) relapsed when switched to placebo. The difference (31.1%) is significant. Of those with a 'placebo initial response pattern,' 5/36 (13.9%) relapsed with continuation mirtazapine, and 12/39 (30.8%) relapsed with placebo substitution. This difference (16.9%) is not statistically significant. Moreover, the relapse rate for 'true-drug initial response pattern' patients switched to placebo (56.1%) was also significantly greater than for 'placebo initial response pattern' patients switched to placebo (30.8%). It has been suggested that patients with late onset and persistence are more likely to have improved because of drug. This hypothesis gains support from this study because of the different relapse rates of 'true-drug' responders on drug and placebo. The low relapse rate for patients with an acute placebo pattern switched to placebo suggests specific drug effect played a smaller role in their initial improvement." [Abstract]

Fawcett J, Barkin RL.
A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety.
J Clin Psychiatry 1998 Mar;59(3):123-7
Mirtazapine-treated patients demonstrated a statistically significant (p < or = .05) reduction in the sum of HAM-D items 9, 10, and 11 (anxiety/agitation) compared with placebo-treated patients at Weeks 1, 2, 4, and 6 and at the endpoint. There was no statistically significant difference between the mirtazapine- and amitriptyline-treated patients at Weeks 1, 3, 4, 5, and 6 and at the endpoint. Similar results were found for the analysis of the mean of HAM-D items 10, 11, 12, 13, 15, 17 (anxiety/somatization or HAM-D Factor Score I) using all treated patients with a post-baseline evaluation in all 8 studies. Mirtazapine-treated patients demonstrated a statistically significant (p < or = .03) greater reduction at Weeks 1-6 compared with placebo, and improvement in the mirtazapine group was comparable to improvement in the amitriptyline group at Weeks 1-6. [Abstract]

Goodnick PJ, Puig A, DeVane CL, Freund BV.
Mirtazapine in major depression with comorbid generalized anxiety disorder.
J Clin Psychiatry 1999 Jul;60(7):446-8
"BACKGROUND: A high proportion of patients with generalized anxiety disorder (GAD) have comorbid depressive illness. The presence of anxiety in depression has significant prognostic implications. Because of mirtazapine's early anxiolytic effects, the present study was undertaken as a preliminary investigation in patients with a diagnosis of major depression with comorbid GAD. METHOD: Mirtazapine was administered to 10 patients with DSM-IV major depressive disorder and comorbid GAD in an 8-week open-label study. Mirtazapine was increased from an initial daily dose of 15 mg to a maximum daily dose of 45 mg. RESULTS: Patients were found to have significant reductions in Hamilton Rating Scale for Depression scores, Hamilton Rating Scale for Anxiety scores, and Beck Depression Inventory scores, with improvement noted after the first week of therapy and continuing improvement over the 8 weeks of study. CONCLUSION: These positive preliminary findings support the further investigation of mirtazapine's potential value as a treatment for generalized anxiety disorder in addition to its established efficacy as an antidepressant drug." [Abstract]

Davidson JR, Weisler RH, Butterfield MI, Casat CD, Connor KM, Barnett S, van Meter S.
Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial.
Biol Psychiatry. 2003 Jan 15;53(2):188-91.
"BACKGROUND: Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder. METHODS: Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured. RESULTS: On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated. CONCLUSIONS: Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms." [Abstract]

Van Veen JF, Van Vliet IM, Westenberg HG.
Mirtazapine in social anxiety disorder: a pilot study.
Int Clin Psychopharmacol 2002 Nov;17(6):315-7
"Fourteen patients with social anxiety disorder (generalized type), according to DSM-IV criteria, were treated with mirtazapine 30 mg for 12 weeks. Twelve patients completed the study. Two patients (14.3%) dropped out due to side-effects. Generally, mirtazapine was well tolerated. Five out of 12 patients (41.7%) were classified as responders, based on a Clinical Global Improvement score of 1 or 2 and a reduction of the Liebowitz Social Anxiety Scale (LSAS) of 40%. The mean total score on the LSAS, as well as the anxiety and avoidance subscores, decreased significantly. This open pilot study suggests that further investigations are warranted to prove the efficacy of mirtazapine in generalized social anxiety disorder." [Abstract]

