Risperidone Beyond Psychoses / 대한정신약물학회지

The authors have compiled the available references on the use of risperidone in 'non-psychotic conditions', not including schizophrenia and bipolar disorders. In addition, information was gathered on the mechanism of action of risperidone in this diverse disorders. Atypical antipsychotics are known to have fewer adverse effects seen with typical antipsychotics, such as tardive dyskinesia (TD), neuroleptic malignant syndrome (NMS), and cognitive disturbances, and they possess a 'broad range of therapeutic efficacy.' The broad psychotropic effects, apart from the antipsychotic action, of risperidone are attributed to their particular pharmacological properties, which differ greatly from those of typical antipsychotics. Risperidone has a greater affinity for the dopamine D2 receptor than for the D1 receptor, but its D2/5-HT2 affinity ratio is low. This fixed D2/5-HT2 ratio may bring about significantly different clinical effects depending on the dosage. The dose-dependent pharmacologic properties of risperidone, in the form of the effects of blocking the 5-HT2 receptors, which are observed at smaller doses, and the effects of D2 blockade, which are manifested progressively with increasing dosage, may be the basis of the efficacy of risperidones in non-psychotic conditions at smaller doses than in psychoses. The authors have also ascertained that risperidone may be of efficacy in the treatment of non-psychotic conditions other than the major psychoses. The authors consider the different dosages depending on the diagnoses to be reflective of differences in the etiopathophysiology between the conditions. In addition, the authors have noted that risperidone, at small doses, shows efficacy in the treatment of a wide variety of disorders other than psychotic disorders, including obsessive symptoms, anxiety. This also demonstrates the greater range of therapeutic efficacy of risperidone other than typical antipsychotics. Despite the fact that risperidone possesses such various therapeutic actions, the first-line drugs in the treatment of non-psychotic conditions are and should be non-antipsychotic psychotropics;risperidone is still an antipsychotic drug, with all the entailing characteristics, and it is not completely free of the side effects common in typical antipsychotics, such as EPS. Wisdom is called for in the appropriate application of risperidone in the treatment regimen of suitable patients following treatment with other non-antipsychotic psychotropics. It seem to review all non-psychotic psychiatric disorders via the clinical applications of risperidone. Through expansion of the indications for risperidone, further insight will be gained on its previously unknown psychotropic effects and the etiopathophysiology of the indicated conditions.

Effective Titration of Risperidone in Patients with Schizophrenia: Open Multicenter Randomized Comparative 8 Weeks Study / 대한정신약물학회지

OBJECTIVE: Subsequent clinical experiences in risperidone treatment indicated that the initially recommended dose schedule resulted in too rapid increment of doses to the maintenance dose. The goal of this study was to establish a new optimal dose-schedule recommendation for risperidone in patients with schizophrenia. METHODS: Two hundred and eighteen schizophrenic patients were randomly assigned to the following three groups. For the first group, 1 mg of risperidone was administered on the first day, 2 mg on the second day, and the dose was increased from the third day depending on the clinical status of the patients. For second group, 0.5 mg was administered on the first two days, 1 mg on the 3-5th day, 1.5 mg on the 6-7th day, 2 mg on the 8th day, and the dose was increased from the 9th day depending on the clinical status. For third group, 0.5 mg was administered on the first three days, 1mg on the 4-8th day, 1.5 mg on the 9-13th day, 2 mg on the 14th day, and the dose was increased from the 15th day depending on the clinical status. The schizophrenic symptoms were rated by the Positive and Negative Syndrome Scale (PANSS) on days 0, 7, 14, 28 and 48 of the risperidone treatment. The tolerance of the treatment was checked by ESRS, modified UKU, and Global Impression of tolerability. The efficacy and tolerability were compared among the three regimen groups. RESULTS: After 8 weeks of treatment, the PANSS total scores, positive scores and negative scores were not significantly different among the three groups. There were no differences among the three groups regarding tolerability ratings and ESRS rating except gait/posture and tremor items which scores were high in first group at the end of the study. The sedation and fatigability items scores in the first group was significantly more higher than in the second and third group. CONCLUSION: These data suggest that the 2-week titration of risperidone may be the most favorable strategy in the treatment of schizophrenia.

