flupenthixol-decanoate and Schizophrenia

The licensed dose range for the long-acting injectable antipsychotic flupentixol decanoate (Depixol®) in the treatment of schizophrenia is very broad. This provides little useful direction to prescribers and may ultimately result in patients receiving unnecessarily high doses.. We aimed to estimate the effect of dose of flupentixol decanoate on relapse rates in schizophrenia and on tolerability by expanding on an earlier review and including non-RCT and German-language studies, as well as using pharmacokinetic and pharmacodynamic data to offer guidance on dosing.. A literature review using EMBASE, Medline, PsycINFO and PubMed was conducted. Treatment success rates at 6 months were extracted or extrapolated from the studies and plotted against dose to estimate a dose-response curve.. Data from 16 studies (n = 514) allowed estimation of a dose-response curve which rises steeply between the chosen placebo anchor (25% success rate) and 10 mg every 2 weeks before reaching a maximum between 20 and 40 mg every 2 weeks (80-95% success rates). Extrapyramidal side effects (EPSEs) were frequently seen (12-71% of participants) in that dose range. Two -weekly injections seem to provide the highest trough plasma concentration per dose administered and the lowest peak-to-trough concentration ratio. Plasma concentration varied up to 5-fold among individuals receiving the same dose.. The optimal dose of flupentixol decanoate is likely to be between 20 mg and 40 mg every 2 weeks although higher doses may be required in some individuals owing to variation in drug handling. Doses of flupentixol should be individually established in the range of 10 to 40 mg every 2 weeks according to response and tolerability.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Dopamine Antagonists; Dose-Response Relationship, Drug; Female; Flupenthixol; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia.. To evaluate the effects of flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes.. We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.. All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought.. Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies.. The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence).. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Flupenthixol; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Tranquilizing Agents

Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment.. To evaluate the effects flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes.. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). The references of all identified trials were inspected for more studies and the first author of each included trial and relevant pharmaceutical companies were contacted.. All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared to placebo or other antipsychotic drugs. All clinically relevant outcomes were sought.. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality.. No trials compared flupenthixol decanoate to placebo. One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). There were no clear differences between the two preparations. When flupenthixol decanoate was compared to other depot preparations, there were no differences between depots for outcomes such as death, global impression, relapse (OR 1.16 CI 0.7-1.9) or leaving the study early (OR 1.00 CI 0.6-1.7). Two small studies suggest that flupenthixol decanoate is responsible for less movement disorders than other depot antipsychotic drugs (OR 0.23 CI 0.08-0.7, NNT 5). This finding did not hold for specific side effects, such as tremor (OR 1.2 CI 0.3-4) and tardive dyskinesia (OR 1.60 CI 0.4-6). Two trials comparing high doses of flupenthixol decanoate to the standard approximately 40mg per injection reported no significant difference for the outcome of relapse (OR 0.32 CI 0.09-1.2). One small (n=59) trial comparing a very low dose of flupenthixol decanoate ( approximately 6 mg/IM) to a very low dose approximately 9 mg per injection also reported no difference in relapse rates (OR 0.3 CI 0.1-1.1).. From the data reported in clinical trials, it would be understandable if those suffering from schizophrenia, who are willing to take flupenthixol decanoate, would request the standard dose rather than the high dose. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. The choice of which depot to use must therefore be based on clinical judgement and the preferences of people with schizophrenia and their carers. Managers and policy makers should expect better data than the research community has provided thus far. This review highlighted the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate, in particular when compared to oral antipsychotics. Future studies should also consider hospital and service outcomes, satisfaction with care and record economic data.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Flupenthixol; Humans; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

To assess the feasibility and effectiveness of depot antipsychotic (flupenthixol decanoate) combined with an assertive monitoring programme (AMP) in first-episode schizophrenia.. This was a prospective, non-comparative, longitudinal study conducted over 12 months assessing patient acceptance, adherence, outcome in domains of psychopathology, functionality and quality of life, and tolerability.. Of 207 participants, 149 (72%) completed 12 months of treatment. Acceptance of and adherence to depot was good. Treatment response was achieved by 170 (82%) participants and remission by 124 (60%). Thirty-three (19%) responders relapsed and 10 (5%) participants met a priori criteria for treatment resistance. Treatment was generally well tolerated.. Combination of depot antipsychotic with an AMP may be an effective and safe intervention in early phases of schizophrenia, and may be particularly suitable for resource-constrained settings.

Topics: Adult; Antipsychotic Agents; Community Mental Health Services; Delayed-Action Preparations; Developing Countries; Female; Flupenthixol; Humans; Male; Medication Adherence; Patient Acceptance of Health Care; Quality of Life; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication.

Topics: Adolescent; Adult; Antipsychotic Agents; Body Mass Index; Brain; Delayed-Action Preparations; Double-Blind Method; Eating; Female; Flupenthixol; Humans; Image Interpretation, Computer-Assisted; Injections, Intramuscular; Magnetic Resonance Imaging; Male; Middle Aged; Risperidone; Schizophrenia; South Africa; Young Adult

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.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Flupenthixol; Fluphenazine; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Movement Disorders; Psychiatric Status Rating Scales; Risperidone; Schizophrenia

