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PubMed1979

A double-blind comparison of flupenthixol, nortriptyline and diazepam in neurotic depression.

A double-blind trial of flupenthixol, nortriptyline and diazepam in neurotic depression using flexible dose schedules suggested that each drug is an efficient treatment for this category of depression although the patterns of response and prevalence of side-effects varied. No differences reaching a level of significance could be shown on rating scales of depression or anxiety, but trends favoured flupenthixol. However, clinical evaluation suggested flupenthixol to be more effective than diazepam on mental state examination (P less than 0.05) and to have a greater overall therapeutic effect than nortriptyline (P less than 0.05). It also had fewer side-effects than nortriptyline (P less than 0.05).

Adjustment Disorders↗
PubMed1984

Therapeutic efficacy of flupenthixol decanoate in schizoaffective disorder: a clinical evaluation.

The present open study was undertaken to evaluate the therapeutic efficacy and side-effects of flupenthixol, a thioxanthene derivative in the treatment of schizoaffective psychosis. A total of twenty in-patients, selected according to specific research criteria were treated with flupenthixol (20 mg to 60 mg i.m. q.2.weeks) for a period of 6 months. During the course of the study, a detailed battery of psychiatric rating scales was completed prior to the commencement of the treatment and at regular intervals thereafter. Additionally, detailed physical examinations and laboratory tests were also carried out at regular intervals. Results show that fifteen patients improved significantly, two patients remained unchanged while three patients deteriorated and were discontinued. Adverse effects were minimal and limited to tremor and akathisia. The present study highlights the usefulness of flupenthixol as a monotherapy in the management of schizoaffective psychosis.

Adult↗
PubMed1976

A double-blind study of flupenthixol ('Fluanxol') in general practice.

A double-blind crossover trial was carried out in the general practice to compare the effectiveness of flupenthixol and placebo in 43 patients with mild to moderate anxiety/depression states. Patients received either 0.5 mg flupenthixol or identical placebo tablets 2 to 4-times daily for 2 weeks and were then crossed over to the alternative preparation for a further 2 weeks. A simple 5-point rating scale was used to assess patients' symptoms at first visit and at subsequent follow-up. Even though there was a high placebo response, the results showed flupenthixol to be significantly more effective than placebo in relieving symptoms. Few side-effects were reported and were mild in nature.

Adolescent↗
PubMed1986

A double-blind comparison of once-daily flupenthixol and mianserin in depressed hospital out-patients.

A double-blind, parallel group study was carried out in 51 mild to moderately depressed hospital out-patients to assess the therapeutic efficacy and side-effects of once-daily flupenthixol (1 mg) administered in the morning compared with once-daily mianserin (30 mg) administered in the evening. Patients were treated over a period of 6 weeks and assessments were made before and during treatment using the Newcastle Rating Scale, the Clinical Global Impression, the Hamilton Depression Scale, the Leeds Self-Rating Scale for Depression, and a check-list of side-effects. The results showed that 91% of flupenthixol patients and 80% of mianserin patients were assessed as 'normal' on completion of the study period. Depressive symptoms decreased progressively in both groups. Reports of side-effects in both groups showed a progressive reduction in number and severity during the study. The reduction at the end of the first week of treatment with mianserin was not as great as that seen with flupenthixol; reports of drowsiness accounted for most of the difference.

Administration, Oral↗
PubMed1975

A comparative trail of fluphenazine decanoate and flupenthixol decanoate.

A double-blind cross-over study is reported which compares the antipsychotic properties and the side effects of depot flupenthixol with fluphenazine decanoate in chronic schizophrenic inpatients. Special emphasis was laid on examining changes in the target symptoms of apathy/anergia and depression in which flupenthixol has been claimed to be particulary effective. No significant differences were found between treatments on schizophrenic symptoms, or as regards the extrapyramidal side effects produced by equipotent doses of the two drugs. Reasons for the essentially negative results are discussed against a background review of earlier optimistic studies of flupenthixol.

Adult↗
PubMed1985

The effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on food-reinforced tracking of a visual stimulus by rats.

