Haloperidol blood levels and clinical effects.
ABSTRACT This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.
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ABSTRACT: Post-mortem studies of the human brain indicate that certain GABA(A) receptor subtypes may be differentially altered in schizophrenia. Increased binding to the total population of GABA(A) receptors using [3H]muscimol is observed in the post-mortem schizophrenic brain, yet a proportion of these receptors which bind benzodiazepines and are labelled with [3H]flunitrazepam, show decreased or unaltered expression. Data from animal studies suggest that antipsychotic drugs alter GABA(A) receptor expression in a subtype selective manner, but in the opposite direction to that observed in schizophrenia. To broaden our understanding of the effects of antipsychotic drugs on GABA(A) receptors, we examined the saturation binding maximum (B(max)) and binding affinity (K(D)) of [3H]muscimol and [3H]flunitrazepam in the prefrontal cortex (PFC), hippocampus and thalamus of male SD rats that received a sucrose solution containing either haloperidol (1.5 mg/kg), olanzapine (6.5 mg/kg) or no drug daily for up to 28 days using quantitative receptor autoradiography. [3H]Muscimol binding density was increased most prominently in the PFC after 7 days, with larger and more prolonged effects being induced by the atypical antipsychotic drug olanzapine in subcortical regions. While no changes were observed in [3H]muscimol binding in any region after 28 days of drug administration, [3H]flunitrazepam binding density (B(max)) was increased for both antipsychotic treatments in the PFC only. These findings confirm that the subset of GABA(A) receptors sensitive to benzodiazepines are regulated differently from other GABA(A) receptor subtypes following antipsychotic drug administration, in a time- and region-dependent manner.Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2008; 32(2):492-8. DOI:10.1016/j.pnpbp.2007.10.003 · 4.03 Impact Factor
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ABSTRACT: The therapeutic spectrum of zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum zotepine concentrations and the clinical efficacy.Human Psychopharmacology Clinical and Experimental 03/1993; 8(2):133 - 139. DOI:10.1002/hup.470080207 · 1.85 Impact Factor
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ABSTRACT: Prior to the 1970s, individual and group psychotherapies for schizophrenia were generally based on psychodynamic theories, or theories that conceived of schizophrenia as being caused by the behaviour or communication patterns of the sufferer's family. Following the introduction of effective antipsychotic medication in the 1960s, there was a shift of focus away from psychological interventions for schizophrenia. Gradually, there was dissatisfaction with the over-reliance on pharmacological treatments for schizophrenia, as it emerged that a high proportion of individuals with schizophrenia continued to experience positive symptoms of psychosis despite taking antipsychotic medication. Thus, controlled trials of psychological interventions designed to promote acquisition of social skills and reduce relapse by improving family atmosphere emerged in the 1980s. Their positive results were well received and promoted increased interest in psychological therapies in this population. Concurrent with these developments, the usefulness of cognitive therapy for the symptoms of depression encouraged clinicians and researchers to extend its techniques to the treatment of medication-resistant positive symptoms of psychosis.Schizophrenia, Volume 2, pages 147 - 241; , ISBN: 9780470842331