Psychiatric Side Effects of Psychotropic Drugs(II): Clinical & Pathophysiological Implications / 대한정신약물학회지

The psychotropic effects of the original psychotropics currently in use, such as chlorpromazine, iproniazide, imipramine, lithium, and clozapine, have been applied to clinical practice through fortuitous discoveries of their psychiatric side effects (PSE). The etiopathophysiology of various psychiatric disorders have been deduced from the action mechanism of original psychotropics, and the designed drugs which selectively act on those neurotransmitters involved in the therapeutic effects of the original drugs are being developed as novel drugs. Psychiatric side effects cannot be considered to necessarily anti-therapeutic, as seen throughout the history of psychopharmacology. The clinical and pathophysiological significance of PSE deduced from their analyses according to the psychiatric symptoms manifested as PSEs are as follows: 1) PSEs are manifested according to the biological characteristics of the patient across diagnosis. This reflects the lack of biological basis in the current diagnostic system. 2) Psychotropics are important as in vivo pharmacological probes or challenges which, upon administration, allow for the biological characterization of the patient brain, i.e. pharmaco-biological typing of the patient may be performed based on the patient responses to the agent (both therapeutic and adverse effects). Such data may be of importance in subsequent prescription of the patient. 3) The hierarchy of a psychiatric disorder may be modified by drug administration, converting the disorder into that of a lower rank and thus into what is more easily treated. 4) A pharmacological approach, rather than a diagnosis-based one, is required. Consequently, more research into the still unknown psychotropic effects of each psychotropic is desired. In the process, clinically significant psychotropic effects currently undefined from the point of diagnosis-based approach may be discovered.

Neutropenia in Psychiatric Out-Patients / 대한정신약물학회지

OBJECT: The study was performed to examine the psychotrophic drugs used in psychiatric out-patients in which neutropenia developed and current state of consultation and to confirm the importance of complete blood count and differential count (CBC/DC). SUBJECTS AND METHODS: The subjects were 60 patients of our university hospital in which neutropenia developed in out-patient department (OPD) of psychiatry during recent three years. The absolute neutrophil counts of patient were below 2,000/mm3. RESULTS: The reasons why exam was performed were mainly to follow-up exam during medications. Mood stabilizers such as carbamazepine, phenytoin, sodium valproate were identified to cause neutropenia in the group using multiple drugs, and clozapine was highly related in the group using single drug. But many kinds of drugs were related with neutropenia. We have not checked well enough the CBC/DC and have not consulted well to hematologist in OPD of neuropsychiatry. CONCLUSIONS: It is important to find neutropenia in the psychiatric out-patients using psychotropic drugs. We had better check CBC/DC routinely and consult to hematologist.

Aspiration Pneumonia during Clozapine Therapy / 대한정신약물학회지

Authors experienced aspiration pneumonia during clozapine therapy in a 31 year-old woman patient with treatment-resistant schizophrenia. Development of aspiration pneumonia appeared to be related with side effects of clozapine including sedation, sialorrhea, and esophageal dysfunction. Each side effect seems to be mild, however it can cause fatal problems such as aspiration pneumonia if they appear simultaneously.

