The two cases of patients with restless legs syndrome induced by a single oral dose of mirtazapine 7.5 mg were reported. Two elderly women were administrated with 7.5 mg of mirtazapine for controlling depression and insomnia. Approximately 1-2 hours after taking the medicine, they experienced unpleasant restless feelings in their arms and legs. They had to rub or move the extremities for alleviating the symptoms. They could not fall asleep due to the severe paresthesia and restlessness until they took benzodiazepines. The next day, the symptoms began to disappear. These symptoms have not developed again after they refused taking mirtazapine. These two cases suggest that a single low dose of mirtazapine can induce restless legs syndrome.
Aged ; Arm ; Benzodiazepines ; Depression ; Extremities ; Female ; Humans ; Leg ; Paresthesia ; Psychomotor Agitation ; Restless Legs Syndrome* ; Sleep Initiation and Maintenance Disorders

A newer atypical antipsychotic, aripiprazole has been shown to be effective in the treatment of schizophrenia and other psychotic disorders. A 44-year-old woman who developed psychotic symptoms and parkinsonism a month after carbon monoxide poisoning and did not respond to other atypical antipsychotics, was successfully treated with aripiprazole. This case suggests that aripiprazole may be helpful to those developed psychotic symptoms and movement disorders associated with toxic brain injury such as carbon monoxide poisoning.
Adult ; Antipsychotic Agents ; Brain Injuries ; Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Female ; Humans ; Movement Disorders ; Parkinsonian Disorders* ; Psychotic Disorders ; Schizophrenia ; Aripiprazole

OBJECTIVE: Although the number of studies are increasing in the pharmacotherapy of posttraumatic stress disorder (PTSD), few studies for the long-term effects of antidepressants on the treatment of PTSD were conducted. The aim of the present study was to investigate the effectiveness of mirtazapine during 24-week continuation treatment in patients with posttraumatic stress disorder. METHODS: Out of 15 patients participating in the previous 8 weeks study, 12 patients completed 24 weeks treatment with mirtazapine. Efficacy was evaluated at 12-week and 24-week using Impact of Event Scale-Revised (IES-R), Short PTSD Rating Interview (SPRINT), Interviewer-Administered Structured Interview for PTSD (SIP) and Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: The scores on the IES-R, SPRINT, SIP and MADRS were significantly reduced by time from baseline to the end-point (F=36.1, df=4, p<0.001 ; F=106.3, df=4, p<0.001 ; F=121.1, df=4, p<0.001 ; F=198.9, df=4, p<0.001). On post hoc analysis, the scores of all 4 measures were significantly reduced at the end point since week 8. But, after Bonferroni correction, the reduced score was statistically significant in only SPRINT. The number of patients, whose scores reduced over 50% in all four scales, tended to increase from 3 at week 8 to 8 at the end point (p=0.063). No serious drug-related side effects were observed. CONCLUSION: This result suggests that the therapeutic effect of mirtazapine is maintained and may be even increased in the long-term treatment of PTSD. More studies in the pharmacotherapy of PTSD will be needed in the future.
Antidepressive Agents ; Depression ; Drug Therapy ; Humans ; Stress Disorders, Post-Traumatic* ; Weights and Measures

OBJECTIVE: Recent studies suggested that the neurotrophic effects might be a major therapeutic mechanism of antidepressants. However, these effects have not been confirmed yet in depressed patients. We investigated whether mirtazapine treatment has the neurotrophic effects in depressed patient by using (1)H-MRS and explored the relationship between these effects and clinical improvements and neuropsychological functions. METHODS: Fourteen female, right-handed patients with major depressive disorder and 12 healthy controls participated in the study. Before the treatment with mirtazapine, we measured severity of illness, neuropsychological functions, and the levels of NAA, Cho and Cr in both hippocampi using (1)H-MRS in the depressed subjects. After the treatment with mirtazapine for 6 weeks, we repeated the measures of the pretreatment condition in the depressed subjects. We also measured variables of severity of illness and hippocampal metabolites with (1)H-MRS in the control group. RESULTS: There were no significant differences in NAA/Cr, Cho/Cr, and Cho/NAA between the depressed subjects and the control group. However, after the treatment with mirtazapine, there were significant improvements in severity of illness, immediate memory, and delayed memory. The posttreatment ratio of the total hippocampal Cho/Cr was significantly lowered than the ratio of the pretreatment Cho/Cr. However, the percent changes of the hippocampal Cho/Cr from the pretreatment Cho/Cr ratio were not correlated with the changes of severity of illness or neuropsychological functions from the pretreatment condition. CONCLUSIONS: These findings indicate that mirtazapine may reduce the level of choline metabolites by stabilizing the effect on the cholinergic neurons, reducing turnover or metabolism of neuronal membranes, or modulating the neuroendocrine systems in the depressed patients. However, this effect is not necessarily related to clinical improvements. Further studies on the therapeutic action of mirtazapine are needed.
Antidepressive Agents ; Choline ; Cholinergic Neurons ; Depression* ; Depressive Disorder, Major ; Female* ; Hippocampus ; Humans ; Magnetic Resonance Spectroscopy ; Membranes ; Memory, Short-Term ; Metabolism ; Neurons ; Neurosecretory Systems ; Repression, Psychology

