No abstract available.
Mood Disorders* ; Risperidone*

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.
Antidepressive Agents ; Antimanic Agents ; Antipsychotic Agents ; Bipolar Disorder ; Depression ; Depressive Disorder, Treatment-Resistant ; Humans ; Lithium ; Mood Disorders* ; Psychotic Disorders ; Psychotropic Drugs ; Risk Factors ; Risperidone* ; Schizophrenia

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.
Autoreceptors ; Bipolar Disorder* ; Bupropion ; Depression ; Depressive Disorder, Major ; Dopamine ; Female ; Humans ; Mood Disorders ; Norepinephrine ; Prevalence ; Risk Factors ; Risk Management

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.
Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Hospital Records ; Hospitals, Psychiatric ; Humans ; Marital Status ; Mood Disorders* ; Occupations ; Schizophrenia* ; Schizophrenia, Paranoid* ; Seasons ; Seoul

No abstract available.
Electrocardiography, Ambulatory*

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.
Antipsychotic Agents ; Depression ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Psychopathology ; Schizophrenia* ; Thinking

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.
Brain ; Chlorpromazine ; Clozapine ; Diagnosis ; Humans ; Imipramine ; Iproniazid ; Lithium ; Neurotransmitter Agents ; Population Characteristics ; Prescriptions ; Psychopharmacology

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.
Antipsychotic Agents* ; Biological Processes ; Biology ; Brain ; Delusions ; Diagnosis ; Dopamine ; Hallucinations ; Humans ; Neurotransmitter Agents ; Population Characteristics ; Psychopharmacology ; Receptors, Dopamine ; Schizophrenia* ; Thinking

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.
Antipsychotic Agents ; Anxiety ; Bipolar Disorder ; Diagnosis ; Humans ; Movement Disorders ; Neuroleptic Malignant Syndrome ; Psychotic Disorders* ; Receptors, Dopamine D2 ; Risperidone* ; Schizophrenia

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.
Blood Cell Count ; Carbamazepine ; Clozapine ; Follow-Up Studies ; Humans ; Neuropsychiatry ; Neutropenia* ; Neutrophils ; Outpatients* ; Phenytoin ; Psychotropic Drugs ; Valproic Acid