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.

Ultraviolet spectrophotometric method for analytical determination of mianserin hydrochloride in coated tablets and comparison with LC

abstract Ultraviolet spectrophotometric (UV) and Liquid Chromatographic (LC) methods for the determination of mianserin hydrochloride in pharmaceutical formulation were developed and validated. The various parameters, such as specificity, linearity, precision and accuracy were studied according to International Conference on Harmonization (ICH, 2005). For UV method, mianserin hydrochloride was determinate at 278 nm using HCl 0.1 M as the solvent. The response was linear in the concentration range of 20.0 - 140.0 µg/mL (r = 0.9998). Precision data evaluated by relative standard deviation was lower than 2%. The UV method was simple, rapid and low cost. Chromatographic analyses were performed in an Ace C18 column and the mobile phase was composed of methanol, 50 mM monobasic potassium phosphate buffer and 0.3% triethylamine solution adjusted to pH 7.0 with phosphoric acid 10% (85:15). LC method was specific, linear, precise, exact and robust. The results confirmed that the both methods are valid and useful to the routine quality control of mianserin hydrochloride in coated tablets. Statistical analysis by Student´s t-test showed no significant difference between the results obtained by UV and LC methods.

resumo Os métodos por espectrofotometria na região do ultravioleta (UV) e por cromatografia líquida (CL) para determinação do cloridrato de mianserina na forma farmacêutica foram desenvolvidos e validados. Os vários parâmetros, como especificidade, linearidade, precisão e exatidão foram avaliados de acordo com o International Conference on Harmonization (ICH, 2005). Para o método de UV, o cloridrato de mianserina foi determinado utilizando o comprimento de onda de 278 nm e HCl 0,1 M como solvente. A resposta foi linear na faixa de concentração de 20,0 a 140,0 µg/Ml (r = 0,9998). A precisão foi avaliada pelo valor de desvio padrão relativo (DPR) inferior a 2%. O método por UV é simples, rápido e de baixo custo. As análises cromatográficas foram realizadas em uma coluna Ace C18 e a fase móvel foi composta por metanol, tampão fosfato de potássio monobásico 50 mM com 0,3% de trietilamina com o pH ajustado para 7,0 com ácido fosfórico 10% (85:15). O método de CL foi específico, linear, preciso, exato e robusto. Os resultados confirmam que ambos os métodos são válidos e úteis para o controle de qualidade do cloridrato de mianserina em comprimidos revestidos. A análise estatística por teste t de Student não mostrou diferença significativa entre os resultados obtidos para os métodos de UV e CL.

Korean Medication Algorithm for Depressive Disorder 2012 (III): The Subtypes of Depression / 대한정신약물학회지

OBJECTIVE: Recently, the pharmacotherapy including antidepressants in treating depression is widely used. However, as a result of newer agents that are continuously introduced, pharmacological treatment strategy is also changing. To catch up this trend, Korean Medication Algorithm Project for Depressive Disorder was developed in 2002 and revised in 2006. Since the last revision, the third revision reflected the new research result and the latest trends in the areas of pharmacological treatment. METHODS: One hundred and twenty three psychiatrists who have vast clinical experiences in depressive disorder are primarily selected then survey was sent to them via mail, 67 surveys were retried. This survey is constructed with 44 questionnaires in which contained from overall treatment strategies to treatment strategies under the specific circumstances. Each treatment strategy or treatment option is evaluated with the overall score of nine and the following 95% confidence interval result treatment option were divided into three phases of recommendation; primary, secondary, tertiary. RESULTS: For dysthymic disorder, antidepressant monotherapy including selective serotonin reuptake inhibitor (SSRI) [(es)citalopram, fluoxetine, sertraline, paroxetine], serotonin-norepinephrine reuptake inhibitor (SNRI) (venlafaxine, duloxetine, milacipran), and mirtazapine, was recommended as the first line medications. For melancholic type, SSRI, SNRI, and mirtazapine were recommended as the first line medications. For atypical type and seasonal pattern, bupropion as well as SSRI, SNRI, and mirtazapine, were recommended as the first line medications. CONCLUSION: The preferences of antidepressants in experts were different according to the subtype of depression. These results suggest that clinicians have to consider the subtype of depression in the treatment of depressive disorders.

