PubMed Health⌕ Search

Biomedical subjects

W Rein

Publications and source records attributed to W Rein.

At least 19 recordsLinked to original sources
PubMed2000

Long-term safety and efficacy of amisulpride in subchronic or chronic schizophrenia. Amisulpride Study Group.

Amisulpride is an atypical antipsychotic with selective affinity for dopamine D2/3 receptors. In this long-term, open, randomised, multicentre trial, patients with chronic or subchronic schizophrenia received amisulpride (n =370) or haloperidol (n = 118) for 12 months. Dosage regimens were flexible (amisulpride 200-800 mg/day, haloperidol 5-20 mg/day). Improvement in mean Brief Psychiatric Rating Scale total score was significantly greater for amisulpride than haloperidol (17.0 versus 12.8, P = 0.01). Positive symptoms (Positive and Negative Syndrome Scale [PANSS] positive) improved in a similar way in each group but amisulpride caused a significantly better improvement in negative symptoms (PANSS negative) (7.1 versus 3.7, P < 0.0001). Improvements in Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) scores were also significantly greater in the amisulpride group (GAF -20.1 versus -13.6, P = 0.001; QLS -0.64 versus -0.30, P = 0.02). Adverse events were mainly psychiatric in nature, and occurred with similar frequency in each group (amisulpride 254/370, 69%; haloperidol 82/118, 70%). Extrapyramidal symptoms were more frequent for haloperidol (48/118, 41% versus 96/370, 26% for amisulpride), leading to a greater requirement for antiparkinsonian medication (haloperidol 66/118, 56% versus amisulpride 118/370, 32%). Haloperidol significantly aggravated parkinsonism, akathisia and involuntary movement compared to amisulpride. The overall incidence of endocrine events was comparable between groups (4% for amisulpride, 3% for haloperidol). Maintenance of efficacy was comparable in both treatment groups; 59% of amisulpride patients and 55% of haloperidol patients improved after 1 month of therapy remained improved throughout the study period. Amisulpride is effective following flexible long-term administration and significantly improves social functioning and quality of life.

Adolescent↗
PubMed2000

Safety profile of amisulpride in short- and long-term use.

OBJECTIVE: To assess the safety of the new atypical antipsychotic drug, amisulpride, in short- and long-term use. METHOD: Studies comparing the safety of amisulpride with that of haloperidol and risperidone, respectively, are reviewed. Safety was monitored by open adverse event reporting, the Simpson-Angus Scale, the Barnes Akathisia Scale and the Abnormal Involuntary Movement scale. RESULTS: In short- and long-term studies, amisulpride induced significantly less EPS and akathisia than haloperidol. Safety ratings were similar to risperidone in short-term studies. In studies of chronic schizophrenia with predominant negative symptoms, amisulpride was similar to placebo. Endocrine effects were similar in amisulpride-, haloperidol- and risperidone-treated patients. Weight gain with amisulpride was significantly less than risperidone in a short-term study. No clinically important effects on haematological, hepatic or cardiac function were recorded. Data obtained in short- and long-term studies have been confirmed in extensive post-marketing surveillance data. CONCLUSION: Amisulpride has a broad spectrum of efficacy in schizophrenia without introducing the iatrogenic consequences associated with older therapies.

Amisulpride↗
PubMed1999

Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride study group.

Amisulpride, a substituted benzamide with high selectivity for dopamine D3 and D2 receptors, was compared with the antipsychotic risperidone in patients with acute exacerbations of schizophrenia. The study was double-blind and involved 228 patients allocated, after a 3-6-day wash-out period, to amisulpride 800 mg (n = 115) or risperidone 8 mg (n = 113) for 8 weeks. Both treatments produced a marked improvement in schizophrenic symptomatology. Decreases in mean BPRS total score were 17.7 +/- 14.9 for amisulpride and 15.2 +/- 13.9 for risperidone, and all of the individual factors on the BPRS showed a numerically greater improvement in the amisulpride than in the risperidone patients. Both treatments were equally effective against positive symptoms on the PANSS positive syndrome subscale; however, there was a trend in favor of greater improvement in negative symptoms assessed on the PANSS negative subscale in patients receiving amisulpride with a decrease of 6.9 +/- 7.5 vs. 5.3 +/- 6.6 for risperidone (P = 0.09). Both drugs demonstrated good safety profiles, and scores on neurological scales (SAS, AIMS, and BAS) did not increase during treatment. A comparable proportion of patients received antiparkinsonian medication, 30 and 23% in the amisulpride and risperidone groups, respectively (P = 0.21). Patients receiving risperidone experienced an increase in body weight, which was significantly greater than for amisulpride (P = 0.026).

