Hepatopatía inflamatoria asintomática asociada a uso de mirtazapina: reporte de caso / Asymptomatic inflammatory liver disease associated with mirtazapine use: case report

Resumen La mirtazapina es un antidepresivo atípico con características complejas, que incluye actividad agonista/antagonista en una amplia variedad de receptores que produce efectos terapéuticos en la ansiedad, depresión y el sueño. Sin embargo, se han reportado casos de lesión hepática inducida por antidepresivos con ausencia de sintomatología, bajo la forma de variantes hepatocelular, colestásica y mixta. Este es el caso de una paciente que de carácter incidental presenta cambios en la analítica hepática tras el uso de mirtazapina a partir del cual se hace una breve revisión de la evidencia encontrada hasta el momento.

Mirtazapine is an atypical antidepressant with complex characteristics, including agonist/antagonist activity at a wide variety of receptors that produces therapeutic effects on anxiety, depression and sleep disorder. However, cases of antidepressant-induced liver injury with no symptoms have been reported, in the form of hepatocellular, cholestatic, and mixed variants. This is the case of a patient who incidentally presents changes in liver analysis after the use of mirtazapine, from which a brief review of the evidence found so far is made.

Does the antidepressant-like effect of mirtazapine and venlafaxine differ between male and female rats? / ¿El efecto de tipo antidepresivo de la mirtazapina y la venlafaxina difiere entre ratas macho y hembra?

Abstract Introduction Depression is a global health problem with nearly 350 million people affected, mainly women. However, nowadays a rising amount of men are being diagnosed. This makes necessary the screening of new treatment options that are effective in women as well as in men. Objective To analyze if the administration of mirtazapine and venlafaxine to male and female rats shows a sex-related antidepressant-like effect, and the possible associated neurochemical mechanisms. Method Mirtazapine (40 mg/kg) or venlafaxine (60 mg/kg) were administered subchronically to young adult male and female (ovariectomized and steroid-primed) rats, and their antidepressant-like effects were evaluated using the forced swim test (FST). The active behaviors, swimming and climbing, were also analyzed. Results a) mirtazapine and venlafaxine reduced immobility in the FST in males and females; b) both antidepressants increased climbing and swimming in male rats; c) in female rats, mirtazapine and venlafaxine only increased swimming. Discussion and conclusion In males, the effects of mirtazapine and venlafaxine seem to be produced by the activation of the serotonergic and noradrenergic systems. Conversely, estradiol might be modulating the mechanisms of action of both antidepressants in females producing only an increased swimming and suggesting the participation of the serotonergic system.

Resumen Introducción La depresión es un trastorno psiquiátrico que representa un problema de salud mundial. Afecta a cerca de 350 millones de personas, predominantemente mujeres. Sin embargo, algunos reportes indican que su incidencia en hombres está aumentando, por lo que es necesario buscar opciones de tratamiento que sean igualmente efectivas en ambos sexos. Objetivo Analizar si existen diferencias relacionadas con el sexo en el efecto de tipo antidepresivo de la mirtazapina y la venlafaxina, y considerar los posibles mecanismos neuroquímicos involucrados. Método se administraron mirtazapina (40 mg/kg) o venlafaxina (60 mg/kg) en esquema subcrónico a grupos independientes de ratas macho y hembra ovariectomizadas tratadas con estradiol y progesterona. Se evaluaron el efecto tipo antidepresivo y las conductas activas (nado y escalamiento) utilizando la prueba de nado forzado (PNF). Resultados a) tanto la mirtazapina como la venlafaxina redujeron la inmovilidad en la PNF en machos y hembras; b) ambos antidepresivos incrementaron las conductas activas en machos; c) en hembras, la mirtazapina y la venlafaxina produjeron un aumento del nado, pero no modificaron el escalamiento. Discusión y conclusión En machos, los efectos de la mirtazapina y la venlafaxina en la PNF se deben a su acción sobre los sistemas serotonérgico y noradrenérgico; en cambio, en hembras sólo se modifica la conducta de nado, lo que sugiere que el estradiol modula las acciones de ambos antidepresivos sobre el sistema serotoninérgico.

