The genetic cytochrome P450 polymorphism is reported in factors affecting the individual response to drugs. The interindividual variation at steady-state levels or also in elimination of drugs, finds an explanation in genetic differences in the metabolism. In particular, activities of the P450-IID6 isoenzyme are related to the sparteine/debrisoquine oxidation polymorphism. Phenotyping such a system has been proposed to analyse variability in the tricyclic antidepressant level. To analyse clinical relevance of a pharmacogenetic approach, we studied the cytochrome P450 CYP2D6 genotypes and the clinical responses to clomipramine in 21 hospitalised patients who met DSM-III-R criteria for major depression. Three patients were predicted as poor metabolizers. We suggested a limitation of clomipramine (CMI) hydroxylation in poor metaboliser (PM) patients which is balanced by a desmethylation. The clinical efficacy pattern does not differ in poor metaboliser and early metaboliser patients. Firstly, there is no significant differences in the evolution of scores on MADRS and specific retardation scale into the two groups. Secondly, outcome of side effects does not occur more frequently in PM patients. Clinical relevance of such an approach needs further study.

The National Comission on Sleep Disorder Research evaluated the status of insomnia and other sleep disorders in the US. The Commission found that insomnia is prevalent affecting 20–30 million Americans, has significant morbidity especially related to attention and memory processes and cost the US an estimated $ 15 billion a year. It also estimated that all of these figures should rise significantly by the year 2000. Other sleep disorders (eg, narcolepsy and sleep apnea) although less prevalent have significant costs to patients and society associated with them. The Commission recommended that the US develop a research and education program to develop new insights into the basic mechanisms of sleep disorder. The education program needs to be directed to the general public; medical practitioners, as well as patients.

A middle aged lady having Manic-depressive psychosis developed neuroleptic malignant syndrome (NMS) on haloperidol. The emergent psychosis after recovery from NMS resolved with judicious use of electro-convulsive therapy (ECT) followed by gradual reintroduction of antipsychotics is reported here.

Psychological and physical signs traditionally considered as indicators of conversion disorder had never been confirmed through empirical data. Nineteen of these signs were sought in 40 patients with proved neurological disorder and in 15 patients with conversion disorder. All neurological patients but one showed at least one of these signs and most presented several signs. All the signs but one were as frequent in neurological patients as in patients with conversion disorder. These signs are lacking specificity. Even when several signs are present, this finding has no diagnostic specificity.

Enuresis is an embarrassing rare side effect of clozapine treatment. Using single-blind placebo-control design, the antienuretic activity of the calcium channel blocker verapamil (up to 80 mg/day per os, at 21.00 hours) was evaluated in a schizophrenic patient with comorbid obsessive-compulsive disorder (OCD) who developed nocturnal functional enuresis during clozapine treatment. Verapamil (80 mg/day) displayed antienuretic activity. No correlation between the bradycardiac effect and the antienuretic activity of verapamil was detected.

Antipsychotic drugs are used in a range of schizophrenic patients from the acutely disturbed to the chronically inert. Acute psychotic breakdowns usually involve secondary phenomena such as anxiety, depression and hostility superimposed on a worsening of the psychotic illness: a threshold of arousal is exceeded. This sets up a vicious circle which requires a major therapeutic effort to interrupt. Unfortunately, patients still relapse despite apparently adequate medication, suggesting only partial protection. Relapse is influenced by drug-related factors such as compliance and substance abuse, psychological factors such as cultural context, family dynamics and life events, and illness features such as poor insight. Treatment strategies, such as low-dose and intermittent medication, have proved disappointing. The most pragmatic model is the classic stressor-vulnerability model, but this does not explain the enhanced efficacy of clozapine.

The mechanism of action of the cyclopyrrolone hypnotic drug zopiclone involves allosteric modulation of the GABAA receptor. Zopiclone displaces the binding of [3H]-flunitrazepam with an affinity of 28 nM, and enhances the binding of the channel blocker [35S]-TBPS. The binding of zopiclone, unlike that of hypnotic benzodiazepines, is not facilitated by GABA. Zopiclone does not distinguish between GABAA receptors containing different α-subunits (BZ1 and BZ2 phenotype). Studies with protein-modifying agents (eg diethylpyrocarbonate) and photoaffinity labelling suggest that cyclopyrrolones bind to a domain on the GABAA receptor different from the benzodiazepine binding domain. The consequence of this interaction with the GABAA receptor is to potentiate responses to GABA, as can be demonstrated by electrophysiological methods. Subchronic treatment of mice with high doses of zopiclone does not produce the changes in sensitivity of the GABAA receptor that are observed with hypnotic benzodiazepines.