A View of Korean Psychiatrists about Electroconvulsive Therapy / 신경정신의학

OBJECTIVES: Electroconvulsive therapy (ECT) is the important treatment method which has a good effect on refractory depression, schizophrenia at acute stage, patients with suicidal ideation. Although ECT results in better effects and less adverse effects in acute stage of illnesses as compared with pharmacotherapy, clinical implications are decreasing. Thus, authors surveyed a view of Korean psychiatrists about ECT to find whether there are prejudices and/or misconceptions for ECT. METHODS: Authors made survey questionaire for the attitudes of ECT, based on the APA task force 14, a clinical study in Korea, Hermann et al's report, and questioned Korean psychiatrists on their opinions for ECT through the internet E-mail, who are the members of Korean Neuropsychiatric Association (KNPA) serving in hospitals with psychiatric inpatient units. RESULTS: 122 psychiatrists answered to survey questionnaire. 89.4% have positive attitude about ECT. They thought that ECT has relatively safe and potent therapeutic effects, and less adverse effects. The rate of psychiatrists who have been no experience to perform ECT was 13.9% (n=16). Interestingly all of them had been trained serve in university hospitals now. The rate of psychiatrists who had experienced practicing ECT past but, not experienced within 2 years recently was 48.7% (n=56). While psychiatrists who have been no experience of ECT were more worried about adverse effects, doctors who experienced practicing ECT thought preferably the aspect of safety and potent effects of ECT. Psychiatrists who prefer psychotherapy were more likely to concern about adverse effect of ECT, but there were no differences in other aspects when compared with others. Most psychiatrists participated in this survey had positive attitudes about application of ECT to geriatric patients, but negative at child&adolescent patients. CONCLUSION: Authors recognized that many Korean psychiatrists agreed with performing ECT, and expected good results, but in reality, it is difficult to expect for them to perform ECT. Several factors may be associated for that: the changes in trend of psychiatric treatment, production of novel psychotropic drugs, researches trends which pharmacotherapy is prevailing in the fields of psychiatry, and problems of education, that is, lack of standard educational curriculums and systemic training course at residency for ECT.

Reliability and Validity of the Korean Version of the Positive and Negative Syndrome Scale / 신경정신의학

OBJECTIVES: We tested the reliability and validity of the Korean version of the PANSS (PANSS-KV). METHODS: The PANSS ratings were obtained from 101 subjects with DSM-IV diagnoses of schizophrenia or schizophreniform disorder. To study the concurrent validity, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were also administrated in 38 patients. Using these data, inter-rater reliability, test-retest reliability, internal consistency, criterion validity and concurrent validity were evaluated. Factor structure was analyzed by the principal axis factoring. RESULTS: The inter-rater reliability of the Korean version of the PANSS was satisfactory in positive (r=0.92) and negative syndrome subscales(r=0.86), but somewhat low in general psychopathology subscale (r=0.78). The test-retest correlations for the 3 PANSS subscales ranged between 0.89 and 0.95, so it showed excellent test-retest reliability. The Cronbach's alpha for the positive, negative and general psychopathology subscales were 0.73, 0.84 and 0.74, respectively and thus the 3 subscales of the PANSS had good internal consistencies. All separate items revealed significant corrected item-total correlations in the positive and negative syndrome subscales, but some items of the general psychopathology subscale showed no or low corrected item-total correlations. The positive and negative syndrome subscales held a high concurrent validity in relation to the SAPS and the SANS. It was confirmed that positive and negative syndromes were independent constructs. The factor analysis by the principal axis factoring produced 5 components: cognitive, excitement, depression, positive and negative. CONCLUSION: These findings prove that the reliability and validity of the PANSS-KV are comparable to those of the original PANSS. So, the PANSS-KV can be widely and extensively used in researches for schizophrenia.

Effects of Risperidone on the Schedule-Induced Polydipsia in Rats / 신경정신의학

OBJECTIVES: This study was designed to evaluate the effects of risperidone on the schedule-induced polydipsia (SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered risperidone as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol as a dopamine antagonist to rats which showed schedule-induced polydipsic behaviour. METHODS: Sprage-Dawley rats weighing 200 - 250gm were individually housed and main-tained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds (FT 60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior (greater than 3 times of water per session on average). 5 groups of rats were administered risperidone (0.1mg/kg, i.p), risperidone (0.5mg/kg, i.p), fluoxetine (5mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.), and vehicle (1cc/kg, i.p. ) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats (N=8) was individually housed and given a single bolus (14.5gm) of food per day which maintained them at their average body weight. RESULTS: The results were as follows; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1mg group and the risperidone 0.5mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsic water intakes. 3) The fluoxetine group (22.5+/-10.4ml) showed significantly lower amounts of water intake than haloperidol group (41.3+/-7.1ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.8+/-3.5ml) showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) and the vehicle control (34.4+/-6.8ml) at 3rd weeks of drug treatment. The risperidone 0.1mg group and the risperidone 0.5mg group showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) at 2nd weeks and the vehicle control (37.5+/-12.5 , 34.4+/-6.8ml) at 2nd and 3rd weeks of drug treatment. CONCLUSIONS: Above findings suggest that the fixed time feeding procedure for schedule induced polydipsia could be applied as an effective animal model of obsessive compulsive disorder for the evaluation of pharmacological challenge study. We confirmed that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the schedule-induced polydipsic behaviour but the onset of effect was later than fluoxetine.

