The Effects of Antidepressants on the Energy Metabolism in LETO Rat / 대한정신약물학회지

Objectives : A diverse range of adverse effects has been linked to the application of antidepressants for the treatment of depressive disorder. Recently, evidence has been emerging of the adverse metabolic effects of antidepressants. This study investigated the effects of antidepressants on plasma glucose and other factors in the fat and muscle tissue relating to metabolism. METHODS : Long-Evans-Tokushima-Ostuka (LETO) rats were used to evaluate the effects of different antidepressants. Amitriptyline, fluoxetine, and mirtazapine were administered to each of three subgroups for 4 weeks, between 11 and 15 weeks old, while a fourth subgroup was administered no antidepressant during the same period. Changes of weight and daily intake were monitored. Tissues and blood were collected at 15 weeks. RESULTS : The fluoxetine subgroup showed lower weight gain and lower food efficacy ratio than did the other subgroups. Blood glucose and other circulating factors showed no significant differences among groups, except for the leptin levels of the fluoxetine subgroup. However, the amitriptyline and mirtazapine subgroups showed similar patterns in the response of mRNA expression of peroxisome proliferator-activated receptors gamma cofactor-1 and uncoupling protein-1, 2, 3. CONCLUSION : These results could indicate possible differences in metabolic response based on the kind of antidepressant used.

Korean Medication Algorithm for Depressive Disorder 2006 (I) / 신경정신의학

OBJECTIVES: Since the publication of Korean Medication Algorithm Project for Major depressive Disorder (KMAP-MD) in 2002, there has been a substantial need for a revision due to rapid progress in the pharmacological management for depressive disorder. We revised KMAP-MD to Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2006. This paper is one of the following 4 papers consisting of Korean pharmacological algorithm for depressive disorder. METHODS: The questionnaire consisted of 4 parts; initial treatment of 1) non-psychotic depressive disorder, 2) psychotic depressive disorder, 3) treatment strategy for clinical subtypes and drug choice considering adverse effects, and 4) treatment for depressive disorder in women. It was composed of 22 questions, and each question had 54 sub-items. The questionnaire was completed by the review committee consisting of 101 experienced Korean psychiatrists. We classified the expert opinion to 3 categories (the first-line, the second-line, or the third-line). RESULTS: For non-psychotic major depression, regardless of the severity of an episode, the antidepressant (AD) monotherapy was the optimal first-line treatment. SSRI, venlafaxine, and mirtazapine were the 1st-line AD. In case of a partial or no response to initial strategy, adding another AD was recommended. For psychotic major depression, combination of an AD and an atypical antipsychotic (AAP) was the treatment of choice. Among AAPs, quetiapine, risperidone, olanzapine were preferred. For non-responder to initial strategy, the next step was adding or changing AD before changing AAP. For women with premenstrual dysphoric syndrome or postpartum depression without psychotic features, AD monotherapty was a preferred strategy while for psychotic postpartum depression, combination of AD and AAP was recommended. Experts recommended various ADs according to adverse effect. CONCLUSION: These results suggest that the medication strategies for depressive disorder are rapidly changing and reflect the recent studies and clinical experiences.

Korean Medication Algorithm for Depressive Disorder 2006 (II): Major Depressive Disorder without Psychotic Features / 신경정신의학

OBJECTIVES: There have been noticeable progresses in the pharmacological management of depressive disorders along with vigorous preclinical and clinical trials of newer antidepressant drugs during the last decade. Since the first development of Korean Medication Algorithm for Major Depressive Disorder (KMAP-MDD) in 2002, there has been a substantial need for the revision of this algorithm. We amended the KMAP-MDD to Korean Medication Algorithm for Depressive Disorders (KMAP-DD) in 2006 and included treatment strategies for other types of depressive disorders. This article is about the treatment of MDD without psychotic features in the KMAP-DD 2006. METHODS: Questionnaires were developed by the executive committee for KMAP-DD. The first part of this questionnaire is about the treatment strategies of MDD without psychotic features, minor depressive disorder and dysthymic disorder. Seven questions and 10 sub-items were prepared to investigate the experts' opinions about treatment of major depressive disorders without psychotic features. The expert review committee composed of 101 experienced Korean psychiatrists was asked to evaluate the medication strategies for various clinical situations of depressive disorders using a 9-point scale. The scale was slightly modified from the format developed by the RAND corporation. We classified the expert opinions into 3 categories (first-line, high second-line and low second-line) by the 95% confidence interval of response score and evaluated the consensus of opinions of Korean experts using Chi2-test. RESULTS: For patients with MDD without psychotic features, antidepressant monotherapy was the optimal first-line treat-ment strategy regardless of the severity of an episode. In case of no or partial response to antidepressant monotherapy for severe episode of MDD, combination treatment with another antidepressant drug or augmentation treatment with triiodothyronine or lithium was considered as the second-line treatment. Meanwhile, for mild-to-moderate episode of MDD without psychotic features, switching to another antidepressant as well as augmentation or combination treatment was also considered as the second-line treatment. Selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine were chosen as the 1st-line antidepressant drugs for MDD without psychotic features in Korea. CONCLUSION: The initial treatment strategy for patients with major depressive disorder without psychotic features is similar to that of the previous medication algorithm (KMAP-MDD). However, combination treatment with two antidepressant drugs and augmentation treatment strategies were considered at a relatively earlier step in this algorithm than in the previous version of Korean medication algorithm (KMAP-MDD) for the severe episode of major depressive disorder. The recent trials of newer antidepressant drugs and the preference of more active treatment strategy in up-to-date clinical psychiatry fields may have affected these changes in Korea.

