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Postoperative delirium: treatment with supplementary oxygen.

We have assessed postoperative delirium in 24 patients undergoing thoracotomy for pulmonary malignancy throughout their stay in hospital. Arterial oxygen saturation was measured with a pulse oximeter on the night before operation and on the second night after operation. Five patients (21%) developed clinically significant postoperative delirium, and delirium occurred in all patients who had inadequate oxygenation. All cases of delirium occurred on day 3 after surgery. Factors which were not associated with delirium were age, intake of alcohol or consumption of drugs before operation, fever, type of operation, duration of surgery, anxiety and psychosocial stress before operation, postoperative metabolic derangement or hypotension during operation. Mean arterial oxygen saturation on the second night after operation (the night preceding delirium) was smaller in patients with delirium than in other patients (median 88% vs 95%, P < 0.05). When patients were delirious, the first treatment of choice was supplementary oxygen and all patients were treated successfully by this simple regimen. In two patients, supplementary treatment with zuclopenthixol 6 mg daily was necessary. We conclude that hypoxaemia may be a contributing factor in postoperative brain dysfunction, as postoperative delirium was associated with hypoxaemia and was treated successfully with supplementary oxygen.

Adult↗

Recurrent priapism as a side effect of zuclopenthixol decanoate.

Priapism has been described as a rare side effect of certain phenothiazine antipsychotics with high alpha1-adrenergic blocking potential. We describe a patient who in the course of clinical treatment with the thioxanthene antipsychotic zuclopenthixol (Clopixol) decanoate had several episodes of priapism. Although the alpha-blocking potential of zuclopenthixol is only moderate, it seems that in sufficient dose, or in combination with other antipsychotics, this drug is capable of inducing priapism.

Adult↗

Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans.

Repeated positron emission tomography (PET) measurements of D2 receptor occupancy, plasma concentrations of zuclopenthixol and reaction time were performed in three healthy subjects after injection of 12.5 mg zuclopenthixol acetate (ZPTA) in an open study design. Five control subjects were examined for reaction time only. D2 receptor occupancy was 51%, 71% and 75% after 7 h and 75%, 83% and 87% after 31 h in the three subjects. The subjects reported sedation, but reaction time was not prolonged. After the low dose of 12.5 mg ZPTA, D2 receptor occupancy exceeded the 70% assumed to be required to induce antipsychotic effect. Extrapolation of data to a clinical dose interval indicates that 50-150 mg ZPTA should induce very high D2 receptor occupancy lasting several days after injection. Such high doses may be required to induce sedation and to avoid frequent intramuscular injections in acutely psychotic patients. However, the simultaneously induced very high D2 receptor occupancy calls for careful assessment of acute extrapyramidal symptoms.

Adult↗

Olanzapine treatment in patients with typical and atypical neuroleptic-associated agranulocytosis.

Two cases are reported of patients who developed agranulocytosis after treatment with typical and atypical antipsychotics. The patients were successfully treated with olanzapine. We suggest the consideration of olanzapine as a safer treatment in patients who require immediate continuation of antipsychotic medication and have a prior history of classic and atypical neuroleptic-induced agranulocytosis.

Adult↗

Treatment with the new antipsychotic sertindole for late-occurring undesirable movement effects.

Conventional antipsychotics are often associated with late-occurring undesirable movement effects. To gain more experience with newer antipsychotic agents, 151 patients in an acute admissions department were switched from treatment with conventional antipsychotics to sertindole between late 1996 and early 1998. Four of these patients had tardive dyskinesia, tardive dystonia and/or tardive akathisia. The effect of changing to sertindole was measured using specific rating scales for undesirable movement effects. Three of the four patients apparently recovered from the movement disorders after switching to sertindole. In one patient, sertindole monotherapy was not sufficient to reduce the movement effects, but combination treatment with tetrabenazine resulted in a greater reduction in extrapyrimidal symptoms. Because these are case reports, no direct conclusions can be drawn. However, the beneficial effect of sertindole on severe, late-occurring movement disorders, as observed in four difficult-to-treat patients, appears to be promising.