Substance use, especially alcoholism, has been recognized as a significant problem in schizophrenic patients, though only a few studies on the effects of pharmacotherapy in these patients have been conducted so far. The thioxanthene neuroleptic flupenthixol, which can be given intramuscularly (i.m.) for improving compliance, has been studied as a possible anti-craving drug both in animal models of alcoholism and some clinical studies. Pilot studies suggest that comorbid schizophrenics with substance use may benefit from treatment with flupenthixol. Efficacy of flupenthixol (10-60 mg i.m.) in reducing alcohol consumption of dual diagnosis patients was studied in an open 6-month clinical trial in 27 schizophrenics with comorbid alcoholism. Twenty-one patients entered the intention-to-treat analysis. Fourteen subjects were completers, 13 dropped out. Six patients completely abstained from alcohol during treatment. Alcohol consumption was significantly reduced compared to baseline (4 weeks before treatment as measured by timeline follow-back interview). In general, while patients showed a marked improvement concerning alcohol consumption, only a slight improvement in psychopathology was recorded. Overall tolerability was good. These data indicate a probable beneficial effect of flupenthixol in schizophrenic patients with comorbid alcoholism. Although the efficacy of flupenthixol as an anti-craving drug in dual diagnosis patients has to be explored in further studies, the drug may be considered a promising medication for these patients.

Topics: Adult; Alcoholism; Antipsychotic Agents; Combined Modality Therapy; Comorbidity; Diagnosis, Dual (Psychiatry); Female; Flupenthixol; Germany; Humans; Injections, Intramuscular; Male; Middle Aged; Patient Dropouts; Schizophrenia; Schizophrenic Psychology; Switzerland; Treatment Outcome

The paper reports on the recruitment of a multicenter study on ambulant prophylactic treatment of schizophrenic disorders.. For a study of the relapse-preventative effect of different dose patterns of Flupentixol, a screening phase was carried out among of 1129 schizophrenic patients. The aim of the screening phase was to establish the criteria for exclusion or inclusion in the treatment phase of the study.. Only 62 patients could be included. The reason for 54 patients not being included was a lack of compliance from either the patient or the clinician. The meaning of patient- and therapist-compliance in carrying out a multicenter study is also discussed.

Topics: Double-Blind Method; Flupenthixol; Humans; Patient Selection; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology; Tranquilizing Agents; Treatment Outcome; Treatment Refusal

Forty-four schizophrenic patients were followed up for five years after their first admission to hospital for a first episode of illness. Thirteen (30%) of 43 patients had not relapsed; 28 of the 30 patients who did relapse did so within the first 42 months. The relapses occurred despite antipsychotic drug therapy. Also, 24% of patients had at least one course of ECT. Only 19% of the patients at five years were in open employment; unemployment was strongly associated with relapse. Eighteen per cent had neither relapses nor schizophrenic symptoms at follow-up. Poor outcome at five years was associated with greater psychological distress among relatives at first admission. At five years 43% of relatives continued to show case level psychological stress.

Topics: Activities of Daily Living; Administration, Oral; Adult; Caregivers; Combined Modality Therapy; Double-Blind Method; Female; Flupenthixol; Follow-Up Studies; Hospitalization; Humans; Male; Marital Status; Pimozide; Psychiatric Status Rating Scales; Psychometrics; Rehabilitation, Vocational; Schizophrenia; Schizophrenic Psychology; Scotland; Social Adjustment

An open clinical trial was carried out in 21 chronic schizophrenics to assess the effectiveness and side-effects of treatment with depot neuroleptics. All patients had been stabilized on fluphenazine decanoate for at least 6 months and on entry to the study were given the choice of continuing with this treatment or changing over to flupenthixol decanoate. Sixteen patients chose to receive flupenthixol decanoate (40 mg) and the other 5 fluphenazine decanoate (25 mg). Doses were given every 4 weeks during the 12-week study period. Clinical assessments were carried out every 4 weeks (Weeks 0, 4, 8 and 12) using the Brief Psychiatric Rating Scale and a side-effects checklist, and the Hamilton Rating Scale for Depression, the Schedule for Affected Disorders and Schizophrenia--Change Version, and the Global Assessment Scale were completed on entry (Week 0) and at the end of the study (Week 12). The results indicated that symptoms of depression, withdrawal, worrying, and psychomotor retardation were improved significantly (p less than 0.05) more with flupenthixol than with fluphenazine. The frequency of side-effects decreased during treatment with flupenthixol and there was a tendency towards fewer side-effects in the flupenthixol group than in the fluphenazine group after 8 weeks of treatment. It is concluded that a group of schizophrenic patients characterized by depressive symptoms or side-effects attributable to a prescribed neuroleptic might benefit from a switch to flupenthixol treatment.

Topics: Clinical Trials as Topic; Female; Flupenthixol; Fluphenazine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Thioxanthenes; Tranquilizing Agents

Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms.

Topics: Clinical Trials as Topic; Double-Blind Method; Family; Flupenthixol; Follow-Up Studies; Humans; Pimozide; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology; Scotland; Social Adjustment; Thioxanthenes

Eighteen chronic schizophrenic patients who had shown improvement from increased maintenance dosages of cis(z)-flupenthixol decanoate were entered into a double-blind study in which half of the patients were randomly allocated to be maintained on 50% of their pre-trial dosage. During the 44 week study the reduced dosage group showed increased morbidity and one-third of these patients had a schizophrenic relapse. The greatest deterioration occurred in patients reduced from above to below 200 mg cis(z)-flupenthixol decanoate biweekly. A review of all the patients entered into the study showed a relationship between deterioration of schizophrenic and depressive features and cis(z)-flupenthixol plasma levels which reflected the administered dosage. Prolactin levels in general did not reflect control of schizophrenic symptoms. Side-effects were few, and there was no emergence of tardive dyskinesia. A multicentre trial is needed for further evaluation.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Flupenthixol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Thioxanthenes

A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested.

