Levosulpiride in somatoform disorders: A double-blind, placebo-controlled cross-over study.

Reliable data on the psychopharmacotherapy of somatoform disorders (SDs) are scanty because of patients' poor psychopathological awareness and compliance, the need for combination treatment, and the lack of suitable instruments for clinical diagnosis and assessment. The aim of the present study was to investigate the efficacy and tolerability of low doses of levosulpiride in the treatment of SDs. Seventy-four patients with SDs diagnosed according to ICD-10 and DSM-IIIR criteria by means of the Comprehensive International Schedule for Somatoform Disorders-Somatoform Disorders Schedule (CISSD-SDS) were treated for 4 weeks either with levosulpiride (50 mg b.i.d.) or placebo, under double-blind, cross-over conditions. The clinical evaluation was performed using CISSD-SDS. Side-effects were evaluated using the Simpson and Angus Extrapyramidal Side Effects Scale (EPSE) and specific check-lists for anticholinergic and endocrine side effects. Levosulpiride significantly reduced the number of SD symptoms compared to placebo ( P =0.007) after 4 weeks of treatment. Eighty per cent of positive responses were observed during treatment with levosulpiride in the placebo-levosulpiride sequence; on the other hand, only 44% of positive responses were found during treatment with active compound in the levosulpiride-placebo sequence ( P <0.002). Levosulpiride also determined a more evident reduction of the total number of SD symptoms compared to placebo ( P <0.001). There were no differences in endocrine and anticholinergic side effects between levosulpiride and placebo. In the levosulpiride group, a higher percentage of patients (13.4 vs. 2.8%; P =0.029) showed signs of extrapyramidal system involvement compared to placebo. Levosulpiride appears to be a well-tolerated and effective drug for the treatment for SDs.

Symptoms, standards of living and subjective quality of life: a comparative study of schizophrenic and depressed out-patients.

The subjective quality of life (QOL) (i.e. individual evaluation of one's life experiences) has been studied according to a series of different parameters such as resource availability, and sociodemographic and clinical variables, at times yielding contradictory results. Subjective quality of life and standard of life from a selected sample of 45 chronic out-patients (25 schizophrenics, and 20 patients with major depression) were evaluated by means of structured interviews. Statistical analysis revealed that subjective QOL was largely independent of standard of living (so long as basic needs were satisfied), diagnosis, and clinical course of illness, and only partly dependent on sociodemographic variables. No correlation was found between clinically evaluated symptoms (both psychotic and depressive) and subjective QOL. On the contrary, significant correlations were found between self-ratings of depression, depressive cognitive attitudes and subjective ratings of QOL.

Effectiveness of restarting lithium treatment after its discontinuation in bipolar I and bipolar II disorders.

OBJECTIVE: This study tested the hypothesis that resumption of lithium treatment of bipolar disorders may be less effective after maintenance treatment has been discontinued. METHOD: Eighty-six patients with type I or II bipolar disorder, not selected according to response to treatment, were followed prospectively during two periods of lithium maintenance treatment averaging 4.6 and 4.4 years. Morbidity (illness episodes per year, hospitalizations per year, percentage of time ill) was assessed, and use of adjunctive medication was rated. RESULTS: Morbidity was similar in the first and second treatment periods (mean number of episodes = 0.83 and 0.94 per year, respectively; mean percentage of time ill = 18.0% and 24.2%), with no differences in numbers of manic and depressive episodes or differences by gender, diagnostic type, length of first treatment, interval between treatments, or discontinuation rate. There was 12.8% more use of adjunctive medication in the second period. CONCLUSIONS: The efficacy of lithium did not differ significantly between the first and second treatment periods.

Reduced morbidity after gradual discontinuation of lithium treatment for bipolar I and II disorders: a replication study.

OBJECTIVE: The aim of this study was to verify reduction of early affective morbidity by gradual, rather than rapid, discontinuation of lithium treatment. METHOD: For 78 patients with bipolar disorders, lithium treatment was discontinued either rapidly (over 1-14 days) or gradually (over 15-30 days). The effects of the two schedules were compared by survival analysis of time to first recurrence. RESULTS: Median time to recurrence was 5.6 times as long for gradual discontinuation (14.0 months) as for rapid discontinuation (2.5 months). The ratios of the median survival times for gradual and rapid discontinuation were similar in I and II subtypes and in depression and mania (4-6:1). The polarities of the episodes at onset and at first recurrence after lithium discontinuation were 83.6% concordant. CONCLUSIONS: These results independently confirm a reduction in morbid risk from slow discontinuation of lithium treatment for bipolar disorders.

Association between psychiatric disorders and Marfan's syndrome in a large Sardinian family with a high prevalence of cardiac abnormalities.