Adult↗

Differential early onset of therapeutic response with risperidone vs conventional antipsychotics in patients with chronic schizophrenia.

The present post-hoc analysis investigated the speed of onset of therapeutic effect of the atypical antipsychotic, risperidone, in direct comparison with conventional antipsychotics. Data were pooled from four double-blind active comparator-controlled clinical trials involving 757 patients with schizophrenia treated for up to 8 weeks with either risperidone (4-6 mg/day) or a conventional antipsychotic such as haloperidol (10 or 20 mg/day), perphenazine (mean dose 28 mg/day), or zuclopenthixol (mean dose 38 mg/day). Primary outcome was assessed using the Positive and Negative Syndrome Scale. A significantly greater proportion of patients treated with risperidone achieved > or =20% reduction from baseline Positive and Negative Syndrome Scale total score at weeks 1, 2, 6, and at end point (last observation carried forward: P< or =0.04). A significant difference exists in mean reduction from baseline to end point in Positive and Negative Syndrome Scale total scores in favor of patients treated with risperidone compared with those treated with conventional antipsychotics (-18.4 vs -13.5; P=0.0013). The mean time to response was 23.8 days with risperidone and 28.2 days with conventional drugs (hazard ratio 1.3; 95% confidence interval 1.1-1.5). These findings are clinically relevant because the faster onset of therapeutic effect with atypical antipsychotics can be important in the acute setting and have a considerable impact on healthcare systems.

Antipsychotic Agents↗

Fluctuation of serum zuclopenthixol concentrations in patients treated with zuclopenthixol decanoate in viscoleo.

Zuclopenthixol serum concentrations were measured in 58 psychiatric patients referred for routine therapeutic drug monitoring (TDM). Patients were treated for prolonged time with zuclopenthixol decanoate in viscoleo in doses of 50-500 mg, administered intramuscularly at 14-day intervals. The serum concentration was determined at days 7 (C7) and 14 (C14) following injection. The mean ratio C7/C14 was 2.0 and was independent of the dosage given. In 14 patients, additional blood samples were drawn at day 3 (C3) following injection. The mean ratio C3/C14 of this group was 3.2. An almost log-linear decline of the serum concentration from day 3 to 14 appeared, which corresponds to an apparent half-life of zuclopenthixol in this dosage form of 7.4 days. The marked fluctuations of serum concentrations of zuclopenthixol from peak to trough levels in patients given fortnightly injections of the depot preparation indicate that shorter intervals between injections should be considered in many cases in order to diminish side effects.

Clopenthixol↗

Search for a therapeutic range for serum zuclopenthixol concentrations in schizophrenic patients.

The aim of our study was to find a therapeutic range for the serum concentration of zuclopenthixol (S-Zu) in chronic schizophrenic patients. S-Zu was measured in 17 patients and dosage reduction was suggested by the laboratory if S-Zu exceeded 15 nmol/L. The clinical symptoms and side effects were evaluated blindly using the Brief Psychiatric Rating Scale (BPRS) and the UKU rating scale, respectively. S-Zu and ratings were repeated 6, 12, and 24 weeks after the final dosage adjustments. In 7 of 10 patients with S-Zu > 15 nmol/L the dosage was reduced by 20-67%. After dosage reduction the S-Zu was below 15 nmol/L in 10 of the 17 patients. The mean BPRS score and the side effects, evaluated by the UKU scale, were reduced in patients in whom the dosage was reduced. It is suggested that S-Zu in the range 5-15 nmol/L may serve as a preliminary therapeutic range for S-Zu.

Adult↗

Influence of Cyp2D6 genetic polymorphism on ratios of steady-state serum concentration to dose of the neuroleptic zuclopenthixol.