Korean Medication Algorithm for Depressive Disorder 2006 (III): Major Depressive Episode with Psychotic Feature / 신경정신의학

OBJECTIVES: Since the publication of Korean Medication Algorithm Project for Major Depressive Disorder (KMAP-MD) in 2002, there has been a substantial need for a revision due to rapid progress in the pharmacological management of depressive disorder. We revised KMAP-MD 2002 and developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) 2006. METHODS: We developed a questionniare for surveying the opinion of experts on pharmacotherapy of depressive disorder. The questionnaire consisted of 4 parts; 1) treatment of non-psychotic depressive disorder, 2) treatment of psychotic depressive disorder, 3) treatment according to clinical subtypes and drugs choice considering adverse effects, and 4) treatment of depressive disorder in women. The questionnaire was completed by the review committee consisting of 101 experienced Korean psychiatrists. It is composed of 22 questions, and each question includes 54 sub-items. We classified the expert opinion to 3 categories (the first-line, the second-line, or the third-line) by Chi2-test. RESULTS: For depressive disorder with psychotic features, most reviewers prefer the combination of antidepressant and atypical antipsychotics. Electroconvulsive therapy and the combination of antidepressant and typical antipsychotics were the second-line treatment. Among antidepressants, venlafaxine was the most preferred, and SSRI and mirtazapine followed. Among atypical antipsychotics, quetiapine, risperidone and olanzapine were the most preferred, in this order. In patients who have no response to the first-line treatment, many reviewers recommended switching to another antidepressant or adding another atypical antipsychotics. CONCLUSION: For severe depressive disorder with psychotic features, the combination of antidepressant and atypical antipsychotics was preferred for the first-line treatment. These results suggest that the medication strategies of depressive disorder are rapidly changing and reflects the recent studies and clinical experiences.

Korean Medication Algorithm for Depressive Disorder 2006 (IV): The Choice of Antidepressant According to the Subtypes of Depression, Adverse Effects of Antidepressant and Treatment Strategies in Women / 신경정신의학

OBJECTIVES: In 2002, the Korean Medication Algorithm Project for Major depressive Disorder (KMAP-MD) was published, but there has been a need for a guideline about detailed issues of depressive disorder. We revised KMAP-MDD and reestablished Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2006. METHODS: A questionnaire had been developed by the executive committee for KMAP-DD. The review committee consisted of 101 experienced psychiatrists. From the total of 22 questions in the questionnaire, 7 questions were evaluated for these subjects . We classified the expert opinions to 3 categories according to its confidence interval; first, second and third line. RESULTS: SSRI and venlafaxine were the first line antidepressants (AD) for atypical and melancholic depression. For dysthymic disorder and minor depressive disorder, SSRI was recommended as the first line medications. Only AD medications was a preferred initial strategy for treating premenstrual dysphoric disorder, mild to moderate and severe non-psychotic postpartum depression. In severe psychotic postpartum depression, combination therapy of AD and atypical antipsychotics was the treatment of choice. SSRI was preferred when considering sedation, anticholinergic and cardiovascular adverse effects. Also, experts recommended mirtazapine against gastrointestinal adverse effects and bupropion in avoiding sexual dysfunction. CONCLUSION: These results suggest that clinicians have to consider both clinical situations and drug adverse effects in the choice of antidepressant medications.

The Effect of Paroxetine in Chronic Schizophrenic Inpatients with Depressive Symptoms: A Double-Blind Placebo-Controlled Study / 신경정신의학

OBJECTIVES: This double-blind placebo-controlled study was conducted to demonstrate the improvement of depressive, positive and negative symptoms, and general psychopatholgy in depressed chronic schizophrenic inpatients with adjunctive paroxetine 20mg therapy in the morning. METHODS: Forty nine chronic schizophrenic inpatients with depressive symptoms were randomly received adjunctive paroxetine or placebo for 6 week study period. Therapeutic effect and side effects were evaluated by means of the Hamilton Rating Scale for Depression (HRSD), the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Extrapyramidal Symptom Rating Scale (ESRS), the UKU side effect rating scale (UKU), and the Clinical Global Impression (CGI) at baseline, first, second, forth, and sixth week of treatment in a controlled double-blind design. RESULTS: 18 patients completed six weeks of paroxetine therapy, and 18 patients placebo therapy. 1) Comparison between paroxetine and placebo groups: (1) HRSD total scores in both groups were significantly decreased (p< 01) but there was no statistically significant difference between 2 groups. This study showed that significant effect in paroxetine group appeared at 2nd week of treatment (p< 01), while in placebo group at 4th week of treatment (p< 01). (2) PANSS, BPRS, CGI, ESRS, and UKU: In both groups, PANSS total scores and CGI scores were significantly decreased respectively (p< 01, p< 05) and thus indicated the improvement of global psychopathology and entire effects. There were no significant differences between 2 groups in positive, negative symptoms, general psychopathology, and drug side effects. 2) Comparison between responding and nonresponding groups in paroxetine adjunctive therapy: (1) Compared with nonresponding group, responding group had significant decrease in HRSD total score (p< 01), in HRSD subitems such as depressed mood, suicide, psychic anxiety, and feelings of guilt (p< 01), and in other subitems such as work and activity, early insomnia, and hypochondriasis (p< 05). (2) Compared with nonresponding group, responding group had significantly decrease in BPRS total score (p< 01) and in general subscale of PANSS (p< 05). CONCLUSION: The results suggest that both paroxetine and placebo groups were improved in depressive symptoms, but paroxetine group had more rapid improvement than placebo group. There were no significant differences in positive symptoms, negative symptoms, general psychopathology, and drug side effects between two groups. Compared with nonresponding group in paroxetine adjunctive therapy, responding group had significant improvement in depressive symptoms and general psychopathology.