Atypical antipsychotics and polydipsia: a cause or a treatment?

Primary polydipsia (PP) is a frequent complication that affects many chronic schizophrenic inpatients. Due to possible lethal consequences, for example, hyponatremia, coma and death, it's fundamental for the physician achieving early diagnosis and treating this condition. The first step is identifying polydipsia by clinical, biochemical and pharmacological means. Nowadays, the pathophysiology of PP remains unclear, and this limits the possibility of detecting an appropriate drug treatment. Typical antipsychotics have been associated to a worsening of polydipsic behavior, while more recently atypical antipsychotics have been reported as being useful. However results are still mixed and controversial. It appears that risperidone and olanzapine are not clearly effective; clozapine may improve symptoms, although it is difficult to manage from a therapeutic point of view; quetiapine has been poorly studied so far, nonetheless it has given interesting results. Through a case study analysis, this report presents a brief, yet selective, overview of the current state of psychopharmacology in the treatment of PP with atypical antipsychotics in schizophrenia.

The potential role of high or low birthweight as risk factor for adult schizophrenia.

OBJECTIVE: Obstetric complications may be an important factor in the development of schizophrenia. The aim of this study is to evaluate the role of these complications in the development of schizophrenia in adult life, with particular attention to the potential role of birth weight. METHOD: We carried out a case-control study, comprising schizophrenics and patients with diseases of the schizophrenia spectrum as cases, and their healthy male brothers as controls. Obstetric complications were assessed using the "Midwife Protocol" of Parnas et al. RESULTS: The main result was that birth weight may be a risk factor for schizophrenia, as indicated by odds ratio analysis. The confidence intervals are very wide and, without compromising the clinical significance of the results, they give a limited indication of the real entity of the risk. CONCLUSIONS: The results contribute to understanding of the role played by a single complications.

Neurological soft signs and cerebral measurements investigated by means of MRI in schizophrenic patients.

Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic prevalence in schizophrenic patients, and correlations between NSS and the most frequently cerebral alterations. The aim of this study was to investigate, by means of MRI, the quantitative alterations of cortical and subcortical structures and their correlation with NSS in a sample of schizophrenic patients. Linear measures of lateral ventricular (Evans ratio), third ventricular (Third Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan and Heinrichs's Neurological Evaluation Scale (NES). Lateral ventricular enlargement showed to be correlated with right stereoagnosia item (p=0.001). Hippocampal atrophy, with right stereoagnosia item (p=0.023), with forefinger-right thumb opposition (p=0.004), forefinger-left thumb opposition (p=0.029 and face-hand extinction (0.26). Third ventricle enlargement showed to be correlated with forefinger-right thumb opposition (p=0.001), forefinger-left thumb opposition(p=0.021) and total sensorial integration (p=0.012). Cerebellar atrophy showed to be correlated with rhythmic drumming item (p=0.042), forefinger-right thumb opposition (p=0.007), forefinger-left thumb opposition (p=0.026), left specular movements (p=0.049), face-hand extinction (p=0.001), right-left confusion (p=0.005) and with left forefinger-nose index (p=0.032). Results obtained confirm the correlation between NSS and neuroanatomical alterations in schizophrenia.

Excess in the spring and deficit in the autumn in birth rates of male schizophrenic patients in Italy: potential role of perinatal risk factors.

OBJECTIVE: The aim of this study was to evaluate whether there were different seasonal variations of births in an Italian population of patients with schizophrenia, with other psychotic disorders, and with personality disorders than in the general population. METHODS: Birth dates of 1270 patients admitted to one university psychiatric unit in Rome between 1990 and 2003, with a diagnosis of schizophrenia, other psychotic disorder (OPD) and personality disorder/cluster A (PD) were analyzed according to seasonal variation. RESULTS: A significant excess of births in spring (with a peak in May) and a deficit in autumn (with a trough in October) was found in the sample of male schizophrenics (n = 506). No statistically significant variations were found in either the sample of female schizophrenics (n = 88) or in the combined sample with OPD and PD (n = 676). CONCLUSIONS: The findings serve to strengthen the existing hypotheses that schizophrenia is related to environmental factors acting on the development of the central nervous system intrauterinely.

[Psychiatry and psychiatrists in the U.S.A. cinema]. / Psichiatria e psichiatri nel cinema Americano.

United States cinema motion pictures from the beginning of 20th century to the present are characterized by massive use of sterotypes to represent psychiatrist's image, as well as psychiatric treatment and inpatients psychiatric facilities. Representation tends to undergo considerable changes between psychiatric different historical periods. Psychiatric disorders also are commonly depicted in movies, often in a not realistic way. The images of psychiatrist and mental disorders shown in movies are likely to impact on the beliefs and attitudes of people towards psychiatry.

Assessment of subjective stress in video display terminal workers.

Stress assessment in the workplace has been focused on its environmental, psychological and biological aspects. We carried out an evaluation of the subjective components of stress in a working population of 60 subjects employed in a large Public Service, 30 Video Display Terminal (VDT) workers (15 men and 15 woman) and 30 office-workers not assigned to VDT (15 men and 15 woman), by using the "Rapid Stress Assessment Scale": a short questionnaire of easy administration in work environment. VDT workers of both sexes showed higher total stress score vs. office workers (respectively p<0.05, p<0.05). Gender differences were present: female VDT workers showed higher scores of clusters anxiety (p<0.001) and aggressiveness (p<0.05); male VDT workers' score were significantly higher in somatization (p<0.05) and aggressiveness cluster. Our results showed that in VDT workers are experienced greater subjective response to stress than "office workers" and confirm the gender differences in stress experiencing.

Neurologic soft signs in schizophrenic patients treated with conventional and atypical antipsychotics.

