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Transcranial magnetic stimulation in mania: a controlled study.

OBJECTIVE: Left prefrontal transcranial magnetic stimulation has been reported to have ECT-like effects in depression; therefore, the authors planned a study of transcranial magnetic stimulation in mania. METHOD: Sixteen patients completed a 14-day double-blind, controlled trial of right versus left prefrontal transcranial magnetic stimulation at 20 Hz (2-second duration per train, 20 trains/day for 10 treatment days). Mania was evaluated with the Mania Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impression. RESULTS: Significantly more improvement was observed in patients treated with right than with left prefrontal transcranial magnetic stimulation. CONCLUSIONS: The therapeutic effect of transcranial magnetic stimulation in mania may show laterality opposite to its effect in depression.

Adult↗

Computerized brain tomography in patients with Schizophrenia.

We carried out brain tomography of 27 patients with schizophrenia and 17 normal control subjects. DSM-IV criteria were used for diagnosis. The parameters studied were: brain volume, lateral and third ventricles, brain surface and brain indexes. Previously the patients were evaluated with the following clinical scales: Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning Scale (GAF) and the GRAFFAR scale to evaluate cultural and socioeconomical levels. We detected an increase in the right and left lateral ventricles: brain ratios, an increase in the width of Sylvian fissures and in the third ventricle index. We did not find differences that could be related to sex or to a familial history of mental disease. No differences were observed in the group receiving medication when compared with the group of untreated patients.

Adult↗

Alpha wave biofeedback training therapy in alcoholics.

This investigation evaluated the therapeutic efficacy of alpha-wave biofeedback treatment for alcoholics. Twenty-five Ss were compared to a matched control group before and after administration of a 3-week alpha-wave biofeedback regimen on a wide variety of criteria that included State-Trait Anxiety, the MMPI, Multiple Affect Adjective Check List, Zuckerman's Sensation Seeking Scale, Watson's Anhedonia Scale, the Brief Psychiatric Rating Scale, and baseline alpha. The experimental Ss received 10 hour-long alpha training sessions. The experimentals showed more improvement than did controls on alpha production and two anxiety measure. Contradictory results appeared on two suspicion/paranoia measures. Alpha training appeared useful in the treatment of anxiety, but not other problems. However, the absence of significant correlations between amount of change on alpha and the anxiety measures suggests that the improvement may be due to a placebo effect.

Adult↗

Clinical effects of a randomized switch of patients from clozaril to generic clozapine.

INTRODUCTION: Clozapine was discovered in 1959 but withheld from the United States market after several deaths due to agranulocytosis. The medication was approved in the United States in 1989 on a compassionate-use basis and was first marketed in 1990 as Clozaril. In 1999, following approval by the U.S. Food and Drug Administration, Zenith Goldline Pharmaceuticals (ZGP) introduced a generic form of clozapine. METHOD: After 5 weeks of data collection (phase I), 24 patients were randomly assigned to group A and 21 patients to group B. Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, or atypical psychosis with mood disorder. In phase II, group A received a mean daily dose of 630 mg of generic clozapine, and group B continued to receive Clozaril at a mean daily dose of 610 mg, each for 8 weeks. In phase III, group A was reassigned to Clozaril, and group B was switched to generic clozapine, each for 8 weeks. At the end of phase III, group B resumed Clozaril. Efficacy was measured with the Clinical Global Impressions-Improvement (CGI-I) scale, the Brief Psychiatric Rating Scale (BPRS), and the Beck Depression Inventory (BDI). RESULTS: Five patients experienced relapse when they were switched from Clozaril to generic clozapine. Eleven patients worsened short of full relapse, 9 while receiving ZGP generic clozapine and 2 while receiving Clozaril. CGI-I scores and BPRS scores favored patients receiving Clozaril significantly. Only BDI scores favored patients receiving generic clozapine significantly. CONCLUSION: Until more studies have been performed, clinicians and administrators should carefully monitor stable Clozaril-treated patients who are being switched to generic clozapine.

Adult↗

Risperidone in adolescents with schizophrenia: an open pilot study.