Acute Disease↗
PubMed1999

Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group.

OBJECTIVE: The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms. METHOD: After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale. RESULTS: Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride. CONCLUSIONS: These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.

Adolescent↗
PubMed1998

Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.

The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.

Adult↗
PubMed1998

Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group.

This 4-week, double-blind, randomized study was undertaken to determine the dose-response relationship of amisulpride in 319 patients with acute exacerbation of schizophrenia. Fixed doses of amisulpride (400, 800 and 1200 mg/day) and haloperidol (16 mg/day) were compared to amisulpride, 100 mg/day, as a potentially subtherapeutic dose. Efficacy data (BPRS total score and PANSS positive subscale) in the amisulpride groups generated a bell-shaped dose-response curve, with 400 mg/day and 800 mg/day being the most effective treatments for positive symptoms. Parkinsonism did not increase significantly between baseline and endpoint with amisulpride 400, 800 and 1200 mg/day compared to the amisulpride 100 mg/day group, whereas the difference was significant for haloperidol (P<0.05). It is concluded that amisulpride 400 mg and 800 mg/day is highly effective in treating the positive symptoms of schizophrenia, with less extrapyramidal side-effects than haloperidol 16 mg/day.

Acute Disease↗
PubMed1997

Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group.

Amisulpride is a substituted benzamide with high selectivity for dopaminergic D2 and D3 receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism.

Adult↗
PubMed1997

Amisulpride versus imipramine and placebo in dysthymia and major depression. Amisulpride Study Group.

Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50 mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients with DSM-III-R criteria for primary dysthymia, dysthymia with major depression or major depression in partial remission. A total of 219 patients were included. Both analyses (intention-to-treat and "per protocol' analysis) detected significant differences between groups (active treatment vs. placebo) on all main rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting at least one adverse event was higher in the imipramine group than in the two other, mainly due to anticholinergic effects. Endocrine symptoms were more frequent in female patients treated with amisulpride. These results confirm the interest of a drug acting on dopaminergic transmission such as amisulpride in the treatment of depressed patients.

Adult↗
PubMed1997

Clinical update on amisulpride in deficit schizophrenia.

Amisulpride is an atypical antipsychotic drug. Low doses increase dopaminergic transmission via presynaptic blockade and are effective in patients with predominantly negative (deficit) symptoms of schizophrenia. In three double-blind studies, two short-term and one medium/long-term, comparing amisulpride with placebo, 272 patients with schizophrenia were carefully selected for a predominance of negative symptoms (low severity of positive symptoms, depression and extrapyramidal side effects). Fixed daily doses of amisulpride (100 and 300 mg) were used in a 6-week dose-range finding study (104 patients). Daily doses of between 50 and 100 mg amisulpride were used in a second 6-week study (27 patients), and in a third study, 100 mg amisulpride was administered for 6 months (141 patients) with an extension of up to 1 year. Mean total scores for the Scale for the Assessment of Negative Symptoms (SANS) at baseline in the different treatment groups varied from 98 to 74, and improved significantly in the amisulpride groups (mean change from 24 to 40 points) compared with the placebo groups. Positive symptoms measured by the Scale for the Assessment of Positive Symptoms (SAPS) were low at baseline, and the change at the end of the studies was minimal. Extrapyramidal side effects were of low severity in these studies and parkinsonism scores for amisulpride were not different from placebo. Overall, these findings indicate that the improvement in negative symptoms was not linked to a concomitant improvement in positive symptoms, parkinsonism or depressive symptoms as would be expected in the case of secondary negative symptoms. The results of these studies thus confirm the efficacy of amisulpride in schizophrenic patients with primary negative or deficit symptoms at a dose of 100 mg/day.

Adult↗
PubMed1997

Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia.