No Association between Serotonin Receptor 2C-759C/T Polymorphism and Weight Change or Treatment Response to Mirtazapine in Korean Depressive Patients

OBJECTIVE: Activation of one or more serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of serotonergic antidepressants. The serotonin 2C (5HT 2C) receptor is known to be associated with antidepressant action and weight gain. We sought to determine whether the 5-HTR 2C receptor -759C/T polymorphism was associated with weight gain and treatment response to mirtazapine in major depressive disorder (MDD) patients. METHODS: The 5-HT 2C receptor -759C/T polymorphism was analyzed in 323 MDD patients. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment. RESULTS: There was no significant difference in the 5-HT 2C receptor -759C/T genotype distribution between responder and non-responder groups. The 5-HT 2C receptor -759C/T polymorphism was not associated with weight change over time after mirtazapine administration. CONCLUSION: The 5-HT 2C receptor -759C/T polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was not associated with weight change after 8 weeks of mirtazapine treatment. Further investigation on other polymorphisms of the 5-HT 2C gene is required to determine whether the 5-HT 2C gene influences treatment response and weight change after mirtazapine administration in patients with major depressive disorder.

Review of Antidepressants Treatment in Late-Life Depression

Late-life depression (LLD) refers to depressive syndromes defined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and in the International Classification of Diseases-10 (ICD-10) that arise in adults older than age 65 years. LLD often affects people with chronic medical diseases, cognitive impairment, or other forms of disability. The phenomenology of LLD differs in part from that of early-life depression. Antidepressants appear to have a neutral or protective effect against suicidal ideation or behavior in the elderly despite having the risk of opposite effect in children, adolescents, and young adults. The treatment of depression may be divided into acute, continuation, and maintenance phases. Currently available antidepressant medications represent several classes of agents with similar antidepressant efficacy. Differences in side effect profile, interactions, and out-of-pocket cost are important determinants in the choice of medication for an elderly patient. To minimize side effects, starting doses for older adults may be lower than those for younger adults, but older adults often require full adults doses for an adequate response. Antidepressants are as effective when given to elderly individuals as they are when given to younger adults. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) the antidepressants of choice, followed by bupropion, and mirtazapine. Tricyclic antidepressants (TCAs) are effective but are no longer considered to be first-line treatments because of their side effects.

Psychotrophic Drug Therapy of the Sexual Offenders or Paraphilia / 대한정신약물학회지

Sexual violence crime causes severe trauma to victim's family as well as the victim, and its aftereffect which is hard to be healed can last for the entire lifetime. And thus plenty of social cost is incurred due to the crime. It has long been reported that paraphilia is associated with sexual offenders and sexual violence. In this study, the previous foreign data on the psychiatric medication used for sexual offender or paraphilia were summarized for the first time in Korea, and the possibility of medication in Korea was examined. As for the drugs used for sexual offender or paraphilia, SSRI was most frequently reported and besides that, tricyclic antidepressant, antipsychotics, antiepileptic drugs, mirtazapine, and naltrexone were reported.

Impulsive Behavior and Recurrent Major Depression Associated with Dandy-Walker Variant

Reported herein is a case of recurrent major depression with impulse control difficulty in a 33-year-old man with Dandy-Walker variant. He was diagnosed as having major depressive disorder a year before he presented himself to the authors' hospital, and had a history of three-time admission to a psychiatric unit in the previous 12 months. He was readmitted and treated with sodium valporate 1,500 mg/day, mirtazapine 45 mg/day, and quetiapine 800 mg/day during the three months that he was confined in the authors' hospital, and the symptoms were reduced within three months but remained thereafter. This is the only case so far reporting recurrent depression with impulse control difficulty associated with Dandy-Walker variant. This case implies that any cerebellar lesion may cause the appearance of recurrent depression with impulse control difficulty in major depressive disorder.