OBJECTIVE: To assess critically the short-term efficacy and safety of risperidone in adolescents with schizophrenia. METHOD: Subjects were adolescents who were attending a research day hospital as outpatients and who had received a diagnosis of schizophrenia. This was an open pilot study; after a 2-week washout period during which all psychotropic medications were gradually discontinued, subjects were treated with risperidone for 6 weeks. Dosage was regulated individually over a period of 3 weeks; starting dose was 2.0 mg/day followed by 1.0-mg increments every 2 days; maximum dose was not to exceed 10 mg/day. The main outcome measures included the Positive and Negative Syndrome Scale of Schizophrenia, the Brief Psychiatric Rating Scale, and the Clinical Global Impression. RESULTS: Ten adolescents between 11 and 18 years of age were enrolled in the study. Risperidone produced clinically and statistically significant improvement on the Positive and Negative Syndrome Scale for Schizophrenia. Brief Psychiatric Rating Scale, and Clinical Global Impression at doses ranging from 4.0 mg/day to 10.0 mg/day (mean = 6.6). There were no major adverse reactions associated with risperidone use. CONCLUSIONS: Risperidone appears to have been effective and well tolerated in this sample of adolescents with schizophrenia.

Adolescent↗

Melperone in the treatment of neuroleptic-resistant schizophrenia.

Melperone is an effective antipsychotic drug that has been reported to have atypical properties, i.e. low extrapyramidal side effect liability at clinically effective doses. It also does not increase serum prolactin levels. Its effectiveness for patients with neuroleptic (treatment)-resistant schizophrenia has not been evaluated. In this study, melperone was administered, in an open trial design of 6 weeks' duration, to 44 patients with chronic neuroleptic-resistant schizophrenia. The Global Assessment Scale (GAS), Brief Psychiatric Rating Scale (BPRS) and measures of extrapyramidal symptoms and other clinical variables were assessed at baseline and 6 weeks. Thirty-seven patients completed the 6-week trial. Melperone significantly improved overall psychiatric status as measured by GAS score for all evaluable subjects [last value carried forward (LVCF) and a completers analysis]. No significant effects on BPRS measures of psychopathology scores were found in the LVCF or completers analysis. Patients who showed > or = 20% decrease in the BPRS Total score (N=7) were more likely to have high baseline psychopathology, as measured by BPRS Total and Anxiety-Depression subscales, than those who showed > or = 20% increase in the BPRS Total score (N=8). Non-responders to melperone generally did not respond to subsequent treatment with clozapine, indicating that this group of patients was very treatment resistant. Melperone was not associated with worsening of extrapyramidal symptoms, elevation in plasma prolactin levels, or an increase in body mass index (BMI). The results suggest that a proportion of neuroleptic-resistant patients with schizophrenia respond to melperone, which requires further controlled study.

Adult↗

Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.

BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.

Adult↗

Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists.

BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. METHOD: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. RESULTS: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). CONCLUSIONS: Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.

Adult↗

The comparison of the behavioral observation system and the brief psychiatric rating scale-expanded.

The construct validity of the Behavioral Observation System (BOS), an observational instrument used by line staff to rate psychopathological behaviors, was studied using comparisons with the Brief Psychiatric Rating Scale-Expanded version (BPRS-E). A sample of 100 inpatient participants was rated using the BPRS-E on the same day they were rated by line staff using the BOS. Pearson product-moment correlations were performed, supporting good convergence and divergence. Principle component analysis on the six BPRS-E scales and the four BOS scales resulted in a three-factor finding. This analysis was supportive of construct validity. Uses of the BOS in light of these findings were discussed.

Adult↗

Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study.

OBJECTIVE: The authors' goal was to test in humans the hypothesis that N-methyl-d-aspartate receptor (NMDAR) antagonism results in increased cortical glutamate activity, as proposed by the NMDAR hypofunction model of schizophrenia. METHOD: 4-T 1H proton magnetic resonance spectroscopy (1H-MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task. RESULTS: As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance. CONCLUSIONS: In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.

Adult↗

Nurse-rating of psychotic behaviour.

The aim of this study was to review six nurse-rating schedules to evaluate their suitability for a British psychiatric unit and current nursing practice. They were compared for their reliability, their concordance with psychiatric ratings and their acceptability to the nursing staff. It was found that psychiatric and nursing observations corresponded over a wide area of psychopathology: anxiety, tension, depression, hostility, preoccupation with hypochondriacal, grandiose and self-depreciatory ideas, hallucinosis, thought disorders, mannerisms, retardation, emotional withdrawal, hypomanic activity and uncooperative behaviour. These were adequately covered by two of the scales, the Brief Psychiatric Rating Scale (BPRS) and the Psychotic Inpatient Profile (PIP), which together took 7 1/2 minutes to complete. Another of the schedules studied, the Nursing Rating Scale (Hargreaves), also had relatively high reliability and a broad effective range.

Evaluation Studies as Topic↗

An open trial of clozapine in 11 adolescents with childhood-onset schizophrenia.