Efficacy and Safety Profile of Risperidone in Schizophrenia: Long-term Follow-up Study / 신경정신의학

OBJECTIVES: The purpose of this study was to evaluate the long-term efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. METHOD: This multicenter open label study included 116 schizophrenic patients drawn from 19 university hospitals. After a wash-out period of 1 week, the patients were treated with risperidone for 56 weeks and evaluated at 8 points:at baseline, and the 8th, 16th, 24th, 32nd, 40th, 48th, 56th weeks of treatment. The dose was started at 2mg of risperidone on day 1, and increased to 4mg on day 2, and 6mg on day 3,7 and adjusted to a maximum of 16mg/day according to the individual's clinical response. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. RESULTS: Eighty-seven(75%) of 116 patients completed the 56-week trial of risperidone. Clinical improvement(as defined by a 20% of reduction in total PANSS score at end point) was shown by 92.0% of the patients. The mean dose of risperidone was 5.0mg/day in the 56 week follow-up. PANSS total scores showed significant improvements between consecutive two points at baseline, 8th, 16th, 24th, 32nd, and 48th week of treatment. CGI scores showed significant reductions between consecutive two points at baseline, 8th, 16th, 24th, and 48th week of treatment. Three PANSS factors(positive, negative, general) showed a significant improvement from the 8th week of treatment, and, after then, remained improved in the rest of the study period. ESRS showed no significant change during the 56 week trial. Laboratory parameters showed no significant changes during the course of treatment. CONCLUSIONS: This multicenter long-term open study suggests that risperidone is a antipsychotic drug with long term efficacy and safety in the treatment of schizophrenic patients.

A Clinical Significance of the Subjective Experiences of Negative Symptoms in the Patients with Schizophrenia / 신경정신의학

OBJECTIVE: Since the evaluation of negative symptoms has depended on the clinician's objective observation, the patients' subjective experience of negative symptoms has been neglected. However, in fact, a lot of patients are aware of their negative symptoms. There are several reports suggesting that patients suffer from the subjective experiences of their deficit symptoms, even though the objective positive and negative symtoms cannot be observed. Under these circumstances, we have attempted this study with the idea that it would be helpful in understanding the psychopathology of schizophrenia. Also it would help clarifying the relationship between subjective experience of negative symptoms and objective positive and negative symptoms, depression, anxiety symptoms, and extrapyramidal symptoms. METHOD: All the 37 patients satisfied the diagnostic criteria of DSM-IV for schizophrenia . The subjective experiences of negative symptoms were evaluated using Scale for the Subjective Experience of Negative Symptoms, Korean version(K-SENS), and for the depression, anxiety, extrapyramidal symptoms, we used Hamilton Rating Scale for Depression(HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Extrapyramidal Symptom Rating Scale(ESRS). The correlation between each psychopathology was tested by calculating Spearman correlation coefficient. RESULTS: There was a significant correlation between the ratio of items experienced as uncomfortable symptoms among 24 items of K-SENS, and the score of PANSS positive subscale(gamma=-0.40, p0.05), or negative subscale score(gamma=-0.20, p>0.05), or general psychopathology subscale score(gamma=-0.08, p>0.05), respectively. There was no significant correlation between the ratio of items experienced as uncomfortable symptoms among 24 items of K-SENS, and HAM-D(gamma=-0.01, p>0.05), or HAM-A(gamma=-0.11, p>0.05), ESRS(gamma=0.34. p>0.05), respectively. CONCLUSION: These results revealed that the negative correlation between the subjective negative symptoms experienced as an uncomfortable ones and the objective positive symptoms such as grandi-osity, suspiciousness/persecution, and hostility. From these results, the possibility that positive symptoms are used as a defense to hide from the subjectively experienced negative symptoms, or that patients may not be aware of their negative symptoms because they are overwhelmed by their positive symtpoms. is suggested. These results also suggest that subjective experiences of negative symptoms are independent from depression, anxiety and extrapyramidal symptoms.