A 10-Week Memantine Treatment in Bipolar Depression: A Case Report. Focus on Depressive Symptomatology, Cognitive Parameters and Quality of Life

Memantine and other glutamatergic agents have been currently investigated in some off-label indications due to glutamatergic involvement in several psychoneurological disorders. We assumed that memantine similarly to ketamine may positively influence mood, moreover having a potential to improve cognition and general quality of life. We report a case of a 49-year-old male hospitalized during a manic and a subsequent moderate depressive episode. After an ineffective use of lithium, olanzapine and antidepressive treatment with mianserin, memantine was added up to 20 mg per day for 10 weeks. The mental state was assessed using the Hamilton Depression Rating Scale, the Young Mania Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Inventory, the World Health Organization Quality of Life Scale and psychological tests. After 10 weeks the patient achieved a partial symptomatic improvement in mood, anxiety and quality of sleep, but his activity remained insufficient. We also observed an improvement in the parameters of cognitive functioning and quality of life. There was neither significant mood variations during the memantine use nor mood changes after its termination. No significant side effects were noted during the memantine treatment. We conclude that using memantine in bipolar depression may improve mood, cognitive functioning and quality of life.

Comparison of Antidepressants Tolerability in Cancer Patients Referred for Psychiatric Consultation / 정신신체의학

OBJECTIVES: Many patients diagnosed with cancer suffer from various psychiatric symptoms such as depression, anxiety and insomnia as well as cancer itself. Patients with cancer are more vulnerable to possible adverse events of psychotropic medications. Although antidepressants are widely used among cancer patients, there is little information about tolerability of antidepressants. This study was conducted to compare tolerability of antidepressants in cancer patients referred for psychiatric consultation. METHODS: The participants were cancer patients who had been referred to psychiatrist for their psychiatric symptoms. We retrospectively analyzed the data of patients diagnosed with cancer from 9 general hospitals in Korea. The discontinuation rate for a 6 months period after treatment initiation for three antidepressants(Escitalopram, Mirtazapine, Paroxetine) were compared. RESULTS: Antidepressants were prescribed for 96.3% of subjects and Escitalopram 150(47.2%), Mirtazapine 92 (28.9%) and Paroxetine 76(23.9%) were prescribed frequently in order There were no significant differences in discontinuation rates among the three antidepressants during the 6 month period after initiation of pharmacotherapy. But there was a difference in discontinuation rates between inpatients versus outpatients(p<0.0001). CONCLUSIONS: In a naturalistic setting for the antidepressant treatment for cancer patients, it seems that there are no differences in discontinuation rates among these three antidepressants. It is therefore essential that such interactions are carefully considered when treating patients of antidepressants who already have cancer.

Tratamiento conjunto con mirtazapina y terapia antiretroviral para la leucoencefalopatía multifocal progresiva asociada a infección por VIH-1: presentación de un caso clínico y revisión de la literatura / Mirtazapine and antiretroviral therapy in the treatment of progressive multifocal leukoencephalopathy associated with HIV-1 infection: report of a case and review of literature

We report a 43 years old HIV-1 infected male who developed a severe subacute neurological damage because of a progressive multifocal leukoencephalopathy confirmed by PCR for JC virus. The patient was treated with antiretroviral therapy in adequate doses for CNS penetration and mirtazapine, an antidepressant inhibitor of serotonin receptors. His evolution during one year follow up has been favorable in both, clinically and images.

Se presenta el caso clínico de un paciente de sexo masculino, de 43 años portador de VIH que desarrolló un grave daño neurológico subagudo debido a una leucoencefalopatía multifocal progresiva diagnosticada mediante reacción de polimerasa en cadena de virus JC. El paciente fue tratado con terapia anti-retroviral de penetración eficiente al SNC y con mirtazapina, un antidepresivo inhibidor de los receptores de serotonina. Su evolución durante un año de seguimiento ha sido favorable tanto del punto de vista clínico como de imágenes.

Effects of Antidepressant Treatment on Sexual Arousal in Depressed Women: A Preliminary fMRI Study