Effect of Mirtazapine Pre-treatment on Haloperidol, Ergometrine and Fluoxetine Induced Behaviours in Albino Rats.

Background: Central 5-HT and 5-HT serotonergic 2A 2Creceptors are mainly involved in the control ofnigrostriatal and mesolimbic dopaminergic neuronalactivity has been well proved and established. 5-HThas facilitatory effect on stimulated dopamine releaseby stimulating central 5-HT receptors and inhibitory 2Aeffect by stimulating 5-HT receptors. Aim and 2CObjectives: To evaluate 5-HT and 5-HT receptor 2A 2Cblocking activity of Mirtazapine (MIR) and the effectof mirtazapine pre-treatment on Ergometrine (ERG)induced behaviours, Fluoxetine (FLU) induced penileerections and Haloperidol (HAL) induced catalepsy inrats. Material and Methods: Each group wassubdivided into different subgroups consisting 6animals in each. Control group received DimethylSulfoxide (DMSO) and other groups received differentdoses of mirtazapine one hour before ERG/FLU/HAL.Values obtained from control group were comparedwith all remaining groups pre-treatment with differentdoses of MIR. Results: MIR (MIR) at 2.5, 5, 10 and 20mg/kg intraperitoneally (i.p) did not produce any per seeffects. Pre-treatment with 5, 10 and 20 mg/kg i.p. MIRsignificantly antagonised ERG induced behaviours. 5mg/kg i.p. MIR significantly antagonised whereas 10and 20 mg/kg i.p. MIR abolished FLU (10 mg/kg)induced penile erections in rats. MIR 5 and 20 mg/kgi.p. significantly antagonised HAL (1mg/kg) inducedcatalepsy at 1 hr testing time interval while 10 and 20mg/kg MIR significantly antagonised HAL (1 mg/kg)induced catalepsy at 2 hr testing time interval.Conclusion: Our results indicate that MIR at 5, 10 and20 mg/kg possesses 5-HT and 5-HT receptors 2A 2Cblocking activity. At 5, 10 and 20 mg/kg MIR, byblocking central 5-HT receptors predominantly, 2Ccauses release of dopamine from nigrostriataldopaminergic neurons and therefore antagonizes HALinduced catalepsy

Meta-analysis of Therapeutic Efficacy and Safety of Mirtazapine Combined with Selective Calcium Ch annel Blocker in the Treatment of Irritable Bowel Syndrome / 中国药房

OBJECTIVE： To systematically review therapeutic efficacy and safety of mirtazapine combined with selective calcium channel blocker （SCCB） in the treatment of irritable bowel syndrome （IBS）， and provide evidence-based reference for clinical medication. METHODS： Retrieved from the Cochrane Library， PubMed， Embase， Medline， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about mirtazapine combined with SCCB （trial group） versus SCCB （control group） for IBS were collected. After literature screening and data extraction， quality evaluation was performed by using Cochrane system evaluator manual 5.1.0 recommend bias risk evaluation tool. Meta-analysis was performed by using Stata 14.0 software. RESULTS： A total of 14 RCTs involving 1 005 patients were included. The results of Meta-analysis showed that the total response rate [RR＝1.34，95％CI（1.25，1.44），P＜0.001]，neuropeptide-Y level after treatment [SMD＝0.77，95％CI（0.49，1.05），P＜0.001]， response rate of abdominal pain therapy [RR＝1.32，95％CI（1.06，1.66），P＝0.014] and response rate of treatment for abnormal stool characteristics [RR＝1.75，95％CI（1.36，2.27）， P＜0.001] were significantly higher than control group； the scores of depression scale after treatment [SMD＝－1.87， 95％CI （－2.35， －1.39）， P＜0.001]， anxiety scale after treatment [SMD＝－2.25， 95％CI （－3.35， －1.15）， P＜0.001]， abdominal pain symptom score after treatment [SMD＝－7.41， 95％CI  （－8.30，－6.51）， P＜0.001]， diarrhea symptom score after treatment [SMD＝－6.39， 95％CI （－7.96，－4.81）， P＜0.001] were significantly lower than those of the control group. There were no statistical significance in response rate of abdominal distension therapy [RR＝1.07，95％CI（0.90，1.28），P＝0.421] and response rate of abnormal defecation therapy [RR＝1.05，95％CI（0.88，1.26），P＝0.588]， the incidence of abdominal pain [RR＝0.45，95％CI（0.11，1.97）， P＝0.291] and exhaustion [RR＝5.00，95％CI（0.60，41.79），P＝0.137] between 2 groups. CONCLUSIONS： Mirtazapine combined with SCCB can significantly improve therapeutic efficacy of IBS patients， promote clinical symptoms， but do not increase the occurrence of ADR as abdominal pain and exhaustion.