A Study of Pharmacotherapy for Bipolar Depression / 대한정신약물학회지

OBJECT: Although there is extensive research. on treatment of acute unipolar depression, few studies examined the treatment of acute bipolar depression. This preliminary study was designed to suggest clinical guideline for treatment of bipolar depression through comparing the pharmacological treatment of bipolar depression with that of unipolar depression. METHOD: We studied 19 patients with bipolar depression and 38 patients with unipolar depression, who were admitted to Kyung Hee University Medical Crater from January 1990 to December 1997. The pattern of treatment and the response to treatment of bipolar depression were investigated compared with unipolar depression. RESULTS: The percentage of prescription in bipolar depression was as follows in order : combination of mood stabilizer and an antidepressant 52.6%, mood stabilizers 15.8%, ECT 15.8%, TCAs 5.3%, SSRIs 5.3%, RIMA 5.3%. In unipolar depression : TCAs 47.4%, SSRIs 28.9%, combination of mood stabilizer and an antidepressant 10.5%, others 13.2%. There was no significant difference in response to treatment in bipolar depression and unipolar depression. CONCLUSIONS: These results suggest a mood stabilizer and an antidepressant together or a mood stabilizer alone would be first line in bipolar depression. Among the antidepressants, bupropion, RIMA and SSRls is more recommended in that order rather than TCAs in consideration of the risk of switching into mania.

Efficacy and Safety Profile of Risperidone in Schizophrenia: Open Multicenter Clinical Trial / 신경정신의학

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. METHOD: This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points: at baseline, and 1,2,4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. RESULTS: 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action: a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. CONCLUSIONS: This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Two Cases of Risperidone-Induced Mania in Schizophrenics / 신경정신의학

We report the first two cases of manic and hypomanic episodes respectively induced by risperidone treatment done to schizophrenics in Korea. One case was a 22-year-old woman with catatonic schizophrenia. Since 3 years ago, she had shown psychotic symptoms, but with was poor treatment compliance. She had mainly negative symptoms such as social withdrawal, decreased flood intake, mutism, and symptoms had been worsened since last 4-5 months. Prior to closed ward admission, she was prescribed 2mg/d of risperidone far a week at OPD. Two days after taking medicine totally 6-8mg, she revealed manic features. After hospitalization, risperidone was discontinued and then, lithium 900mg/d and high dosage of conventional antipsychotics(chlorpromazine 1200mg/d or haloperidol 20mg/d) were prescribed. About on the l0th day of hospitalization, there was limited improvement of her manic symptoms. The other case was a 29-year-old man with a 3-year history of paranoid schizophrenia. He was never exposed to antipsychotics before. His main symptoms were delusions of being poisoned and of persecution. His positive and also negative symptoms were alleviated by 38 days of risperidone 2mg/d trial. However, one week after dosage increment to 3mg/d, hypomanic symptoms appeared. Risperidone medication was discontinued and was replaced by chlorpromazine 300mg/d. The hypomanic episode was resolved over 5 days. In both of the two cases, manic episodes occurred by monotherapy of risperidone without mood stabilizer, and there were no history of substance abuse and other psychiatric disorders, family history of psychiatric disorders, and comorbid physical illnesses. It is hypothesized that the potent blockade effect on serotonin(5-HT2) receptor of risperidone causes antidepressant effect, as well as therapeutic effect for negative and affective symptoms in schizophrenia. Risperidone would induce manic or hypomanic features in schizophrenic patients. And there are few case reports of risperidone-induced mania or exacerbation of preexisting manic symptoms by risperidone treatment in mood disorder and schizoaffective disorder. Risperidone is being used more widely, even for obsessive-compulsive disorder and other psychiatric disorders. It is necessary for clinicians to recognize manic switch, one of psychiatric side effects by risperidon trial. It is recommended that the combination of mood stabilizer with risperidone or usage of the minimum effective dose of risperidone may bewefal especially in the patients with mood disorders or schizoaffective disorders. Clozapine which has mood-stabilizing properties is also beneficial in risk groups of risperidone-induced mania.

