The effect of subchondral oedema in T2-weighted Dixon MRI sequence evaluation of sacroiliac joint erosion in axial spondyloarthropathy.

AIM: To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy. MATERIALS AND METHODS: Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient. RESULTS: The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k = 0.747 and 0.712), and moderate for opposed-phase images (k = 0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively. CONCLUSION: The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.

Generic and trade-name antipsychotic drugs: clinical equivalence.

The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant.

A comparison of patients who refuse and consent to neuroleptic treatment.

A recently enacted regulation in California requires that voluntary mental patients give signed informed consent for treatment with antipsychotic drugs. To evaluate the law's effects on schizophrenic patients, the authors compared 15 patients who refused to give consent with a matched group of 15 who gave consent. Refusers had significantly higher scores on the Brief Psychiatric Rating Scale for conceptual disorganization, emotional withdrawal, and unusual thought content. They were also more hostile, uncooperative, and mistrustful of the treatment team and more likely to believe they were not ill. The authors raise questions regarding the most appropriate consent process for schizophrenic patients.

Coma following ECT and intravenous droperidol: case report.

A 60-year-old man with psychotic depression became comatose following the administration of intravenous droperidol given for post-ECT delirious agitation. The differential diagnosis, which included neuroleptic malignant syndrome and the possibility that droperidol may have uniquely detrimental effects in the context of post-ECT delirium, are discussed. In light of recent publications advocating droperidol as the pharmacologic treatment of choice for severe agitation, this case illustrates a need for greater caution in its use for the treatment of post-ECT delirium.

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients.

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.

Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal.

Haloperidol and reduced haloperidol plasma concentrations were measured in twelve schizophrenic patients upon cessation of haloperidol decanoate (HLD) treatment. Each patient received HLD 100 mg every 4 weeks for five injections. After the fifth injection, HLD was discontinued. Haloperidol and reduced haloperidol plasma concentrations were obtained prior to cessation and at weeks 1, 3, 4, 5, 7, 9, 11, and 13 post-injection. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC. Both haloperidol and reduced haloperidol plasma concentrations were detectable 13 weeks post HLD discontinuation. Maximal haloperidol plasma concentrations were observed at one week post cessation and gradually declined. The mean elimination half-life for haloperidol was 27.4 +/- 8.6 days (range 19.0-47.0 days). Reduced haloperidol plasma concentrations declined very slowly. Our results show that both haloperidol and reduced haloperidol plasma concentrations can remain for extended time periods after HLD is discontinued.

Lack of pharmacokinetic interaction between buspirone and haloperidol in patients with schizophrenia.

The pharmacokinetic interaction between buspirone and haloperidol was evaluated in schizophrenic patients in two different groups. In both groups, haloperidol doses (10-40 mg/day) remained constant for 6 weeks before the addition of buspirone 10 mg three times daily. Serial blood samples were obtained from the 11 patients in group I at baseline (before addition of buspirone) and after administration for 24 hours. The pharmacokinetic parameters of haloperidol were determined alone and with coadministration of buspirone. In group II, buspirone 10 mg three times daily was added to treatment with haloperidol in 27 patients. Blood samples were obtained before addition of buspirone and at weeks 2 and 6 of treatment with buspirone. Samples were obtained 10 to 12 hours after administration of the evening dose and before the morning dose. Haloperidol and its metabolite, reduced haloperidol (RH), were assayed by means of high-performance liquid chromatography with electrochemical detection. Significant changes in the pharmacokinetic parameters of haloperidol were not found in group I; a mean increase in the half-life (t1/2) of haloperidol from 21.5 to 28.1 hours was observed, but this finding was not statistically significant. Under steady-state conditions, plasma levels of haloperidol in the patients in group II did not change significantly from baseline to week 6. Plasma concentrations of RH remained unaltered in both groups. The results indicate that coadministration of buspirone does not markedly affect the pharmacokinetics or plasma concentrations of haloperidol.

Comparison of haloperidol and reduced haloperidol plasma levels in four different ethnic populations.

