In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.

In this retrospective pragmatic study, we define the necessary conditions that allow outpatient low dose intravenous neuroleptization, when hospitalization should otherwise be required. Intravenous neuroleptization is infrequently used in the outpatient treatment of acute psychotic decompensation. Rapid tranquilization with high dosage neuroleptics is controversial, and has a high risk of side effects. The indications for and potential advantages of this method in the perspective of a long-term ambulatory treatment are discussed by comparing a group of outpatients treated with infusions to a group of hospitalized patients. The method offers a satisfactory alternative to hospitalization for subjects who are not in imminent danger (current GAF rating between 20 and 40) and whose normal functioning is good (past year GAF rating = 70). Previous repeated hospitalizations favor the choice of hospitalization over infusion. Its potential advantages are the rapid evolution of the condition, with controlled regression but without psychosocial withdrawal, and an improvement in the patient's attitude towards treatment.

Psychosis of epilepsy (POE) is a term applied to a group of psychotic disorders with a distinct phenomenology in which potential etiopathogenic mechanisms are believed to be closely related to a seizure disorder. POE can present as interictal psychotic episodes, which may often differ semiologically from primary schizophrenic disorder. They may present as ictal or postictal psychotic episodes and may be the expression of an iatrogenic process to pharmacologic and/or surgical interventions.Epilepsy and POE have a complex and bidirectional relation, as not only are patients with epilepsy at greater risk of developing a psychotic disorder, but patients with a primary psychotic disorder are also at greater risk of developing epilepsy. The prevalence of POE is more than 7 times higher than the frequency of primary schizophreniform disorders in the general population. While POE has been associated with focal epilepsy of temporal and frontal lobe origin, its etiology and pathophysiology of POE have yet to be established.The treatment of all forms of POE, with the exception of ictal psychotic episodes, requires the use of antipsychotic drugs, preferably the atypical antipsychotic agents with a very low or negligible potential to lower the seizure threshold (eg, risperidone, apiprazole), starting at a low dose with stepwise increments.

Objective - Following the introduction of guidelines of rational drug use, the pharmacoepidemiology of psychotropic drugs was investigated in a sample of long-stay patients living in a Italian psychiatric hospital. Design - Aprospective, longitudinal two-year follow-up study was carried out. Information about sociodemographic and clinical characteristics of the inpatientpopulation, and about medications prescribed, was collected at baseline and after one and two years of follow-up. Setting - Three wards of the psychiatric hospital of Milan. Main outcome measures - Number of patients taking psychotropic drugs, number of patients taking more than one neuroleptic or benzodiazepine, mean neuroleptic dose, psychopatological status according to the Brief Psychiatric Rating Scale (BPRS). Results 70 patients were recruited and followed for two years. At follow-up a reduction in the number of patients taking neuroleptic drugs was recorded, together with a 50% decrease in the number of patients taking more than one neuoleptic. A reduction in the use of depot formulations was in addition shown. Patients taking benzodiazepines decreased of 50%. According to the BPRS, no psychopatological changes were observed during the study. Conclusions - These data suggest that education in psychopharmacology may guide towards a more rational use of drugs; longitudinal clinical audits should be implemented to monitor everyday practice.

African trypanosomes are parasitic protozoa causing sleeping sickness in humans and related diseases in domestic animals against which no entirely satisfactory forms of chemotherapy are yet available. It was previously shown that related species of trypanosomes, as well as procyclic (insect) forms of Trypanosoma brucei are extremely sensitive to the action of phenothiazine neuroleptic drugs in vitro. In this work, we have carried out a more detailed investigation of the effects of thioridazine, one of the most potent neuroleptic phenothiazine drugs known, on the morphology of the infective bloodstream forms of T. brucei, with particular reference to the parasite's prominent pellicular membrane complex. Our data show that this drug induces rapid changes in cell shape that appear to involve some reorganization of the microtubular membrane skeleton, but does not affect the structural integrity of the microtubular complex. Another early consequence of drug action involved damage to nuclear and cytoplasmic membranes and the appearance of tubular arrays of coated membrane within the flagellar pocket. It was also revealed that the drug induces a rapid release of the variant-specific glycoprotein (VSG) which makes up the surface coat protecting bloodstream forms of the parasite against the host immune system. Our evidence suggests that this release of VSG involves cleavage of the protein's glycosyl-phosphatidylinositol (GPI) membrane anchor by endogenous GPI-specific phospholipase C, probably as a consequence of minor damage to the parasite plasma membrane induced by the drug.

Objective: A recurring question is whether evidence from systematic reviews has any impact on medical practice. We have studied this question in relation to some conclusions in seven reports, where relatively simple means to monitor trends could be used.

Results: As recommended, in the report preoperative routines the number of preoperative examinations diminished at six hospitals, during around 3,000 operations studied, a savings of SEK 130 million. After the report on moderately elevated blood pressure sales of the preferred drugs, diuretics and beta-blockers, stopped falling while calcium blockers and ACE inhibitors stopped rising. As concluded in the report, general prostate cancer screening has not been introduced, but tests as a sign of opportunistic screening have increased. Bone density measurements were not recommended for screening, and sales of equipment have declined after the report. The use of neuroleptics as unspecific calming therapy for old persons was discouraged due to the serious side effects. The frequency of patients given this medication diminished from 34% to 28% at nursing homes after 1 year. For smoking cessation, the use of nicotine substitution medications has increased, which is in line with suggestions presented in the report. For stomach pain proton pump inhibitors given for functional dyspepsia have diminished in a region of the country after special efforts to disseminate the message.

Conclusions: It appears to be possible to monitor changes in practice corresponding to selected conclusions in systematic reviews. After rather extensive disseminating efforts, some results look encouraging.

The disinhibitory effect has long been described as a therapeutic property of some neuroleptic drugs (NL) able to improve negative symptoms.

In pharmacology behavioral models indicate a functional facilitation of dopaminergic transmission. Moreover, a group of negative symptoms very similar to those improved by disinhibitory NL may be induced as a side effect by other NL. Therefore the syndrome improved by these few NL could be linked to functional hypodopaminergic modifications. The improvement of negative symptoms by these few NL is linked in the Animal and in Man to the administration of low doses. We propose that these drugs be called “energizing neuroleptics”. Recent clinical studies have answered various important questions concerning this effect:

• • patients with predominant negative or positive symptomatology do need different dosages of these NL;

• • the low doses of these energizing NL are more effective for the treatment of negative symptoms than low doses of other NL;

• • the energizing effect is not specific for schizophrenic patients, but can be shown if a negative syndrome is present. A subgroup of dysthymic patients could present a relatively pure hypodopaminergic syndrome. Even if anhedonic, these patients are not really depressed; we propose to call them psychasthenic.

The energizing effect presents an original mecanism of action and a target “transnosological” syndrome. The corresponding group of NL should appear in the classifications alongside sedative and antihallucinatory (or antiflorid) NL.