Epidemiology of first- and second-generation antipsychotic agents in Lombardy, Italy.

INTRODUCTION: This study investigated the age and gender distribution of antipsychotic prescribing in Lombardy, a region of nine million inhabitants in northern Italy. METHODS: From the Regional Administrative Database of Lombardy, all ambulatory prescriptions of antipsychotics dispensed during 2001 were extracted and prevalence data were calculated by dividing users by the total number of male and female residents in each age group. RESULTS: During the study period 86,187 subjects were dispensed antipsychotic agents, yielding a prevalence of use of 0.87 (95 % CI: 0.86, 0.88) per 100 males and 1.01 (95 % CI: 1.00, 1.02) per 100 females. The prevalence of use progressively rose with age in both sexes, with the highest rates in old and very old subjects. The prevalence of use of first-generation antipsychotics progressively increased with age and dramatically increased in old and very old subjects; in contrast, the prevalence of use of second-generation antipsychotics remained substantially stable or slightly decreased up to 65 years of age and increased thereafter. CONCLUSION: Antipsychotic agents are prescribed widely in the general population, and very high rates were observed in those aged 80 years or more.

Prescribing second-generation antipsychotics and the evolving standard of care in Italy.

The present study was carried out to investigate the routine use of second-generation antipsychotic drugs in the Italian psychiatric care system. Seven outpatient psychiatric services enrolled a consecutive case series of patients who were being treated, or had started treatment, with clozapine, olanzapine, risperidone, or quetiapine. Information on sociodemographic and clinical variables, current psychotropic drug use, side-effects and past use of typical drugs was collected. In addition, patient symptoms and functional status were evaluated by the Health of the Nation Outcome Scale. Patients receiving off-label prescribing of second-generation antipsychotics were identified. A total of 209 patients were collected. In comparison with patients receiving other second-generation antipsychotics, living in residential facilities, unemployment, long psychiatric histories, and problems with activities of daily living and living conditions were more common in clozapine-treated patients. Nearly 80 % of patients receiving clozapine had schizophrenia compared to less than 50 % of those receiving other second-generation antipsychotics. Overall, 109 patients (52 %) received off-label prescriptions of second-generation antipsychotic drugs. This survey indicates that clozapine was mostly reserved for severe cases and poor responders; the high rate of off-label prescriptions highlights the gap existing between recommendations derived from randomised clinical trials and the current use of drugs.

Direct and indirect costs of schizophrenia in community psychiatric services in Italy. The GISIES study. Interdisciplinary Study Group on the Economic Impact of Schizophrenia.

BACKGROUND: The present work is a cost-of-illness (COI) study that aims at assessing total direct and indirect costs of schizophrenic patients in community psychiatric services in Italy and identifying the variables that influence costs. METHODS: A retrospective prevalence-based multi-centre COI study, was designed. Ten community mental health centres (CMHC) were involved and 100 patients were recruited. Data on patients' costs were gathered through specifically designed instruments. RESULTS: More than half total direct costs were attributed to CMHC interventions. The yearly average costs of schizophrenia per patient amounted to nearly ITL 50 million: 30% for direct costs and 70% for indirect costs. CONCLUSION: CMHCs tend to manage long-term ill patients by adopting a strong community-based system of care. Schizophrenia is correlated to loss of working days and lack of well-being. From the results of this study, it might be argued that the de-institutionalisation programme has produced 'spillovers' in terms of families' greater involvement in patients management.

The costs of pharmacological treatment for major depression. The Italian Prospective Multicentre Observational Incidence-Based Study.

OBJECTIVE: To describe the pharmacological treatment for major depression under the conditions of routine Italian public mental health facilities, assess its costs, and study its main predictors according to a societal perspective. DESIGN: This was a prospective multicentre observational study designed to evaluate the economics of treatment of major depression using a specifically designed 65-item questionnaire. Data on drug consumption were collected in a section of the questionnaire and are presented here. PATIENTS AND PARTICIPANTS: 60 mental health facilities were selected and 556 patients were enrolled and followed up for 15 months. RESULTS: Pharmacological treatment appears to be the most common treatment for major depression. 98% of patients were prescribed an antidepressant. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed antidepressants. Patients treated with SSRIs suffered from less severe depression than those treated with tricyclic antidepressants. Benzodiazepines were prescribed for 84% of patients enrolled. The total drug cost was 1,120,000 Italian lire ($US707) per patient (1995 values). Less than 20% of this cost was borne by the Italian National Health Service, as the majority of drugs used were not reimbursed. CONCLUSIONS: The costs of the most widespread approach to treating major depression (pharmacological treatment) are not currently covered by the Italian National Health Service. Prescribing of drugs seems to diverge from the standards of treatment indicated by the Italian Drug Committee.