One hundred and nineteen psychiatric patients undergoing therapeutic drug monitoring (TDM) of the neuroleptic zuclopenthixol were genotyped with regard to Cyp2D6. Twelve patients (10.1%) were of the poor metabolizer genotype. The extensive metabolizers comprised 58 patients receiving no potentially interacting drugs and 38 patients concomitantly treated with other drugs competing for metabolism by Cyp2D6. Information on the rest (11 patients) was missing. The median steady-state serum concentration-to-dose ratio (C/D) of the PM group (2.00 nmol/L/mg) was close to that of the EM group receiving potentially interacting drugs (1.80) and approximately 60% higher than that of the remaining EM group (1.25) (p < 0.01). When judging the clinical importance of this difference, the total group variability in C/D of nearly 10-fold should be kept in mind (0.5-4.2 nmol/L/mg). In terms of serum concentrations not corrected for dose, the three groups had about similar levels, with median values from 16 to 21 nmol/L. We consider that TDM adequately takes into account dose adjustments for both EM and PM subjects in the context of this neuroleptic.

Adolescent↗

Therapeutic drug monitoring of haloperidol, perphenazine, and zuclopenthixol in serum by a fully automated sequential solid phase extraction followed by high-performance liquid chromatography.

In Denmark, haloperidol, perphenazine, and zuclopenthixol are among the most frequently requested antipsychotics for therapeutic drug monitoring. With the number of requests made at the authors' laboratory, the only rational analysis is one that can measure all three drugs simultaneously. The authors therefore decided to develop an automated high-performance liquid chromatography (HPLC) method. Two milliliters serum, 2.0 mL 10 mmol/L sodium phosphate buffer (pH 5.5), and 150 microL internal standard (trifluoperazine) solution were pipetted into HPLC vials and extracted on an ASPEC XL equipped with 1 mL (50 mg) Isolute C2 (EC) extraction columns and acetonitrile-methanol-ammonium acetate buffer (60:34:6) as extracting solution. Three hundred fifty microliters was analyzed by HPLC; a 150 x 4.6-mm S5CN Spherisorb column with a mobile phase of 10 mmol/L ammonium acetate buffer-methanol (1:9), a flow rate of 0.6-1.7 mL/min, and ultraviolet detection at 256 and 245 nm were used. Reproducibility was 5-12% and the lower limit of quantitation was 10, 1, and 5 nmol/L (4, 0.4, and 2 ng/mL) for haloperidol, perphenazine, and zuclopenthixol, respectively. The method was found to be sufficiently selective and robust for routine analysis.

Antipsychotic Agents↗

Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics.

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.

Adult↗

A double-blind comparison of zuclopenthixol tablets with placebo in the treatment of mentally handicapped in-patients with associated behavioural disorders.

Fifty-two mentally-handicapped in-patients with associated behavioural disorders were entered into this double-blind trial comparing zuclopenthixol dihydrochloride tablets (10 mg) with placebo. The study consisted of a 6-week open phase, in which all patients were treated with zuclopenthixol tablets, followed by a 12-week double-blind phase where approximately half of the patients were transferred to placebo tablets. Demographic data was obtained from the patients at entry to the study. Clinical assessments were performed at weeks 6, 7, 8, 10, 14 and 18 using the Clinical Global Assessment (CGA), a Behavioural Disorder Assessment prepared specially for this study, and a side-effect check list. Analyses of the rating scales showed significant differences in favour of zuclopenthixol at end-point on the item 'improvement in behaviour disorder' from the CGA and at week 14 and end-point on the Assessment of Behavioural Disorder. All other results demonstrated a favourable trend towards the zuclopenthixol treatment. Side-effects were reported slightly more frequently in the zuclopenthixol group, but generally, they were not a problem.

Adult↗

Schizophrenic relapse after drug withdrawal is predictable.

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.

Adult↗

Zuclopenthixol acetate in Viscoleo--a new drug formulation. An open Nordic multicentre study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses including mania and exacerbation of chronic psychoses.

Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients.

Acute Disease↗