OBJECTIVE: To review the response of 11 adolescents with childhood-onset schizophrenia to a 6-week open clozapine trial. METHOD: Eleven children meeting DSM-III-R criteria for schizophrenia had a 6-week open trial of clozapine (mean sixth week daily dose 370 mg). Behavioral ratings included the Brief Psychiatric Rating Scale and Children's Global Assessment Scale. RESULTS: More than half showed marked improvement in Brief Psychiatric Rating Scale ratings by 6 weeks of clozapine therapy compared to admission drug rating and compared to a systematic 6-week trial of haloperidol. CONCLUSIONS: This open trial indicates that clozapine may be a promising treatment for children and adolescents with schizophrenia who do not respond well to typical neuroleptics. A double-blind placebo-controlled study is ongoing.

Adolescent↗

Effects of antipsychotic withdrawal in elderly nursing home residents.

OBJECTIVE: To study the effects of antipsychotic withdrawal in elderly nursing home residents. DESIGN: Longitudinal prospective study. SETTING: 12 community nursing homes that participated in a randomized controlled trial of an educational program designed to reduce antipsychotic use. SUBJECTS: 271 residents receiving antipsychotics at baseline and remaining in the home for approximately 6 months thereafter. These were placed into two groups: those with continued use of antipsychotics at follow-up (n = 207) and those with drug discontinued (n = 64). MEASUREMENTS: Change between baseline and follow-up for several standard measurements. These included behavior problems, as reported by both regular care providers (Nursing Home Behavior Problem Scale) or a blinded study rater (items from the Brief Psychiatric Rating Scale), observer-rated psychiatric symptoms (subset of the Brief Psychiatric Rating Scale), and other standard tests of function (Activities of Daily Living, Mini-Mental State Examination, Geriatric Depression Scale, and Abnormal Involuntary Movements Scale). RESULTS: The frequency of behavior problems did not increase in residents with antipsychotics discontinued. For these residents, observer-rated psychiatric symptoms decreased by 21% (P = 0.003), which resulted from a 27% decrease in adverse affective symptoms (P = 0.0002). Residents with drug discontinued had no deterioration in any of the measures of function. CONCLUSION: In this sample, nursing home residents whose antipsychotics were discontinued had significantly improved affect and no discernable adverse effects.

Activities of Daily Living↗

A statewide evaluation system for early psychosis.

OBJECTIVE: We describe a system of outcome evaluation for early psychosis programmes and present preliminary data. The Early Psychosis Outcome Evaluation System (EPOES) was designed for use in a naturalistic, prospective study of a cohort of early-episode psychosis patients. We describe patients in terms of symptoms, substance use, social functioning and family burden, and examine the effectiveness of treatment programmes. METHOD: Four sites in Perth, Western Australia, participated. Outcome was evaluated from three sources: case manager (CM), patient (P) and family member (FM). Seven clinical outcome measures were used: the Brief Psychiatric Rating Scale (CM), Brief Symptom Inventory (P), Substance Use (CM); Social Functioning Scale (P); Global Assessment Scale (CM); Burden Assessment Scale (FM), and the General Health Questionnaire-12 (FM). Measures were collected at intake (baseline) into a specialist early psychosis service and thereafter every 6 months until discharge from the service. RESULTS: After the first year of data capture, 84 baseline assessments have been completed, and 23 patients have been followed up at 6 months. Clinicians and patients reported significantly less psychopathology at 6 months. Sixty per cent of patients reported marijuana use within 3 months of baseline assessment, and 30% amphetamine, ecstasy or cocaine use. Increased levels of psychopathology were recorded for substance-using patients. Family members (59%) reported psychological distress at baseline; this was reduced at 6 months. Patient social functioning and family burden did not improve measurably. CONCLUSIONS: The EPOES is an effective system that provides feedback on the clinical status of early-episode psychosis patients. Both observed and self-rated psycho-pathology and family psychological distress, is improved after 6 months of intervention. Family burden and patient social functioning did not demonstrate improvement. Patient social functioning is an important area for treatment. Substance use is associated with poorer psychopathology. EPOES provides a feasible system of measuring outcome in early psychosis intervention.

Adult↗

Ball experiments in 32 acute akinetic catatonic patients: deficits of internal initiation and generation of movements.

