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Diurnal variation of urinary MHPG in unipolar and bipolar depressives.

In eight bipolar depressives, 11 unipolar depressives, and 15 healthy controls urinary excretion of MHPG was measured at 3-h intervals over one 24-h period. Bipolars excreted smaller amounts of MHPG than unipolars and controls, especially at night. MHPG excretion was significantly dependent on time of day in the control group only. In the patients maximum excretion showed a tendency to occur earlier in the day than in controls. Minima were unaffected. There were indications that tricyclic antidepressants advance MHPG phases.

Adult↗

Adverse drug reactions. An epidemiological study at psychiatric hospitals.

A drug monitoring system has been established at psychiatric university hospitals in Berlin, Goettingen, and Munich since 1979 in order to investigate adverse reactions to psychotropic drugs. This report describes the system and presents results obtained over 3 years. 504 randomly selected patients were observed by Intensive Drug Monitoring; 75% of them had an adverse drug reaction (ADR) during hospitalization that was assessed as possible, probable, or definite including all grades (I-III) of severity. 5,096 other patients were monitored by Organized Spontaneous Reporting during treatment with psychotropic drugs: ADRs were responsible for drug withdrawal (severity grade III) in about 10% of them. Parkinsonism, psychomotor disturbance, akathisia, delirium, oversedation and increased transaminases were the most frequent ADRs of this kind. The relative frequency of ADRs was calculated, and ADR-profiles established for drugs most frequently withdrawn. The impact of ADRs on ongoing therapy of patients was assessed. Reliable data obtained by drug monitoring systems can be expected to aid in therapeutic decisions in patients with special risks of side effects to psychotropic drugs.

Adult↗

Is levomepromazine a useful drug in treatment-resistant schizophrenia?

Levomepromazine (LMP) unexpectedly improved 16 of 23 chronic treatment-resistant schizophrenic patients who were hospitalized in most cases for at least 2 years and who manifested positive symptoms, irritability and, in many cases, restlessness, hostility, uncooperativeness, poor concentration and aggressive behavior. Improvement led to discharge in 7 (6 to a foster home), placement on a waiting list for a foster home in 4 and improved behavior and autonomy in 5 patients. Five subjects developed seizures and 1 agranulocytosis. Whether improvement with LMP is caused by unique antischizophrenic properties or by diminished liability to induce side effects such as akathisia, a formal controlled study of LMP in treatment-resistant schizophrenia is merited.

Adult↗

Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics.

Eleven chronic schizophrenic patients with abnormal skin pigmentation associated with neuroleptic treatment were withdrawn from chlorpromazine (CPZ), which was replaced by levomepromazine (n = 4), trifluoperazine (n = 1) or thioproperazine (n = 1) as the sole neuroleptic, by a combination of these phenothiazines (n = 4) or with haloperidol plus pipotiazine (n = 1). Seven patients showed complete resolution of abnormal skin pigmentation over a period of 1-5 years and 4 markedly improved over 2.0-2.6 years of follow-up. Our observations suggest that neuroleptic-induced abnormal skin pigmentation is (i) predominantly, if not exclusively, a side effect of CPZ and (ii) reversible, providing that CPZ is withdrawn and sufficient time is allowed to elapse.

Adult↗

Levomepromazine receptor binding profile in human brain--implications for treatment-resistant schizophrenia.

The receptor binding profile of levomepromazine (LMP) in human brain was compared with that of clozapine (CLOZ) and chlorpromazine (CPZ). LMP showed significantly greater binding affinity for both alpha-1 and serotonin-2 binding sites than either CLOZ or CPZ, and significantly greater binding to alpha-2 sites than CPZ. A potent pharmacological effect at these receptor sites may explain the beneficial effect of LMP on psychotic symptoms and akathisia in treatment-resistant schizophrenia recently described in 2 open studies. LMP requires further appraisal as a potentially useful neuroleptic in the management of treatment-resistant schizophrenia.

Adolescent↗

Is there any specific personality disorder or personality disorder cluster that worsens the short-term treatment outcome of major depression?

