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Biomedical subjects

T Silverstone

Publications and source records attributed to T Silverstone.

At least 55 records · Page 3Linked to original sources

Appetite suppressants. A review.

Centrally acting appetite suppressant drugs used in the treatment of obesity fall into 2 broad pharmacological categories; those which act via brain catecholamine pathways and those which act via serotonin pathways. Of the former group, amphetamine and phenmetrazine are no longer recommended because of their stimulant properties and addictive potential. The remaining drugs in this class include amfepramone (diethylpropion), phentermine, mazindol and phenylpropanolamine. All have been shown to reduce appetite and lower food intake, thereby helping obese patients more easily keep to a low-calorie diet and lose weight. They all have some sympathomimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They are fenfluramine, together with its recently introduced dextrorotatory stereoisomer dexfenfluramine, and fluoxetine. They reduce appetite and food intake and are effective in the treatment of obesity. Anorectic drugs should be reserved for those who are clinically at risk from being overweight, and then only as part of a comprehensive weight-reducing programme including regular dietary counselling. Although current licensing regulations only allow their use over a relatively short period (12 to 16 weeks), clinical trials have shown them to be effective over longer periods, particularly in preventing weight regain. Of the compounds currently indicated for use in obesity, dexfenfluramine appears to have the most suitable pharmacological profile, although it should not be given to patients with a history of depression. When used appropriately, appetite suppressants can be of real therapeutic benefit, and pose little risk.

Appetite Depressants↗

Positive and negative symptoms, depression and social disability in chronic schizophrenia: a comparative trial of bromperidol and fluphenazine decanoates.

A 1 year double-blind trial of bromperidol decanoate and fluphenazine decanoate was conducted in the maintenance treatment of 47 outpatients with schizophrenia. Six patients relapsed on bromperidol decanoate and none on fluphenazine decanoate, a difference which is statistically significant. No significant differences in positive and negative symptoms, nor depression measures were found between treatment groups when comparisons were made for change in score from entry to last visit. However, patients on fluphenazine decanoate achieved significantly better changes on social disability (Morningside scale) compared to those on bromperidol decanoate. The incidence of extrapyramidal side-effects was similar in both groups, and no statistically significant differences emerged in body weight change between treatments.

Adult↗

Tardive dyskinesia in bipolar affective disorder: a catchment area study.

The prevalence of tardive dyskinesia in a consecutive series of 69 patients with bipolar affective disorder admitted to a catchment area service was found to be 19%. Prevalence increased with age and was related to the age of onset of bipolar disorder and number of previous episodes. Patients with tardive dyskinesia were significantly slower on a simple test of cognitive function (Trails B).

Adult↗

Lithium and weight gain.

Lithium prophylaxis leads to weight gain in a high proportion of patients treated, with up to a quarter becoming clinically obese. This can have detrimental effects on compliance and is also a health risk. The mechanism of such lithium-induced weight gain is unknown, but increased calorie intake, particularly in the form of high calorie drinks, has been implicated. Remedial steps such as adjusting the lithium dose and giving appropriate dietary advice should be taken at the first sign of weight gain.

Bipolar Disorder↗

Clinically relevant differences between antipsychotic compounds.

All currently available antipsychotic drugs in general clinical use for the treatment of schizophrenia have in common the pharmacological property of dopamine receptor blockade and it is upon this that their anti-psychotic effects are thought to depend. Where they differ is in the spectrum of side effects they may produce, in their clinical profile, in potency, and in time course. Such differences reflect variations in pharmacological properties, both pharmacodynamic and pharmacokinetic. The substituted benzamides (sulpiride, remoxipride) are highly selective D2 receptor blockers and this pharmacological specificity confers important clinical advantages. In practice the choice of which antipsychotic drug to use in any given clinical situation depends on the degree of psychopathology present, the purpose for which treatment is being given, and the patient's age and general physical health.

Antipsychotic Agents↗

Seasonal affective disorder following brain injury.

Seasonal affective disorder has not previously been linked with neuroanatomical abnormalities despite its relationship to biological rhythms. A 45-year-old woman is described with an arteriovenous abnormality in the right frontotemporal region who developed recurrent winter depression and summer hypomania.

Brain Injuries↗

The effect of the 5-HT re-uptake inhibitor fluoxetine on food intake and body weight in healthy male subjects.