Topics: Adult; Aged; Ambulatory Care; Dose-Response Relationship, Drug; Double-Blind Method; Female; Flupenthixol; Humans; Male; Middle Aged; Random Allocation; Schizophrenia; Thioxanthenes; Tranquilizing Agents

Thirty-nine chronic schizophrenic patients were selected for a 12-month double-blind evaluation of the effectiveness of pipothiazine palmitate (PPT) and flupenthixol decanoate (FPX) in the maintenance management of their illness. Allocation was at random and, in order to allow constant injection intervals, the patients typically received every 2 weeks either 40 mg of flupenthixol decanoate or alternating injections of 100 mg of pipothiazine palmitate and placebo. At monthly intervals the patients were assessed using both a battery of rating scales (which included the Brief Psychiatric Rating Scale (BPRS), the Extrapyramidal Symptoms Rating Scale (EPS] and a general side-effects evaluation. At 3-monthly intervals they were also rated on the Comprehensive Psychiatric Rating Scale (CPRS) and the Zung Depression Scale. Haematological and biochemical tests were performed every 3 months. Both drugs provided good control of psychotic symptoms and side-effects were not troublesome. No substantial difference was detected on the CPRS and the Zung scales. There was a trend in favour of PPT on the BPRS survey, detectable at 6 months and reaching statistical significance by 12 months. We conclude that the PPT regime is at least as effective as the FPX treatment and probably more so. It is possible that even longer periods of control could be obtained with PPT.

Topics: Adult; Antipsychotic Agents; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Female; Flupenthixol; Humans; Male; Middle Aged; Phenothiazines; Psychiatric Status Rating Scales; Random Allocation; Schizophrenia; Thiazines; Thioxanthenes; Time Factors; Tranquilizing Agents

Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.

Topics: Adult; Double-Blind Method; Female; Flupenthixol; Haloperidol; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Topics: Adolescent; Adult; Aged; Chronic Disease; Clinical Trials as Topic; Delayed-Action Preparations; Female; Flupenthixol; Humans; Length of Stay; Male; Middle Aged; Schizophrenia; Thioxanthenes; Tranquilizing Agents

Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Depression; Double-Blind Method; Flupenthixol; Fluphenazine; Humans; Middle Aged; Random Allocation; Recurrence; Schizophrenia; Thioxanthenes; Time Factors

A double-blind randomized investigation compared withdrawal (placebo) with continued use of long-acting neuroleptics (fluphenazine decanoate or flupenthixol decanoate) in 41 chronic schizophrenic outpatients. After 6 weeks there was a tendency toward higher depressive scores in the placebo group, a difference which became statistically significant (p less than .05) at week 24. These results do not support earlier observations that neuroleptic drugs cause depression. Further analyses of the data indicated that depressive symptomatology could be an early sign of relapse.

Topics: Adult; Depressive Disorder; Double-Blind Method; Female; Flupenthixol; Fluphenazine; Humans; Male; Psychiatric Status Rating Scales; Random Allocation; Recurrence; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Thioxanthenes; Tranquilizing Agents

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12 months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91 ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12 months more women than men had hyperprolactinemia (defined as more than 20 ng/ml for males, and as more than 25 ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12 months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.

Topics: Adolescent; Adult; Age Factors; Female; Flupenthixol; Humans; Hyperprolactinemia; Male; Propafenone; Schizophrenia; Sex Factors; Tranquilizing Agents; Treatment Outcome; Young Adult

While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised.. We assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic.. This single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models.. There was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight.. Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

Topics: Adolescent; Adult; Antipsychotic Agents; Cognition; Female; Flupenthixol; Health Personnel; Humans; Longitudinal Studies; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Young Adult

Treatment-emergent weight gain is associated with antipsychotic efficacy in schizophrenia patients treated with clozapine and olanzapine. However, few studies have investigated this relationship in first-episode patients treated with other antipsychotics, in particular those with a lower obesogenic potential. Aim To investigate the relationships between weight gain and associated metabolic changes with psychopathology improvement in relation to age, sex, ethnicity, substance use, treatment duration and antipsychotic dose in first-episode schizophrenia spectrum disorder patients.. This single site cohort study included 106 minimally treated or antipsychotic-naive patients treated with flupenthixol decanoate over 12 months. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) and BMI, fasting blood lipids and glucose were assessed at regular intervals. Linear regression models were constructed to determine the effects of socio-demographic, clinical and metabolic factors as predictors of change in total PANSS score and factor-derived domains.. BMI change scores were inversely correlated with change in PANSS total (R = -0.25; p = 0.011), positive (R = -0.23; p = 0.019), depressive anxiety (R = -0.21; p = 0.031) and disorganized symptoms (R = -0.32; p < 0.001). Linear regression analysis showed that increased BMI and treatment duration both predicted improvement in global psychopathology and disorganized symptoms independent of age, sex, ethnicity, substance use, co-medication with antidepressants and/or anticholinergics, as well as the dose and duration of antipsychotic exposure.. Our findings suggest that the relationship between treatment-emergent weight gain and psychopathology improvement is not limited to patients treated with antipsychotics most associated with weight gain, and is not confounded by treatment duration and dose.

Topics: Adult; Body Mass Index; Dopamine Antagonists; Female; Flupenthixol; Humans; Longitudinal Studies; Male; Outcome Assessment, Health Care; Schizophrenia; Severity of Illness Index; Weight Gain; Young Adult

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies.