OBJECTIVE: Atypical antipsychotics have been reported to induce the elevation of serum transaminase frequently in Korea, although most of them don't cause severe liver injury. Some hepatoprotectants are commonly prescribed in order to reduce the serum level of transaminase in patients with schizophrenia. We performed the chart review retrospectively for investigating the effect of two hepatoprotectants, biphenyl dimethyl dicarboxylate+garlic oil combination (BDD), and silymarin+silybin combination (SMR14) on the serum transaminase (AST/ALT) elevated by atypical antipsychotics. METHODS: We reviewed the clinical records of 54 schizophrenic patients who experienced the elevation of serum AST/ALT after the treatment with atypical antipsychotics. Patients with preexisting liver disease or elevated AST/ALT above in-house normal limitation at admission were excluded. We obtained the level of serum AST/ALT at the time of hepatoprotectants administration, 1 week, 2 weeks and 4 weeks after the administration. Repeated Analyses of variance were conducted in order to identify sequential change of serum AST/ALT level, and Fisher's exact test were performed to compare the number of patients whose AST/ALT levels were normalized after 4 weeks between two groups. RESULTS: 33 males and 21 females were included in this study and the mean age of those subjects was 36.28+/-10.92. Among all the patients, 35 were treated with BDD and 19 were treated with SMR14. After administration of hapatoprotectants, both serum AST and ALT level were significantly reduced during 4 weeks (F=10.56, p<0.001;F=17.92, p<0.001). BDD was superior to SMR14 in the number of patients whose ALT level reduced below in-house upper limitation after 4 weeks of treatment with hepatoprotectants (p=0.012), but there was no difference between BDD and SMR14 in aspect to AST level. CONCLUSION: Both hepatoprotectants, BDD and SMR14 were effective in reducing serum AST/ALT level which had been elevated by atypical antipsychotics. BDD was superior to SMR14 in normalizing serum ALT level within 4 weeks. Increased liver enzyme is prevalent in patients during the treatment with atypical antipsychotics. More research will be needed in this field.
Antipsychotic Agents* ; Female ; Humans ; Korea ; Liver Diseases ; Liver* ; Male ; Retrospective Studies ; Schizophrenia

OBJECTIVE: This study was designed to investigate the effects of long term clozapine treatment on changes of weight, glucose and cholesterol levels and their relation to clozapine and its metabolite blood levels in outpatients with chronic schizophrenia. METHODS: Among outpatients diagnosed with schizophrenia according to the DSM-IV criteria, 19 consented subjects receiving long-term treatment of clozapine, its dosage level had been constant for last one month, were selected for the study. The serum level of clozapine, metabolites as well as body weight, BMI, glucose level, cholesterol level, insulin, and c-peptide were gathered and analyzed before and after the use of clozapine. RESULTS: Glucose increase after clozapine treatment was statistically meaningful but it was due to two patients who got diagnosed with diabetes. Glucose levels of other patients are all below 120 mg/dl. Cholesterol level showed significant increase after the treatment. Weight and BMI changes over the treatment are not statistically meaningful overall, but 8 out of 17 showed more than 7% increase. The changes of weight and BMI were positively correlated with weight and BMI of pre-treatment. Mean serum level of clozapine, metabolites were not correlated with glucose, cholesterol level, insulin, and C-peptide. CONCLUSIONS: Results indicate that long term treatment of clozapine is correlated with increase of glucose and cholesterol level and weight gain of the patients. Clinicians should be aware of the potential risks of diabetes, hyperlipidemia, and weight gain in patients taking clozapine.
Blood Glucose* ; Body Mass Index ; Body Weight* ; C-Peptide ; Cholesterol ; Clozapine* ; Diagnostic and Statistical Manual of Mental Disorders ; Glucose ; Humans ; Hyperlipidemias ; Insulin ; Outpatients ; Schizophrenia* ; Weight Gain