Insight and Psychopathology in Schizophrenics / 신경정신의학

OBJECTIVES: Patients with poor insight are commonly observed among schizophrenics and they show poor drug compliance and prognosis. This study aimed at examining the characteristics of psychopathology in patients with schizophrenia who have no insight. Understanding the features of inner psychopathology in schizophrenic patients with poor insight, we assumed, could lead to insight-promoting clues. METHODS: The subjects consisted of 69 patients with schizophrenia diagnosed by DSM-IV criteria. For identifying insight level in the patients, Scale to Assess Unawareness of Mental Disorder(SUMD) was applied. After subjects were divided into two groups depending upon insight level, psychopathological differences were evaluated by Kyung Hee-Frankfruter Beschwerde Fragebogen(K-FBF), which was known as one of the subjective psychological tests for the schizophrenics. RESULTS: There was no significant differences in demographic variables, duration of illness, and dose of medication between two groups. However, significantly high rate of involuntary admission and tendency of high frequency of admission were revealed in schizophrenic patients with poor insight. And, also poor insight group showed significantly high scores in the factors of sensorimotor disorder(subscales of psychomotor disorder, perceptual disorder and blocking symptoms included) and in language-cognitive disorder factor(subscales of language disorder and cognitive floating included) compared with patients who have insight. CONCLUSION: We was assumed that lack of insight in schizophrenics could include one of the symptoms based on neuropsychological or neurobiological abnormalities in brain. Moreover, it was revealed that patients with poor insight evaluated themselves as having more serious psychopathologies than patients who had insight. It has been already known that schizophrenic patients who lack in insight are reluctant to taking psychiatric care and lack in awareness of their illness. However, this study suggests that their inner psychopathology associated with insight can be understood with the use of subjective psychological test, i.e. K-FBF. For understanding the schizophrenic patients who lack in insight, not only checking the insight but also applying the subjective test such as K-FBF seems to be helpful.

Stress Among Chinese, Korean-Chinese and Korean High School Students: A Transcultural Study / 신경정신의학

About 40% of patients suffering from postencephalitic or idiopathic parkinsonism experience distressing and ill-defined sensations. Antipsychotic-induced acute extrapyramidal syndromes (EFSs) share phenomenological, pharmacological, and biochemical characteristics with these parkinsonisms. Thus, it is conceivable that antipsychotic-induced acute EPSs may also be associated with primary sensory symptoms. The aim of this study was to test this hypothesis, first by examining the frequency and risk factors of primary sensory symptoms and then by contrasting the clinical characteristics in patients with or without antipsychotic-induced acute EFSs and in patients who did or did not report sensory symptoms. The study group comprised 107 patients who receiving antipsychotics. The authors used DSM-IV criteria and Yale Extrapyamidal Symptom Scale for acute EFSs and modified McGill Pain Questionnaire for sensory symptoms. The results were as follows: 1) Twenty-one(19.6%) of 107 patients receiving antipsychotics reported sensory symptoms. Among these 21 patients, 12(57.1%) reported paresthesia, 6(28.6%) reported pain, 3(14.3%) reported both. 2) fifteen(34%) of the 44 patients with antipsychotic-induced EFSs reported sensory symptoms, while only 6(9.5%) of the 63 patients without EFSs reported sensory symptoms(p<0.01). The severity of sensory symptoms was significantly correlated with the EPSs rating score(p=0.001). 3) In the patients with sensory symptoms, the women significantly outnumbered the men(p<0.05). Any risk factor of sensory symptoms, however, couldn't be found in age, diagnosis, and drug. The subjective response including sensory symptoms were associated with drug response, drug compliance, quality of life and prognosis. It is suggested that further systematic investigation and interest about sensory symptoms and subjective response of the acute EPSs should be needed.