Neurologic soft signs (NSS) are considered a somatic feature associated with schizophrenia (DSM-IV) that are present in neuroleptic-treated, as well as untreated or first-episode patients. The aim of this study was to determine the incidence and severity of NSS in groups of schizophrenic patients treated with either a conventional neuroleptic medication, haloperidol (n = 37), or atypical antipsychotic medications, risperidone (n = 19), clozapine (n = 34), and olanzapine (n = 18). NSS were assessed with the Neurological Evaluation Scale (NES), whereas extrapyramidal symptoms (EPS), which occur more commonly with conventional neuroleptic treatment, were evaluated using the Simpson-Angus Scale. NES scores were not significantly different between groups. Slight differences were found for 2 items only. The haloperidol group showed higher scores for the "Romberg test," whereas the clozapine group showed higher scores for "short-term memory." There were significant correlations between EPS and NES total score in the haloperidol and risperidone groups. These results demonstrate an overall overlapping of NSS among the groups, confirming their substantial independence from neurologic implications of neuroleptic treatment.

Deficit of executive functions in schizophrenia: relationship to neurological soft signs and psychopathology.

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups ('good performers' and 'poor performers') that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The 'poor performers' group showed greater severity of NSS: significant differences emerged for the NES total score and for the 'sequencing of complex motor acts' score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.

Reduction of night/day difference in melatonin blood levels as a possible disease-related index in schizophrenia.

OBJECTIVE: Aim of this study was to verify if a simple index as night-day plasma MLT level variation is able to confirm the existing data on circadian melatonin alterations in schizophrenia and if a relationship to disease itself instead of the actual clinical state can be suggested. SETTING AND DESIGN: Ten consecutively admitted male schizophrenic inpatients were examined. METHODS: The blood samples for melatonin were collected at 3.00 a.m. and 15.00 p.m. and consequently calculated the values of Delta () (MLT h.3.00- MLT h.15.00). We divided the sample into two subgroups: < 30 pg/ml and > 30 pg/ml taking 30 pg/ml as an arbitrary value, based on literature data, that should indicate a physiologically correct value of. RESULTS: The 70% of the sample was under the 30 pg/ml value of (13.61 +/- 4.0) or was lacking of the characteristic circadian pattern of MLT secretion, whilst the 30% of the sample was over the 30 pg/ml value of (83.60 +/- 16.34) or was in presence of the characteristic circadian pattern of MLT secretion (p=.0001). No correlation was found between values and the scale and subscales scores for the assessment of psychopathology. MAIN FINDINGS: The data confirm the lack of the characteristic circadian pattern of MLT secretion in schizophrenics. CONCLUSION: The absence of significant correlation between night / day melatonin level differences and actual psychopathology variables should indicate that the suppression of is mostly related to the disease and independent from the clinical state. A neuroleptic-treatment effect cannot be excluded so far.

A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder.

S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression.

Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies.

BACKGROUND: S-Adenosyl-L-methionine (SAMe), a natural compound, is the most important methyl donor in the central nervous system. In several clinical trials, SAMe showed antidepressant activity. OBJECTIVE: Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18] to confirm the efficacy and safety of SAMe in the treatment of major depression. In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies, the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design. DESIGN: In MC3, 143 patients received oral SAMe and 138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk. In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint. Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders, responders being those patients showing a decrease in HAM-D score of >or=50% from baseline. RESULTS: In both studies, the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure. However, significantly fewer adverse events were observed in the patients treated with SAMe. CONCLUSIONS: The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally, but SAMe is significantly better tolerated.

Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness.

Several investigations have suggested pineal gland abnormalities in the pathogenesis of schizophrenia. The pineal volume on brain magnetic resonance imaging scans was calculated in 15 male schizophrenic inpatients and in 16 matched control subjects. The statistical comparison found a significant difference of pineal gland volume between schizophrenics and controls (P = 0.022), with a smaller pineal volume in the schizophrenics. These results do not confirm the previous data of Schizophrenia Res. 14 (1995) 253, showing no significant pineal volumetric differences between schizophrenics and normal controls. Since the present study is based on a smaller but more homogeneous sample of patients, this could reduce the heterogeneity features of the schizophrenic disease. No correlation was found between pineal volume and clinical and psychopathological features of the schizophrenic subjects. Volume reduction in schizophrenia could be at least partially included in the wider brain developmental abnormalities of the illness or in the late effects of previous neuroleptic treatments.

Paroxetine versus amitriptyline in patients with recurrent major depression: A double-blind trial.

INTRODUCTION: Long-term exposure to antidepressants is required to prevent relapses and recurrences in patients with recurrent major depression. Furthermore, a good pharmacological compliance is the key to successful long-term treatment. Since the early phases of a treatment influence long-term compliance and compliance is adversely affected by poorly tolerated treatments, efficacy and tolerability of paroxetine and amitryptiline over 12 weeks were compared as an introduction to the issue of long-term compliance to these two agents. METHOD: A 12-week, randomized, double-blind, doubledummy, parallel-group trial which involved 129 patients with recurrent major depression. RESULTS: Both paroxetine and amitriptyline were effective in controlling the symptoms of depression, as shown by the reduction in HAMD total score and CGI severity-of-illness score at endpoint compared to baseline. There was no statistically or clinically significant difference between the two treatments in terms of efficacy. However, marked numerical differences were noted in tolerability: the percentage of patients who reported treatment-emergent adverse experiences was greater in the amitriptyline group (40.0% vs 28.1%). This difference was mainly due to anticholinergic adverse events, which were six times more frequent with amitriptyline than with paroxetine. CONCLUSION: When compared with amitriptyline, paroxetine should allow patients with recurrent major depression to receive an equally effective treatment with a relatively lower incidence of adverse experiences.