Topics: Adolescent; Adult; Adult Survivors of Child Adverse Events; Antipsychotic Agents; Female; Flupenthixol; Gene-Environment Interaction; Haplotypes; Humans; Male; Matrix Metalloproteinase 9; Polymorphism, Genetic; Schizophrenia; Treatment Outcome; Young Adult

Topics: Adult; Amantadine; Antipsychotic Agents; Bupropion; Catatonia; Female; Flupenthixol; Humans; Psychomotor Performance; Schizophrenia; Schizophrenic Psychology; Stereotyped Behavior; Transcranial Direct Current Stimulation

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.. We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).. Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.. Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

Topics: Adult; Antipsychotic Agents; Cerebral Cortex; Delayed-Action Preparations; Female; Flupenthixol; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Psychotic Disorders; Schizophrenia; Treatment Outcome; White Matter; Young Adult

Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response.. Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103).. Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10. This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.

Topics: Adolescent; Adult; Antipsychotic Agents; Chromosome Mapping; Cohort Studies; Female; Flupenthixol; Genetic Variation; Genome-Wide Association Study; Humans; Male; Polymorphism, Single Nucleotide; Schizophrenia; South Africa; Treatment Outcome; Young Adult

Neurological soft signs (NSS) are proposed to represent both state- and trait-related features of schizophrenia.. We assessed the course of NSS with the Neurological Evaluation Scale (NES) over 12months of standardised treatment in 126 patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder, and evaluated their state- and trait-related associations with psychopathology, functionality, cognition and antipsychotic treatment. We considered change scores from baseline to be state-related and endpoint scores to be trait-related.. Significant effects for time were recorded for all NSS domains. For state-related change-scores greater improvements in sensory integration were predicted by more improvement in working memory (p=0.01); greater improvements in motor sequencing scores were predicted by more improvement in working memory (p=0.005) and functionality (p=0.005); and greater improvements in NES Total score were predicted by more improvement in disorganised symptoms (p=0.02). There were more substantial associations between trait-related endpoint scores than for state-related change scores. For endpoint scores lower composite cognitive score predicted poorer sensory integration (p=0.001); higher Parkinsonism score predicted poorer motor co-ordination (p=0.0001); lower composite cognitive score (p=0.001) and higher Parkinsonism score (p=0.005) predicted poorer motor sequencing; higher Parkinsonism score (p=0.0001) and disorganised symptoms (p=0.04), and lower composite cognitive score (p=0.0007) predicted higher NES total score.. NSS improved with treatment, but were weakly associated with improvements in psychopathology. Studies investigating NSS as trait-markers should ensure that patients have been optimally treated at the time of testing, and should take possible effects of extrapyramidal symptoms into account.

Topics: Antipsychotic Agents; Cognition; Female; Flupenthixol; Humans; Interview, Psychological; Linear Models; Longitudinal Studies; Male; Memory, Short-Term; Motor Activity; Neurologic Examination; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome; Young Adult

To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects.. We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months.. Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P<.0001), waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P=.008). The only significant predictor of BMI increase was non-substance abuse (P=.002).. The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.

Topics: Adult; Antipsychotic Agents; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol; Cohort Studies; Female; Flupenthixol; Humans; Male; Metabolic Syndrome; Metabolome; Schizophrenia; South Africa; Triglycerides; Weight Gain

The goals of this study were to (i) estimate the rate of non-response to first-line treatment in first-episode schizophrenia, (ii) evaluate other outcomes associated with symptom non-response and (iii) identify demographic, baseline clinical and early treatment response predictors of non-response.. This was a single-site, longitudinal cohort study assessing the effects of treatment with flupenthixol decanoate according to a standardised protocol over 12 months in patients with schizophrenia, schizophreniform and schizo-affective disorders.. Of 126 patients who received at least one dose of study medication, 84 (67%) completed the study. Fifteen (12%) met our predefined criteria for non-response. Non-responders were younger and at baseline had more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS) and lower body mass index. At endpoint, the non-responders were characterised by higher levels of symptomatology in all domains, poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and lower body mass index. The strongest predictors of non-response were more prominent baseline NSS and poor early (7 weeks) treatment response.. Results are consistent with a lower rate of refractoriness to treatment in first-episode schizophrenia compared with multi-episode samples.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Body Mass Index; Cohort Studies; Female; Flupenthixol; Humans; Longitudinal Studies; Male; Psychotic Disorders; Quality of Life; Schizophrenia; Treatment Outcome; Young Adult

We describe the profile of NSS across the one-year course of schizophrenia in 84 Nigerian first-episode patients. They were assessed at baseline and 3 monthly for 12 months using the Neurological Evaluation Scale and the Positive and Negative Syndrome Scale (PANSS), and treated with flupenthixol decanoate. The pattern of NSS total and sub-category scores obtained from repeated measurements were investigated for responders (≥ 50% reduction of baseline PANSS scores) and non-responders using the method of repeated measures analysis of variance. Trait-like features of NSS categories were quantified using intraclass correlation coefficients (ICCs). NSS were present in 96.4% of the patients at baseline (mean 21.5 ± 11.1). The motor-sequencing sub-category was found unrelated to changes in schizophrenia psychopathology with treatment (positive, r=0.19, p=0.136., negative, r=0.12, p=0.350; disorganization, r=0.16, p=0.245; overall, r=0.20, p=0.112). Regardless of decrements in psychopathology, motor-sequencing scores remained relatively unchanged across the course of the disease (main effects: 'responders' F=2.44, p=0.930, 'poor responders' F=0.27, p=0.764, entire sample F=1.87, p=0.160). ICC was "substantial" at 0.8 (95% C.I=0.6-0.9). Only the motor-sequencing NSS appear to be trait marker of schizophrenia in this sample. Other NSS seem to reflect symptomatic states of the disorder.