Eleven healthy male subjects of normal body weight received either 60 mg of the 5-HT re-uptake inhibitor fluoxetine (FXT) or matching placebo daily for two weeks, with a minimum one month wash-out period between treatments. Subjects attended on days 1, 8 and 15 from 08.50 h to 15.15 h in each treatment period when food and fluid intake, body weight, pulse and blood pressure, pupil diameter and plasma levels of FXT and NorFXT were measured and visual analogue scales (VAS) for subjective ratings of hunger, satiety, thirst, mood, arousal, nausea and gastric discomfort were completed. The trial was of a double-blind randomised crossover design, each subject acting as his own control. FXT reduced food intake by 15.7 per cent on day 1; by 12.6 per cent on day 8 but not on day 15. Hunger ratings were lowered by FXT on days 8 and 15 but not on day 1. Subjects were less thirsty when taking FXT but there was no concomitant reduction in fluid intake. FXT produced some mydriasis and slowed heart rate. In two weeks treatment with FXT there was a statistically significant weight loss of 1.07 kg compared to a mean weight gain of 0.15 kg on placebo. The incidence of reported side effects was low, drowsiness and stomach discomfort were reported by some subjects on days 8 and 15.

Adolescent↗

Efficacy, safety and tolerability of raclopride, a specific D2 receptor blocker, in acute schizophrenia: an open trial.

Fifteen acutely ill patients (8 male, 7 female) aged 19 to 63 who met DSM-III criteria for schizophrenic disorder or schizophreniform disorder participated in a 4-week open trial of raclopride. The starting dose of raclopride was 2 mg increasing to 4 mg twice daily in the first week, further increments to 6 mg twice daily at day 14, and 8 mg twice daily at day 21 depending on response. Weekly assessments were made using the BPRS, Montgomery Schizophrenia Scale, Krawiecka-Goldberg Scale and Clinical Global Impression Scale. Extra-pyramidal symptoms and other side-effects were recorded weekly. Four patients failed to complete. Two were withdrawn because of clinical deterioration, and 2 others left hospital against advice after 2 weeks having shown initial improvement. Of the 11 completers, 4 were very much improved and 6 much improved; one was minimally worse. Extra-pyramidal symptoms were infrequent: 3 patients expressed occasional mild akathisia. Six patients complained of mild drowsiness. No major deviations were found in biochemical and physiological safety parameters. Plasma concentrations of raclopride were stable throughout treatment or proportional to dose changes. There was approximately a 6-fold inter-individual difference in steady-state drug concentrations. Plasma levels of prolactin increased transiently after raclopride intake to a maximum of up to 80 and 130 ng/ml in male and female patients respectively.

Acute Disease↗

The neuroendocrine response to oral dextroamphetamine in normal subjects.

In 24 male subjects oral dextroamphetamine 20 mg caused a statistically significant rise in cortisol, prolactin, TSH, FSH, and LH compared to placebo. Dextroamphetamine caused a short-lived rise in growth hormone and attenuated the later rise which occurred after placebo. The findings are discussed in the light of previous reports of the neuroendocrine response to dextroamphetamine in normal subjects and in psychiatric patients.

Adolescent↗

The role of dopaminergic and noradrenergic receptors in human TSH and LH release.

The present study was undertaken to evaluate the relative roles of noradrenergic (NA) and dopaminergic (DA) neurotransmission in the control of thyrotropin (TSH) and luteinizing hormone (LH) release. Oral dextroamphetamine 20 mg caused a rise in the serum levels of TSH and LH in 24 healthy male volunteer subjects. The increase in TSH secretion was augmented by prior treatment with pimozide and reduced by thymoxamine. Conversely the LH response to destroamphetamine was reduced by pimozide and possibly accentuated by thymoxamine. The results confirm an inhibitory role for DA receptors in the control of TSH release and indicate that NA receptors may exert a facilitatory role. The converse would appear to be the case with LH, with DA being facilitatory and NA possibly inhibitory.

Adult↗

Carbamazepine compared to haloperidol in acute mania.