Bahk WM, Pae CU, Tsoh J, Chae JH, Jun TY, Chul-Lee, Kim KS.
Effects of mirtazapine in patients with post-traumatic stress disorder in Korea: a pilot study.
Hum Psychopharmacol 2002 Oct;17(7):341-4
"This study was aimed at testing the efficacy and tolerability of mirtazapine in the treatment of Korean patients with chronic post-traumatic stress disorder (PTSD). Mirtazapine was administered for 8 weeks using a flexible-dose regime in 15 Korean patients with PTSD based on the DSM-IV criteria. We evaluated the patients at baseline and at weeks 4 and 8 after treatment with the interviewer-administered structured interview for PTSD (SIP), short PTSD rating interview (SPRINT), impact of event scale-revised (IES-R) and the Montgomery Asberg depression rating scale (MADRS). Scores on the SIP, SPRINT, IES-R and MADRS had significantly reduced after 8 weeks treatment. In this pilot study, mirtazapine was found to be effective and well tolerated in the treatment of patients with PTSD. This calls for further evaluation of the effect of this drug on subjects with PTSD with randomized placebo-controlled studies." [Abstract]

Connor KM, Davidson JR, Weisler RH, Ahearn E.
A pilot study of mirtazapine in post-traumatic stress disorder.
Int Clin Psychopharmacol 1999 Jan;14(1):29-31
"Recently, studies of pharmacotherapy for post-traumatic stress disorder (PTSD) have been focused on serotonin-selective reuptake inhibitors (SSRI), despite a number of treatment-limiting side-effects. Mirtazapine, a novel drug with both noradrenergic and serotonergic properties, may be effective in individuals who demonstrate intolerance to side-effects of and a limited response to SSRIs. Six outpatients with severe, chronic PTSD were treated with mirtazapine, up to 45 mg/day for 8 weeks. Efficacy assessments and side-effect monitoring were performed at baseline and weeks 2, 4, 6 and 8. Fifty percent of the sample demonstrated improvement of 50% or more from baseline using a global rating. In addition, improvements were noted on both interviewer-administered and self-rated scales of PTSD and of depression. The drug was well tolerated with few significant side-effects. Mirtazapine was associated with clinical improvement in 50% of subjects with severe, chronic PTSD, suggesting a need for further investigation in double-blind, placebo-controlled trials." [Abstract]

Sarchiapone M, Amore M, De Risio S, Carli V, Faia V, Poterzio F, Balista C, Camardese G, Ferrari G.
Mirtazapine in the treatment of panic disorder: an open-label trial.
Int Clin Psychopharmacol 2003 Jan;18(1):35-8
"The aim of this open label trial was to evaluate mirtazapine tolerability and effectiveness in controlling symptomatology of patients with panic disorder. Forty-five patients with panic disorder, with or without agoraphobia, 11 of them with a comorbid diagnosis of major depression, were included. Patients were assessed with a structured psychiatric interview and their symptomatology evaluated with specific psychometric scales. Three study participants dropped out due to adverse events. Mirtazapine was administered at an established dose of 30 mg daily for 3 months. Patients were assessed at weeks 2 and 4, and then at monthly intervals. All psychometric measures showed statistically significant reductions in total scores at the rated time points, with a pronounced decline in number and intensity of panic attacks and anticipatory anxiety throughout the study. Mirtazapine was well tolerated as signified by the low discontinuation rate (6.3%), and all patients showed a significant symptomatic improvement. The improvement did not appear to be linked to the concurrent presence of a depressive illness." [Abstract]

Ribeiro L, Busnello JV, Kauer-Sant'Anna M, Madruga M, Quevedo J, Busnello EA, Kapczinski F.
Mirtazapine versus fluoxetine in the treatment of panic disorder.
Braz J Med Biol Res 2001 Oct;34(10):1303-7
"After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P < or = 0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 +/- 1.3 vs 14.0 +/- 1.0 mg for fluoxetine at the endpoint." [Abstract]