Rats were trained to respond to one of two levers under a random ratio schedule of food reinforcement. Which of the levers was correct was redetermined before each response and signalled by a light. The effects of d-amphetamine (0.2-3.2 mg/kg), chlordiazepoxide (1-8 mg/kg), and the neuroleptic alpha-flupenthixol (0.03-0.33 mg/kg) on the efficiency of rats tracking this visual cue were examined. d-Amphetamine increased the proportion of responses made on the correct lever at low and intermediate doses, but reduced the proportion at 3.2 mg/kg. At the highest dose, chlordiazepoxide produced a small increase in this measure, together with a reduction in response rate, but alpha-flupenthixol had no effect, even at a dose reducing response rate. Low doses of amphetamine also increased switching between the levers, producing a proportionately greater increase in switching from the correct lever to the incorrect lever than vice versa. The results are interpreted as showing that d-amphetamine facilitates tracking performance as a result of its action of enhancing response switching, and supporting the hypothesis that facilitation of performance by amphetamine-like drugs depends on the effect of the drug on response output coinciding with task requirements.

Animals↗
PubMed1979

A comparative trial of the decanoates of flupenthixol and fluphenazine.

A double-blind trial was carried out comparing the effects of decanoates of flupenthixol and fluphenazine on the symptoms, ward behaviour and functional capacity in occupational therapy in 51 chronic schizophrenic patients. The patients were carefully selected on the basis of rigid criteria for diagnoses. To exclude nonresponders to neuroleptics the patients were first taken off neuroleptic drugs and only those who appeared to show deterioration were included in the trial. The dosage of drugs was varied according to clinical indications. The length of the trial was initially 4 months and 31 patients were followed for an additional 4 months. To ensure reliability multiple assessments were made at the start and the end of the trial. Most of the statistical tests showed no differences between the treatments, but some of those relating to affective symptoms showed an advantage for flupenthixol as compared with fluphenazine. There were no differences in the incidence of extra-pyramidal side-effects which required treatment in only 32% of the patients on each drug.

Adult↗
PubMed2004

Attenuation of d-amphetamine-induced disruption of conditional discrimination performance by alpha-flupenthixol.

RATIONALE: Previous evidence suggests that manipulation of forebrain dopamine (DA) systems may impair the use of conditional information to inform goal-directed performance, and this may be related to impairments in the ability to use task-setting cues in schizophrenia. OBJECTIVE: To investigate, using the indirect DA agonist d-amphetamine and the D1/D2 receptor antagonist alpha-flupenthixol, the influence of DAergic manipulation on discrimination performance that requires the use of conditional information to inform goal-directed performance. METHODS: Both instrumental and Pavlovian conditional discriminations were employed in which rats learned to respond appropriately according to the presence of auditory conditional stimuli, and results from these experiments were contrasted with a control Pavlovian-instrumental transfer task. RESULTS: Experiment 1 showed a disruption of instrumental conditional discrimination performance by d-amphetamine at 1.5 mg/kg and attenuation of correct responding following 1.0 mg/kg. Disruption with both doses was observed in experiment 2 using a conditional discrimination based on Pavlovian, conditioned responding. Results from a control Pavlovian-instrumental transfer task (experiment 3) revealed that d-amphetamine (0.5, 1.0 and 1.5 mg/kg) did not have any detrimental effect on subjects' basic sensory, motor or motivational processes. Experiment 4 showed that d-amphetamine disruption of instrumental conditional discrimination was attenuated by pre-treatment with the D1/D2 receptor antagonist alpha-flupenthixol. CONCLUSION: These results demonstrate that tasks dependent on conditional relationships are highly sensitive to manipulation of DAergic systems.

Animals↗
PubMed2003

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics.

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.

Adult↗
PubMed1983

Persistent increase in striatal dopamine stimulated adenylate cyclase activity persists for more than 6 months but disappears after 1 year following withdrawal from 18 months cis-flupenthixol intake.

Administration of cis-flupenthixol to rats for 18 months enhanced apomorphine-induced stereotyped behaviour, increased the number of specific [3H]spiperone binding sites in striatum and potentiated striatal dopamine stimulated cyclic AMP formation, but did not alter specific [3H]piflutixol binding. Following withdrawal of cis-flupenthixol intake, apomorphine-induced stereotypy returned to control values after 1 month and Bmax for [3H]spiperone binding returned to normal after 3 months. In contrast, the increased dopamine stimulated adenylate cyclase activity remained elevated 6 months after drug removal, but was normal 1 year after drug withdrawal.

