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A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis.

OBJECTIVE: Randomized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis. However, these results may not be generalizable to routine clinical practice. We evaluated the effectiveness, tolerability, and safety of olanza-pine, risperidone, and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical settings. METHOD: 172 patients participated in a practical clinical trial and were randomly assigned to haloperidol (N = 56), risperidone (N = 61), and olanzapine (N = 55). The mean modal daily doses were 5.4 mg/day for halo-peridol, 4 mg/day for risperidone, and 15.3 mg/day for olanzapine; 98.3% of subjects were drug naive at baseline. Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal (February 2001 to February 2005) intervention program of first-episode psychosis (schizophrenia spectrum disorders, DSM-IV criteria) are reported. RESULTS: All 3 treatments showed similar effectiveness in reducing the severity of general, negative, and positive symptomatology after 6 weeks of treatment, as reported by mean change in total Clinical Global Impressions-Severity of Illness scale, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks. The proportion of study subjects responding, defined as 40% or greater BPRS total score improvement from baseline, was 57.1% (N = 32 of 56) haloperidol, 52.5% (N = 32 of 61) risperidone, and 63.6% (N = 35 of 55) olanzapine, with no statistical differences among groups. The frequency of extrapyramidal symptoms (chi(2) = 24.519; p < .001) and concomitant anticholinergic medication use (chi(2) = 57.842; p < .0001) was greater with haloperidol than olanzapine or risperidone. Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups (p < .001). CONCLUSION: Relatively low doses of haloperidol, risperidone, and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice.

Acute Disease↗

Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study.

BACKGROUND: Bipolar disorder (BPD) is associated with high rates of substance abuse. We previously reported favorable results with lamotrigine in 30 patients with BPD and cocaine dependence. This report examines lamotrigine therapy in an additional 32 cocaine dependent patients. Data on these 32 participants are presented as a replication study. In addition, we extend the previous findings by combining data from both groups, and by exploring predictors of response. METHOD: Participants received a baseline evaluation and assessment for up to 36weeks with the 17-item Hamilton Rating Scale for Depression (HRSD(17)), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS(18)), and Cocaine Craving Questionnaire (CCQ). Urine samples were obtained, and participants reported drug use during the previous week. RESULTS: In the replication sample (n=32), significant improvements were observed in HRSD(17), YMRS, BPRS(18), and CCQ (baseline to exit), as well as on dollars/week spent on cocaine. In the extension study, the original sample (n=30) and the replication sample (n=32) were combined for a total of 62 participants in the intent-to-treat sample. HRSD(17), YMRS, BPRS(18), and CCQ scores, as well as dollars spent on cocaine, decreased significantly. LIMITATIONS: The study has an open-label, uncontrolled design. CONCLUSION: Lamotrigine treatment was associated with significant improvements in mood, drug craving, and drug use. Controlled trials are needed.

Adult↗

The actual process of rating the global assessment of functioning scale.

The Global Assessment of Functioning Scale (GAF) was developed for the overall assessment of psychological, social, and occupational functioning. While the advantage of the GAF lies in this comprehensiveness, questions have been raised on whether clinicians rate appropriately. To clarify this issue, the actual process of how clinicians assign GAF scores was investigated. A total of 2,462 inpatients of 19 psychiatric hospitals in Japan were assessed by their primary psychiatrists using the following rating scales: GAF, Brief Psychiatric Rating Scale (BPRS), World Health Organization Psychiatric Disability Assessment Schedule (DAS), and physical Activities of Daily Living (ADL) index. A tree-based model analysis (also referred to as Automatic Interaction Detector [AID] or Classification and Regression Tree [CART]) was used to construct a statistical model with the GAF score as the dependent variable. The statistically best-fitted tree to predict the GAF score is as follows. The first split is based on the "conceptual disorganization" score in the BPRS, followed by splits based on DAS item scores, such as "conversation" and "underactivity." The tree model obtained suggests that Japanese clinicians judge the level of global functioning by integrating the information on both the severity of psychiatric symptoms and the level of impaired behaviour and social functioning. This logic structure was clinically acceptable and agreed well with the concept of the GAF.