Carli V, Sarchiapone M, Camardese G, Romano L, DeRisio S.
Mirtazapine in the treatment of panic disorder.
Arch Gen Psychiatry 2002 Jul;59(7):661-2
"Moreover, mirtazapine has demonstrated a robust pharmacotherapeutic end point from the first week of treatment. There is an evident decrease in both depressive and anxiety symptoms at T15. All patients reported improvement just 3 or 4 days after starting treatment. No patient experienced panic attacks after 1 week of therapy, and the Z-SAS score decreased even more than the score on the HARS, implying that the patients perceived their clinical improvement.
...
The comparison between the perfusion 99mTc-HMPAO SPECT analysis performed at T0 and that performed at T90 showed a complete normalization in 12 of the 15 patients. The defects reported at T0 may be considered a state marker of panic disorder, and their normalization, together with the remission of symptoms, is an additional confirmation of the effectiveness of pharmacotherapeutic treatment." [First 150 words]

Boshuisen ML, Slaap BR, Vester-Blokland ED, den Boer JA.
The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind placebo run-in period.
Int Clin Psychopharmacol 2001 Nov;16(6):363-8
"The results of this open label study in panic disorder suggest that mirtazapine seems to be a fast and effective treatment alternative for SSRIs in panic disorder." [Abstract]

Carpenter LL, Leon Z, Yasmin S, Price LH.
Clinical experience with mirtazapine in the treatment of panic disorder.
Ann Clin Psychiatry 1999 Jun;11(2):81-6
"Data from treatment trials and biological challenge studies implicate involvement of both the serotonergic and the noradrenergic neurotransmitter systems in the pathophysiology of panic disorder. Mirtazapine, a newer antidepressant with a novel mechanism of action enhancing both norepinephrine and serotonin levels without reuptake inhibition, is a good candidate for the treatment of panic disorder. Ten adult outpatients with a primary diagnosis of panic disorder were treated openly with mirtazapine. Starting dose and titration were determined by individual clinical characteristics. Data on emergent side effects and clinical response were obtained at all follow-up visits, which typically occurred biweekly for 16 weeks. At the first follow-up visit (week 2-3), 4 of 10 patients met the criteria for response. Based on all available data, seven of the original sample demonstrated an acute response (defined as CGI = 2 or 3) by weeks 5-7, and six continued to have a positive long-term response at the 16-week end point. Side effects were reported by seven patients, with increased appetite and weight gain the most common. Prominent antihistaminic side effects such as sedation, enhanced appetite, and anxiolysis were often desired in the initial phase of treatment." [Abstract]

Thase ME, Nierenberg AA, Keller MB, Panagides J; The Relapse Prevention Study Group.
Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.
J Clin Psychiatry 2001 Oct;62(10):782-8
"BACKGROUND: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. METHOD: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. RESULTS: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a newonset adverse event. CONCLUSION: Continuation-phase therapy with mirtazapine is effective and well tolerated." [Abstract]

Fava M, Dunner DL, Greist JH, Preskorn SH, Trivedi MH, Zajecka J, Cohen M.
Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial.
J Clin Psychiatry 2001 Jun;62(6):413-20
"OBJECTIVE: To evaluate the efficacy and safety of mirtazapine in depressed outpatients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: In this open-label, 8-week study, the efficacy and safety of mirtazapine among 103 outpatients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI (fluoxetine, paroxetine, or sertraline) were evaluated. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17), and safety assessments included reported adverse events, routine laboratory assessments, physical examinations, and assessments of vital signs. A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine. RESULTS: Based on mean HAM-D-17 scores at endpoint and response rates of 48% based on the criterion of > or = 50% reduction in HAM-D-17 score, mirtazapine was found to be an effective treatment for a substantial proportion of patients for whom an SSRI was ineffective and/or poorly tolerated. Mirtazapine was well tolerated, with sedation and appetite increase/weight gain the most commonly reported adverse events. In addition, no difference in efficacy, safety, or tolerability was observed for patients undergoing an immediate switch from an SSRI (after having been tapered to the minimal effective dose) to mirtazapine, compared with those undergoing the imposition of a 4-day drug-free washout. CONCLUSION: These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who cannot tolerate or do not respond to SSRIs." [Abstract]