Mental health care in Italy: organisational structure, routine clinical activity and costs of a community psychiatric service in Lombardy region.

The Magenta Community Mental Health Centre (CMHC) is the public agency responsible for providing adult psychiatric care to about 85,000 adult residents. In 1995, it had 1,145 clients and incurred costs of Euro 1.9 millions. Average cost per patient and per adult resident were Euro 1,661 and Euro 22.2, respectively. These values mask large variation across diagnosis: while patients with schizophrenia and related disorders had an average cost of Euro 3,771, those with neurotic and related disorders had an average cost of Euro 439. Patients with schizophrenia and related disorders (28% of the patients) absorbed about 60% of total costs and made extensive use of several types of services (hospital, outpatient, domiciliary, social and rehabilitative care). Since integrating different types of services is the key element of Italian psychiatric care, the new fee-for-service system adopted by the NHS to fund providers does not appear appropriate, particularly for schizophrenic patients.

Health care costs of therapy-refractory schizophrenic patients treated with clozapine: a study in a community psychiatric service in Italy.

This study evaluates the utilization of clozapine in the treatment of therapy-refractory schizophrenia in terms both of patterns of care and of health care costs in a community psychiatric service in Italy. Data covering the year prior to commencing clozapine and the year following the initiation of the therapy were collected. Clinical outcome was assessed by means of the Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) scales. Cost analysis followed a two-step procedure: (i) to record all health care services provided to patients and (ii) to assign a monetary value to each service. Three of the 15 patients enrolled in the study dropped out before the end of the 12-month period of therapy. Considering the 12 patients on clozapine treatment for at least 1 year, clinical improvements are associated with a substantial modification of the pattern of care. While patients in the pre-clozapine period were mainly managed in hospital settings, patients on clozapine were prevalently placed in the community and participated in intensive rehabilitative programmes. The higher costs of drug therapy and community services in the post-clozapine period were more than offset by the lower costs of acute hospital care.

From Bassini to tension-free mesh hernia repair. Review of 1409 consecutive cases.

The short and long-term results of traditional and tension-free inguinal hernia repairs have been assessed in three surgical units. In order to standardise the results, hernias were classified according with Nyhus. There were 109 type I, 311 type II, 854 type III, and 125 type IV hernias. Follow-up was possible in 1201 patients (1249 hernia repairs). Postoperative course, postoperative pain, and recurrences were analysed. Recurrences ranged from 0.7% up to 9.3%. The tension-free methods of repair provided the most important advantages in term of low recurrence rate and early return to work even if, in our series, recurrences resulted mainly related to the type of hernia than to the type of repair. The Authors conclude that any hernia repair should be sized to the type of hernia defect in order to avoid over-treatment and abusive placing of a foreign body such as polypropylene mesh.

[Economic perspectives in the care and treatment of patients diagnosed with schizophrenia]. / La prospettiva economica nell'assistenza e nel trattamento dei pazienti con diagnosi di schizofrenia.

OBJECTIVE: To consider the main problems associated with care and treatment of patients with diagnosis of schizophrenia in the light of the more recent literature of the economic aspects of this pathology. METHOD: An analysis of the literature related to the social costs of schizophrenia, the economic analysis of different health-care models, and the evaluation of the costs of antipsychotic treatments has been carried out. RESULTS: Schizophrenia is a pathology creating huge social costs. The health costs associated with the care of schizophrenia take up a significant amount of the resources of healthcare systems in the principal industrialised countries. Indirect costs, due mainly to the patients' exclusion from work, exceed the direct costs of treatment. In those countries where community care has been supported by a real organisational effort to create community and residential services, it has proved to be a cost-effective solution compared with psychiatric hospital-based care and provides patients and family members with better results. The introduction of new antipsychotic drugs and the development of psychosocial support could represent the means of encouraging new healthcare strategies. CONCLUSIONS: From an economic perspective, the organisation, technological means, and strategies which would allow the available resources to be invested in a rational way must be considered. Consideration of these issues appears to be unavoidable today, not only for the administrators and the policy makers but also for mental health service professionals.

