Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients

Browne, F.W.A.; Cooper, S.J.; Wilson, Richard H.; King, D. J.

doi:10.1177/026988118800200204

Cited by 9 publications

(2 citation statements)

References 34 publications

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“…greater (26.8 ~mol.h.l-1 versus 18.1 ~mol.h.l-1), suggesting that patients may experience higher and longer lasting plasma remoxipride concentrations than healthy volunteers. Since the patients in this study were relatively 'treatment-resistant' (12 patients having been in hospital for more than a year, see Table 2), these data suggest that, as with haloperidol (Hollister and Kim, 1982;Browne et al, 1988), pharmacokinetic differences would be unlikely to account for a poor response to remoxipride. The mean t, (5.5 h) corresponded very closely to that reported by Chouinard (1987) in a similar group of chronic schizophrenic patients following the last dose after 6 weeks treatment with remoxipride (mean 5.9 h, range 4.1-10.7 h).…”

Section: Discussionmentioning

confidence: 78%

Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

King

Devaney

Cooper³

et al. 1990

J Psychopharmacol

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Single dose pharmacokinetics and the antipsychotic effect of 4 weeks treatment with three fixed dose levels of remoxipride (a selective D(2) receptor antagonist) were studied in chronic, stable schizophrenic inpatients. After a placebo washout of 1 month, 15 patients entered the study. Of these, 11 patients received a single 50 mg oral dose of remoxipride for pharmacokinetic evaluations. All 15 patients were randomly assigned to treatment with oral remoxipride either 25 mg t.i.d., 50 mg t.i.d. or 100 mg t.i.d. for 4 weeks. Blood samples for remoxipride and prolactin assays were taken at 0, 0.33, 0.5, 0.66, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 28, 32 and 48 h after drug intake. The pharmacokinetic characteristics were similar to those previously found in normal healthy volunteers: the mean peak plasma concentration of remoxipride after 50 mg was 3.3 μmol/l, the mean time to reach this was 2.1 h; the mean area under the plasma concentration/time curve was 27.8 μmol/1.h.1( -1) and the mean elimination half-life of remoxipride was 5.5 h. A significant increase in prolactin levels was detected 2 h after administration of remoxipride but they had reverted to normal 8 h after drug intake in all but one patient. Antipsychotic effects were estimated using the brief psychiatric rating scale (BPRS) and the Krawiecka rating scale (KRS) at admission, baseline (end of the 4 week placebo washout period) and after 7, 14 and 28 days treatment. Following an increase in mean psychosis ratings for both positive and negative symptoms during the placebo washout period, these decreased during active treatment and at the end of the study were similar to the scores on admission. Thus the possible efficacy of remoxipride in chronic patients with negative symptoms should be further explored in placebo controlled studies. Remoxipride was well tolerated. Sleep disorders occurred in three patients, extrapyramidal symptoms were not aggravated and no clinically significant effects were observed on the cardiovascular system, in clinical chemistry or haematology.

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Section: Discussionmentioning

confidence: 78%

Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

King

Devaney

Cooper³

et al. 1990

J Psychopharmacol

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“…Severe symptoms required a higher serum concentration. This would indicate that more severe conditions may, not unexpectedly, require more intensive treatment than less severe conditions (see also Bjorndal and Aaes-Jorgensen 1984;Browne et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Perphenazine decanoate andcis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients

et al. 1991

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Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long-term maintenance treatment of schizophrenia.

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Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia

et al. 2016

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In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION At least 2 independent reviewers selected published and unpublished single-and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (−0.29; −0.56 to −0.02), haloperidol (−0. 29; −0.44 to −0.13), and sertindole (−0.46; −0.80 to −0.06); clozapine was more effective than haloperidol (−0.22; −0.38 to −0.07) and sertindole (−0.40; −0.74 to −0.04); and risperidone was more effective than sertindole (−0.32; −0.63 to −0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evid...

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Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients

Cited by 9 publications

References 34 publications

Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

Perphenazine decanoate andcis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia

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