[Assessment of the clinical activity of fluoxetin (Prozac) according of the "Stars of Liège" model]. / Evaluation de l'activité clinique de la fluoxétine (Prozac) selon "les étoiles de Liège".

Ten psychiatrists have independently rated the clinical profile of fluoxetin (Prozac) at the daily dose of 20 mg according to a "Stars of Liège" model comprising three parameters of therapeutic activity (antidepressant, psychostimulant and anxiolytic) and three parameters of side-effects (anticholinergic, sedative and hypotensive). Each parameter, graduated from 0 to 5 (no, very weak, weak, moderate, potent, very potent effect) was rated by each investigator according to his personal experience with at least 10 patients. Mean ratings given to fluoxetine show a moderate antidepressant effect, equal to amitriptyline (Rédomex, Tryptizol 75 mg/d, clomipramine (Anafranil 75 mg/d and nialamide (Niamide 100 mg/d, weak psychostimulating and anxiolytic effects, a very weak sedative effect and a lack of anticholinergic and hypotensive effects. Digestive side-effects of moderate intensity were also noted as well as a very weak anorexia. The important variability between investigators in the rating of the clinical profile of fluoxetine suggests that more experience is needed in order to define better its physiognomy.

[Novel comparative profile of the clinical activity of antidepressive agents]. / Une physionomie comparée originale de l'activité clinique des antidépresseurs.

In order to develop practical criteria to guide in the selection of antidepressant medication according to depressive symptomatology, we propose a graphical representation of the clinical activity of 24 antidepressants according to a "star" model. Six parameters have been evaluated from 0 to 5 in comparison to reference drugs (rated 5) by 11 independent "blind" psychiatrists expert in pharmacotherapy. Three parameters were used as measures of therapeutic activity: antidepressant, psychostimulant, and anxiolytic, with iproniazide 75 mg/d, metamphetamine 15 mg/d, and diazepam 20 mg/d as reference drugs respectively. Three additional parameters assessed the level of side-effects: anticholinergic, sedative, and hypotensive, with atropine 0.75 mg/d, phenobarbital 200 mg/d, and iproniazide 75 mg/d as reference drugs respectively. The defined dose represented the standard maintenance daily dose for depressive outpatients. Mean values for each parameter, rounded off to the closest number, were used for the graphical representation. Results showed an excellent agreement among evaluators for the clinical profile of classical tricyclic and MAOI antidepressants, but serious divergences for the more recent drugs (e.g., viloxazine and mianserine), possibly reflecting more atypical or more variable clinical profile of these compounds.

Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression.

The therapeutic effect and safety of alprazolam and doxepin were studied in 126 outpatients suffering from primary unipolar depression. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with a flexible dose of 1.0-4.5 mg of alprazolam and 50-225 mg of doxepin per day. The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin. The results indicate that alprazolam and doxepin were equally efficacious. The incidence of side-effects was lower in the alprazolam treatment group.

Methodology required to show clinical differences between benzodiazepines.

Clinical differences exist between the benzodiazepines but demonstration of such differences requires a more specialized methodology than that normally used in comparative trials. It is recommended that double-blind studies should be carried out in hospitalized patients with severe and chronic anxiety, selected according to precise criteria, and that the trials should be designed as crossover rather than as parallel group studies, with randomization of the stages and flexible dosage. A simple graphic method of representing the clinical profile of individual benzodiazepines is described and it is suggested that this could help clinicians adapt their prescribing to each patient's symptoms.

Lormetazepam and amobarbital sodium in the outpatient treatment of insomnia: a controlled trial.

In a double-blind clinical trial, 50 psychiatric outpatients with moderate insomnia (requiring daily treatment with a hypnotic drug) were treated for two weeks with lormetazepam (1 mg) or amobarbital sodium (100 mg). In interviews before and after treatment, data were collected on the patients' demographic characteristics, sleep disturbances, concomitant organic or psychiatric disorders, and opinions of the drug taken during the two-week period. During the trial the patients took notes on their use of the drug, the quality and duration of their sleep, and any adverse effects of the drug they were using. Lormetazepam and amobarbital were equivalent in the amount of time it took patients receiving each drug to fall asleep and in the duration of the patients' sleep, but insomnia disappeared (or the condition improved) in a larger proportion of patients receiving lormetazepam, and there were fewer adverse effects (eg, hangover in the morning, sedation in the morning and during the day, and dry mouth) in patients receiving lormetazepam than in patients receiving amobarbital.

[Lormetazepam and amobarbital in the treatment of insomnia in psychiatric outpatients. A controlled study]. / Lormetazepam et amobarbital dans le traitement ambulatoire de l'insomnie. UneXétude contrôlée.

During a double-blind clinical study, a new hypnotic benzodiazepine, lormetazepam (Wy 4082), was compared at a fixed dose of 1 mg to sodium amobarbital at a fixed dose of 100 mg for the treatment of moderate insomnia in 2 groups of 25 psychiatric outpatients. The medication was given at bedtime and the duration of the study was limited to 2 weeks. The quality of sleep was evaluated by the patient after the first night and at the end of the first and second week and by investigator at the end of the 2 weeks trial. The two products appeared effective on global assessment, but with an advantage in favour of lormetazepam: earlier onset of sleep and excellent acceptability on the final evaluation. Fifty two per cent of patients treated with amobarbital had side effects, mainly hangover and sedation during the morning, while only one patient treated with lormetazepam complained of headaches in the morning.

Biochemical and neuroendocrine approaches to a malignant syndrome of neuroleptics.

A 20 year old patient who has been hospitalized for depressive schizoidia is treated by nomifensine (75 mg/d) plus pimozide (4 mg/d). Four days later, he shows a typical neuroleptic malignant syndrome (Syndrome malin de Delay et Deniker). The biological explorations show that inflammatory blood tests are increased, hepatic tests are disturbed and the pituitary tests suggest a hypothalamic disturbance of the balance between NE and DA (reduced STH, FHS and LH) with a relative NE predominance, but also an increase of DA (increased HVA in CSF. A pathogenic interaction between nomifensine, an antidepressant inhibiting the reuptake of NE and DA, and pimozide, a neuroleptic blocking dopaminergic postsynaptical receptors is to be considered.