Cost Effectiveness of Clozapine and Risperidone in

OBJECTIVES: Risperidone and clozapine beling to a new generation of antipsychotics that are reportedly more effective and better tolerated than conventional neuroleptics. However, each of these agents costs far more per unit than conventional neuroletics. The purpose of our retrospective study was to ascertain the total cost and effectiveness of treatment before and after administration of risperidone and clozapine in 'revolving door' schizophrenia patients. METHOD: Data collected on revolving door schizophrenics for 2 years before clozapine and risperidone treatment and for at least 2 years after clozapine and risperidone treatment. Direct cost of inpatient and outpatient treatment was measured. Effectiveness was scaled as 'years of mild disability gained'. RESULT: Both risperidone and cloazpine result in higher costs and additional benefits to patients, for example, increased mild disability, reduced number of relapse, and reduced hospital length-of-stay. An ICER of risperidone was less than Rc and ICER of clozapine was greater than Rc. According to decision-analytic this model, risperidone had favorable cost-effectivenss ratios relative to clozapine. CONCLUSION: We have assumed that risperidone is more cost-effective than clozapine.

An Open Assessment of the Efficacy and Safety of Venlafaxine (EFEXOR) in Patients with Major Depression / 신경정신의학

OBJECTIVE: A Multicenter open-label study was conducted to evaluate the clinical efficacy and safety of venlafaxine for the treatment in patients with major depression. METHOD: The study was done in patients with major depression diagnosed by DSM-IV who accepted venlafaxine medication. In cases of the patients taking other antidepressants, 6 weeks of venlafaxine medication was carried out after 14 days of drug excretion period and evaluation using HAM-D, MADRS, and CGI was done at baseline, and after 1, 2, 4, and 6 weeks. Regarding all side effects that had occurred during the period of our study such as their developed/disappeared time, severities, incidences, relationship with venlafaxine, managements and results have been putted into the records. RESULTS: A total of 141 patients were enrolled. Among 94 of them finished the 6 weeks of research and 41 of them did not make it through the research. Total HAM-D scores showed significant decrease after 1 week of venlafaxine medication and continous decrease through the study period. Total scores of MADRS also showed significant improvement after 1 week and continuous decrease through the study period. Similarly, CGI showed significant improvement between baseline, 1, 2, 4, and 6 weeks. There were no significant changes in vital sign, CBC, chemistry, and EKG. The commonly reported side effects of venlafaxine were nausea (10.6%), indigestion (9.5%), constipation (8.5%), and dizziness (8.5%). CONCLUSION: According to the results, venlafaxine was effective and safe in the treatment of patients with major depression.

Antipsychotics Induced Etrapyramidal Symptoms in Schizophrenics in Relation to Cytochrome P450 2D6 Genotype

The genetically determined CYP2D6 activity may be considered to be associated with antipsychotic induced extrapyramidal side effects with inter-individual variation. Genetic polymorphism of CYP2D6 was determined by polymerase chain reaction(PCR) and Mspl restriction fragment length polymorphisms(RFLP) for 194 schizophrenics. Subjects with a 334bp band were classified a1a1, those with 229bp and 105bp bands a2a2, and those with all three bands a1a2. We did not identify schizophrenic subject with poor metabolizer. 194 schizophrenic patients previously treated neuroleptic medication, were assessed by Extrapyramidal Symptom Rating Scale(ESRS). The cases were composed of 33 akathisia, 47 parkinsonism, 21 tardive dyskinesia. These results are similar to the previous understanding that the poor metabolizer is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6 genotypes have maybe no association with schizophrenia and extrapyramidal side effects in Koreans.

Beyond the SSRIs

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of monoamine oxidase inhibitors, tricyclic antidepressants, and lithium. Following the introduction of SSRIs, the options have expanded and now include SSRIs nefazodone, venlafaxine, mirtazapine, reboxetine, tianeptine. Newer antidepressants possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacological characteristics among the drugs.

Efficacy and Tolerability of Moclobemide Compared with Amitriptyline in Dysthymic Disorder

BACKGROUND: Since dysthymia begins in late childhood or adolescence and has a chronic course, long-term pharmacotherapy may be required. New generation antidepressant, moclobemide, with more acceptable side effect profiles, is effective in the treatment of dysthymia. The main objective of this study was to determine whether they exhibit comparable efficacy and tolerability in dysthymia to amitriptyline. METHOD AND MATERIALS: The efficacy and tolerability of the moclobemide and amitriptyline, were compared in a eight-week single-centre double-blind study in patients(n=37) with dysthymia using he HAMD-17, the Clinical Global Impression Scale(CGI), the Montgomery-Asberg Depression Rating Scale(MADRS), Efficacy Index-Therapeutic Index(EITE), 4-point Index Side Effect Scale(4-PISES), and Efficacy Index-Side Effect Scale(EISE). RESULTS: A total of 37 patients entered the study, 19 were randomly assigned to the moclobemide group and 18 to be amitriptyline group. Demographic and illness characteristics were similar in both groups. There were no significant difference between two groups at the total 17-HDRS score, the HAMD-17% improvement, the total MADRS score, CGI response, and the EITE. In the comparison of EISE between two groups, the scores of the moclobemide group were relatively lower than the amitriptylinen group in full treatment. And the differences were significant(moclobemide group 1.39+/-0.61 ; amitriptyline group 2.00+/-0.85, p<.001). At the 4-PISE. There was no serious or treatment threatening side effects. And there was no specific difference in side effects between two groups. The moclobemide group reported higher EIR scores than the amitriptyline group at every follow up day, but the differences were not significant. And there was no significant differences in the scores of five HRQOL subcategories which is compared between two groups at every follow up days. CONCLUSIONS: In terms of 17-HDRS and MADRS, moclobemide and amitriptyline are equally effective at least in allevating dysthymic symptoms. But moclobemide tended to be less troubling and better tolerated than amitriptyline. Therefore, moclobemide treatment can be used as a safe, and higher satisfactory treatment strategy for the dysthymia.