Adult↗

Welfare status and psychosocial adjustment among 100 Hmong refugees.

Although the mental health of recently employed persons has been well studied, the mental health of welfare recipients is not well understood. Among our increasing refugee population, many receive welfare benefits at some point. The Hmong are among those who are highly represented among welfare recipients in several areas of the United States. Do psychiatrists have anything to contribute toward the resolution of high welfare rates? This question is especially relevant in refugee populations who are at increased risk for several psychiatric disorders, including depression, paranoia, and adjustment disorders. This study was undertaken among 100 Hmong refugees who had been in the United States for 8 years. Indices of mental health included two rating scales (the Zung Depression Scale and the SCL-90), five-axis DSM-III diagnoses, Hamilton Anxiety and Depression Scales, Global Assessment Scale, Brief Psychiatric Rating Scale, Inpatient Multidimensional Scale, and Mini-Mental State Exam. These indices were compared with current welfare status and the duration of time on welfare. Other comparisons with welfare included demographic characteristics, material possessions, acculturation characteristics, health and social problems, and nonoccupation avocations. Results indicate that welfare recipients show lower acculturation and elevated psychiatric symptom levels. Suggestions for ameliorating this situation are extrapolated from studies in the literature on chronically unemployed persons.

Acculturation↗

Control group bias in randomized atypical antipsychotic medication trials for schizophrenia.

CONTEXT: It has been suggested that the need for concurrent placebo control groups in new schizophrenia studies might be minimized by making comparisons with external placebo. This strategy requires an assumption of constancy, that the novel medication will perform the same way in a study with only active controls as it would have in a placebo-controlled trial. OBJECTIVE: To test this constancy assumption in active- and low dose-controlled trials vs placebo-controlled trials of atypical antipsychotic medications. DATA SOURCES: A comprehensive search of bibliographic databases, conference proceedings, and Food and Drug Administration databases through November 24, 2003. STUDY SELECTION: English-language, randomized, double-blind clinical trials of newer atypical antipsychotic medications in otherwise unselected acutely ill adults with schizophrenia or schizoaffective disorder that reported baseline and intent-to-treat end point change values for the Brief Psychiatric Rating Scale. DATA EXTRACTION: Study number, sample size, reported dosage for each arm, trial duration, percentage of men, average age, trial arm treatment completion rate, baseline and within-arm end point change in the Brief Psychiatric Rating Scale, method of scoring the Brief Psychiatric Rating Scale, and date of publication were extracted from each study independently by 2 of us (S.W.W. and C.B.B.) each. DATA SYNTHESIS: There were 32 studies comprising 66 risperidone, olanzapine, quetiapine, and ziprasidone arms including 7264 patients. Random-effects analysis revealed that in atypical antipsychotic medication arms, the degree of improvement was nearly double in active-controlled trials than that seen with the same drugs and dosages in placebo-controlled studies. An effect of design was also observed in low dose-controlled studies vs placebo-controlled studies in ineffective and intermediate antipsychotic medication dose ranges. CONCLUSIONS: The observed control group bias indicates that the constancy assumption does not hold in recent antipsychotic medication trials. These results suggest that caution is indicated when considering active- or low dose-controlled studies requiring comparisons with external placebo as alternatives to placebo-controlled trials for establishing efficacy of new medications for schizophrenia.

Age Factors↗

Measuring thought disorder with clinical rating scales in schizophrenic and nonschizophrenic patients.

The distinction between disorders of thought structure and disorders of thought content in a diagnostically heterogeneous psychiatric population was empirically tested using factor analysis applied to the item scores on two common clinical rating scales, the Brief Psychiatric Rating Scale and Andreasen's Thought, Language, and Communication Scale. The factor structure supported the separation of disordered thinking into disorders of thought content and disorders of thought structure or communication. Additionally, our results indicate that both aspects of disordered thinking are present in schizophrenic and manic patients; neither is specifically characteristic of schizophrenia. Indeed, disordered thought structure appears to be more common or worse in the manic patient than in the schizophrenic patient.