Topics: Adult; Antipsychotic Agents; Black People; Female; Flupenthixol; Humans; Male; Neurologic Examination; Psychiatric Status Rating Scales; Schizophrenia; Young Adult

We use longitudinal patient-level data from a German sickness fund with 7.26 million insured in a Markov-simulation model to assess the cost-effectiveness of long-acting injectable risperidone (LAI-RIS) compared with long-acting injectable flupentixol (LAI-FLX) in the long-term management of schizophrenia. We simulate treatment costs from the payer's perspective, hospitalization, the probability to be prescribed co-medication, and treatment discontinuation over a 2-year time horizon. Model inputs were derived from 935 patients hospitalized with schizophrenia between 2005 and 2008 who received either LAI-RIS or LAI-FLX for at least 1 month. After 2 years, 89.4% (95.8%) of patients who were initiated on LAI-RIS (LAI-FLX) discontinued the initial regimen. The number of days spent in hospital per month and patient was slightly lower with LAI-RIS (1.08 vs. 1.28 days, p<0.001). The proportion of patients receiving side-effect co-medication was lower with LAI-RIS (8.3 vs. 15.0% per month, p<0.001). Mean total costs of treatment per patient and month were 1,015 € under LAI-RIS and 395 € under LAI-FLX, resulting in an ICER of 3,088 € (95% CI [-913 €; 3,551 €]) for an avoided hospital day per patient and month in the base case scenario with a 15.1% probability of LAI-FLX being the dominant treatment strategy. Cost differences were mainly attributable to the higher drug costs of LAI-RIS. The effectiveness of LAI-RIS in preventing hospital days appears to be similar to LAI-FLX, with a slight superiority in side-effect and switching rates. This comes at the cost of substantially higher treatment expenses. From a decision-maker's point of view, the use of health insurance data as a source of input for decision models appears to be a reasonable alternative to models driven by clinical data only.

Topics: Adult; Antipsychotic Agents; Cost-Benefit Analysis; Delayed-Action Preparations; Female; Flupenthixol; Hospitalization; Humans; Male; Markov Chains; Middle Aged; Models, Econometric; Risperidone; Schizophrenia

The reduction of the frequency of rehospitalisation is important for improving the outcomes for patients with schizophrenia.. This study compares the rate of rehospitalisation between patients with antipsychotics in depot-form (n = 77) and oral second-generation antipsychotics (SGA) (n = 156).. Patients with antipsychotics in depot-form had lower risk of rehospitalisation than with SGAs in oral-form after 24 months (p = 0.027) and 36 months (p = 0.018) (Kaplan-Meyer survival analysis, Log-Rank). Long intervals between two hospitalisations were found for flupentixol depot and clozapine.. Antipsychotics in depot-form require and active and close outpatient treatment, which may account for long intervals between hospitalisation improved outcomes for patients with schizophrenia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Delayed-Action Preparations; Female; Flupenthixol; Hospitals, Psychiatric; Humans; Male; Middle Aged; Patient Readmission; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Abscess; Adult; Antipsychotic Agents; Buttocks; Delayed-Action Preparations; Flupenthixol; Humans; Injections, Intramuscular; Injections, Subcutaneous; Male; Obesity; Schizophrenia

Atypical neuroleptics have a lot of advantages compared with conventional substances. It is still disadvantageous that a depot-medication is missing. The role of the form of application has been studied in a schizophrenia-out-patient department. In 25 out-patients under therapy with atypical neuroleptics the time of rehospitalisation per year was retrospectively determined and compared with that of 25 out-patients receiving depot-medication. Both groups were comparable with regard to some patient-characteristics and predictors of the course of the disease. It turned out that for patients with depot-neuroleptics the time spent in hospital per year was half of that for patients under atypical drugs. It had been in the same range in both groups 4 to 6 years ago and had decreased until the last year of the catamnesis in patients with depot-medication, but not in those with atypics. Typical neuroleptics as oral medication are disadvantageous in this respect. Despite efforts to reach a good compliance in all patients, preferable effects of atypical drugs with regard to negative symptoms are opposed by less favourable rehospitalisation times. This has to be taken into consideration in differential indication.

Topics: Administration, Oral; Adult; Ambulatory Care; Antipsychotic Agents; Delayed-Action Preparations; Female; Flupenthixol; Germany; Humans; Male; Middle Aged; Patient Readmission; Psychiatric Status Rating Scales; Recurrence; Retrospective Studies; Risk; Schizophrenia; Treatment Outcome

Treatment of patients suffering from schizophrenia is very expensive. However, by consistently and methodically performed medical prophylaxis the disease can be controlled sufficiently well. Regular prophylactic treatment compared to repeated treatment of acute episodes has both medical advantages and reduces cost by reducing the rate of hospitalisation. Prophylactic treatment with Flupentixoldecanoat can save up to 68% of costs.

Topics: Adult; Aged; Ambulatory Care; Cost Savings; Dopamine Antagonists; Female; Flupenthixol; Germany; Humans; Male; Middle Aged; Patient Readmission; Recurrence; Schizophrenia; Schizophrenic Psychology; Social Security

Attitude towards treatment, side-effects, mental state and quality of life was assessed in 53 chronic schizophrenic out-patients on maintenance treatment with depot neuroleptics. It was found that 60% of the patients viewed depot medication positively, while only 8% viewed it negatively. Only 70% of patients complained about side-effects, even though 94% had scored as having them. Hypokinesia and hyperkinesis were the side-effects least noticed by the patients, but most noticed by the treating physician, while the opposite was the case with psychic side-effects. Only 49% of patients thought they had a psychotic illness, and there was no correlation between the patients' own evaluation of the severity of their illness and their score on the Positive and Negative Symptom Scale (PANSS) or the treating physician's evaluation. Quality of life did not correlate with either side-effect score or PANSS score. The schizophrenic patients' assessment of their condition was therefore in general different both from that of the treating physician and from that determined using rating scales.