BACKGROUND: Marfan's syndrome is an inherited disorder of connective tissue associated with characteristic abnormalities of the skeletal, ocular, and cardiovascular systems. Marked clinical variability and age dependency of all manifestations of Marfan's syndrome may render the unequivocal diagnosis difficult in mildly affected, young subjects. HYPOTHESIS: The study and care of a 32-year-old woman with evidence of Marfan's syndrome, several cardiac abnormalities, and paranoid schizophrenia led to an investigation of her consenting relatives to verify the penetrance of Marfan's syndrome and the degree of comorbidity between the disease and psychiatric disorders. METHODS: The patient and 12 subjects belonging to three generations of her family underwent cardiovascular, skeletal, ophthalmologic, and psychiatric examinations. Two-dimensional and Doppler echocardiography were performed. RESULTS: One female index patient and six of her first-degree relatives were found to be affected by Marfan's syndrome. All seven patients were found to have mitral valve prolapse associated with other cardiac abnormalities. Four of these patients were affected by the following psychiatric disorders: generalized anxiety disorder, major depressive disorder, paranoid schizophrenia (two cases). Six more relatives without Marfan's syndrome showed mitral valve prolapse in association with other echocardiographic features. Two of these were found to be affected by a major depressive disorder. CONCLUSIONS: The present data support the hypothesis that a psychiatric condition, associated with a significantly high frequency of cardiac involvement, may be part of the phenotype of Marfan's syndrome.

Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders.

BACKGROUND: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorder patients discontinuing successful long-term maintenance on lithium, but previous small samples have limited analyses of subgroups. METHOD: DSM-IV bipolar disorder patients (N = 161) were pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. RESULTS: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence of mania and depression (4.4 vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold). The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. CONCLUSION: These pooled results strengthen the concept or a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders.

Evaluation by multidimensional instruments of health-related quality of life of elderly cancer patients undergoing three different "psychosocial" treatment approaches. A randomized clinical trial.

Our study belongs to the clinical trials in which the health-related quality of life (HQL) evaluation constitutes the primary endpoint. It was carried out with the aim of comparing the impact of three different types of psychological intervention, namely a psychopharmacological treatment alone, the same treatment plus social support carried out by volunteers (SSV) and a third treatment modality including "structured psychotherapy" (autogenous training), on improving the HQL of elderly cancer patients undergoing antineoplastic therapy with symptoms of anxiety and/or depression related to their disease. The eight questionnaires used for HQL evaluation were generally self-rated and multidimensional but unidimensional models were also employed. Seventy-four patients aged over 65 years with either solid tumors in different sites or hematological malignancies, generally in advanced stages (III-IV), were enrolled in the study. Of these patients, 72 (42 men and 30 women, mean age 70.68 years, range 66-85) were evaluable. Our study highlighted the usefulness of the pharmacological therapy (alprazolam + sulpiride) and of other specific ancillary treatments in reducing the incidence of the main HQL-related side-effects of antineoplastic therapy and the superiority of an "integrated" strategy, based both on psychopharmacology and psychosocial interventions, such as SSV with or without structured psychotherapy. The one-way analysis of variance carried out by us did not allow us to draw definitive conclusions about which of the two integrated treatments was to be considered the treatment of choice, as they proved to be almost equally effective.

[The family burden in chronic diseases. The study of validity and reproducibility of the questionnaire on the impact of the chronic disease on the family (IMPAT)]. / I1 carico familiare nelle malattie croniche. Studio di validazione e di riproducibilità del questionario sull'impatto della malattia cronica sulla famiglia (IMPAT).

OBJECTIVE: The "Questionario sull'Impatto della Malattia Cronica sulla Famiglia" (IMPAT) ("Impact-on-Family Scale", by Stein & Reissman) in its Italian version (by Casari & Fantino, modified) has been used to evaluate family burden in relatives of chronic patients with cancer, chronic patients with other internistic pathology and acute patients. The aims of the study were to evaluate validity and reliability of the Impat and to compare family burden and anxoius/depressive symptoms in the three groups of relatives. METHOD: 35 relatives of cancer patients, 20 relatives of patients with chronic, non neoplastic illness and 20 relatives of acute patients were studied. 85% of relatives of cancer patients was assisted continuously by volunteers and psychiatrists with regard to their psychological problems. Impat questionnaire, Beck Depression Inventory and State-Trait Anxiety Inventory were used for psychological evaluation. RESULTS: Validity of the Impat was confirmed. Mean scores from relatives of chronic patients were higher than scores from relatives of acute patients (ANOVA, f = 38.0; df = 2,72; p < 0.0001). Test-retest analysis was satisfactory (Person's test, N = 20 r = 0.77, p < 0.0001). Both groups of relatives of chronic patients showed higher level of anxious-depressive symptoms compared to relatives of acute subjects. No differences were found between relatives of neoplastic and non neoplastic chronic patients. CONCLUSIONS: The italian version of Impat has been confirmed as a useful and simple means of evaluation of family burden in this context. Psychosocial support seems to reduce distress in relatives of cancer patients.