Bipolar Disorder↗

MDA-assisted psychotherapy with neurotic outpatients: a pilot study.

Ten neurotic patients (five males and five females) were treated over a period of 2 to 6 months (mean, 4.1) as outpatients. The study allowed for a maximum of 75 hours of psychotherapy (mean, 51.55 hours). During the course of treatment, two to four (mean, 3.5) administrations of MDA (3,4-methylenedioxyamphetamine) were employed as adjunctive aids in an effort to enhance the psychotherapeutic process. The mean duration of the drug sessions was 8 hours (range, 6 to 14 hours). The first administration of MDA took place when, in the therapist's judgment, sufficient rapport had been established with the patient. All patients received an initial dose of 75 mg of MDA; subsequent dosage was allowed to range up to 200 mg. On these occasions, the drug appeared to be well tolerated with no serious side effects or complications observed. Psychometric assessments were obtained pre- and post-treatment, employing the Minnesota Multiphasic Personality Inventory (MMPI), Wittenborn Psychiatric Rating Scales (WPRS), and Brief Psychiatric Rating Scale (BPRS). In addition, follow-up evaluations were obtained 6 months after the termination of therapy by the use of the MMPI, WPRS, BPRS, and a Social History Questionnaire (SHQ) which had also been administered before treatment was initiated. Clinically, the impression was obtained that psychotherapy and the adjunctive use of MDA appeared to facilitate improvement in these patients. This impression was substantiated by significant reductions in scores on the psychometric assessments measuring depression, anxiety, and obsessive-compulsive traits. The meaures evaluating the sense of well-being and self-actualization also were encouraging. Although some of the patients were not as responsive as others, there were no observations to suggest that the condition of any of these patients had become worse.

Adjustment Disorders↗

An open-label trial of divalproex in children and adolescents with bipolar disorder.

OBJECTIVE: This study evaluated the safety and effectiveness of divalproex sodium (Depakote ) in the treatment of youths with bipolar disorder. METHOD: Forty bipolar disorder patients aged 7 to 19 years, with a manic, hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks). RESULTS: Twenty-two subjects (61%) showed > or =50% improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant ( <.001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis. CONCLUSION: This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths.

Adolescent↗

Glycosaminoglycan polysulfate in the treatment of old age dementias.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Activities of Daily Living↗

Predictors of short-term deterioration and compliance in psychiatric emergency patients: a prospective study of 457 patients referred to the emergency room of a general hospital.

The aim of this study was to identify predictors of (1) short-term outcome and (2) short-term compliance with treatment (for non-hospitalized patients) in psychiatric emergency patients. Subjects comprised 457 patients referred to the emergency ward of a French general hospital and requiring examination by a psychiatrist. Clinical and therapeutic assessments were carried out at baseline, using DSM-IV diagnoses and overall psychopathological scoring scales [Brief Psychiatric Rating Scale (BPRS) and Symptom Checklist-90 Revised]. Clinical outcome and compliance were assessed 3 weeks after entry. For each of the two issues assessed, stepwise logistic regression analysis was performed following univariate comparisons. The three best predictors of deterioration at 3 weeks were lack of compliance to treatment, presence of a previous psychiatric history, and a low BPRS hebephrenic factor score. The best predictors of compliance in non-hospitalized patients were a previous psychiatric history, marital status, a low BPRS hostility factor score, and older age. The main predictor of deterioration was non-compliance. Thus, we emphasize the importance of improving compliance, especially among young patients with no previous psychiatric history.

Adult↗

[Disturbances of body-experience in acute anxiety and depressive disorders - neuroticism or somatization?].