1. Plasma haloperidol and reduced haloperidol concentration were measured in four ethnic populations. 2. Plasma samples were obtained under steady-state conditions and obtained 10-12 hours post bedtime dose and prior to the morning dose. 3. Haloperidol and reduced haloperidol plasma levels were assayed by radioimmunoassay and liquid chromatography. 4. A wide interpatient variability between haloperidol dose and plasma concentration was observed for each ethnic group. 5. The Chinese group differed from the other ethnic populations. 6. A nonlinear relationship was observed between haloperidol and reduced haloperidol plasma levels in each ethnic group. Further, the relationship of haloperidol to reduced haloperidol plasma levels differed for each ethnic group. These results suggest that various ethnic groups could metabolize haloperidol and reduced haloperidol differently.

Reduced haloperidol/haloperidol ratios after oral haloperidol and decanoate administration in schizophrenics.

1. Haloperidol and reduced haloperidol plasma concentrations were measured in thirteen stable schizophrenic patients that received both oral haloperidol and haloperidol decanoate. 2. Significant correlations between reduced haloperidol/haloperidol ratios from oral haloperidol and haloperidol decanoate occurred at week two and week 16, respectively. 3. The formation of RH was consistent during haloperidol decanoate treatment.

Plasma reduced haloperidol/haloperidol ratios in schizophrenic patients treated with high dosages of haloperidol.

Plasma haloperidol (HL) and reduced haloperidol (RH) levels were measured in 60 schizophrenic patients treated with high to very high HL doses of 40-200 mg/day. Plasma samples were obtained at steady-state conditions and 10-12 h after the evening dose and prior to the morning dose. RH/HL ratios were shown to be dose-dependent. In the lowest dose group of 40-45 mg/day, 77% of the patients had RH/HL ratios < 1.0. At the higher dose of 60-80 mg/day, these results were reversed as 79% of the patients had RH/HL ratios > 1.0. All patients with HL doses greater than 100 mg/day had RH/HL ratios > 1.0. All patients safely tolerated the high haloperidol dosages and only five patients had extrapyramidal side effects that were unresponsive to trihexyphenidyl. Therapeutic improvement was not observed in each patient. Based upon the dose-dependent increase in the RH/HL ratios in schizophrenic patients, the possible mechanism of a 'therapeutic' window for HL is discussed.

Ketone reductase activity and reduced haloperidol/haloperidol ratios in haloperidol-treated schizophrenic patients.

Twenty schizophrenic patients were treated with a fixed haloperidol (HL) dose of 20 mg/day for 4 weeks. The conversion of HL to its reduced metabolite (reduced haloperidol, RH) occurs via the ketone reductase enzyme. RH is also converted back to HL by the cytochrome P450 2D6 isozyme. Ketone reductase activity can be measured in red blood cells. Plasma HL and RH levels were assayed by high performance liquid chromatography. Blood samples were obtained at baseline and during weeks 2 and 4 of HL therapy. Seventeen of 20 patients had ketone reductase values < 3. A significant correlation between ketone reductase and RH/HL plasma ratios was observed at week 4 in these 17 patients. Patients with ketone reductase activity < 3 could represent a subgroup of patients that metabolize HL differently. The wide interpatient variability observed with HL and RH plasma levels in HL-treated patients could reflect differences in ketone reductase activity and the metabolic status of debrisoquin hydroxylase (cytochrome P450IID6) in psychiatric patients.

Disposition of remoxipride in Chinese schizophrenic patients.

The disposition of remoxipride was evaluated in 13 male chronic schizophrenic patients. A single 150 mg dose of remoxipride was administered and blood sampling performed over the following 48 hours. The mean (SD) oral clearance and half-life of remoxipride were 74.46 (25.9) ml/min and 5.46 (0.87) hours, respectively. The mean (SD) AUC for remoxipride was 25,320 (9,820) ng.h/ml. A wide interpatient variability was observed. Compared to Caucasian studies there were no significant differences in the disposition of remoxipride.