The Italian DAS as a screening instrument for depression in the elderly.

The accuracy of the 14-item Italian version of the Dysfunctional Attitudes Scale (IDAS-14) as a screening tool for depression among elderly people is evaluated and compared with the BDI. Results for the IDAS-14 are most satisfactory, since high levels of both specificity (0.95) and sensitivity (0.89) may be obtained at a given cut-off score (56).

Psychiatric morbidity and family burden among parents of disabled children.

Twenty parents of mentally retarded children and 20 parents of children with neurological impairments were interviewed to determine their levels of psychiatric symptoms and of subjective and objective burden associated with care for their disabled child. The parents of disabled children had significantly higher levels of psychiatric symptoms and were more likely to meet criteria for depressive disorders, compared with a matched control group of parents of children without disabilities. The two groups of parents of disabled children reported considerable subjective and objective burden, although there were no differences between those groups in the level of burden.

[Multiple sclerosis and major depression resistant to treatment. Case of a patient with antidepressive therapy-induced mood disorder, associated with manic features]. / Sclerosi multipla e depressione maggiore resistente al trattamento. Il caso di una paziente con disturbo dell'umore indotto dalla terapia antidepressiva, con caratteristiche maniacali.

Patients with multiple sclerosis show higher prevalence of psychiatric disorders compared to general population, that are hardly managed by pharmacotherapy. In the present report a female patient, 44 years old, with diagnosis (according to DSM-IV) of 340 multiple sclerosis, 296.32 major depressive disorder, recurrent, moderate, 292.84 antidepressant-induced mood disorder, with manic features, is described. In this patient depressive symptoms did not respond to a number of drugs, including tricyclic antidepressants, selective serotonine re-uptake inhibitors hand lithium. Moreover, she had hypomanic and manic episodes induced by two different antidepressant, hydroxy-tryptophan and clorimipramine. Until today, only amisulpride (50 mg/die for four months, then 50 mg every two days for two months) has shown a significant effect on depressive symptomatology, moreover, this drug has not induced the occurrence of manic symptoms.

[Clinical course and social outcome in schizophrenia. Results from a retrospective study]. / Decorso clinico e disabilità sociale nella schizofrenia. Risultati di uno studio catamnestico.

OBJECTIVE: The aim of the present study is to investigate the possible clinical and symptomatological determinants of social outcome in schizophrenic patients. METHOD: 40 schizophrenic patients (DSMIII-R), 21 males and 19 females, mean age 4 +/- 5 years, have been evaluated in the present retrospective study. All of them had first undergone psychiatric hospitalization between 1978 and 1981. The following data have been collected: socio-anagraphic features and course of the illness (AMDP), contacts with community health centre and pharmacological compliance. Social disability has been investigated by means of a semi-structured interview developed from the "Disability Assessment Schedule" named "Accertamento Disabilità e Carico Familiare" (ADC), which has been administered to the main carer, usually a cohabitant relative. Presence and level of social support have also been evaluated. One Way Analysis of Variance (ANOVA), "t" test with Bonferroni correction and Pearson Correlation test have been used for data analysis. RESULTS: Patients with less severe social disability (lower scores at ADC) were mainly those with recurrent course of illness without residual symptoms or remitted ones (p = 0.0001), better pharmacological compliance (p = 0.004), more frequent and regular contacts with community health centres (p = 0.0001) and better social support (p = 0.01). On the contrary, score at ADC resulted positively correlated with number of hospitalizations (r = 0.57, p = 0.01), number of compulsory admission (r = 0.32, p = 0.01) and length of illness (r = 0.40, p = 0.01). CONCLUSIONS: Although in our study the influence of severity of illness on social disability has been confirmed, suggestive evidence about importance of other factors, such as compliance or social support, may be drawn.

Lifetime prevalence of major depression and dysthymia: results of a community survey in Sardinia.

Epidemiological data about depressive disorders emerging from European and North American community surveys are not easily comparable due to several methodological differences. Only in recent years have studies performed with the Composite International Diagnostic Interview (CIDI) supplied comparable data. They support the evidence of higher prevalence rates of major depression (DSM-IIIR criteria) in European than in US and Canadian community studies carried out in the 1980s. Moreover, a new nationwide USA survey, using CIDI, confirmed a higher frequency of depressive disorders compared to ECA results. This report is part of a survey ('Health in Sardinia') which involved five urban districts of Cagliari, three rural areas and the same mining district involved in a previous community study. The present data concern four of the five urban districts and one rural area. Subjects were clinically interviewed with the CIDI Simplified, in the Italian version. Diagnoses were made according to DSM-IIIR criteria. Our study seems to confirm the general trend toward higher prevalence rates of major depression (lifetime prevalence 13.3) shown in earlier community studies.