Chronic dosing with mirtazapine does not produce sedation in rats

Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Clinical research of ear acupuncture combined with mirtazapine in the treatment of insomnia / 中国基层医药

Objective To observe the clinical efficacy of ear acupuncture combined with mirtazapine in the treatment of insomnia.Methods Sixty-two patients with insomnia diagnosed by CCMD-Ⅲ were randomly divided into two groups,31 patients in each group.The patients in the observation group were treated by ear acupuncture combined with mirtazapine,and the patients in the control group were treated by mirtazapine.The clinical efficacy was evaluated by SDRS after 4 weeks of treatment.Results The SDRS score of the observation group significantly decreased after one week of treatment [(13.40±5.79)points vs.(21.79±6.12)points,t=2.204,P＜0.05].The SDRS score of the control group significantly decreased after one week of treatment [(14.68±5.88)points vs.(22.67±6.06)points,t=2.198,P＜0.05].After 4 weeks of treatment,the clinical efficacy of the observation group was significantly better than that of the control group (z=-2.209,P＜0.05),the SDRS score of the observation group was also significantly better than that of the control group (t=2.163,P＜0.05).Conclusion Ear acupuncture combined with mirtazapine has better effect in the treatment of insomnia patients,it has less side effects and lasting effects.

Effect of mirtazapine in depressive functional dyspepsia patients with weight loss / 中华行为医学与脑科学杂志

Objective To discuss the effect of mirtazapine in depressive functional dyspepsia patients with weight loss (FD-WL).Methods As a randomized and controlled trial,seventy-two FD patients with weight loss and depression were randomly divided into mirtazapine group(n=24),paroxetine group(n=23) and conventional group(n=25),and all patients were treated for 8 weeks.The Nepean Dyspepsia Index (NDI)-symptom checklist,the Hamilton Rating Scale of Depression (HAMD),body weight were assessed before the treatment and after 2,4,6,8 week.Results (1) After 2-week treatment,the scores of NDI-symptom checklist and HAMD in mirtazapine group were significantly lower than that in paroxetine group and conventional group.After 4-week,6-week and 8-week treatment,the score of HAMD in mirtazapine group((13.34±1.52),(11.65±1.56),(10.15±1.36)) and paroxetine group((13.65±1.81),(11.34±1.21),(9.58±1.41))was significantly lower than that in conventional group((18.15±1.61),(17.20±2.14),(15.30±1.56)) (all P0.05).(2) After 6-week and 8-week treatment,the body weight in mirtazapine group((53.17±6.46)kg,(53.55±6.52)kg)was significantly higher compared with that in paroxetine group((49.47±5.72)kg,(49.57±5.81)kg)and conventional group((48.69±5.60)kg,(48.68±5.65)kg)(all P<0.05).After 8-week treatment,patients in mirtazapine group experienced a weight gain of(3.34±1.82)kg.Conclusion Mirtazapine not only can significantly improve dyspepsia symptoms and depressive scoring,but also can increase body weight.

