Intractable epilepsies. An open trial with Clobazam.

Clobazam was used as an added treatment in 28 patients with intractable epilepsies: 26 subjects had associated handicaps. A good response was observed during the first two-three months of Clobazam treatment: the reduction in seizure frequency of 73% for partial seizures and 62% for GTCs. A tolerance to Clobazam treatment was observed after the third month of treatment: at the end of the sixth month, the seizure frequency was reduced to 36% for partial seizures and 39% for GTCs. Out of 28 patients 4 were seizure free at the end of the sixth month; we have not found any specific characteristic in these patients. The AA. suggest the possibility of an intermittent use of Clobazam for this type of patients.

Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation.

Growth hormone (GH) response to clonidine and growth hormone-releasing hormone (GHRH) stimulation, together with baseline somatomedin C (SmC) levels, were examined in parallel in a group of 21 patients with anorexia nervosa (AN) and in 10 controls. In addition, the Hamilton Rating Scale for Depression (HRS) was administered to the patients. Clonidine (2.5 micrograms/kg body weight, iv) induced GH elevations that were not significantly different between patients and controls. In contrast, GHRH (1 microgram/kg body weight, iv) produced a significantly higher GH response in anorectics than in controls. The ratio between GH responses (area under the curve, or AUC) to GHRH and to clonidine was significantly higher in patients than in controls. Baseline SmC levels (6 patients) were significantly lower in anorectics than in controls. Minor depressive symptomatology was present in all patients. When viewed in relation to the GH hyperresponsiveness to GHRH, the apparent normality of the response to clonidine in anorectics reflects the existence of an actual alpha 2-adrenoceptor subsensitivity. As clonidine reportedly acts via release of endogenous GHRH, an excessive, rather than a normal, GH response to clonidine was to be anticipated.

Neuropeptide therapies in chronic schizophrenia: TRH and vasopressin administration.

Twenty-three chronic undifferentiated schizophrenics, 13 women and 10 men, aged 37-64 years with 15-to 40-year histories of the disease were given either thyrotropin-releasing hormone (TRH) (10 subjects) or DDAVP (13 subjects) with the aim to improve the negative symptoms of the disease and memory. TRH (600 micrograms i.v.) and DDAVP (4 micrograms i.m.) were administered every other day for 30 days. Negative symptoms were monitored by the Andreasen rating scale and by the Honingfeld NOSIE rating scale, memory by the Folstein 'Mini mental State' rating scale and by the Luria-Nebraska rating scale before therapy and then at days 15, 16, 30 and 31 of treatment. Both therapies significantly improved negative symptoms. Memory was significantly improved in all the patients treated with TRH and in 9 of the 13 patients treated with DDAVP, who presented less severe cognitive impairments. A peripheral mechanism of action of DDAVP was excluded by the observation that plasma electrolytes and osmolality, blood pressure, ECG patterns, 24-hour urine volume and specific gravity, basal plasma cortisol and growth hormone levels and weight of the patients were unchanged during therapy. TRH treatment induced a transient borderline hyperthyroidism at day 15 and a progressive decrease of the thyrotropin response to TRH stimulation. A common mechanism of action of the two peptides on the central noradrenergic system is suggested.

Bromocriptine therapy in chronic schizophrenia: effects on symptomatology, sleep patterns, and prolactin response to stimulation.

Ten chronic schizophrenic patients were given bromocriptine in doses increasing from 1.25 to 5 mg over 6 days (the low-dose therapy) and then up to 40 mg over 15 days (the high-dose therapy). Psychopathological status was assessed using the Brief Psychiatric Rating Scale, twice daily the first 6 days, and every 2 days thereafter. The prolactin (PRL) response to haloperidol stimulation (1 mg i.v.) was measured in five cases before and 3 days after the end of high-dose therapy, and in one patient before and 3 days after the end of low-dose therapy. Electroencephalographic sleep studies were carried out before therapy and every 2 nights during low-dose therapy in five patients, and in two cases during high-dose therapy. Bromocriptine therapy modified neither clinical symptomatology nor sleep patterns. The PRL response to haloperidol after therapy was markedly lower than that before therapy in the five patients treated with high doses, and markedly higher in the single patient tested who was treated only with low-dose therapy.

Abnormal anterior pituitary responsiveness to hypothalamic hormones in primary affective disorders. Effect of desipramine therapy.

Abnormal anterior pituitary responsiveness to acute administration of thyrotropin-releasing hormone was investigated in 8 patients, 6 women and 2 men, with primary affective disorders in a depressive phase and in 2 women with schizoaffective disorders. Thyrotropin-releasing hormone, 500 micrograms i.v., induced a rise of plasma growth hormone levels in 1 patient suffering from primary affective disorders and in the 2 schizoaffective subjects, a rise of follicle-stimulating hormone in 1 schizoaffective patient, of luteinizing hormone in the 2 schizoaffective patients, an excessive prolactin rise in 5 patients with primary affective disorders and in 1 schizoaffective subject and a flat response of thyroid-stimulating hormone in 4 patients with primary affective disorders and in 2 schizoaffective patients. Desipramine was given at a dose of 50-100 mg/day for 3-5 weeks. The thyrotropin-releasing hormone stimulation test was repeated when the patients were improving or after 5 weeks of treatment without improvement. The hormonal impairments tended to disappear in those patients showing symptomatic improvement and were still present in those who did not improve.