In view of the uncertain relationship between body related "Boundary loss" and anxiety as well as depression symptoms we carried out the following study. Our aim was to explore these symptoms in their diagnostic and clinical significance and to define body distortions and organic disturbances. We examined the body perception (via Image Marking Procedure), aspects of body image via Body Distortion Questionnaire and via Visual Analogue Scales on self-perception of body weight and size) and body cathexis/satisfaction (via Visual Analogue-Scale) and their changes during hospital treatment in 28 patients with anxiety disorders (ICD-10, F40 - F41) and 40 patients with depressive disorders (ICD-10, F32 - F34). The phenomena were assessed by following instruments: Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Anxiety Scale, State-Trait Anxiety-Scale, Brief Psychiatric Rating Scale. Functional somatic complaints were assessed by Zerssen Complaint list three days after admission and again two and four weeks after inpatient treatment. Body size estimation was also assessed longitudinally in a control group of 44 healthy individuals (ward staff). On average, both patient groups displayed body dissatisfaction and high scores in the somatic complaint list as well as somatic depersonalisation and boundary loss, but in comparison with the control group there were no relevant disturbances of body size estimation. The body related phenomena were all closely correlated among each other as well as with psychopathology scores of anxiety and depressive disorder. The symptoms decreased significantly together with reduction of the psychopathological phenomena. The results could be regarded as body related equivalent of these psychopathological disturbances or they could be interpreted as symbolic (somatized) bodily represented negative cognitions and emotions. The hypothesis that these body-related phenomena outlasting the acute phase of illness could be used as neuroticism markers was not confirmed.

Acute Disease↗

Open-label risperidone for Asperger's disorder: negative symptom spectrum response.

OBJECTIVE: Asperger's disorder consists of negative symptoms similar to those seen in schizophrenia, autism, schizoid personality disorder, and schizotypal personality disorder. We investigated whether risperidone, which is effective in treating the negative symptoms of schizophrenia, would improve such symptoms observed in Asperger's disorder in a prospective, open-label trial. METHOD: Thirteen male patients aged 6 to 18 years who were diagnosed with Asperger's disorder by DSM-IV criteria were enrolled in a 12-week, prospective, open-label pilot study from March 13, 2002 to August 11, 2003. All subjects were started on risperidone 0.25 mg twice per day. Doses were increased based on clinical indication and tolerability. The primary efficacy variable was the Scale for the Assessment of Negative Symptoms (SANS). Each subject's baseline score served as his control. Secondary efficacy measures included the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Montgomery-Asberg Depression Rating Scale, Global Assessment Scale, and a modified Asperger Syndrome Diagnostic Scale. RESULTS: We found a statistically significant improvement from baseline for last-observation-carried-forward (LOCF) analyses as well as for analyses of 12-week completers (N = 9) in our primary outcome measure, SANS scores (F = 13.41, p < .0001 for 12-week completers; F = 9.64, p < .0001 for LOCF). We also found statistically significant improvement in all secondary efficacy measurements (F values range, 8.41 to 15.73, p values range, < .0001 to < .005 for 12-week completers; F values range, 6.53 to 7.75, all p < .0001 for LOCF). CONCLUSIONS: Subjects' symptoms significantly improved after risperidone. The open-label nature of this small pilot study suggests caution in interpreting these data, but the results suggest that placebo-controlled trials should follow.

Adolescent↗

[Cause of mortality in schizophrenic patients: prospective study of years of a cohort of 150 chronic schizophrenic patients].

