Plasma levels of fluphenazine and prolactin in psychiatric patients.

A total of 100 patients receiving fluphenazine (FPZ) decanoate for at least 12 months (96 schizophrenics and 4 other diagnoses) were investigated for plasma levels of FPZ and prolactin on the day of injection (day 0) and 7 days later (day 7). The plasma FPZ level significantly correlated with the weekly dose of FPZ. The plasma FPZ level per weekly FPZ dose multiplied by 100 (the FPZ ratio) showed a 20-fold variation. The FPZ ratio was significantly higher in the day- and in-patients (hospital-patients) than in out-patients. The plasma prolactin level significantly correlated with the plasma FPZ level but the prolactin to FPZ ratio negatively correlated with the plasma FPZ level. The prolactin to FPZ ratio was lower in the hospital patients than in the out-patients. This may suggest either that the high prolactin to FPZ ratio is an indicator of the therapeutic efficacy of FPZ or that there are at least two biologically distinct subgroups, one with a sharp prolactin response to FPZ, therefore with good prognosis, and another with the reverse direction.

Plasma levels of fluphenazine decanoate. Effects of site of injection, massage and muscle activity.

Depot neuroleptics are now commonly used for maintenance therapy of schizophrenia. Their physicochemical composition makes them ideal for such use because they are long-acting and show stable blood levels for prolonged periods. Their absorption from the site of injection may, however, be affected by local muscle factors. This paper describes three such factors in relation to fluphenazine decanoate: varying the site of injection; massage of the injection site; and effects of muscular exercise. Our results suggest that fluphenazine pharmacokinetics are not significantly affected by any of these factors.

Autoradiography of nadolol and propranolol in the rat.

Whole-body autoradiography of rats dosed with [14C]propranolol or [14C]nadolol have confirmed physicochemical predictions that nadolol, in contrast to propranolol, penetrates the CNS only to a slight extent, if at all. Differences between the CNS penetration of different beta-blockers have implications for the mechanism of the hypotensive action and the prevalence of side-effects associated with disturbance of the CNS.

Fluphenazine/nortriptyline in the irritable bladder syndrome. A double-blind placebo controlled study.

A double-blind, placebo controlled, randomised order crossover study was carried out on the effect of Motival (0.5 mg fluphenazine with 10 mg nortriptyline) 3 times daily on the bladder function and psychiatric morbidity of 13 women without evidence of infection, complaining of recurrent dysuria and frequency. Bladder function was assessed symptomatically and by ambulatory urodynamics, and patients completed the General Health Questionnaire, a validated instrument for the detection of psychiatric disturbance. Correction of the urodynamic abnormalities was associated with Motival treatment in 5 of the 8 patients with unstable bladders, compared with none of 7 patients receiving placebo (P less than 0.02). Motival was also associated with a greater frequency of symptomatic improvement. Only 2 patients were classified as psychiatrically disturbed, suggesting that the therapeutic effect of Motival is not related to its psychotropic properties.

Mixed anxiety/depressive illness in general practice. A therapeutic comparison of nomifensine with fluphenazine/nortriptyline.

The effect of the dopamine agonist antidepressant drug, nomifensine, on mixed anxiety/depressive states in general practice was assessed by means of a double-blind comparison with a standard fluphenazine/nortriptyline preparation. 57 patients were randomly allocated to 4 weeks' treatment with either nomifensine 25-50 mg taken three times daily, or a tablet containing 1.5 mg fluphenazine with 30 mg nortriptyline (Motipress) taken once daily. The overall response to both treatments was satisfactory, but Motipress was significantly superior (P less than 0.01) to nomifensine in the relief of fatigue and loss of energy, irritability, poor concentration and difficulty in coping, and there was also evidence of greater relief of depressive symptoms. In mixed anxiety/depressive states in general practice, nomifensine offers no advantage over a simple one tablet daily Motipress regimen.

Influence of drug treatment on the irritable bowel syndrome and its interaction with psychoneurotic morbidity.

Sixty per cent of the patients referred to two gastroenterological clinics and diagnosed as suffering from the irritable bowel syndrome (IBS), were found to have significant psychoneurotic morbidity on the basis of the General Health Questionnaire. A double-blind, completely randomised, placebo controlled comparison of treatment with a combined anxiolytic/antidepressant (Motipress) found a significantly better effect of Motipress than placebo on diarrhoea and abdominal pain. Detailed analysis of the results suggests that there is no direct relationship between psychoneurotic illness and IBS, but the presence of the former has an adverse effect on the short-term outcome of the bowel disorder.

Doctor's versus patient's judgement in the assessment of mixed anxiety/depressive illness. Implications for measurement of therapeutic response.

The relationship of doctors' assessments to their patients' self-assessments was examined in a double-blind comparison of Motipress and Anafranil in patients suffering from mixed anxiety/depressive states. Significant differences between doctors' ratings were revealed which were largely parallelled by their patients' self-ratings done independently, suggesting differences between subgroups of patients within the whole population. Appropriate statistical analyses eliminated these factors in the data and showed that they did not affect the conclusions of a conventional statistical analysis of the two treatment groups as a whole; there were no significant differences between the major improvements associated with each treatment.

Psychiatric disturbance in mentally handicapped patients. A prospective study of current clinical usage of depot fluphenazine in hospitals for the mentally handicapped.

One hundred and two mentally handicapped and severely mentally handicapped patients with behaviour disorders and superadded mental illnesses which, in most cases, had not responded adequately to oral medication, entered a 12-week study of fluphenazine decanoate depot injections. Some of the patients had the additional complications of epilepsy, organic brain damage, and physical handicap. Highly significant overall improvements occurred, irrespective of such factors as the patient's age, sex, degree of mental handicap, or co-existence of epilepsy, or brain damage. Hyperpyrexia was not encountered. Extrapyramidal disturbance in 22 of the patients, were mostly well controlled by antiparkinson medication; eight of the 12 patients with pre-trial extrapyramidal abnormalities lost these during the study. Fluphenazine decanoate injections proved a reliable drug-delivery system, which may improve difficult behaviours and enable the mentally handicapped patient to be more receptive to behaviour-shaping exercise, aimed at improving long-term personality adjustment.

Recurrent oral ulceration treated with Mysteclin: a controlled study.

Twenty patients with recurrent oral ulceration participated in a placebo-controlled, double-blind trail of Mysteclin syrup (tetracycline hydrochloride and amphotericin) used as a mouthwash. Though a small, consistent improvement occurred with placebo, there was a significant reduction in mean pair scores and numbers of new ulcers recorded daily during the active-treatment periods, the effect lasting for at least four weeks after treatment was stopped. In contrast to topical steroid preparations, Mysteclin syrup is efficacious when begun at any stage of the disorder and is not associated with adverse systemic effects.

Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man.

1 Fluphenazine (1,2-ethanol 14C) was administered to seven human subjects as the dihydrochloride and as the enanthate and decanoate esters. 2 The subjects had previously been treated with fluphenazine injections for at least 6 months. 3 Fluphenazine was separated from its radioactive metabolites by selective solvent extraction. Plasma concentrations were measured for up to 21 days after dosing. 4 The preparations showed differences in peak concentrations, times of the peaks and half-times of the elimination phase. The longest half-times occurred with the decanoate and the shortest with the dihydrochloride. 5 It is postulated that the differences in kinetics relate principally to the release of the compound from the site of injection. 6 There was no evidence for presence of the esters in plasma, urine or faeces.