Topics: Adult; Aged; Antipsychotic Agents; Chronic Disease; Clopenthixol; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Flupenthixol; Humans; Male; Middle Aged; Neurologic Examination; Perphenazine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Sick Role

Stability of neuroleptic medication has been associated with optimal clinical effect and minimal side-effects. Depot administration is assumed to yield better stability.. Thirty patients on depot neuroleptic treatment were followed during three years with repeated measurements of plasma level and concurrent ratings of clinical symptoms and side-effects.. Of 120 blood samples 35 (29%) measurements were outside +/-2 s.d. measurement error (expected 5%). Perphenazine levels were more variable (46%) than haloperidol (25%) and flupenthixol (12.5%). No relationship was found between side-effect ratings and fluctuations of plasma levels.. Depot neuroleptic medication does not eliminate a clinically unwanted and sometimes marked variation in plasma level.

Topics: Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Drug Monitoring; Female; Flupenthixol; Follow-Up Studies; Haloperidol; Humans; Injections, Intramuscular; Long-Term Care; Male; Middle Aged; Neurologic Examination; Perphenazine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Dystonia; Flupenthixol; Humans; Laryngeal Diseases; Long-Term Care; Schizophrenia; Voice Disorders

There is growing evidence that substance abuse is a major problem in patients with schizophrenia. With respect to alcohol, alledegly the most frequently abused drug among schizophrenics, clinical and epidemiological studies would suggest that the risk of alcoholism is approximately four times greater (Cuffel, 1992; Mueser et al., 1990; Soyka et al., 1993; Soyka, 1994). A variety of hypotheses have been proposed to explain this phenomenon, including the so-called "self-medication hypothesis". Some authors feel that substance abuse in schizophrenics might be due to extrapyramidal and other side-effects caused by neuroleptic treatment or inadequate remission of psychotic symptoms. There remains, at present, an obvious lack of both psychosocial and psychopharmacological studies of treatment in "dual diagnosis" schizophrenics (Mueser et al., 1992). Changes in dopaminergic neurotransmission and dopamine-receptor dysfunction have been linked both to the development of psychotic symptoms and to alcoholism/substance abuse, and thus give rise to the question as to whether some dual diagnosis patients might benefit from neuroleptic treatment in both domains. A number of dopamine receptor subtypes in different regions of the brain seems to be involved in the development of schizophrenia and substance abuse. Modifications of D2-receptor subtype function have been implicated in psychotic symptoms, and changes in the D1- and D2-receptor function in substance abuse such as cocaine abuse and alcoholism (Spealman et al., 1990; 1991; 1992), especially in the mesolimbic dopaminergic reward system. Accordingly, the "ideal" neuroleptic drug for dual diagnosis schizophrenics should be effective in both receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Alcoholism; Flupenthixol; Humans; Male; Schizophrenia; Schizophrenic Psychology; Tranquilizing Agents

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

Topics: Administration, Oral; Amitriptyline; Anxiety Disorders; Benperidol; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Doxepin; Drug Administration Schedule; Flupenthixol; Fluspirilene; Haloperidol; Humans; Imipramine; Injections, Intramuscular; Promethazine; Psychotropic Drugs; Pyrimidines; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Single-Blind Method

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

Topics: Administration, Oral; Antipsychotic Agents; Chronic Disease; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Injections, Intramuscular; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology

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.

Topics: Adult; Chronic Disease; Dose-Response Relationship, Drug; Female; Flupenthixol; Humans; Male; Middle Aged; Outpatients; Perphenazine; Psychiatric Status Rating Scales; Schizophrenia

Of 49 schizophrenic patients followed up 12 months after their first admission to hospital, only about 45% had experienced no relapse and had no schizophrenic symptoms; a poorer outcome was more often found in Feighner positive than Feighner negative schizophrenic patients. The patients' overall level of unemployment had more than doubled to 51%. In patients whose acute episodes responded to treatment, pimozide taken once weekly as maintenance therapy was as effective as intramuscular flupenthixol decanoate, but tardive dyskinesia appeared in two patients receiving weekly pimozide; the repeat psychometric assessment at 12 months found modest improvements, i.e. no evidence of intellectual decline, in Matrices, Block Design, and Digit Copying tests. Forty per cent of relatives still showed significant psychological distress, which correlated with patients' schizophrenic symptoms, and the relatives' social functioning remained poorer than that of a normal community sample.

Topics: Adaptation, Psychological; Cognition; Family; Flupenthixol; Follow-Up Studies; Hospitalization; Humans; Interpersonal Relations; Pimozide; Prognosis; Schizophrenia; Schizophrenic Psychology; Scotland; Social Adjustment; Thioxanthenes; Tranquilizing Agents

Platelet-rich plasma from healthy controls was pre-treated with neuroleptics of the phenothiazine, butyrophenone or benzamide variety before aggregation with one of the following agonist agents: ADP, adrenaline, 5-HT, collagen, platelet activating factor or ristocetin. All compounds effective as antipsychotics, except sulpiride, depressed aggregation. Unmedicated schizophrenics showed aggregation responses indistinguishable from healthy controls. However, within days of treatment with either trifluoroperazine or haloperidol responses became abnormal in acutely psychotic patients. Increased responses to 5-HT and depressed responses to platelet activating factor were detected. After 4 weeks of treatment responses tended to return to normal. Aggregation responses were normal in those patients on long-term depot neuroleptics.