OBJECTIVE: Several lines of pharmacological evidences including the data of animal studies indicate that serotonin 2C receptor (5HT2C) is involved in the pharmacodynamic process of serotonin dopamine antagonists (SDA)-induced weight gain. Controversial data have been reported on the association between the polymorphisms of 5HT2C receptor gene and antipsychotics-induced weight gain. This study aims at investigating the association between the polymorphisms of 5HT2C receptor gene and SDA-induced weight gain in korean schizophrenic patients. METHODS: Seventy-seven schizophrenia patients in their first episode or patients who did not take any antipsychotics for the previous two months were recruited. All the patients were administered with one of the SDAs (risperidone, olanzapine, quetiapine, clozapine) for 8weeks. Body mass index (BMI) were measured weekly during the 8weeks. The subjects were genotyped for the -759 C/T and -697 G/C polymorphism of the 5HT2C receptor gene. RESULTS: The degree of linkage disequilibrium between the two polymorphic loci genotyped are almost 100%. Significant association was not observed between polymorphisms of the 5HT2C receptor gene (-759 C/T and -697 G/C) and SDA-induced weight gain after 8 weeks of treatment. CONCLUSION: Our data do not support the involvement of the polymorphisms of 5HT2C receptor gene (-759 C/T and -697 G/C) in SDA- induced weight gain. Further studies with sufficient sample size are warranted to follow up on the trend of high weight gain in the male patients having -759 T (-697 C) allele.
Alleles ; Animals ; Antipsychotic Agents ; Body Mass Index ; Dopamine Antagonists ; Dopamine* ; Follow-Up Studies ; Humans ; Linkage Disequilibrium ; Male ; Receptor, Serotonin, 5-HT2C ; Sample Size ; Schizophrenia* ; Serotonin* ; Weight Gain* ; Quetiapine Fumarate

OBJECTIVE: To evaluate maintained effectiveness and tolerability when treated with long-acting risperidone compared to the previous antipsychotics in patients with schizophrenia or other psychotic disorders and to compare maintained effectiveness between oral risperidone and non-risperidone subgroups. METHODS: Subjects aged at least 18 years who required long-term antipsychotic therapy and who have been symptomatically stable on a stable dose of antipsychotics during the last month were enrolled in the non-randomized, single-arm, multi-center, 12 weeks duration study. Antipsychotic medications were switched from oral antipsychotics to long-acting risperidone. Injections were administered every 2 weeks. Most patients were started on 25mg long-acting risperidone injection or 37.5mg in some patients. The dosage were adjusted according to the patients' symptoms and responses to treatment at the discretion of investigators. Oral antipsychotics were continued at the same dose as before for 2 weeks and then were stopped or tapered off within next 7days. RESULTS: A total of 204 patients with schizophernia (N=192) and other psychotic disorder (N=12) from 20 sites in Korea were enrolled. The drop-out rate was 22.5% at 12 weeks. LOCF analysis has been performed. At 12 weeks after switching from oral antipsychotics to long-acting risperidone, statistically significant improvement was observed from baseline across all symptom domains including PANSS total, positive, negative, general subscale, CGI-S (Clinical Global Impression-Severity) scores and GAF (Global Assessment of Functioning) scores. The proportion of responders was 36.8% where response was defined as > or =20% reduction from baseline PANSS total score. The proportion of symptom worsening at 12 weeks was 7.4% (N=15) where symptom worsening was defined as > or =20% increase from baseline in PANSS total score or drop-out due to insufficient response or any 2 points change on any of 4 PANSS psychotic items (delusion, conceptual disorganization, hallucinatory behavior, suspiciousness/persecution) excluding changes in which the ratings remained at nonpsychotic levels (i.e >3). Significant improvement from baseline was also observed in the measure of parkinsonism assessed using Extrapyramidal Symptom Rating Scale (ESRS). In addition, overall, patients were satisfied with long-acting risperidone injection on a single item measure of satisfaction. When subgroup analysis was performed on the basis of previous antipsychotics before switching to long-acting risperidone, no statistically significant differences were detected between oral risperidone (N=139) and non-risperidone subgroup (N=65) on all measures of effectiveness and tolerability including baseline demographic and clinical characteristics, symptom improvements, proportion of symptom improvement or worsening and ESRS score changes. CONCLUSION: Our study results demonstrated maintained effectiveness and tolerability of long-acting risperidone microsphere and also could confirm successful switching from not only oral risperidone but also non-risperidone to long-acting risperidone injection.
Antipsychotic Agents* ; Humans ; Korea ; Microspheres ; Parkinsonian Disorders ; Psychotic Disorders ; Research Personnel ; Risperidone* ; Schizophrenia

