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Biomedical subjects

T Silverstone

Publications and source records attributed to T Silverstone.

At least 19 recordsLinked to original sources

A comparison of the effects of d- and l-fenfluramine and d-amphetamine on energy and macronutrient intake in human subjects.

The anorectic activity of the d and l isomers of d-fenfluramine (d-FF) (l-FF) were compared with d-amphetamine (d-amp) when given separately and together in 12 healthy male volunteers. The study was double blind and placebo controlled. Food intake was measured using an automated food dispenser. Anorectic activity was examined using a) total energy intake b) nutrient selection c) selection of foods categorised by nonsweet/sweet taste. Total energy intake was significantly reduced by d-FF (17%) d-amp (26%) d-FF + d-amp (36%) and l-FF + d-amp (31%). d-Amp and both combinations significantly reduced energy intake from all macronutrients in the total food. d-FF reduced carbohydrate but not fat or protein intake derived from all foods. When nonsweet and sweet tasting foods were examined separately, l-FF also significantly reduced energy (by 19%), fat and carbohydrate intake from nonsweet food. Neither d-FF nor l-FF reduced protein from nonsweet food. No anorectic drug given alone reduced sweet food intake, only d-amp given with d-FF had this effect. In contrast to nonsweet food, d-FF did not reduce carbohydrate from sweet foods. The results are in agreement with previous work that d-FF spares protein consumption but suggest that d-FF does not selectively reduce carbohydrate intake per se.

Adult

Life events and relapse in bipolar affective disorder.

In a 2 year study of life events and relapse in a cohort of 62 patients with bipolar affective disorder, an excess of events was found during the month immediately preceding relapse. Of 52 relapses 19% were preceded by a severe event in the previous month, compared to a background rate of 5% of patients experiencing a severe event each month at other times. The rate of life events prior to relapse was not apparently different between manic and depressive relapse, though the number of depressive episodes was small.

Adult

Centrally acting anorectic drugs: a clinical perspective.

This paper reviews the anorectic activity and effectiveness of catecholamine and serotoninergic anorectic drugs in the management of obesity. It discusses the clinical implications of the experimental findings and suggests prescribing strategies for effective long-term therapeutic benefit. The authors advocate that there is a role for the recently developed serotonin-mediated anorectic compounds in the treatment of obesity, particularly in those individuals with abnormal glucose tolerance or who are hypertensive.

Appetite Depressants

The effects of lithium on body weight and food intake in normal subjects--a pilot study.

The possibility of lithium increasing hunger and food intake was examined in an open, pilot study involving five healthy male volunteers each of whom took lithium for 1 month at a dose to give mean 12 h serum lithium level of 0.5-0.8 mmol/l. Before starting lithium, after the first dose and again after 1 and 4 weeks on lithium, subjects attended the unit at lunch time. They were starting lithium, after the first dose and again after 1 and 4 weeks on lithium, subjects attended the unit at lunch time. They were weighed and ate their lunch time meal from a food dispenser similar to those in canteens. Subjective rating scales were completed before and after eating. No change in weight was seen. Food intake was slightly increased at the end of the month on lithium compared with the start but had fluctuated during the intervening weeks. There was no relationship between food intake and weight change.

Adult

New aspects in the treatment of depression.

Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future.

Depressive Disorder

Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder.

A 12-month double-blind trial of carbamazepine vs lithium, given as sole treatment for the prophylaxis of bipolar affective disorder, was carried out in 31 patients. All were previously stable on lithium; 15 were switched over to carbamazepine and 16 remained on lithium. Although the overall relapse rate was similar in the 2 groups (6 on carbamazepine, 8 on lithium), nearly all the relapses in carbamazepine occurred in the first month, probably precipitated by lithium withdrawal. Two patients on carbamazepine developed a rash and were withdrawn. More side effects were noted during the early stages on carbamazepine. Patients on lithium tended to gain weight (+4 kg) compared with carbamazepine (-3.1 kg). It is concluded that carbamazepine is as effective as lithium in the prophylaxis of bipolar affective disorder; changeover from lithium to carbamazepine should be done slowly.

Adult

Season and manic relapse.

The episodes of mania occurring in a cohort of 86 patients with bipolar affective disorder were recorded over a 6-year period. Of the 54 patients who had at least 2 episodes, 8 (15%) met our criteria for a seasonal pattern of relapse. There was no particular season in which these relapses clustered. Overall, the time of year of the first recorded episode during the 6-year period did not predict the timing of subsequent episodes.

Bipolar Disorder

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