Carpenter LL, Yasmin S, Price LH.
A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.
Biol Psychiatry 2002 Jan 15;51(2):183-8
"26 adult outpatients with persistent major depression despite adequate antidepressant monotherapy were randomized to receive 4 weeks of mirtazapine or placebo augmentation. Mirtazapine was begun at 15 mg at bedtime, with possible titration to 30 mg at bedtime per physician's discretion after week 1. RESULTS: Categorical positive response rate at end point was 64% for active drug and 20% for placebo. Remission rates were 45.4% and 13.3% for active drug and placebo groups, respectively, Mirtazapine demonstrated statistically significant superiority to placebo on most major outcome measures, and was associated with improvement in overall functioning and quality of life. There were no significant group differences with regard to emergent side effects, weight change, or serum concentrations of primary antidepressants." [Abstract]

Bech P.
Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression.
Int J Neuropsychopharmacol 2001 Dec;4(4):337-45 [Abstract]

Liappas J, Paparrigopoulos T, Malitas P, Tzavellas E, Christodoulou G.
Mirtazapine improves alcohol detoxification.
J Psychopharmacol. 2004 Mar;18(1):88-93.
"The objective of the present study was to determine whether a combined psychotherapeutic-psychopharmacological (with mirtazapine) treatment of collateral anxiety and depressive symptomatology during the post-withdrawal phase of alcoholism facilitates the process of alcohol detoxification, which is a decisive stage in the treatment of alcohol-dependent individuals. For that purpose, the rate of remission of anxiety and depressive symptoms over a 4-week detoxification period was evaluated between two groups: the first group followed a standard detoxification protocol (n = 33) and the second group was assigned to mirtazapine in addition to standard treatment (n= 35). A marked reduction of anxiety and depressive symptoms was demonstrated in both groups. However, patients on mirtazapine improved more and at a faster rate compared to controls. Thus, mirtazapine, used adjunctively to short-term psychotherapy, may help the detoxification process by minimizing physical and subjective discomfort. Consequently, it may improve patient compliance in alcohol detoxification programs and facilitate the initial phase treatment of alcohol abuse dependence." [Abstract]

Liappas J, Paparrigopoulos T, Tzavellas E, Christodoulou G.
Alcohol detoxification and social anxiety symptoms: a preliminary study of the impact of mirtazapine administration.
J Affect Disord. 2003 Sep;76(1-3):279-84.
"BACKGROUND: Social anxiety disorder is fairly prevalent among alcohol abusing/dependent subjects. The objective of the present study was to investigate: (a) the incidence of social anxiety symptoms in inpatient alcoholics, (b) the effect of alcohol detoxification on these symptoms, and (c) whether a combined psychotherapeutic/mirtazapine treatment during the post-detoxification phase of alcoholism has a greater impact on the aforementioned symptoms than a non-pharmacological approach. METHOD: Social anxiety symptoms were assessed through the Liebowitz Social Anxiety Scale (LSAS) following a 4-5-week detoxification period in two groups: group A (n=21) that followed a detoxification protocol of cognitive-behavioral orientation and group B (n=33) that was assigned to mirtazapine in addition to the standard protocol. Concomitant psychopathology was monitored through the HARS and HDRS, and level of functioning through the GAS. RESULTS: A marked reduction of social anxiety symptoms was evidenced in both groups. However, patients on mirtazapine improved significantly more compared to controls. LIMITATIONS: A single measure of social anxiety, i.e., the LSAS was used. Also, a longer follow-up period is needed to ascertain remission of social anxiety symptoms. CONCLUSIONS: The present study found a rather high incidence of social anxiety symptoms in inpatient alcoholics which subsided following alcohol detoxification; moreover, it provides preliminary evidence that a combined psychotherapeutic/mirtazapine treatment (30-60 mg/daily) has a greater impact on the aforementioned symptoms than non-pharmacological treatment alone." [Abstract]