OBJECTIVE: There was a recent study to explore the cerebral regions associated with sexual arousal in depressed women using functional magnetic resonance imaging (fMRI). The purpose of this neuroimaging study was to investigate the effects of antidepressant treatment on sexual arousal in depressed women. METHODS: Seven depressed women with sexual arousal dysfunction (mean age: 41.7+/-13.8, mean scores of the Beck Depression Inventory (BDI) and the 17-item Hamilton Rating Scale for Depression (HAMD-17): 35.6+/-7.1 and 34.9+/-3.1, respectively) and nine healthy women (mean age: 40.3+/-11.6) underwent fMRI before and after antidepressant treatment. The fMRI paradigm contrasted a 1 minute rest period viewing non-erotic film with 4 minutes of sexual stimulation viewing an erotic video film. Data were analyzed by SPM 2. The relative number of pixels activated in each period was used as an index of activation. All depressed women were treated with mirtazapine (mean dosage: 37.5 mg/day) for 8 to 10 weeks. RESULTS: Levels of brain activity during sexual arousal in depressed women significantly increased with antidepressant treatment (p<0.05) in the regions of the hypothalamus (3.0% to 11.2%), septal area (8.6% to 27.8%) and parahippocampal gyrus (5.8% to 14.6%). Self-reported sexual arousal during visual sexual stimulation also significantly increased post-treatment, and severity of depressive symptoms improved, as measured by the BDI and HAMD-17 (p<0.05). CONCLUSION: These results show that sexual arousal dysfunction of depressed women may improve after treatment of depression, and that this improvement is associated with increased activation of the hypothalamus, septal area, and parahippocampal gyrus during sexual arousal.

Clinical Characteristics and Use of Antidepressants among Cancer Patients Referred for Psychiatric Consultation : A Korean Multicenter Survey / 신경정신의학

OBJECTIVES: Antidepressants are frequently used for treatment of psychological distress among cancer patients. The aim of this study is to investigate the characteristics of psychiatric consultations and antidepressant use for cancer patients. METHODS: Participants in the study included cancer patients who had been referred for psychiatric consultation. A total of 488 patients were recruited from nine general hospitals in Korea. Questionnaires based on medical records, including antidepressants prescribed, were investigated by psychiatrists. RESULTS: The most common psychiatric diagnosis of subjects was depressive disorders (72.4%), followed by anxiety disorders (13.0%), and adjustment disorders (7.3%). Antidepressants were prescribed for 96.3% of subjects and escitalopram, mirtazapine, and paroxetine were prescribed frequently, in order. Anxiolytics and hypnotics were used for 58.2% of the subjects, for which lorazepam and alprozolam were preferred. During the study period, 226 (46.8%) subjects discontinued treatment and the most common cause was improvement of symptoms (123, 54.4%). CONCLUSION: Our results showed a tendency of prescription of antidepressants and anxiolytics and common psychiatric problems in Korean cancer patients. We suppose that these data would be helpful to clinicians who manage psychiatric symptoms of cancer patients.

Changes of Medication Usage in Inpatients of Major Depressive Disorder: One University Hospital among Year 2001, 2006 and 2010 / 대한정신약물학회지

OBJECTIVE: Prescription patterns have changed rapidly due to development of new drugs, results of new researches, and increment of clinician's experience. The goal of this study was to examine and compare the trend of prescription patterns for major depressive disorder at a university hospital among year 2001, 2006, and 2010. METHODS: We reviewed the medication usage of inpatients with major depressive disorder in 2001, 2006 and 2010, including antidepressants used as first choice, switching, and combination, and various augmentation agents. And we investigated the time to switching and combination of antidepressant in 2001, 2006 and 2010. RESULTS: The antidepressants used as first line drug were selective serotonin reuptake inhibitor (SSRI) (49.7%), mirtazapine (24.5%), and tricyclic antidepressant (TCA) (4.9%) in 2001, and SSRI (49.4%), mirtazapine (25.6%) and serotonin-norepinephrine reuptake inhibitor (SNRI) (20.2%) in 2006, SSRI (42.7%), mirtazapine (19.5%) and SNRI (18.3%) in 2010 in frequency order. The antidepressants used as switching drug were TCA (33.3%), mirtazapine (25.0%), and nefazodone (16.7%) in 2001, SSRI (35.0%), mirtazapine (35.0%), and SNRI (20.0%) in 2006, and SSRI (50.0%), SNRI (30.0%) and mirtazapine (20.0%) in 2010. As combination treatment, SSRI and TCA combination was used mostly by far in 2001 (51.1%), but in 2006 and 2010, various combination were used. In 2010 year, SNRI and mirtazapine, SSRI and TCA, SSRI and mirtazapine (42.1%, 21.1%, 15.8%, respectively) combination treatment were used in frequency order. The use of typical antipsychotics as augmentation agent decreased and the use of atypical antipsychotics increased significantly in 2010. Most frequently used atypical antipsychotic was quetiapine in 2010. The use of thyroid hormone was significantly decreased after 2006, but the use of mood stabilizer was increased between 2001 and 2010 (p=0.001). CONCLUSION: The results of the present study suggested that there were lots of change in prescription patterns for major depressive disorder between 2001 and 2010. Especially, these changes could be seen in use of various antidepressants, increment in use of atypical antipsychotics and lamotrigine. It can reflect not only the current progress of psychopharmacology and clinical experience, but also the clinical complexity of treatment of depression.