In a double-blind, between-patient clinical trial carbamazepine (CBZ) (n = 8) was compared to haloperidol (HP) (n = 9) in patients presenting with mania (DSM III). Seven patients on HP and 2 on CBZ failed to complete 4 weeks treatment. In 4 of the HP group this was because of extrapyramidal side-effects (EPS). Two patients on CBZ and 2 on HP were withdrawn because of lack of efficacy. Statistically significant clinical improvement was seen in both groups within the first 2 weeks of treatment with HP acting more quickly. In addition to EPS which occurred in HP patients, drowsiness was experienced in 4 on CBZ and 3 on HP, and gastrointestinal symptoms in 3 on CBZ. No serious haematological changes, nor abnormalities in clinical chemistry occurred in either group. We conclude that CBZ appears to be a potentially useful drug in the treatment of acute mania.

Acute Disease↗

Two regimens of lithium prophylaxis and renal function.

Two regimens of lithium prophylaxis with different pharmacokinetic characteristics were compared under double-blind conditions in 25 bipolar patients in remission already stabilized on lithium, to determine the relative effects of each regimen on renal function. Once-daily lithium carbonate (Priadal), which gives a peak lithium plasma level 2-3 h post-administration with a low level 24 h later, was compared with twice-daily lithium citrate (Litarex), which maintains a steadier 24 h plasma level. Patients were allocated randomly to one of the 2 regimens. They were seen monthly for clinical ratings over the course of 12 months. A comprehensive battery of renal function tests was undertaken at the start of the trial, between 6-9 months after the start and again after 1 year. No significant differences were observed in clinical outcome, side effects or renal function between the 2 regimens.

Acetylglucosaminidase↗

Bipolar affective disorder: causes and prevention of relapse.

The majority of patients with bipolar affective disorder relapse at least once during their lifetime, most several times, often with disastrous consequences. In this review we examine those factors which appear to play a facilitatory and in some cases, a causal role in determining whether a relapse will occur and, if so, when. Such factors include: the season of the year, with most admissions for mania in the British Isles occurring in the summer months; change in endocrine status, as after childbirth or when there is impaired thyroid function; treatment with drugs affecting central monoamine, particularly dopamine, neurotransmission; untoward life events. We evaluate the relative efficacy of treatments for the prevention of relapse, such as lithium, carbamazepine and antipsychotics, in the context of social and psychological support systems.

Bipolar Disorder↗

Differential effect of d-fenfluramine and metergoline on food intake in human subjects.

This study investigated the effect of the 5-HT receptor blocker metergoline (MTG) on d-fenfluramine (d-FF)-induced reduction of food intake in 13 normal male human volunteer subjects. Food was freely available for 2h, 4h after drug administration, from a four-channel automated food dispenser. d-FF (30 mg) reduced total food intake and exerted a marked effect on non-sweet food which was attenuated by the addition of MTG (4 mg). d-FF had less effect on sweet-tasting food while intake of sweet food was significantly increased by MTG. There was a significant interaction between d-FF and MTG on sweet-tasting foods. No effect on MTG was observed on d-FF-induced changes in ratings of hunger.

Adolescent↗

Cortisol, prolactin and growth hormone levels with clinical ratings in manic patients treated with verapamil.

Six bipolar patients in a manic episode were treated with the calcium antagonist verapamil. A decrease in the level of psychopathology was noted in 5 of the 6, though there was a tendency for patients to relapse in the third week of treatment. Cortisol levels decreased steadily with clinical improvement while growth hormone levels tended to rise. In contrast to traditional antipsychotics verapamil did not alter prolactin levels. Its neuroendocrine profile suggests its therapeutic effects are not mediated by dopamine receptor blockade.

Adult↗

A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients.

Fluoxetine, a selective serotonin reuptake inhibitor, was compared with mianserin and placebo in a double-blind study. In total, 81 depressed patients were included. Patients were rated weekly on the Hamilton Depression Rating Scale (HDRS) and the Montgomery & Asberg Depression Rating Scale (MADRS). The duration was 6 weeks, and 52 patients completed the study. Significantly more patients on fluoxetine improved than patients on placebo. For mianserin no significant differences were found with either fluoxetine or placebo. Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine, but not for mianserin, than placebo. Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3. Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7. Fluoxetine induced weight loss, while patients on mianserin gained weight. Side effects were present in most patients on the two active drugs; those on fluoxetine experienced nausea and vomiting, and those on mianserin drowsiness.

Adolescent↗