UNLABELLED: Overmortality in schizophrenic patients in comparison to the reference population has been found. At the present time this over mortality is mainly due to suicide or certain natural causes such as respiratory, cardio-vascular and cerebro-vascular diseases. In France there are not psychiatric cas registers that could allow us to study the mortality of psychiatric patients. The aim of the study was first to determine the standardized mortality ratio (SMR) in a group of 150 chronic schizophrenics followed during 8 years and secondly to detect the variables that could predict this mortality. METHOD: The subjects filled out the RDC criteria for definite chronic schizophrenia and were included from 1991 to 1995. The subjects were inpatients or outpatients and their evaluation was made by psychiatrist. The subjects were selected from the different departments of two psychiatric hospitals corresponding to two French geographic areas (the Somme and Oise, two French "département"). At the initial assessment socio-demographic, clinical and psychometrical variables were collected: sex, age, educative level, number of hospitalizations, mean duration of the illness, scores on the Physical Anhedonia Scale, Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS). For the BPRS and PANSS, negative, positive and general subscales were extracted. In May 1999 all the subjects were contacted in order to know if they are alive or not and if they are death to know the date and the causes of their death. For the subjects that were still alive we used either direct assessment by interview of their psychiatrist or general practioner or indirect assessment by interview of their family. For the deceased subjects, we obtained informations about the date and the causes of the death by their psychiatrist or general practioner. If the patients were lost sight of we send a letter to the city of their place of birth in order to know if they are alive or not and if they are dead to know the date of their death. Moreover demographic data concerning the French and the Somme populations as well as the corresponding data concerning the mortality according to age and gender were obtained. A comparison of global mortality between patients and the French general or the Somme populations was made by the SMR. Moreover the deceased subjects and the survivors were compared by unidimensional statistical tests (chi 2 analyses for qualitative variables or Student's t test for quantitative variables) for the sociodemographic, clinical or psychometric variables. For each significant difference at p level < or = 0.05, the corresponding variable was retained for a multivariate step by step discriminant analysis. RESULTS: We found 13 deaths (10 males, 3 females): 3 suicides, 3 cardiac diseases, 2 cancers, 1 respiratory disease, 1 car crash, 1 homicide, 1 infectious disease, 1 respiratory arrest. The mortality rate (without correction for age) were 1.08% for both sexes, 1.44% and 0.6% for males and females respectively. The mortality rates (corrected for age) were 2.47% in our cohort and 0.988% in the Somme population. The corresponding SMR was 2.5. (chi 2 = 3.15, df = 1, p < 0.01). The overmortality was found only for males (chi 2 = 2.57, df = 1, p < 0.01) and not for females (chi 2 = 0.034, df = 1, p > 0.05). Concerning the comparisons between the deceased subjects and the survivors, there were five significant differences: gender, age, duration of the illness, neuroleptic dosage, negative symptoms (BPRS negative subscale). The deceased subjects were older, there was more men, the duration of the illness and the neuroleptic dosage were higher and the BPRS negative subscale was lower. These five variables were introduced in the discriminant analysis to explore notably their respecting weight. The corresponding power of the five variables were in decreasing order: neuroleptic dosage, negative symptoms, age, gender, duration of the illness. DISCUSSION: Our study confirm the overmortality in schizophrenic patients, this overmortality was especially explained by natural and non natural causes of death. The overmortality concerned only schizophrenic males patients whereas schizophrenic females did not have an overmortality. This negative result could be explain by a bias selection, the males being overrepresented in our cohort. Among the variables that were linked to the overmortality, the low level of negative symptomatology confirmed previous studies that have shown a low suicide rate in deficit schizophrenic. Moreover a high level of positive symptomatology could lead to high risk behaviors (suicide attempts, sexual disinhibition...). The neuroleptic dosage was the variable whom discriminate power was the highest. At least two explanations can be proposed. (ABSTRACT TRUNCATED)

Adolescent↗

[Comparison between the effectiveness of fluphenazine decanoate and oxyprothepin decanoate in schizophrenia (double-blind crossover study)].

The efficacy of the long-acting neuroleptic oxyprothepin decanoate (HD), a new Czechoslovak drug, was evaluated in comparison with that of fluphenazine decanoate (FD). Within a year two groups consisting, respectively, of 19 and 17 patients were treated. The patients of the first group received FD for 6 months and then HD for the next 6 months. The patients of the second group received the same drugs, but in the reverse order (cross-testing). The degree of the psychic disturbances was assessed according to a special scale (Brief Psychiatric Rating Scale) with subsequent determination of the statistical significance of the differences revealed. As regards the efficacy HD appeared to be close to FD. No statistically significant differences between them were noted. The seeming superiority of HD over FD disappeared on introducing the correction for the order of their administration (the drug administered first produced a more marked therapeutic effect). Side effects due to both drugs were minor, however HD caused them in a far lesser number of patients than FD.

Adult↗

Positive treatment effect of estradiol in postpartum psychosis: a pilot study.