Mirtazapine Is Effective in Steroid Withdrawal Syndrome Related Depression: A Case Report

Steroid withdrawal syndrome (SWS) following steroid dependence is becoming a common clinical condition. It may be associated with body image disorder. Though selective serotonin reuptake inhibitors (SSRIs) are found to be effective SWS associated depression, data for this clinical condition is limited. We present a case of SWS associated with body image disorder which improved with mirtazapine. Mirtazapine might be better option than SSRIs in this subgroup of patients for its noradrenergic property and better gastrointestinal profile. More research should explore its efficacy in this clinical condition.

Clinical study on EEG biofeedback therapy combined with mirtazapine in the treatment of depressive disorder / 中国基层医药

Objective To investigate the clinical effect and safety of EEG biofeedback therapy combined with mirtazapine in the treatment of depressive disorder.Methods 124 patients with depressive disorder were selected and randomly divided into the observation group and the control group,62 cases in each group.The control group was given mirtazapine treatment,while the observation group was given EEG biofeedback therapy combined with mirtazapine.All the two groups were treated for 8 weeks.Before and 2,4,8 weeks after treatment,the clinical effects in the two groups were evaluated by Hamilton depression scale (HAMD),Montgomerie depression rating scale (MADRS) and the clinical global impression scale (CGI).The side effects scale(TESS) assessment was used to assess the side effects.And the serum norepinephrine (NE),5-hydroxytryptamine (5-HT) and dopamine (DA) levels were measured before and 8 weeks after treatment.Results The total effective rate of the observation group was 87.5％,which was significantly higher than 66.1％ in the control group (x2 =7.213,P ＜ 0.05).In the two groups,2,4,8 weeks after treatment,the HAMD scores were significantly lower than those before treatment (t =9.391,19.349,26.349,5.026,12.610,19.518,all P ＜ 0.05),the M ADRS scores were significantly lower than those before treatment (t =8.646,22.190,33.101,4.986,13.185,25.959,all P ＜ 0.05),and the CGI scores were significantly lower than those before treatment(t =17.471,29.482,42.256,13.136,28.358,35.661,all P ＜ 0.05).In the observation group,after treatment for 2,4,8 weeks,the HAMD scores were significantly lower than those in the control group(t =4.093,4.537,5.655,all P ＜ 0.05),and the MADRS scores were significantly lower than those in the control group (t =3.622,9.740,7.490,all P ＜ 0.05),while the CGI scores were significantly lower than those in the control group(t =8.608,11.024,12.598,all P ＜ 0.05).After treatment,the levels of 5-HT,NE and DA were (148.5 ± 4.9) ng/mL,(60.6 ± 4.2) ng/L and (78.0 ± 4.1) ng/L in the observation group,which were significantly higher than before treatment [(79.8 ± 4.3) ng/mL,(30.3 ± 4.0) ng/L and (43.5 ± 4.0) ng/L,t =82.977,41.134,46.837,all P ＜ 0.05].In the control group after treatment,the levels of 5-HT,NE and DA were (125.4 ± 4.1) ng/mL,(40.2 ± 4.0)ng/L and (50.3 ± 4.3)nig/L,which were significantly higher than those before treatment [(79.2 ± 3.9)ng/mL,(30.5 ±4.1)ng/L and (43.2 ±3.6)ng/L,t =64.287,13.334,9.969,all P ＜0.05],but which those in the observation group increased more significantly (t =28.469,27.695,36.286,all P ＜ 0.05).4 weeks and 8 weeks after treatment,the TESS scores in the observation group were (3.0 ± 1.0) points and (4.3 ± 1.2) points,which in the control group were (2.8 ± 1.2) points and (4.1 ± 1.3) points,there were no significant differences in terms of TESS scores (t =1.150,0.846,all P ＞ 0.05).Conclusion EEG biofeedback therapy combined with mirtazapine in the treatment of depression is better,the adverse reactions is not significantly increased,and it also has higher clinical safety compared with mirtazapine alone.