Anxious symptoms influence delayed-type hypersensitivity skin test in subjects devoid of any psychiatric morbidity.

The present study aimed to evaluate the relationship between anxious/depressive symptoms and cell-mediated immunity (Delayed-type Hypersensitivity skin test, DTH) in subjects devoid of any psychiatric morbidity. Forty-eight females and twenty-four males were studied, ages ranging 21-60. These subjects completed the Beck Depression Inventory (BDI) for evaluation of depressive symptoms and the State-Trait Anxiety Inventory (STAIX1, STAIX2) for evaluation of anxious symptoms; subsequently on the same day they were tested for DTH using the Multitest CMI system (Merieux Institute, France). Subjects were split into three groups using the 33rd and 66th percentiles of DTH response (cumulative induration diameter). In females, subjects with larger DTH response (DTH > 8 mm) had significantly lower levels of "state" anxiety (scores at STAIX1; Kruskall-Wallis test, P = .04). On the contrary, no differences were observed between groups considering scores obtained by males at self-evaluation rating scales. Our data seem to support the hypothesis that activity of immune system as measured by DTH skin test may be influenced by affective status in the context of everyday life.

Standardization of a psychiatric screening test for use by general practitioners in Sardinia. Preliminary results.

The use of screening test for case-finding studies was introduced only a few years ago in Italy. This study aimed to define the degree of accuracy of the Italian version of the 24-item Self Reporting Questionnaire (SRQ-24) applied by general practitioners to their patients. The latter was carried out by comparing results with those obtained by means of the Present State Examination performed by a qualified psychiatrist. About 37% of patients interviewed could be considered as cases. In particular, 23% were affected by anxiety disorder and 14% by a depressive disorder. The receiver operating characteristic analysis showed a fairly good degree of accuracy of SRQ-24 for cut-off points between 7 and 8.

Prevalence of mental disorders in Sardinia: a community study in an inland mining district.

Using standardized interviews 374 subjects randomly selected among people living in two villages in a mining district in Sardinia (Italy), were studied. Of these, 57 subjects (15.2%) were identified as 'cases'. Ten per cent of the sample was affected by a depressive syndrome and 4% by an anxiety disorder. Females were significantly more at risk for anxiety disorders, while a trend towards a major risk for depression emerged among middle-aged and elderly people. Of the sample 9.8% were taking benzodiazepines, with a significant over representation of females. Depressed subjects took benzodiazepines more frequently than anxious subjects, while the use of antidepressants was negligible.

[Unemployment and depression. Results of a psychometric evaluation]. / Inoccupazione e depressione. Risultati di una valutazione psicometrica.

The Authors evaluate the issue about the search of first employment and the depressive effects possibly linked to it. The research includes two groups of unemployed and two control groups of workers. Sex difference has been taken into account. After a preliminary semi-structured interview, all subjects have been evaluated by the means of psychological tests. The psychometric values considered include the D and Ma scales of MMPI and their difference as proposed by Diamond, and the Beck Depression Rating Scale. The results do not show a significant correlation between the search for first employment and the presence of depressive traits.

[Depressive features in unemployed individuals]. / Valenze depressive in cassintegrati.

The present research deals with a psychometric evaluation of depressive features in a group of laid-off compared with a control group of full-time workers. Sex differences has been taken into account in the comparison. (The laid-off workers belong to a group under an unemployment fund, Cassa Integrazione Guadagni, which continues paying about 80% of the ex-employee's last wage for an undetermined period of time). The psychometric elements considered include the D and Ma scales of MMPI and their difference as proposed by Diamond, and the Beck Depression Rating Scale. The results, still preliminary, show that work deprivation, even with the financial subsidy from the unemployment fund, can be considered a life event able to provoke a depressive symptomatology.

[Discontinuation of chronic treatment with lithium salts]. / La sospensione del trattamento cronico con sali di litio.

The present research reports some results concerning the discontinuation of a long-term treatment with lithium in two groups of bipolar patients, BPI and BPII. The aim of the research is the evaluation of the causes leading to the discontinuation of the treatment and its effects. In all subjects the treatment, not combined with other medications, was effective for at least two years before discontinuation. The results show a percentage of recurrences similar to that reported by other Authors, with significant differences that point out a greater risk of recurrences after an abrupt discontinuation. The hypotheses concerning early recurrences are discussed, taking into account the different features of the recurrences in the two groups.

The course of a seasonal bipolar disorder influenced by caffeine.

A longitudinal case report shows a sudden remission of the severe course of a seasonal bipolar disorder after 10 years of psychopharmacological treatments. The discontinuation of heavy caffeine intake appears to have contributed to the outcome.