BACKGROUND: Postpartum illnesses with psychiatric symptoms and serious adverse sequelae are highly prevalent during the childbearing years. Despite multiple medical contacts, these illnesses often remain unidentified and untreated. To study the association between estradiol and puerperal psychosis, we measured serum concentration of estradiol and performed an open-label trial of physiologic 17beta-estradiol in women with this disorder. METHOD: Ten women with ICD-10 psychosis with postpartum onset consecutively recruited from a psychiatric duty unit were studied. Serum estradiol concentration was measured at baseline and weekly during sublingual 17beta-estradiol treatment for 6 weeks. The treatment effect was evaluated by a clinician-rated psychiatric symptom scale (the Brief Psychiatric Rating Scale [BPRS]). RESULTS: The baseline serum estradiol levels (mean = 49.5 pmol/L; range, 13-90 pmol/L) were even lower than the threshold value of gonadal failure, and the patients exhibited high scores on the psychiatric symptom scale (mean BPRS total score = 78.3; range, 65-87). During the first week of 17beta-estradiol treatment, psychiatric symptoms diminished significantly (BPRS score decreased to a mean of 18.8, p < .001). Until the end of the second week of treatment, serum estradiol concentrations rose to near the values normally found during the follicular phase, and the patients became almost free of psychiatric symptoms. CONCLUSION: The reversal of psychiatric symptoms in all patients by treating documented estradiol deficiency suggests that estradiol plays a role in the pathophysiology and may have a role in the treatment of this condition. There was a rebound of psychotic symptoms in the 1 patient who discontinued estradiol treatment. Given the small number of patients, this area deserves further study.

Administration, Sublingual↗

Cytochrome P450 3A inhibitor itraconazole affects plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients.

BACKGROUND AND OBJECTIVE: Despite the belief that cytochrome P450 (CYP) 2D6 alone is responsible for the metabolism of risperidone, several studies suggest that CYP3A may be involved. The aim of this study was to evaluate the effect of itraconazole, a CYP3A inhibitor, on the plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients in relation to CYP2D6 genotype. METHODS: Nineteen schizophrenic patients treated with 2 to 8 mg/d of risperidone received 200 mg/d of itraconazole for a week. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured immediately before and after itraconazole treatment, as well as at 1 week after itraconazole treatment was stopped, together with clinical assessment by use of the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale and the Brief Psychiatric Rating Scale. RESULTS: Dose-normalized plasma concentrations of risperidone and 9-hydroxyrisperidone before itraconazole treatment (0.9 +/- 0.8 ng.mL(-1).mg(-1) and 6.9 +/- 3.3 ng.mL(-1).mg(-1), respectively) were significantly elevated after itraconazole treatment (1.6 +/- 1.3 ng.mL(-1).mg(-1) and 11.3 +/- 4.5 ng.mL(-1).mg(-1)) and decreased 1 week after its discontinuation (1.0 +/- 0.8 ng.mL(-1).mg(-1) and 7.2 +/- 3.7 ng.mL(-1).mg(-1)) (P < .01). However, the ratio of risperidone/9-hydroxyrisperidone, an index of CYP2D6 activity, did not differ before itraconazole treatment (0.14 +/- 0.13), after itraconazole treatment (0.15 +/- 0.13), and 1 week after discontinuation (0.14 +/- 0.13) (P > .05). Itraconazole increased the concentrations of risperidone by 69% (P < .001) and 75% (P < .01) in CYP2D6 extensive and poor metabolizers, respectively. In addition, the active moiety (risperidone plus 9-hydroxyrisperidone) also increased similarly, by 71% (P < .001) and 73% (P < .05), respectively, with itraconazole, without a significant difference between CYP2D6 genotypes. The scores on the Brief Psychiatric Rating Scale decreased significantly but only by 6% after itraconazole treatment (P < .05); however, the scores on the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale were not changed. CONCLUSIONS: Our results provide in vivo evidence of the involvement of CYP3A in the disposition of risperidone and 9-hydroxyrisperidone. In addition to CYP2D6, treatment with CYP3A inhibitor(s) including itraconazole may influence clinical symptoms and risperidone side effects.

Adult↗

Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome.

In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.

Adolescent↗

Subjective and objective measures of quality of life have different predictors for people with schizophrenia.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

Adult↗