Adenylyl Cyclases↗
PubMed1981

Sequelae of 6 months continuous administration of cis(Z)-and trans(E)-flupenthixol in the rat.

Rats were treated continuously with cis(Z)- or trans (E)-flupenthixol via drinking water for 6 months. Stereotypy responses to 0.15 mg/kg apomorphine (APOM) were enduringly, and stereospecifically, antagonised by cis (Z)-flupenthixol at either 0.5-1.0 or 1.4-3.0 mg/kg per day. Responses to 1.0 mg/kg APOM were antagonised after 5 days but enhanced after 6 months on cis (Z)-flupentixol (1.4-3.0 mg/kg per day). Distinct dopamine-dependent processes may be differentially sensitive to adaptation during extended neuroleptic treatment.

Animals↗
PubMed1995

Behavioral effects of the reversible dopamine antagonist flupenthixol are not potentiated by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in the preweanling rat.

In the preweanling rat, the irreversible dopamine (DA) receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) does not diminish behaviors induced by the nonselective DA agonist R(-)-propylnorapomorphine (NPA). To determine whether EEDQ was simply inactivating an insufficient percentage of DA receptor antagonist) and/or EEDQ. When given alone, flupenthixol (0.04, 0.1, and 0.4 mg/kg, intraperitoneally [IP]) produced a dose-dependent decrease in the behavioral effects induced by 1.0 mg/kg NPA. Unexpectedly, EEDQ (7.5 mg/kg, IP) did not potentiate flupenthixol's actions. This suggests that EEDQ's inability to block the NPA-induced behaviors of preweanling rats was not the result of an insufficient percentage of DA receptors being inactivated.

Animals↗
PubMed1983

Flupenthixol in depression. A study of serum levels and prolactin response.

The relationship between improvement in symptomatology and changes in prolactin and serum cis-flupenthixol levels has been evaluated in 16 patients with a clinical diagnosis of depression, who were treated with 1 or 2 mg of flupenthixol in a once daily morning dose. No significant differences in clinical response were noted between those on 1 and 2 mg, and side effects were few. The presentation of some side effects, in particular extrapyramidal symptoms, were related to higher serum levels and prolactin levels particularly in the early stages of the study. Improvements in depressive symptoms were unrelated to serum levels, but at day 56 of the trial were positively correlated to changes in prolactin levels. Improvements in anxiety symptoms were positively related to serum levels at day 3 but negatively related at day 56. These results are discussed in the light of possible influences of dopamine antagonism in relation to an antidepressant effect.

Adult↗
PubMed1999

D2 dopamine receptor but not AMPA and kainate glutamate receptor genes show altered expression in response to long term treatment with trans- and cis-flupenthixol in the rat brain.

Glutamate receptor function has been hypothesized as an important factor in both the aetiology and treatment of schizophrenia. We have used a multiprobe oligonucleotide solution hybridization (MOSH) technique to examine the regulation of gene expression of the GluR1-7, KA1, and KA2 glutamate receptor subunits in the left rat brain following treatment with the optical isomers of flupenthixol at a dose of 0.2 mg kg-1 day-1 over a period of 4, 12, 24 weeks in order to understand how specific glutamate receptor genes are involved in the treatment of schizophrenia. The GluR2/3 and GluR6/7 subunit immunoreactivity in the right brain following 4 and 24 weeks of drug treatment was also examined by Western blotting. Neither trans- nor cis-flupenthixol was found to alter the gene expression of any of the 9 non-NMDA glutamate receptor subunits. On the other hand, we found a nearly two-fold increase in gene expression of the D2 dopamine receptor in specific brain regions. These results suggest that non-NMDA types of glutamate receptor subunits, in contrast to NMDA receptors, are less likely to have a role in the action of antipsychotic drugs.

Amino Acid Sequence↗
PubMed2003

Acute and maintenance ECT with flupenthixol in refractory schizophrenia: sustained improvements in psychopathology, quality of life, and social outcomes.