BACKGROUND: Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors. The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia. METHOD: This was a multi-centre, randomised, parallel-group, double-blind study. Patients received either amisulpride (100 mg/day) or placebo over a six-month treatment period. RESULTS: A total of 141 patients were included, 69 received amisulpride, 72 placebo. Fifty-eight patients (41%) had received neuroleptic treatment prior to inclusion. The percentage of amisulpride patients completing the study (55%) was significantly higher than that with placebo (32%), and drop-out rates due to lack of efficacy were 27% with amisulpride and 47% with placebo. All efficacy assessments were statistically in favour of amisulpride compared with placebo. The overall incidence of extrapyramidal symptoms was comparable in both groups; only five patients started anti-Parkinsonian treatment during the study (one in the placebo and four in the amisulpride group). CONCLUSION: Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms.

Adult↗
PubMed1996

[Methodological constraints in evaluating anti-deficit effects].

Several types of limitations are inherent in the evaluation of changes in negative symptoms during clinical trials. Some of these limitations can be listed as follows: the need to select homogeneous study populations (use of a standardized diagnosis), identification of negative dimensions which feature deficitary forms of schizophrenia (qualitative criteria and threshold scores using negative symptom rating tables), strict control of variables which may induce secondary negative symptoms (treatments, other associated disorders particularly of a depressive type, lack of environmental stimulus), follow-up of stability of negative symptoms and, finally, an adequate time interval for evaluation in order to exclude spontaneous and non-specific fluctuations of symptomatology.

Antipsychotic Agents↗
PubMed1987

[Changes in slow evoked potentials in depressed patients treated with amitriptyline and oxaprotiline].

Using a simple S1S2-R paradigm, acoustically evoked potentials, CNV, and PINV were recorded in 59 patients with major depressive disorder before and during a 4 week double blind pharmacological treatment with either amitriptyline (AT) or oxaprotiline (OT). In parallel, 30 healthy subjects were investigated 3 times, in identical intervals of 2 weeks. In the depressed state patients exhibited significantly smaller CNVs than the controls. In the AT-group clinical improvement and drug plasma levels of nortriptyline (NT, the principal metabolite of AT and an active antidepressant by itself) were positively related to increases in CNV-area; in the OT-group the reverse was true: increase in CNV-area was related to smaller OT plasma levels and less favourable outcome. The control group displayed a steady decline in CNV area during the 3 test sessions. N1P2 amplitude and PINV were not significantly different between groups and exhibited only minor variations during treatment.

Adult↗
PubMed1987

Autonomic nervous system differences as predictors of short-term outcome in schizophrenics.

Skin conductance and heart rate of 19 drug-free acute schizophrenic patients were measured before neuroleptic therapy was started. The patients were divided into two groups according to therapeutic outcome. The Discriminant Analysis revealed a difference in the ANS activity pattern between the group with low improvement and the group with a more favorable outcome. The low improvement group showed a paradoxical ANS reactivity pattern: relatively lower activity in skin conductance level under demand (attention task) and relatively higher activity, as reflected by the cardiovascular response to neutral stimuli (orienting stimuli), which suggests poor adaptation of ANS arousal to the environment in these schizophrenics. This finding agrees with those reported in other short-term outcome studies that considered differences in ANS activity in a schizophrenic population. The authors' findings indicate that these differences in the ANS response in schizophrenics should be included in future biochemical and pharmacotherapeutic investigations on schizophrenia.

Adult↗
PubMed1986

Amitriptyline and oxaprotiline in the treatment of hospitalized depressive patients. Clinical aspects, psychophysiology, and drug plasma levels.

Amitriptyline (AT) and the noradrenaline reuptake inhibiting antidepressant oxaprotiline (OT = hydroxymaprotiline) were compared in 59 primary depressive inpatients in a 4-week double blind parallel group design. In the Hamilton Depression Rating Scale and 2 self-rating scales AT proved to be more efficient than OT, mainly with respect to disturbances of appetite and sleep. Agitated patients receiving OT needed more additional tranquilizing medication. The number of side-effects did not differ. Both drugs increased heart rate and skin resistance level (SRL) to about the same degree and did not influence the number of spontaneous fluctuations of SRL, habituation of SRL orienting responses (OR), frequencies of respiration and blinking. Salivation was temporarily more impaired by AT. All physiological variables differed between patients and 30 healthy controls during the whole 4-week trial. Clinical outcome showed a linear relation to OT plasma levels. For AT a therapeutic window was confirmed for concentrations of AT and its metabolite nortriptyline between 125 and 200 ng/ml. Patients whose SRL-OR habituated rapidly had a better outcome than slow habituators. Urinary excretion of 3-methoxy-4-hydroxyphenylglycol was lower in patients than in controls but could not predict outcome with either drug.