New Insights into Schizophrenia through Novel Antipsychotics / 대한정신약물학회지

This review serves as new insights into schizophrenia through novel antipsychotics. The observation that 'chlorpromazine' and other early neuroleptics all produced extrapyramidal side effects led patients to think that these were necessarily linked to the therapeutic response. This all reinforced the central role of dopamine(D2) in therories of schizophrenia. It is likely that the original dopamine hypothesis is too simplistic, however, the probable heterogeneity of schizophrenia makes it difficult to establish specific disease-related abnormalities in a single neurotransmitter system. The discovery of 'clozapine' and other novel antipsychotics has forever altered the conventional wisdom that held all antipsychotics to be equally efficacious and uniformly neurotoxic. The drugs that are more effective in the treatment of schizophrenia and that also have important effects on neurotransmitters other than dopamine has further widened both our understanding of the complexities of and our search for more effective and less damaging treatments. Although dopamine remains the key neurotransmitter of interest in research on the cause of schizophrenia, we have moved from a simple dopamine hypothesis to a multiple dopamine receptor hypothesis and on to a dysregulated dopamine system hypothesis, the latter emphasizing the loss of balance between dopamine and other neurotransmitters and the restoration of that balance of the neurotransmitters between different brain regions in the treatment of schizophrenia. The search is therefore on for more specific and 'cleaner' antipsychotics, with or without direct antidopaminergic effects. Unfortunately, when we study schizophrenia, we are studying a 'dirty disease' in the sense that it is undoubtedly the final common expression of many pathophysiologies. In addition, the antipsychotics we use for treatment are 'dirty drugs'; they have multiple effects on multiple systems. Therefore, previous research efforts on understanding the pathophysiologies of schizophrenia through the mechanism of action of antipsychotics(symptoms --> [symptomatic] diagnosis --> [symptomatic] treatment --> causes) are 'diagnosis-targeted' psychopharmacology and merely on the road toward the causative diagnosis and treatments. Now, I propose carefully the following alternative approaches for the 'causative diagnosis and treatment'. 1) 'Modified diagnosis-targeted' psychopharmacology: The likelihood of drugs increasingly tailored to different 'causative subtypes' of schizophrenia within present diagnostic systems(symptoms --> [symptomatic] diagnosis --> causative subtypes --> [causative] treatment) is not far beyond the horizon. 2) 'Symptom-targeted' psychopharmacology: New treatment for schizophrenia may actually be targeted at 'specific aspects or symptoms' of the illness, such as hallucinations or delusions, rather than at the illness as a whole(symptoms --> causes --> [causative] diagnosis --> [causative] treatments). Schizophrenia will eventually be treated with combinations of different drugs(rational polypharmacy). In order for combined treatment to be used for schizophrenic patients, however, symptoms have to be defined correctly and identified accurately. Only recently, owing to the many scientific developments in understanding the biology of schizophrenia, has there been a potential benefit to making specific subdivisions among the symptoms of schizophrenia and relating them to specific biological processes. 3) 'Cause-targeted' psychopharmacology: For the possibilities of different causes relating similar symptoms, pharmacological tailoring according to causes that are detected by biological tests performed firstly in patients showing psychiatric symptoms is recommended(causes --> [causative] treatments --> [causative] symptoms --> [causative] diagnosis). This review represent a major shift of traditional thinking influenced by the recent obstacles in our understanding of schizophrenia, the developments in methodology which have influenced scientifically informed notions of our clinical practice, and the introductions of antischizophrenic drugs, antidelusional drugs, antihallucinatory drugs and antideficit drugs which are likely to develop in future. Also this changing concepts about diagnosis and treatments are applied to other psychiatric disorders.

A Study of Depressive Symtoms in Chronic Schizophrenia / 대한정신약물학회지

OBJECTIVES: For the understanding and effective treatment of depressive symptoms in chronic schizophrenia, this study investigated the frequency of depressive symptoms and examined associations between depressive symptoms and positive symptoms, negative symptoms, general psychopathology in chronic schizophrenia. METHOD: The authors assessed the frequency of depressed schizophrenia with 30 or higher scores of HRSD in 135 DSM-IV chronic schizophrenia. We measured PANSS, BPRS in depressed(n=37) and non-depressed schizophrenia(n=37) who were matched in sex, age and dose of antipsychotics to compare positive, negative symptoms and other psychopathology. Also, we evaluated correlation between depressive symptoms and positive symptoms, negative symptoms, other psychopathology in depressed schizophrenic patients. RESULTS: 1) The depressive symptoms were present in 27.4% of chronic schizophrenia. 2) The positive scale of PANSS were significantly higher in depressed than in non-depressed schizophrenia(p<.01), and the negative scale of PANSS were higher in depressed schizophrenia but there were no statisical significance. Thinking disturbance and depressive-anxiety factors of BPRS were significantly higher in depressed than in non-depressed schizophrenia(p<.01, p<.01). 3) The positive and negative scale of PANSS correlated with HRSD in depressed schizophrenia(p<.01, p<.05), and thinking disturbance and depressive-anxiety factors correlated with HRSD in depressed schizophrenia(p<.01, p<.01). CONCLUSION: The depressive symptoms are relatively commom and important part of schizophrenic symptomatology, and they are more related to positive symptoms than negative symptoms of schizophrenia. Thus this study suggest that appropriate assessment and therapeutic intervention for depressive symptoms is especially necessary to the schizophrenic patients with severe positive symptoms.