Clinical Observation of Mirtazapine Combined with Citalopram in the Treatment of Sleep Disorder of De-pressive Patients / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of mirtazapine combined with citalopram in the treat-ment of sleep disorder in depressive patients. METHODS:One hundred and sixty-five depressive patients with sleep disorder were selected and divided into control group (82 cases) and treatment group (83 cases) according to random number table. Control group took Escitalopram oxalate tablet 10 mg,once every night,increasing to 20 mg according to disease condition;treatment group was additionally given Mirtazapine tablet 15 mg,once every night,increasing to 30 mg one week later. Both groups re-ceived treatment for consecutive 6 months. HAMD-17 and MADRS were observed in 2 groups before and after treatment,and the sleep quality of 2 groups were evaluated by PSQI before and after treatment;the sleep structure was measured by using polysom-nography before and after treatment;clinical efficacies and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in HAMD-17,MADRS and PSQI score,sleep structure between 2 groups (P>0.05);after treatment,above scores and indexes of 2 groups were all improved significantly,and the treatment group was sig-nificantly better than the control group,with statistical significance(P0.05). CONCLUSIONS:Citalopram combined with mirtazapine shows sig-nificant therapeutic efficacy for sleep disorder of depressive patients,and can significantly improve sleep structure,adjust sleep cy-cle and improve sleep quality with good safety.

Association between the Alu Insertion/Deletion Polymorphism in the Tissue-Type Plasminogen Activator Gene and Mirtazapine Response in Koreans with Major Depression

OBJECTIVES: To determine the relationship between the Alu insertion/deletion (I/D) polymorphism in the tissue-type plasminogen activator (tPA) gene and the clinical outcome of mirtazapine treatment in Korean major depressive disorder (MDD) patients. METHODS: We enrolled 422 patients in this study. Symptoms were evaluated using the 21-item Hamilton Depression Rating (HAMD-21) Scale. After 1, 2, 4, and 8 weeks of mirtazapine treatment, the association between the Alu I/D polymorphism in the tPA gene and remission/response outcomes were evaluated. RESULTS: The proportion of I/I homozygotes in responders was higher than that in non-responders, whereas the proportion of D/D homozygotes in responders was lower than that in non-responders at 8 weeks of treatment (p = 0.032, OR = 1.57). The percentage decline of HAMD-21 scores in I allele carriers was larger than that of D/D homozygotes at 2 and 8 weeks of treatment (p = 0.035 and 0.007, respectively). I allele carriers were associated with remission at 8 weeks of treatment (p = 0.047, OR = 2.2). CONCLUSIONS: These results show that treatment response and remission to mirtazapine were associated with the Alu I/D polymorphism of the tPA gene. This suggests the Alu I/D polymorphism may be a potential genetic marker for the prediction of therapeutic response to mirtazapine treatment in patients with MDD.

A prospective study on sleep disorders related to antidepressant drugs use in a tertiary care teaching hospital.

Background: Prescription of antidepressants has been increased from the last decade and responsible for producing sleep disorders as adverse drug reactions (ADRs). Sleep disorders can be divided into 3 large groups: (1) insomnia, (2) primary complaint of daytime sleepiness, and (3) Association of disruptive behaviours during sleep, the disorders of arousal. So active surveillance is needed to access these ADRs. Aims and Objective: To analyze the sleep disturbances as ADRs of various antidepressants prescribed to the patients attending psychiatry outpatient department (OPD). Methods: This prospective study was conducted on patients aged ≤74 years attending Department of Psychiatry OPD and were prescribed Antidepressants for the duration of 8 months (December, 2013-July, 2014). The ADRs reported were confirmed by WHO UMC Causality Assessment Scale. Results: Total number of patients enrolled on the basis of inclusion and exclusion criteria (n=50). Total number of ADRs related to drugs prescribed were found to be n=69. Total number of patients with sleep disturbances as ADRs were found to be n=28. Conclusion: The drug, most frequently implicated to cause sleep disturbances, was mirtazapine. Increased sleep was the most common ADR, found to occur. Unusual ADRs such as sleep talking was also seen.