Topics: Adolescent; Adult; Antipsychotic Agents; Chlorpromazine; Delayed-Action Preparations; Flupenthixol; Fluphenazine; Haloperidol; Humans; Male; Platelet Aggregation; Procyclidine; Schizophrenia; Sulpiride; Trifluoperazine

Tracer doses of 11C-SCH 23390 and 11C-raclopride, selective D1-dopamine and D2-dopamine receptor antagonists, respectively, were injected intravenously into three healthy male volunteers and two drug-treated schizophrenic patients. Regional radioactivity in brain and plasma was followed during 1 h by positron emission tomography (PET). After injection of both ligands a high accumulation of radioactivity was observed in the dopamine-rich caudate putamen. Experiments with 11C-SCH 23390, but not 11C-raclopride, showed a conspicuous accumulation of radioactivity also in the neocortex. None of the ligands accumulated in the dopamine-poor cerebellum. Specific binding of 11C-raclopride in the putamen was reduced by more than 80% in schizophrenic patients treated with antipsychotic doses of sulpiride or cis(Z)-flupentixol decanoate. 11C-SCH 23390 binding was slightly reduced in both the cortex and the putamen after treatment with cis(Z)-flupentixol decanoate but not after sulpiride. The results indicate that clinical antipsychotic drug treatment with sulpiride and cis(Z)-flupentixol decanoate causes a substantial blockade of D2-dopamine receptors in the basal ganglia but has only a minor effect on D1-dopamine receptors.

Topics: Adult; Benzazepines; Brain; Carbon Radioisotopes; Flupenthixol; Humans; Male; Middle Aged; Raclopride; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Sulpiride

Twenty-six chronic schizophrenic patients on well-established depot neuroleptic regimes with stable doses (16 on fluphenazine decanoate, 10 on flupenthixol decanoate) had serum neuroleptic levels measured by radioreceptor assay (RRA) and were followed for six months. The serum prolactin (PRL) concentration and resting electrocardiogram (ECG) were also taken at the beginning of the study period. Correlations had previously been noted between RRA measured neuroleptic levels and outcome in both acute and chronic patients on oral medication. However, in this study of depot medication no significant correlations were found between serum neuroleptic concentration, serum prolactin concentration and the clinical state or outcome. The prevalence (33%) and type of ECG abnormality observed was similar to that previously reported.

Topics: Adult; Delayed-Action Preparations; Dose-Response Relationship, Drug; Electrocardiography; Female; Flupenthixol; Fluphenazine; Heart; Humans; Male; Middle Aged; Prolactin; Radioligand Assay; Schizophrenia; Thioxanthenes

24 patients have been treated with cis(z)-flupenthixol decanoate for 6-12 months. Intramuscular injections were given about every 3 weeks. Before treatment and on each day of injection the mental state was assessed by BPRS and registration of side effects was performed. Blood samples were taken 7 days after each injection and on the last day of the dosage interval. Neuroleptic activity was determined in serum by RRA and expressed in cis(z)-flupenthixol equivalents. The drug level was significantly correlated to the dose. No clear relationship between drug level and clinical results as well as side effects was found. Less pronounced variations of the drug level between subsequent injections resulted in a positive therapeutic response.

Topics: Adult; Female; Flupenthixol; Humans; Injections; Male; Middle Aged; Radioligand Assay; Schizophrenia; Thioxanthenes

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Male; Prognosis; Schizophrenia

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.

Topics: Adult; Aged; Clopenthixol; Female; Flupenthixol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Recurrence; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Thioxanthenes

The authors describe the first case report in the psychiatric literature of death from an overdose of amantadine hydrochloride used to treat neuroleptic induced extrapyramidal side effects. The pharmacology, adverse reactions and risks of using amantadine are briefly reviewed.

Topics: Adult; Amantadine; Drug Therapy, Combination; Flupenthixol; Humans; Male; Schizophrenia; Schizophrenic Psychology; Suicide

Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Humans; Middle Aged; Psychotic Disorders; Schizophrenia

Attempting to improve long-term neuroleptic treatment of schizophrenic patients several injectable depot neuroleptics have been developed. Moreover pharmacokinetic data increasingly have been clinically applied. On this background the purpose of the present paper has been to make an updated review of the clinical and pharmacokinetic knowledge of depot neuroleptic treatment. First, general aspects of antipsychotics have been summarized, and an outline of methodological questions relevant to clinical-pharmacological trials are given. Subsequently general aspects including pros & cons of depot administration are examined. Finally the available data of the various depot preparations have been scrutinized. It is concluded that our present pharmacokinetic knowledge of the particular preparations is incomplete. Thus more information of clinical relevant aspects are needed, e.g., the existence of a therapeutic range, maximum/minimum concentration ratio, and the significance of active metabolites. Comparing the various depot neuroleptics, no significant differences are seen regarding the clinical effects. However, the decanoate esters seem clinical superior to the corresponding enanthate esters explained by the more flat concentration curve of the decanoates. Apart from that, a comparison of the pharmacokinetic data is difficult because of the heterogenecy of the available data. Haloperidol, clopenthixol and perphenazine decanoates are among the best examined preparations in pharmacokinetic respects. A controlled double-blind comparative study of these preparations would be of interest.