Seasonsits of the First Onset in Schizophrenia and Mood Disorder: Mainly in Paranoid Schizophrenia and Bipolar I Disorder / 신경정신의학

This study aimed 1) at determining the seasonal pattern of the first onset and 2) at examining different demographic and clinical factors by the seasonality of first onset, for shizophrenia, mood disorder and subtypes of each diagnosis. Finally, the 52 subjects with paranoid schizophrenia were selected from all patients who fulfilled DSM-IV criteria far schizophrenia who had been admitted to the National Seoul Mental Hospital from March 1994 to February 1995. And the 44 subjects with bipolar I disorder were selected from all patients who fulfilled DSM-IV criteria for mood disorder who had been admitted to the hospital from March 1994 to February 1996. This study was done by reviewing the hospital records about season of the first outset, demographic factors(sex, age, occupation, educated period, religion, marital status, residence and socioeconomic status) and clinical factors(age at the first onset, duration of illness, family history, length of admission, frequency of admission and treatment result). The seasonal pattern of the first onset and the different demographic and clinical factors by the season of the first onset in paranoid shizophrenia and I disorder were analyzed. The results were as follows: 1) There was no significant seasonal variation of the first onset for paranoid schizophrenia. 2) There was a significant seasonal variation of the first onset with a maximum in spring for bipolar I disorder. 3) There was no significant seasonal variation of the first onset in case of bipolar I disorder that began with the manic episode. 4) There was nonsignificant seasonal tendency to peak in spring/summer in the case of the first manic episode for bipolar I disorder. 5) There were no significant differences in demographic and clinical factors by the season of the first onset for paranoid schizophrenia and bipolar I disorder.

Antiepressant-Associated Mania / 신경정신의학

To examine the causative agents, clinical characteristics, management, risk factors, and neurochemical mechanism of the antidepressant-associated mania, MEDLINE searches were conducted. Mania can occur by chance during antideressant treatment or withdrawal, particularly in patients predisposed to mood disorder. Antidepressant-associated mania, especially withdrawal mania, appears to be milder and a more time-limited syndrome than a spontaneous mania and may represent a distinct clinical entity. MAOI, especially RIMA or bupropion may be associated with milder and less manic inductions than either TCA or SSRI. The possible risk factors for antidepressant-induced mania are female, mood disorder, especially bipolar type I, past and family history of mood disorder, especially bipolar type I, long-term treatment, high dose, and combined therapy in treatment-resistant depression, the possible for withdrawal mania are female, mood disorder, especially major depressive disorder, past and family history of mood disorder, especially major depressive disorder, long-term treatment, high dose, abrupt discontinuation or dose reduction, TCA or MAO(except RIMA?). Antidepressant-induced mania can result from dysfunction of mechanisms that maintain noradrenaline/acetylcholine balance associated with the antidepressant-induced activation of noradrenaline system. The mechanism of withdrawal mania with TCA is cholinergic-monoaminergic interaction theory, and with MAOI is related a hyperdopaminergic state due to loss of drug-induced subsensitivity of dopamine autoreceptors. The prevention of these side effects will require further well-designed study on risk factors.

Risperidone as a Janus in Mood Disorder

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cased of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory chronic schizophrenias, especially with initial response ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effect of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and the D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blockade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neruochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3mg/d) of RIS, and maintenance of mood stabilizer in the cases. with risk factors of RIM are recommended in mood disorder.