Mirtazapine-induced acute angle closure.

Acute angle closure (AAC) is an ocular emergency with symptoms including blurred vision, eye pain, headache, nausea, vomiting and reddening of the eye those results from increased intraocular pressure. This clinical condition can lead to permanent damage in vision, thus causing blindness by generating progressive and irreversible optic neuropathy if left untreated. There are several reasons of AAC, including several types of local and systemic medications; mainly sympathomimetics, cholinergics, anti‑cholinergics, mydriatics, anti‑histamines, antiepileptics like topiramate, tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, antipsychotics, sulfa‑based drugs and anticoagulants. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, is an atypical antidepressant with a complex pharmacological profile. This case report describes a patient with major depressive disorder, who experienced AAC after the first dosage of mirtazapine treatment, and highlights the importance of close monitoring of individuals under antidepressant treatment particularly immediately after initiation of the drug.

Clinical Observation of Mirtazapine in the Treatment of Perimenopausal Syndrome with Sleep Disorders / 中国药房

OBJECTIVE:To observe the efficacy and safety of mirtazapine in the treatment of perimenopausal syndrome with sleep disorders. METHODS:100 perimenopausal patients with sleep disorders were randomly divided into study group(52 cases) and control group(48 cases). Study group was given Mirtazapine tablet with initial dose of 15 mg,once a day,taking 1-2 hours before going to bed,increased and maintained to 30 mg after 1 week. The control group was given Oryzanol tablet 10 mg after meals,3 times a day. Both groups were treated for 8 weeks. Scores of HAMD-17 and PSQI before and after treatment were ob-served,efficacy of depression and sleep were evaluated and and incidence of adverse reactions in 2 groups was observed. RE-SULTS:After treatment,HAMD-17 scores and PSQI scores in 2 groups were significantly lower than before,and study group was lower than control group,8 weeks0.05). CONCLUSIONS:Mirtazapine can improve the sleep disorders of peri-menopausal syndrome with rapid onset,but the adverse reactions need futher observation.

Cost-effectiveness Analysis of Duloxetine, Escitalopram Oxalate and Mirtazapine in the Treatment of De-pression / 中国药师

Objective:To evaluate the cost-effectiveness of duloxetine, escitalopram oxalate and mirtazapine in the treatment of depression. Methods:Totally 120 cases of patients were randomly divided into three group. Group A was given duloxetine 40mg twice a day, group B was with escitalopram oxalate at the initial dose of 10mg per day, and up to 20mg per day in 2 weeks, and group C was treated with mirtazapine 30mg per day. The treatment course was eight weeks. At the 1st, 2nd, 3rd, 4th and 8th weekends after the treatment, Hamilton depression scale ( HAMD) was used to evaluate the total effective rate, and treatment emergent symptom scale ( TESS) was applied to assess the adverse drug reactions. Results:The total effective rate of group A, B and C was 87. 5%,90% and 92. 5% with the cost of 23 822. 22 yuan,33 866. 02 yuan and 19 586. 62 yuan, respectively. The cost-effectiveness ratio respectively was 27 225, 37 629 and 21 175. The incidence of adverse reactions respectively was 30%, 30% and 17. 5%. Conclusion:The cost-effectiveness of mirtazapine is the lowest in the treatment of depression, which can be considered as the best treatment regimen.