We undertook ball experiments in 32 akinetic catatonic patients in order to determine specific functional deficits in the motor system in akinetic catatonia. Standardized ball experiments (catching, throwing, stopping, kicking) were conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21. Additionally, associated psychopathology was evaluated using different scales on days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale, the Hamilton-Anxiety Scale, the scale for the assessment of negative symptoms (SANS), and the Simpson scale for extrapyramidal side effects (SEPS). Significantly more patients were able to perform more externally guided tasks (catching, stopping) than internally guided tasks (throwing, kicking). Patients showed significantly more posturing and awkward movements on day 0 than on day 21. There was a significantly positive correlation between hypokinetic extrapyramidal features (SEPS) and negative symptoms with their cognitive alterations (SANS) on day 0. The findings suggest a deficit of internal initiation, as in parkinsonism, as well as a dysfunction in the generation of voluntary movements in akinetic catatonia. We assume an underactivity in the dorsolateral prefrontal cortex and the supplementary motor area with consecutive down-regulation of the cortical-striatal-thalamic circuit, the "motor loop," in catatonia.

Acute Disease↗

A randomized, controlled, dose-ranging trial of sertindole in patients with schizophrenia.

Sertindole is a novel antipsychotic agent with high selectivity for the mesolimbic dopaminergic pathway and nanomolar affinities for dopamine D2, serotonin 5-HT2, and norepinephrine NE alpha 1 receptors. This 40-day randomized, placebo-controlled, dose-ranging multicenter study was designed to assess the effect of sertindole on previously neuroleptic-responsive, hospitalized schizophrenic patients (n = 205). Sertindole doses began at 4 mg/day and were increased to 8, 12, or 20 mg/day, depending on randomization. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Extrapyramidal symptoms (EPS) were assessed by movement rating scales, EPS-related adverse events, and use of anti-EPS medications. A dose-related improvement was observed for PANSS, BPRS, and CGI, with statistically significant mean differences (P < 0.05) between placebo and 20-mg/day sertindole (decreases from baseline of -5.8 versus -16.9 for PANSS, -4.8 versus -10.4 for BPRS, respectively). The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9, respectively. EPS-related events were comparable in the placebo and sertindole groups. In conclusion, sertindole 20 mg/day was effective, well tolerated, and not associated with significant motor system abnormalities.

Adult↗

Double-blind study of mirtazapine and placebo in hospitalized patients with major depression.

The purpose of the present 6-week multicenter dose finding study was to compare the efficacy and tolerability of mirtazapine (preferentially presynaptic alpha 2-adrenergic receptor blocker) to placebo in hospitalized patients with major depression. The clinical efficacy was evaluated with the Hamilton Depression Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Self-Rating Depression Scale, Global Assessment Scale (GAS), and Brief Psychiatric Rating Scale (BPRS). The side effects were recorded on a checklist of emergent symptoms (ROSE) and physical examinations, ECG, clinical chemistry, and hematology tests were carried out. The dosages of mirtazapine were gradually raised from 15 mg to 50 mg. One hundred and fourteen patients were included. Twenty-two patients (37%) in mirtazapine group and 24 (44%) in the placebo group were prematurely withdrawn from the study mainly due to inadequate efficacy. The decrease in HAM-D and MADRS was generally more pronounced in the mirtazapine group than in the placebo group. Minor side effects were reported in less than 15% of the patients in both groups. Only fatigue and faintness were slightly more pronounced in the mirtazapine group than in the placebo group. No significant changes were found in laboratory parameters. Because of methodological flaws like combining a dose finding study with a placebo controlled study, further conclusions should not be made on the efficacy of mirtazapine when treating depressive patients.

Adrenergic alpha-2 Receptor Antagonists↗

Right prefrontal TMS versus sham treatment of mania: a controlled study.

OBJECTIVE: Left prefrontal transcranial magnetic stimulation (TMS) has been reported to have ECT-like effects in depression and we therefore planned a study of TMS in mania. Sixteen patients completed trial of right versus left prefrontal TMS at 20 Hz, 2-sec duration per train, 20 trains per day for 10 treatment days. Mania was evaluated using the Mania Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impression. Significantly more improvement was observed in patients treated with right prefrontal TMS than with left prefrontal. We now report a follow-up study of right active TMS versus right sham TMS with the same indications and parameters. METHODS: Twenty-five patients entered and 19 completed right TMS versus sham right TMS. RESULTS: Right TMS was no more effective than sham TMS. CONCLUSIONS: It is possible that the previous results were due to an effect of left TMS to worsen mania. Alternatively, it is noted that the present patient group had much more psychosis than the previous study of TMS in mania, and depression studies have reported that psychosis is a poor prognostic sign for TMS response.

Adult↗