Efficacy and Safety of Risperidone in Mood Disorders / 신경정신의학

OBJECTIVE: Although typical neuroleptics are commonly used in the treatment of bipolar disorder and psychotic depression, newer atypical antipsychoticss, like risperidone, may be more effective and better tolerated. This study evaluated the efficacy and safety of lithium/risperidone combination therapy in patients with mood disorders. METHODS: A total of 97 patients were included if they met DSM-IV criteria for bipolar I disorder, manic episode and major depressive disorder with psychotic feature and were treated with lithium/risperidone combination therapy and lithium/haloperidol combination therapy. Patients were rated using the CGI(Clinical global impression) GAF(Global assessment of functioning) Adverse events also assessed by medical personnel. RESULTS: Of 97 patients, 81 were diagnosed with bipolar I disorder, manic episode and 16 with major depressive disorder with psychotic feature. 81 patients who diagnosed with bipolar manic disorder were divided into two groups, with lithium/risperidone combination group and lithium/haloperidol combination group. There was no significant difference in age, sex, baseline CGI scores, and baseline GAF scores between two groups. 31 patients who received lithium and risperidone(2.07+/-0.46)were much more improved based on CGI scores than 50 patients who received lithium and haloperidol(2.58+/-0. 85) 25(80.6%)of lithium/risperidone combination group were rated much improved or very much improved, and 25(50%)of lithium/haloperidol combination group were rated response. Mean dose of risperdidone in responders(CGI< or =)is lower than partial respnders(CGI=3)4.50+/-1.92mg/d versus 4.88+/-3.31mg/d) While 16%(8 of 50)patients discontinued haloperidol and lithium because of delirium and confusion, lithium/risperidone combination group did not experienced intolerable side events. No patients was experienced worsening of manic symptoms while receiving lithium/risperidone. Antidepressant/risperidone combination group were much more improved based on CGI and GAF score. CONCLUSIONS: This study suggests risperidone is effective and well tolerated when added to lithium. We found no evidence of risperidone leading to an induction of manic symptoms.

D3 Receptor Gene Variant and Tardive Dyskinesia in Schizophrenic Patients / 신경정신의학

Tardive dyskinesia(TD)is one of the serious side effects caused by long-term treatment with neuroleptic medication. It has been known that dopamine D3 receptors are mainly located on the postsynaptic membrane where they display an inhibitory action on locomotor activity. In this study, we investigated the genetic variation of the dopamine D3 receptor gene(DRD3)as a putative risk factor for TD in schizophrenic patients receiving long-term antipsychotic medication. Fifty schizophrenic patients previously treated neuroleptic medication, were assessed for TD severity using Extrapyramidal Symptom Rating Scale(ESRS) Genomic DNA was amplified by PCR and Digestion with MluI yield two bands of 111bp and 47bp in all subjects. Subjects with a 304bp band were classified a1a1, those with 206bp and 98bp bands a2a2, and those with all five bands a1a2. The allelic distributions in TD patients and non-TD patients were not significantly different(x2=.852, df=2, p=.653) The number of each genotype observed in the schizophrenic group, did not differ significantly from the values expected according to Hardy-Weinberg equilibrium(x2=.29, df=2) This result did not support that dopamine D3 receptor gene variant were susceptible to TD in schizophrenic patients. The role of dopamine D3 receptors as a putative risk factors of TD may therefore be less important than previously thought.

Factors Affecting the Severity of Depressive Symptoms in the Elderly / 신경정신의학

The depressive symptoms are frequent and important ones in the elderly population. We studied the various factors affecting the severity of depressive symptoms in the elderly population. The Korean elderly (more than 65 years old; n=490) in Seoul area (city) were studied on the identifying data and medical and psychiatric history, Mini-Mental State Examination (MMSE) Geriatric Depression Scale (GDS) Korean Depression Scale(KDS: under development)were also administered. In our study, the significant effect of sex, age, education, marital status, and the status of medical security on the severity of depressive symptoms were not found. Significantly higher GDS and KDS scores were found in the elderly who have more than one physical illness, subjective memory complaints, and seven life events. To examine the strength of association of these variables of depression, we conducted logistic regression. Depressive symptoms were associated with 1)the loss of spouse, 2)a current physical illness, and 3)low socioeconomic status. These results showed that depression in the elderly may be correlated with the loss of spouse, a current physical illness, and low socioeconomic status.

Association between Schizophrenia and the T102C Polymorphism of the 5-HT2A

The 5-HT2A receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has 5-HT2A antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of 5-HT2A receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.