Efficacy and Tolerability of Generic Mirtazapine (Mirtax) for Major Depressive Disorder: Multicenter, Open-label, Uncontrolled, Prospective Study

OBJECTIVE: Mirtax is a generic mirtazapine widely used since 2003. We conducted an open-label, uncontrolled 6-week study to evaluate the efficacy and safety of Mirtax for major depressive disorder (MDD). METHODS: Ninety three MDD patients with the diagnosis of MDD and 17-item Hamilton Depression Rating Scale (HDRS) score > or =14 were recruited. The HDRS, Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity Scale (CGI-S) were administered at baseline, 1, 2, 4 and 6 weeks. Response (> or =50% decrease in the HDRS or MADRS score), remission (absolute HDRS score < or =7 or MADRS score < or =10) and CGI-I score < or =2 were also calculated. Adverse event (AE) frequency and severity, weight, blood pressure, and pulse rate were checked to assess safety. RESULTS: The starting dosage was 11.5+/-6.4 mg/day, and the maintenance dosage was 23.1+/-9.4 mg/day. During 6 weeks, HDRS, MADRS and CGI-S scores decreased from 25.1+/-5.6 to 11.9+/-8.6 (mean change -13.1+/-8.3, p<0.001), from 30.2+/-6.3 to 13.73+/-10.40 (mean change -16.5+/-9.8, p<0.001), and from 5.0+/-0.8 to 2.5+/-1.3 (mean change -2.5+/-1.3, p<0.001), respectively. The percentages of responders, remitters by HDRS and patients with a CGI-I score < or =2 were 64.6%, 35.4% and 52.7%, respectively. Significant decreases in HDRS, MADRS and CGI-S scores were confirmed at week 1. The total rate of AEs was 32.3%; the most frequently reported AEs were sedation (4.3%) and constipation (4.3%). Weight was increased from 58.8+/-10.6 to 60.3+/-9.3 kg (mean change 0.7+/-1.7 kg, p=0.004). CONCLUSION: This study, as the first clinical trial of generic mirtazapine, demonstrated the efficacy and tolerability of Mirtax for MDD using a single treatment design.

Clinical Observation of the Effects of Mirtazapine on Life Quality Improvement in Malignant Tumor Patients with Moderately Severe Depression / 中国医科大学学报

Objective To observe the effects of mirtazapine to improve the life quality of malignant tumor patients with moderate or severe depres-sion. Methods Patients with mood disorders screened by the physician were then graded by the Hamilton Depression Scale(HAMD)under the tu-telage of ward psychological consultant. Fifty patients with moderate or severe depression were selected by psychological doctors and recruited for the study. After obtaining consent,the patients received 15-60 mg/d mirtazapine every night for 9 weeks. According to the Quality of Life Rating Scale (QOL),the scores of these patients were evaluated at the pretreatment,the 3rd week and the 9th week of the post-treatment. Then,the life quality conditions before and after treatment were revaluated. Results The scores of HAMD were 33.16±7.25,28.74±6.24,and 22.58±6.71 at the pretreat-ment,the 3rd week and the 9th week of the post-treatment,respectively. There were significantly different among the HAMD scores at the pretreat-ment,the 3rd week and the 9th week of the post-treatment.(F=30.99,P<0.01). The scores of HAMD were improved significantly between the pre-treatment and the 3rd week of the post-treatment(P<0.05). The scores of HAMD were also improved significantly between the 3rd week and the 9th week of the post-treatment(P<0.05). After treatment by mirtazapine,the appetite,spirit,sleep,fatigue,pain,the reorganization of cancer,the attitude towards treatment,the side effect of treatment and the facial expression were significantly improved(P<0.01). Conclusion Mirtazapine could improve the life quality of malignant tumor patients with moderate or severe depression.