[Costs of psychiatric services: a study performed at a public mental center in the Lombardy Region, Italy]. / I costi delle prestazioni in psichiatria: un'analisi condotta in un Centro Psico-Sociale (CPS) pubblico in Lombardia.

OBJECTIVE: The implementation of a simple methodology to estimate full costs of services provided by a public mental health centre. SETTING: CPS (NHS Mental Centre) Ussl 35, Magenta, Lombardy Region. METHOD: To estimate full costs of 16 types of service we followed a two step procedure. The first step was to estimate all costs attributable to the CPS. In the second one, we allocated this estimate to each type of service provided. We attributed to the CPS the following cost items: personnel, utilities (telephone, electricity, water, heating and cleaning), land & building, transports (for services provided outside the clinic) and a share of general cost of the USSL to which the CPS belongs. Full cost of each service was then calculated on the base of the yearly number of services provided and the time spent by each health professional. RESULTS: In 1995, the CPS provided 14,562 services. Total costs amounted to L 1,356 million, and more than three quarters of this amount was attributable to the personnel working at the CPS. Unit costs ranged from L 5,300 (drug administration) to L 442,400 (family therapy involving two professionals for 90 minutes) The unit cost of psychiatric visits, psychologist consultations and nurse domiciliary visits were L 105,300, L 106,600 and L 78,000, respectively. CONCLUSIONS: This approach requires accessible data and is relatively simple to manage. Some refinements are required, especially to improve the methodology for the determination and the allocation of overheads. However, we are convinced that this cost accounting procedure provides acceptable estimates of the services provided by the CPS. These estimates suggest that charges to be used to fund NHS providers may be too low, especially if fee-for-service will be the main funding source.

Clinical pharmacokinetics of fluoxetine.

Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 micrograms/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the 'serotonergic syndrome'. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds.

The use of antidepressants for long-term treatment of recurrent depression: rationale, current methodologies, and future directions.

Present strategies for long-term treatment of major depressive disorder stem from the following three observations: the high frequency of recurrent depression, the length of a depressive episode, and the ability of antidepressants to prevent recurrences. Two different phases of long-term antidepressant treatment are now considered: continuation and a "true" maintenance or prophylactic phase. Moreover, it seems important to discriminate between relapse (from a previous episode) and recurrence (a new episode). However, there are some unresolved questions, such as (1) the duration of antidepressant treatment, (2) the type and posology of antidepressants to be used, and (3) some methodological aspects, such as the choice of comparators, definition of response, and combination with other therapies. This paper deals with all of these aspects, finally suggesting different prophylactic strategies in relation to factors like severity of symptoms, frequency of episodes, compliance, and susceptibility to side effects.

[Laparocele in the aged]. / Il laparocele nell'anziano.

Especially in the old patients (over 70 years) the incisional hernias represents an invalidating pathology whose treatment, for the high incidence of associated diseases of respiratory and cardiocirculatory apparatus in the aged, offers difficulties connected both to surgical methods and to the perioperative evaluation and preparation of patients. The infections of the surgical incision are very important in the pathogenesis of these diseases. In order to reduce the incidence of incisional hernias the systematic use of perioperative antibiotic therapy is desirable in every operation of abdominal surgery. In order to offer the best guarantees of recovery and to improve the postoperative course of patients, the perioperative antibiotic prophylaxis, together with the use of synthetic prosthesis material, is also essential at the moment of surgical correction of incisional hernia. Although the incisional hernia may sometimes stay silent and asymptomatic for years, it inevitably ends sup by representing a reason for acute and subacute pathologic events; an early surgical treatment is therefore desirable once the incisional hernia has been diagnosed. By this way it is possible to avoid the treatment in the old patients, as the old age is a less favourable period for people who have to be subjected to a surgical operation.

Alternative prophylactic treatments to lithium in bipolar disorders.