Theobald DE, Kirsh KL, Holtsclaw E, Donaghy K, Passik SD.
An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms.
J Pain Symptom Manage 2002 May;23(5):442-7
"This open-label pilot study suggests that mirtazapine may be effective for improving multiple symptoms, depression and quality of life in patients with advanced cancer. A controlled trial of this drug would be valuable." [Abstract]

Kast RE.
Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy.
Support Care Cancer 2001 Sep;9(6):469-70 [Abstract]

Joffe H, Groninger H, Soares C, Nonacs R, Cohen LS.
An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy.
J Womens Health Gend Based Med 2001 Dec;10(10):999-1004
"Twenty-two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 score < or =7 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p < 0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers." [Abstract]

Waldinger MD, Berendsen HH, Schweitzer DH.
Treatment of hot flushes with mirtazapine: four case reports.
Maturitas 2000 Oct 31;36(3):165-8
"OBJECTIVE: To evaluate the effect of mirtazapine on the severity of hot flushes and bouts of perspiration in women. Method: In two women with depression a reduction in hot flushes was noticed by serendipity during treatment with mirtazapine 15-30 mg/daily. On the basis of this observation clinical studies were extended with two non-depressed and non-anxious women with hot flushes. Both subjects were prescribed mirtazapine daily. RESULTS: Four cases are described as case reports. All subjects reported a practically complete disappearance of hot flushes and associated perspiration, within the first week of treatment. CONCLUSION: Mirtazapine appears to have a substantial ameliorating effect on hot flushes and perspiration bouts. It is postulated that the 5-HT(2A) blocking properties of mirtazapine is accounted in the symptomatic relief of hot flushes. In addition it is hypothesized that the serotonergic system is crucially involved in the pathogenesis of hot flushes and perspiration bouts. Further evaluation in double-blind placebo-controlled studies is encouraged." [Abstract]

Raji MA, Brady SR.
Mirtazapine for treatment of depression and comorbidities in Alzheimer disease.
Ann Pharmacother 2001 Sep;35(9):1024-7
"Three patients with dementia and depression complicated by weight loss, insomnia, and anxiety were treated with mirtazapine at an outpatient memory loss clinic of a university hospital. DISCUSSION: Despite the persistence of memory loss, the patients experienced a prompt and sustained response to mirtazapine. There was a complete remission of poor appetite, weight loss, sleep disturbances, and anxiety. Other depression symptoms, including sad mood, anhedonia, and energy level, were also substantially improved. CONCLUSIONS: The clinical response of our patients underscores the usefulness of mirtazapine in the treatment of the comorbid symptoms of weight loss, insomnia, and anxiety. The effectiveness of mirtazapine in depressed Alzheimer patents may be a reflection of its enhancement of brain serotonergic and noradrenergic neurotransmission. The usefulness of mirtazapine in depressed Alzheimer patients merits further study in a large randomized, controlled, clinically comparative trial." [Abstract]

Konstantinidis A, Stastny J, Ptak-Butta J, Hilger E, Winkler D, Barnas C, Neumeister A, Kasper S.
Intravenous mirtazapine in the treatment of depressed inpatients.
Eur Neuropsychopharmacol 2002 Feb;12(1):57-60
"This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients." [Abstract]

Claghorn JL, Lesem MD.
A double-blind placebo-controlled study of Org 3770 in depressed outpatients.
J Affect Disord 1995 Jun 8;34(3):165-71
"90 patients between 18 and 65 years, with a DSM-III diagnosis of moderate or severe major depressive episode, were randomized to 6 weeks of treatment with Org 3770 or placebo in a double-blind trial. On main efficacy parameters, the 17-item HAMD, MADRS and CGI, Org 3770 was significantly superior to placebo (P < or = 0.05) in weeks 1-4 and at endpoint and recommended as continuation treatment to significantly more patients. The tolerability of Org 3770 was good: the only significant differences as compared with placebo were in the incidences of somnolence and increased appetite. The results show that Org 3770 is an effective and well-tolerated drug for the treatment of major depressive disorder." [Abstract]