Reversal of haloperidol-induced motor deficits by mianserin and mesulergine in rats

Although haloperidol is widely prescribed for the treatment of schizophrenia, its beneficial effects are accompanied by extrapyramidal side effects [EPS]. Role of 5-HT-2A/2C receptors in the attenuation of acute Parkinsonian-like effects of typical antipsychotics is investigated by prior administration of mianserin and mesulergine to rats injected with haloperidol. In the first part of study effects of various doses of haloperidol [0.5, 1.0, 2.5 and 5.0 mg/kg] were determined on motor activity and a selected dose [1 mg/kg] was used to monitor attenuation of parkinsonian effects by two different doses of 5-HT-2A/2C receptor antagonists mianserin [2.5 and 5.0 mg/kg] and mesulergine [1.0 and 3.0 mg/kg]. Rats treated with haloperidol at doses of 0.5-5.0 mg/kg exhibited impaired motor coordination and a decrease in exploratory activity in an open field. The dose response curve showed that at a dose of 1 mg/kg significant and submaximal effects are produced on motor coordination and exploratory activity. Coadministration of mianserin and mesulergine attenuated and reversed haloperidol-induced motor deficits in a dose dependent manner. The mechanism involved in the attenuation / reversal of haloperidol-induced parkinsonian like symptoms by mianserin and mesulergine is discussed. Prior administration of mianserin or mesulergine may be of use in the alleviation of EPS induced by conventional antipsychotic drugs. The findings have potential implication in the treatment of schizophrenia and motor disorders

Mirtazapine Augmentation for Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: A Retropective Investigation

The aim of the present study was to retrospectively identify sexual dysfunction changes in the patients under mirtazapine-augmented serotonin reuptake inhibito (SSRI) treatment. The study comprised medical records of 20 outpatients, under mirtazapine-augmented SSRI treatment for their major depressive disorder, who had been selected among the patients that had developed sexual dysfunction to previous treatment as monotherapy, with SSRI for at least six weeks. These drugs were maintained and mirtazapine were added (15-45 mg/day). There was a significant difference in scores between baseline and week 4 or week 8 on the both Hamilton Depression Rating and Arizona Sexual Experience Scale. According to Clinical Global Impression-Improvement, 68.4% of the patients were responders. The use of low-dose mirtazapine as an add-on treatment to SSRIs appears to be an effective and well-tolerated augmenttaion for sexual dysfunction caused by SSRIs.

Psychiatric Co-morbidity and Efficacy of Mirtazapine Treatment in Young Subjects With Chronic or Cyclic Vomiting Syndromes: A Case Series

The aim of this case report was to evaluate the psychiatric co-morbidity and efficacy of mirtazapine treatment in young subjects with chronic or cyclic vomiting syndromes. This is a case series of 8 young subjects (age range of 6-16 years, 11.12 +/- 3.52 years) who were referred or consulted to child psychiatry department. They were referred or consulted by pediatric gastroenterology or surgery departments for the presence of non-remitting and medically unexplained vomiting. They were investigated for co-morbid psychiatric disorders using a structured psychiatric interview. An open trial of mirtazapine was conducted for the treatment and/or prevention of vomiting. Primary outcome measure was Clinical Global Impression-Improvement scale. Subjects were diagnosed with chronic (n = 5) or cyclic (n = 3) vomiting syndromes. Duration of vomiting ranged from 6 months to 10 years (3.5 +/- 3.2 years). All subjects received multiple psychiatric diagnoses with anxiety disorders being the most frequent. Maximum mirtazapine dosage was 7.5-30 mg/day (16.00 +/- 6.16 mg/day). Three subjects showed complete remission and 5 subjects showed much to very much improvement in vomiting. Most frequent side effects were increased appetite, weight gain and sedation. Young subjects with chronic or cyclic vomiting may frequently suffer anxiety and/or depressive symptoms or disorders. Mirtazapine could be an effective treatment option for the treatment of vomiting and co-morbid anxiety or depressive disorders in these subjects. More systematic research are needed on this topic.