The research literature on alternative drug treatments to lithium therapy for the prevention of recurrences in bipolar disorders is discussed. In particular, the data on anticonvulsants (carbamazepine and valproic acid), antidepressants (alprazolam), and calcium channel blockers (verapamil) are reviewed and original data on clonazepam (CLN) are reported. In a preliminary study on six patients with bipolar disorders (DSM-III-R) without a history of psychotic features in which lithium prophylaxis was ineffective, contraindicated, or badly tolerated, CLN was administered in combination with low-dose neuroleptics or antidepressants in all but one case. All subjects were followed for 13 to 34 months. There were no relapses during the observation period with CLN dose regimens ranging from 1.5-8 mg/day p.o. Side effects were minimal and mostly consisted of transient sedation.

Residual neuroleptic-induced parkinsonian symptoms in schizophrenia. A naturalistic study with orphenadrine.

A naturalistic study was performed on 44 schizophrenic outpatients diagnosed according to DSM III-R and presenting neuroleptic-induced extrapyramidal side-effects. All patients had been treated continuously for the previous 10-12 weeks with haloperidol (HL) combined with orphenadrine (ORD). The dosages of HL and ORD remained unchanged for at least four weeks before the evaluations. All patients were assessed for depressive features (HRS-D), extrapyramidal (EPSE) and anticholinergic (ACS check list) side-effects. The plasma levels of ORD and its metabolite tofenacine (TOF) were determined by gas chromatography. There was a positive relationship between HRS-D and EPSE total scores, while there was a negative relationship between age and EPSE total scores. No relationship between the administered dose and plasma levels of ORD was found. The HL daily dose (mg/kg), ORD plasma levels and the TOF/ORD plasma level ratio seem to influence significantly the severity of residual extrapyramidal side-effects.

Dexamethasone suppression test in positive and negative schizophrenia.

Fifty-four inpatients with a DSM-III diagnosis of schizophrenia were studied. Patients were divided into positive and negative subtypes of schizophrenia according to Andreasen's criteria. Blood samples were obtained from all patients for 2 consecutive days to determine plasma cortisol concentrations before and after a single administration (1 mg, p.o.) of dexamethasone at 11 p.m. The results revealed a significant increase in plasma cortisol levels in schizophrenic patients, with 40% of the patients being nonsuppressors on the dexamethasone suppression test. A higher percentage (62.5%) of patients with the negative form of schizophrenia were nonsuppressors.

Urinary sodium levels related to jaundice duration in the assessment of postoperative risk of hepatorenal syndrome in elderly patients undergoing surgery for biliary obstruction.

The early diagnosis of hepatorenal syndrome (HRS) is based chiefly on biochemical alterations and in particular, the relationship between urinary sodium levels and duration of jaundice seems to offer the most reliable prognostic index. Urinary sodium levels were determined in 32 elderly patients, who underwent surgery for benign or malignant biliary obstruction, without, major organ resection; in this group 4 patients died of HRS (12.5 per cent). The diagnostic accuracy of the method reached 97 per cent.

Efficacy and tolerability of fluoxetine in the elderly: a double-blind study versus amitryptiline.

Twenty-eight elderly in-patients suffering from major depressive episodes received randomly, on a double-blind basis, amitryptiline or fluoxetine for 5 weeks. There were 4 drop-outs in the amitryptiline group and 2 drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for HRS-D scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitryptiline group. Weight gain was detected only in patients receiving amitryptiline.

Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial.

Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.

Dysplasia-carcinoma sequence in diminutive polyps of the large bowel.

The personal endoscopic experience regarding diminutive polyps (5 mm or less in diameter) of the colon and rectum is reported in order to evaluate the increased cancer risk related to these lesions. A total of 462 colo-rectal diminutive polyps, endoscopically removed by diathermy, have been considered in this study. The histopathologic examination of these lesions evidenced a high incidence of adenomatous polyps (69.9%), with dominance of the tubular histologic type. While mild dysplastic alterations were prevalent, moderate and severe dysplasia were observed to a lesser extent (18.9 and 1.9%) and only one case with focal carcinomatous area (1/323 = 0.3%) was recognized. In conclusion, for these lesions, even if minute in size, a dysplasia-carcinoma sequence should be considered whenever the adenomatous histologic type is evidenced and their increased risk of developing into cancer should be carefully evaluated for a correct diagnostic and therapeutic approach.