Topics: Administration, Oral; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Haloperidol; Humans; Kinetics; Long-Term Care; Patient Compliance; Perphenazine; Schizophrenia; Schizophrenic Psychology; Thiazines

Topics: Adult; Chronic Disease; Female; Flupenthixol; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

In a prospective follow-up the outcome of 60 chronic schizophrenic patients who discontinued neuroleptic therapy after remaining stable 12-48 months was compared with controls continuing medication. Not only did the drug-discontinued patients have more relapses (P less than 0.001), but the form of relapse was both more severe and acute, resulting in differences of self-injury (P less than 0.05), anti-social behaviour (P less than 0.01), inpatient admissions (P less than 0.001), and the use of compulsory powers (P less than 0.01). In patients who relapsed, both social and work function was affected adversely for some months. Patients who remained relapse-free without drugs (20%) had a level of work and social function similar to medicated patients. At the end of 18 months the patients who discontinued depot maintenance therapy were found to have been prescribed one-third more neuroleptic drugs than controls, with a possible increase in the risk of long-term tardive dyskinesia.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Drug Administration Schedule; Female; Flupenthixol; Fluphenazine; Humans; Male; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thioxanthenes

Serum concentrations of cis(Z)-flupentixol have been measured in patients on cis(Z)-flupentixol decanoate injections during successive dosage intervals of 2-4 weeks. The calculation of the fluctuation of the serum concentration in the dosage interval indicates that each individual patient should have his own dosage interval. For the 2-week group a significant correlation was found between weekly dose and preinjection concentration (r = 0.79) although an interindividual variability of X 4 was found. For this group the relative within-patient variation in the pre-injections concentration was calculated to be 9.6%, showing that a constant dosage regimen in the individual patient leads to an almost constant drug load.

Topics: Adult; Aged; Delayed-Action Preparations; Flupenthixol; Humans; Middle Aged; Schizophrenia; Thioxanthenes; Time Factors

The antidepressive and anxiolytic efficacy of flupenthixol has been investigated in numerous controlled and open trials involving patients with endogenous, reactive as well as senile depressions. When administered at a mean daily single or multiple dose of 1-2 mg, flupenthixol proved to be a very effective and well-tolerated antidepressant. As opposed to some of the currently available antidepressants, flupenthixol has a rapid onset of action which is often displayed within the first 2-3 days following its application. Flupenthixol decanoate has also a pronounced antidepressive and anxiolytic effect which appears to be adequate enough for treating mild to moderately severe syndromes of depression. This depot neuroleptic has been given at a fortnightly dosage ranging between 2.5 and 30 mg. However, if the aspect of efficacy in relation to tolerance has to be taken in to consideration, then 5 mg are apt to be an appropriate dose. Patients with an agitated depression and/or suicide ideation should, however, be excluded from therapy with this drug. Extrapyramidal movement disorders which may appear during treatment are a disadvantage of this medication. Apparently such disorders are rarely encountered if the dose is kept below 10 mg. Other untoward effects are very seldom indeed. A final and conclusive judgement on the possible application of flupenthixol decanoate in the prophylaxis of phases in patients with bipolar and periodical depressions is as yet not feasible. Further clinical trials are necessary before flupenthixol decanoate can be classified as a possible 'depot antidepressant'.

Topics: Anxiety Disorders; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Flupenthixol; Humans; Schizophrenia; Thioxanthenes

Nine chronic schizophrenic patients selected from three hospital departments were treated with flupentixol (orally and IV) and cis(Z)-flupentixol decanoate in Viscoleo (IM) in a three-phase pharmacokinetic study. Oral administration (single and repeated dosage) showed a relatively slow absorption with maximum serum concentration around 4 h after administration. Intravenous injection indicated multicompartment kinetics for cis(Z)-flupentixol. The biological half-lives calculated after the different doses were the same, indicating that the pharmacokinetics of cis(Z)-flupentixol does not differ between single and repeated administration and does not change when moderately higher doses are given. The bioavailability of orally administered cis(Z)-flupentixol was calculated to be about 40% with IV injection as reference. After IM administration maximum serum concentration was seen between 4 and 10 days in most patients. Calculation of a disappearance half-life gave very variable results, indicating that the release of the drug from the oil depot is not a monoexponential process. The intramuscular depot had a much lower bioavailability than IV injection, which means that steady state has not been obtained after 8 weeks of depot treatment. Serum prolactin concentrations were elevated during neuroleptic treatment, but no correlation was found between prolactin concentrations and the serum concentrations of cis(Z)-flupentixol. A correlation between the changes in clinical ratings and concentrations of cis(Z)-flupentixol or prolactin was not found.

Topics: Administration, Oral; Adult; Chronic Disease; Female; Flupenthixol; Half-Life; Humans; Injections, Intravenous; Male; Middle Aged; Prolactin; Schizophrenia; Thioxanthenes

Anterior pituitary response to TRH 200 micrograms i.v. was studied in ten chronic schizophrenic patients during long-term neuroleptic treatment. Nine patients had normal prolactin (PRL) response as compared with controls but in one the response was blunted; one patient had an exaggerated response. Prolactin increment was higher following TRH than haloperidol challenge. No growth hormone (GH) response to TRH was found and TSH responses were comparable to controls.

Topics: Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Female; Flupenthixol; Fluphenazine; Growth Hormone; Haloperidol; Humans; Male; Middle Aged; Pituitary Function Tests; Prolactin; Schizophrenia; Stimulation, Chemical; Thyrotropin-Releasing Hormone

Topics: Adult; Antipsychotic Agents; Female; Flupenthixol; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Topics: Adult; Aged; Delayed-Action Preparations; Esters; Female; Flupenthixol; Humans; Male; Middle Aged; Piperazines; Schizophrenia; Thioxanthenes; Tranquilizing Agents