Safety analysis of new type antidepressants in treatment of depression in patients with coronary heart disease / 天津医药

Objective To evaluate the safety of new-generation of antidepressants and amitriptyline in the treatment of depression in patients with coronary heart disease (CHD). Methods A total of 194 patients with first-episode depression with CHD were divided into amitriptyline group(n=40), venlafaxine group(n=40), mirtazapine group(n=48)and escitalo?pram group(n=66). The blood routine test, liver function, blood lipids and blood glucose (GLU) were monitored after treat?ment for six weeks, and which were compared before and after treatment. Results The levels of white blood cells (WBC) and neutrophil count (NE) were significantly lower in amitriptyline group after 6-week treatment (P<0.05), but the levels of acid alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (T-CHO) and GLU were significant?ly increased after treatment than those before treatment (P<0.05). The levels of WBC, NE and GLU were significantly de?creased in venlafaxine group after 6-week treatment (P<0.05). The levels of ALT, AST, low density lipoprotein (LDL) were significantly increased in mirtazapine group after six-week treatment (P<0.05). In escitalopram group, the level of three ac?yl glycerin (TG) was significantly increased after six-week treatment than before treatment ( P<0.05). There was a signifi?cant difference in AST change after treatment between venlafaxine group and mirtazapine group (P<0.05). There was a sig?nificant decrease in WBC in amitriptyline group than that of mirtazapine group after six-week treatment ( P<0.05). There was a significant decrease in NE in amitriptyline group than that of mirtazapine group and escitalopram group ( P<0.05). The increase level of AST was significant higher in amitriptyline group than that of venlafaxine group (P < 0.05). Conclusion Three different kinds of new-generation of antidepressants have fewer influence in routine blood test, liver function, blood lipids and blood glucose than those of amitriptyline in the treatment of depression in patients with CHD.

Comparison of effect between duloxetine combined with small-dose of mirtazapine and duloxetine in treatment of refractory depression in elder patients / 中国生化药物杂志

Objective To compare effect and security between duloxetine combined with small-dose of mirtazapine and duloxetine alone in treatment of refractory depression in elder patients.Methods A total of 100 cases elder refractory depression patients were randamly divided into study group (duloxetine+mirtazapine, 50 cases) and control group(duloxetine, 50 cases).Compared HAMD,HAMA and CGI-SI between two groups, as well as the side reactions and TESS.Regression analysed mirtazapine blood concentration and HAMD subtraction rate.Results The effective rate of study group was 92.00%, while in control group was 76.00%, the difference was statistically significant(P<0.05).After treatment, the HAMD, HAMA and CGI-SI of each group significantly increased, and the difference of HAMD, HAMA and CGI-SI at 2w, 4w and 8w between two groups were statistically significant(P<0.05).The TESS and side reaction of two groups had no statistical difference.Conclusion Effect of duloxetine combined with small-dose of mirtazapine in treatment of refractory depression is better than duloxetine alone use, without significant side reaction.

R347C Polymorphisms in ADRA1A Genes and Mirtazapine Treatment Response in Koreans with Major Depression

OBJECTIVES: Adrenergic alpha 1 and 2 receptors work as pathways to control the serotonergic neuron moderation and mirtazapine acts as antagonist of these receptors. The adrenoreceptor alpha 1a (ADRA1A) gene, which encodes adrenergic alpha 1 receptor, has Arg347Cys genetic polymorphism and the polymorphism has strong relationship with many neuro-psychiatric diseases. In this study, we explored the relationship between ADRA1A R347C polymorphism and mirtazapine treatment response in Koreans with major depression. METHODS: 352 patients enrolled in this study, and the symptoms were evaluated by 17-item Hamilton Depression Rating (HAMD-17) scale. After 1, 2, 4, 8, and 12 weeks of mirtazapine treatment, the association between ADRA1A R347C polymorphism and remission/response outcomes was evaluated. RESULTS: Treatment response to mirtazapine was significantly better in T allele carriers than C allele homozygotes after 12 weeks of mirtazapine monotherapy. The percentile decline of HAMD-17 score in T allele carriers was larger than that of C allele homozygotes. ADRA1A R347C genotypes were not significantly associated with remission. CONCLUSIONS: The result showed that treatment response to mirtazapine was significantly associated with ADRA1A R347C genetic polymorphism. T allele carriers showed better treatment response than C allele homozygotes. It can be supposed that T allele carriers have a trend of better treatment response to mirtazapine monotherapy.