This study attempted to identify a specific personality disorder (PD) or PD cluster that independently worsens the 4-month treatment outcome of major depression under adequate antidepressant. The material of the study was 96 consecutive outpatients with major depression. For the Axis I and Axis II diagnoses, the Structured Clinical Interview for DSM-III-R (SCID) was used. In the material, the presence of any PD significantly worsened the 4-month outcome. The discriminant function analysis, conducted to identify a specific PD or PD cluster that influences the outcome, found that the number of PD from only cluster A and the number of criteria met for only schizoid PD was significantly correlated with the 4-month outcome of depression.

Adult↗

Pharmacokinetics and first-pass metabolism of levomepromazine in the rat.

The time course of the blood concentrations of levomepromazine and its two major non-polar metabolites in man were studied in the rat after single oral and intraarterial doses of levomepromazine hydrochloride. The blood levels of N-monodesmethyl levomepromazine were on average 179% of the levomepromazine levels after oral doses, but only 15% of the levomepromazine levels after intraarterial doses. The blood levels of levomepromazine sulfoxide, relative to the levomepromazine levels, were also generally higher after oral doses than after parenteral doses, on average 65% and 25%, respectively. Large interindividual variations were observed in the blood levels of levomepromazine and in the systemic availability of the drug after oral doses. The distribution phase lasted for about 8 hrs, the mean apparent volume of distribution was 16.6 l/kg, and the total body clearance was on average 12.3 ml/min. It is concluded that the rat provides a suitable model for the kinetics of levomepromazine in man, and that the sulfoxide and N-monodesmethyl metabolites of the drug are mainly formed by first-pass metabolism after oral doses in the rat, either in the liver or in the gut.

Animals↗

The antibacterial effect of selected neuroleptics on Vibrio cholerae.

The present investigation has been undertaken to illustrate the anti-bacterial effect of chlorpromazine, clopenthixol and levomepromazine-maleate. It has been shown that clopenthixol has the strongest antibacterial effect. It is known that chlorpromazine also has an antisecretory activity. The fact that clopenthixol exists in cis(Z)- and trans(E)-isomerical compounds, and that these compounds both have an antibacterial effect, but only the cis-compound has an antisecretory and neuroleptic effect, might suggest the development of more specific pharmaceuticals in these new fields.

Antipsychotic Agents↗

Effect of anaesthetizing the region of the paraventricular hypothalamic nuclei on energy metabolism during exercise in the rat.

The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The region of the PVN was anaesthetized with bupivacaine before running (26 m min-1) or continued rest, via previously implanted bilateral brain cannulas aimed at the dorsal aspect of the PVN. Control rats were treated identically to PVN-anaesthetized rats, but were not infused. Blood, for determination of plasma concentrations of metabolites and hormones, was drawn from a tail artery, and 3H-glucose was infused in a tail vein for glucose turnover determinations. At rest, no significant changes in plasma concentrations of metabolites or hormones were induced by anaesthesia of the region of the PVN. During exercise, glucose production and utilization and plasma concentrations of glucose, lactate, glycerol, noradrenaline, adrenaline, corticosterone, and glucagon increased (P < 0.02) and plasma insulin decreased (P < 0.02) in all rats. However, initially in exercise, adrenaline (4.3 +/- 0.8 vs. 7.9 +/- 1.0 nmol l-1 in controls, P < 0.05, t = 6 min) and later corticosterone levels (1.37 +/- 0.06 vs. 1.69 +/- 0.10 nmol l-1 in controls, P < 0.05, t = 20 min) were attenuated by PVN anaesthesia. Initially during exercise, glucose utilization was higher and plasma glucose lower in PVN-anaesthetized rats compared to controls (16.6 +/- 0.8 vs. 12.7 +/- 0.6 mumol min-1 100 g-1 and 7.1 +/- 0.2 vs. 8.1 +/- 0.2 mmol l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toxic "ictal" confusion in middle age: treatment with benzodiazepines.

In adult and elderly non-epileptic subjects psychoactive drugs may cause an altered state of consciousness and repetitive irritative EEG discharges. The neurotoxic pathogenesis of this drug-induced confusion and the differentiation from absence status are discussed. Dramatic relief by intravenous benzodiazepines is detailed. Recovery is complete and prognosis is excellent on withdrawal of the offending drug.

Adult↗