The Tolerability of Mirtazapine Augmentation in Schizophrenic Patients Treated with Risperidone: A Preliminary Randomized Placebo-controlled Trial

OBJECTIVE: Some patients with schizophrenia may need mirtazapine augmentation to improve negative and cognitive symptoms. However there have been a few studies about the tolerability of mirtazapine augmentation to antipsychotics such as akathisia, extrapyramydal symptoms, weight gain, and body mass index (BMI). METHODS: This study was an eight-week double-blind, randomized controlled trial (RCT) of mirtazapine augmentation to risperidone. Twenty-one stabilized participants diagnosed with schizophrenia and undergoing treatment with risperidone were randomized to adjunctive treatment with mirtazapine (15 mg/day for the first two weeks, 30 mg/day for the next six weeks) or placebo. Eleven patients were assigned to the mirtazapine group, and nine patients were given placebo. RESULTS: There was no significant difference between the mirtazapine and placebo groups with respect to Barnes Akathisia rating Scale (BAS) and Sympsom-Angus Scale (SAS). However, the mirtazapine group exhibited a statistically significant increase in weight and BMI (p<0.05). CONCLUSION: These results suggest that mirtazapine augmentation can be tolerable in schizophrenic patients treated with risperidone; however, we should pay attention to the weight gain with mirtazapine. Our results should be replicated in a large-scale lengthy trial.

Determination of mirtazapine in spiked human plasma and tablets by first derivative spectrofluorimetric method

A sensitive first derivative spectrofluorimetric method [[1]D-spectrofluorimetry] was developed for the determination of mirtazapine. Calibration graph for mirtazapine determination was established using the first derivative amplitudes of the mirtazapine emission spectrum [lamda[ex]= 314 nm] in 0.1 M sulphuric acid measured at 375-435 nm from peak to peak, as the analytical signals. Moreover, the ratio of [1]-spectrophotometric peak amplitudes at these wavelengths was calculated and used for the detection of the presence of interferences. Linearity range was found to be between 1 and 40 ng ml[-1] with correlation coefficient [r] = 0.9999. The limit of quantitation [LOQ] was 1.0 ng ml[-1] and the limit of detection [LOD] was 0.2 ng ml[-1]. The proposed method was validated according to ICH; and it has been applied for the drug determination in human plasma without prior extraction and in tablets. The proposed method's accuracy, reproducibility, selectivity and simplicity suggest its application in quality control analysis of the drug

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (II) : Medication Algorithm & Long-Term Medication Treatment Strategy / 신경정신의학

OBJECTIVES: This study was performed to investigate the consensus about medication algorithms, including long-term medication treatment strategies, in the treatment of generalized anxiety disorder (GAD). METHODS: The executive committee of the Korean Medication Algorithm Project for GAD developed questionnaires about the psychopharmacologic treatment strategies for patients with GAD. Fifty-five (65%) of 84 experts of a reviewing committee answered the questionnaires. The consensus of expert opinion was classified into three categories, and the treatments of choice were selected by use of 95% confidence intervals and chi-square-tests. RESULTS: The consensus on the first-line treatment strategy for GAD was as follows. Step 1 is the use of the one of a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenaline reuptake inhibitor (SNRI) and buspirone for at least four to six weeks. Step 2 is to switch from a SSRI to a SNRI or buspirone or vice versa. Step 3 is to augment medication with an atypical antipsychotic or add a benzodiazepine or antihistamine. Step 4 is to switch to another combination, which includes a SSRI, a SNRI, mirtazapine or a tricyclic antidepressant Step 6 is to review the diagnosis, and 'benzodiazepines including clonazepam and alprazolam can be combined with another drug even from the initial period'. In terms of long-term medication treatment, the consensus first-line tr-eatment strategy involved the use of venlafaxine XR, escitalopram, fluoxetine, paroxetine CR, sertraline and buspirone. CONCLUSION: This study provided information about the consensus among Korean experts regarding medication algorithms, including long-term medication treatment strategies, in the treatment of GAD.

An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.