Amitriptyline↗
PubMed1983

Prediction and evaluation criteria in perazine therapy of acute schizophrenics. Methodological considerations, sample population, and research variables.

In an open study of schizophrenic patients treated with perazine (Taxilan), a multidimensional approach comprising the following three areas was chosen: 1. psychopathology (AMDP, BPRS); 2. psychophysiology (habituation of skin resistance reaction, pulse rate); 3. pharmacokinetics (perazine-desmethylperazine plasma levels). Looking beyond the known global effect of the neuroleptic drug, interactions between these three areas were studied. Furthermore, methodological questions concerning possible predictor variables for treatment outcome were examined. Finally, an improved method for analyzing psychopathological data was employed. The methodological framework of the study, the examination techniques, and patient population are presented.

Acute Disease↗
PubMed1983

Prediction and evaluation criteria in perazine therapy of acute schizophrenics: psychopathological results.

In a pharmacopsychiatric pilot study 28 patients with an acute schizophrenic illness were treated for 4 weeks with perazine (Taxilan). Research goals in the psychopathological investigation were: (1) to assess the range of efficacy, target symptoms and syndromes of perazine and to compare these results with previous studies; (2) to compare the quality, interrater reliability, and practicability of two instruments of psychopathological assessment (AMDP and BPRS) for measuring change during treatment; (3) to apply new mathematical methods for finding statistically significant changes in symptomatology on the item level as well as on the levels of syndrome and total score; (4) to test whether pre-treatment prediction based on psychopathological evaluation or psychophysiological data is possible. The target symptoms and syndromes of perazine were the "positive" schizophrenic syndromes, above all thought disturbances and delusional phenomena. This result was consistent with a former perazine investigation. The BPRS proved to be a practicable and reliable instrument for a more global evaluation of change in psychopathology. The AMDP seemed to be especially useful for evaluating the homogeneity of a sample and showing differentiated psychopathological profiles. On this scale, changes in symptomatology became statistically apparent more clearly and more quickly on the syndrome level rather than on the level of single items. As to interrater reliability, both scales perform well. Dichotomizing the original scaling may mean a loss of information from both scales (AMDP and BPRS) in their evaluation of change. Hence it seems necessary to introduce new mathematical procedures (e.g., Friedman and Dunn-Rankin tests) into pharmacopsychiatric research.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1983

Prediction and evaluation criteria in perazine therapy of acute schizophrenics. Pharmacokinetic data.

Twenty-eight patients with acute schizophrenic illness received an oral daily dose of 200-800 mg perazine (Taxilan) for 4 weeks. Weekly plasma level determinations showed a constant perazine concentration from day 7 to day 28, whereas the equilibrium level of its metabolite desmethyl perazine was only achieved at day 14; on an average it amounted to twice the level of perazine. Additional measurements were carried out 2 and 4 h after administration of the morning dose on day 14. The maximal increase of the perazine concentration was usually reached after 2 h; though it varied between 7 and 240% of the morning level, a close correlation existed between minimal and maximal levels. The perazine fraction not bound to plasma proteins was found to be 3.1-5.5% on day 21. The percent improvement in target syndromes during 4 weeks of neuroleptic therapy, as documented with the AMDP system, was most marked in those patients who had perazine levels in the 100-230 ng/ml range at day 28; patients with lower or higher levels improved significantly less. Curvilinear relationships also appeared to exist between improvement and free perazine concentration as well as maximal level on day 14. With regard to total scores on the Brief Psychiatric Rating Scale or scores of higher-order factors, no significant relationship between improvement and perazine level was found. The desmethyl perazine concentration did not exhibit a significant relationship to the therapeutic result. The pharmacokinetic parameters investigated seem to have a limited influence on the clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