Lithium ratio, phospholipids and the incidence of side effects.

The main aims of our Lithium Centre, which has been operating since 1985, are as follows: 1. the treatment of affective disorders and particularly the recurrent ones; 2. the emphasis of the Li-ratio as a predictive index of therapeutic effects on the one hand, and of the appearance of side effects on the other hand; 3. the prevention and pharmacological control of side effects and research about their mechanism of arising.; 4. organization of a computerized bibliographic service.

Lithium-TCA induced malignant syndrome. Case report.

1. The authors describe some adverse reactions, induced by lithium and TCA administration, in a 71 years old woman treated for mixed bipolar disturbance. 2. The case history here described, is perfectly compatible with a diagnosis of Malignant Hyperthermia (MH). 3. Utility of the association of hypothalamic phospholipid liposomes (HPL) and myorelaxants in the reduction of these lithium side effects, is discussed.

Clinical notes on buspirone.

The main aspects of the recent development of non-benzodiazepine anxiolytic drugs are the following: the possibility of giving drugs with peculiar anxioselective profile and with no benzodiazepine side-effects; the possibility of discriminating the anxiolytic from the hypnotic activity; the possibility of a nosographic delimitation: buspirone is used mainly in the treatment of generalized anxiety disorders. All these factors point to the possibility of a guided or planned anxiolysis with a more active participation from the patients.

Notes on human behavioural pharmacotoxicology.

1. After 30 years of psychopharmacological therapy we are able to identify some aspects which can be referred to a "collateral behavioural effect". The apparent rarity of this depends on the facility of confusing behavioural modifications (often sine materia), with patological ones (normally of a physical nature). 2. Memory, learning, the ability of evoking, problems regarding reality, paradoxical reactions, "makefobic" behaviour, passivity and social and behavioural withdrawal, form part of the Human Behavioural Pharmacotoxicology. 3. This ought to deserve greater attention on the part both of research workers and health authorities.

Evaluation of circadian, circaseptan, and circannual periodicity of attempted suicides.

A retrospective investigation has been carried out on the incidence of attempted suicides registered at the Fatebenefratelli Hospital in Milano, during the span from June 27, 1978 to November 11, 1980. On a total of 451 cases, the age, sex, hour, day of the week and date of the attempted suicide have been recorded for each single case. The cosinor analysis for tau = 24 h has shown that a circadian periodicity is statistically significant both for the total of men (phi =-265 degrees +/- 17) and for the total women (phi =-285 degrees +/- 13), with p less than 0.01. The maximum incidence occurs during the later afternoon (approximately between 1700 and 1900). The results are similar to those obtained for the younger subjects only (up to 22 years), while for the following range of age, (22 to 40 years), and after 40 years, the rhythm is not so well demonstrable. As regards the circaseptan rhythm, it is quite evident for women, both up to 22 years (maximum incidence on Friday) and between 23 years and 40 years (maximum incidence Thursday), and from 40 years onwards, but it is not demonstrable for men. A circannual rhythm is demonstrable, on the contrary, both for men and women: the maximum incidence is in May for men and in February for women.

Growth hormone response to thyrotropin-releasing hormone and gonadotropin-releasing hormone stimulation in heroin addicts.

Previous endocrine investigations have demonstrated the presence of multiple impairments of pituitary-target gland function in heroin addicts suggesting a possible hypothalamic involvement. Since the response of the pituitary to nonspecific stimuli is considered an expression of hypothalamic dysfunction, indicating a disconnection between the central nervous system and the anterior pituitary, we thought it worthwhile to study the GH response to stimulation with thyrotropin-releasing hormone (TRH) or gonadotropin-releasing hormone (GnRH) in heroin addicts. 23 male heroin addicts, aged 18-40 years, with histories of addiction to heroin alone from 8 months to 4 years, and daily i.v. heroin intakes between 200 and 2,500 mg of the drug (containing 18% pure heroin) were studied. 8 patients received TRH 500 micrograms, GnRH 150 micrograms and 5 saline only, intravenously, and GH levels were assayed radioimmunologically in bloods taken 30 min before, at the moment of stimulation and 15, 30, 60, 90 and 120 min thereafter. The results show normal base GH levels. Stimulation with TRH and GnRH induced marked GH hypersecretion in 8 of the 18 patients examined. These results suggest that the hypothalamo-pituitary function may be impaired in heroin addiction.

Plasma concentrations of amitriptyline during single nightly and thrice daily administration. Cross-over study.

Plasma amitriptyline and nortriptyline concentrations were measured in ten depressed in-patients after administration of amitriptyline hydrochloride 75 mg in three divided doses or as a single nightly dose. Mean steady state plasma concentrations during the two dosage regimens were similar. Plasma level differences between dosage schedules at sampling times were small and not significant. It was concluded that the single nightly administration of amitriptyline is a helpful therapeutic schedule which can be used instead of the divided dose when the opportunity is given.

Amitriptyline: comparison of three different dosage schedules in neurotic depression.

Three groups of neurotic depressed patients were treated with amitriptyline, one group receiving the customary three daily doses, another a single dose in the morning, and the third a single dose at night. All three groups showed significant decrements of total scores on the Hamilton Scale for Depression and the Zung Self-Rating Depression Scale without significant differences. Patients taking the drug at night showed a lower incidence of side effects.

Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in heroin addicts.

To determine whether the pituitary-gonadal deficiency in heroin addicts is related to heroin's effect on the hypothalamus, the authors administered gonadotropin hormone-releasing hormone (GnRH) to 10 male heroin addicts and 5 controls and measured follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response. Basal FSH and LH levels were significantly lower in addicts; after GnRH stimulation the addicts' FSH and LH values increased but not significantly compared to controls. The difference between the two groups' response was highly significant. The authors suggest that heroin causes an incomplete blocking of gonadotropin secretion at the pituitary level, inducing a hypophyseal-gonadal deficiency and a long-lasting depletion of the endogenous releasing factor, which accounts for the reduced response to GnRH.

Sulpiride and headache syndromes.

Numerous studies have indicated that sulpiride exerts a positive effect upon several psychosomatic symptoms. This effect is generally believed to depend on the thymoanaleptic activity of the molecule. Since headache can often represent the warning symptom of a masked depression, in the present study sulpiride has been administered to patients suffering from nonorganic headache syndromes. The results obtained confirm the efficacy of sulpiride in relieving headache and other psychosomatic discomforts.

Sulpiride and extrapyramidal syndromes in chronic heroin addiction.

During the treatment of 53 young heroin addicts with intramuscular sulpiride for the prevention of withdrawal symptoms, the emergence of extrapyramidal manifestations involving the head, neck and upper trunk in about 40 percent of the patients has been observed. These symptoms occurred with sulpiride dosages in the 'antineurotic' range (not more than 400 mg daily), which practically never produce such symptoms in patients receiving the drug for other clinical indications. The symptoms appeared soon after the first few injections of sulpiride, and yielded readily to a single or repeated intravenous diazepam administration (10 mg). The possible mechanism involved in the production of extrapyramidal manifestations from sulpiride, and a tentative explanation of why such symptoms are produced by doses of this drug lower than those needed to produce the same effects in nonaddicts, are discussed.