OBJECTIVE: Treating patients with bipolar disorder has many problems such as recurrent various episodes, breakthroughs, treatment resistance, switching and worsening of its course. In addition to these obstacles, recent developments of psychiatric medications make it difficult to choose the appropriate pharmacological options. This study was performed to survey the expert opinion of medication treatment for bipolar disorder. METHODS: The survey questionnaire used in 'The Expert Consensus Guideline Series-Medication Treatment of Bipolar Disorder 2000' was translated in Korean and amended by executive committee according to Korean situations. Forty eight of 50 (96%) members of review committee completed the survey. RESULTS: In acute manic episode lithium or divalproex is a first-line drug as a monotherapy, and combination treatment is considered in partial or non-responder. Carbamazepine is also a first-line drug in dysphoric and mixed episodes. For moderate and more severe depression, an antidepressant is added with a mood stabilizer. For psychotic bipolar disorder, mania or depression, both atypical antipsychotics and high potency typical antipsychotics are preferred, but the latter is less likely to be recommended. A mood stabilizer should be used in rapid cycling bipolar illness. For manic episode in rapid cycler a mood stabilizer and an atypical antipsychotic drug are recommended in combination as an initial treatment. CONCLUSION: Most experts present strong consensus for many options concerning to initial strategies and first-line medications, although there are some non-consensus and gaps between research data and clinical usage in some steps. Nevertheless these data might be a cornerstone for producing the Korean medication algorithm for bipolar disorder.
Advisory Committees ; Antipsychotic Agents ; Bipolar Disorder ; Carbamazepine ; Consensus ; Depression ; Expert Testimony ; Humans ; Lithium ; Questionnaires ; Valproic Acid

The characteristics and changes after methylphenidate treatment of executive functions were conducted. Forty elementary school children, over 85 in intelligence quotient, were selected as experimental group. They are diagnosed to have Attention Deficit Hyperactivity Disorder (ADHD). 40 normal control group were also selected. For comparing of executive functions, ADHD subjects were tested executive functions before and 4 weeks after methylphenidate. Normal control group were also tested. Several behavioral checklists were used, and Kaufman Assessment Battery for Children, Conners Continuous Performance Test, Stop Signal Task, Trail-Making Test (patr B), and Maze test were used. The executive functions and intelligence of ADHD were generally lower than normal control group. On CPT, ADHD showed significantly lower performances in commissions, hit reaction time standard errors, variability of standard errors, and attentiveness. On SST, ADHD presented significantly lower performance in probability of inhibit, stop signal reaction time, Z Score of relative finishing time, Mean delay time on each block, and primary standard deviation. On WCST, ADHD had meaningfully lower performance in total corrects, total errors, nonperseverative errors, completed category, and trials to 1st category completed. After medication, intelligence was not changed, but simultaneous processing ability was improved significantly. And the behavioral problems were improved, but still had differences comparing to control. Commission of Conners' CPT, all aspects of SST and total corrects of WCST were improved.
Attention Deficit Disorder with Hyperactivity ; Checklist ; Child* ; Executive Function ; Humans ; Intelligence ; Methylphenidate ; Reaction Time