OBJECTIVE: To determine the effects of ECT combined with antipsychotic medication therapy on psychopathology, quality of life, and social functioning in patients with refractory schizophrenia. METHOD: An open acute (Phase I) and maintenance (Phase II) study of the combination of ECT and flupenthixol in the treatment of 46 schizophrenic patients who were nonresponsive to antipsychotic medication from at least two different classes. Scales used: the Brief Psychiatric Rating Scale (BPRS), the Quality of Life Scale (QLS), Social and Occupational Functioning Assessment Scale (SOFAS), Global Assessment of Functioning (GAF), and Mini-Mental State Exam (MMSE). The duration of Phase II was 1 year. RESULTS: In Phase I, there were marked reductions in the BPRS scores, and substantial increases in the QLS, SOFAS, GAF, and MMSE scores. During Phase II, the BPRS negative symptoms worsened but remained improved from baseline. Changes in other outcome measures were negligible. CONCLUSION: ECT and MECT combined with flupenthixol were effective in improving psychopathology in patients refractory to antipsychotic medication alone. Ratings of psychopathology, quality of life, and social functioning all improved in Phase I and were generally sustained during Phase II in patients who had remitted.

Acute Disease↗
PubMed1991

Molecular structure and dynamics of cis(Z)-and trans(E)-flupenthixol and clopenthixol.

The three-dimensional structures and molecular electrostatic potentials of the cis(Z) and trans(E)-isomers of flupenthixol and clopenthixol were examined by computer graphics and molecular mechanical and quantum mechanical calculations, and their internal molecular motions were studied by molecular dynamics simulations in vacuo and in aqueous solution. The simulations demonstrated that both the side chains and the tricyclic ring systems of clopenthixol and flupenthixol are highly flexible. The angle between the two phenyl ring planes varied between 105 and 171 degrees during the simulations in solution. The electrostatic potentials around the 2-substituent were significantly more negative in the trans(E)-isomers than in the cis(Z)-isomers. The stronger negative potentials may weaken electrostatic receptor interactions and, thereby, cause the trans(E)-isomers to be less active than cis(Z)-isomers. Differences both in three-dimensional structure and in electronic structure may cause the difference in pharmacological activity between cis(Z)- and trans(E)-thioxanthenes.

Clopenthixol↗
PubMed2004

[Quality of life and therapeutic result in outpatients with schizophrenia under flupenthixol treatment].

The objective of this phase IV surveillance study was to document the efficacy and tolerability of flupenthixol as well as the quality of life of patients suffering from schizophrenia and to gain insights into which doses were actually used in specialists outpatients care. The observational variables in this study include demographic variables, details of the diagnosis as well as concomitant diseases. Further evaluations included the assessment of CGI-Scale and subjective patient quality of live assessment using a standardised questionnaire. This questionnaire SWN-K (subjective well-being under neuroleptic treatment; short version) includes 20 items on the state of health with a six-point scale from "absolutely not" to "very strong" respectively. 66.3 % Patients were treated with the depot form of flupenthixol, the rest with oral medication with mean doses of 9.2 mg/d i. m. and 6.3 mg/d p. o. respectively. 78.8 % of patients improved on the CGI-Scale, 5.5 % had an adverse event and in 4.6 % of patients this event was related to the medication. 0.3 % of patients had a serious adverse event. The mean of SWN-K improved from 61.2 to 78.5 in the course of study. The CGI improved from 5.83 to 3.43 in the course of treatment.

Adult↗
PubMed1975

The actions of flupenthixol upon 5-hydroxytryptamine-induced aggregation and the uptake of 5-hydroxytryptamine and dopamine by human blood platelets.

The effects of the alpha- and beta-isomers of flupenthixol on 5-hydroxytryptamine (5-HT)-induced platelet aggregation and on 5-HT and dopamine uptake were investigated. Alpha-Flupenthixol was 185 times more potent than the beta-isomer as an inhibitor of platelet aggregation. In contrast both isomers were equipotent as inhibitors of uptake of 5-HT and dopamine. The data suggest that 5-HT-induced aggregation and uptake are separate processes.

Blood Platelets↗