Second-generation antipsychotic effect on cognition in patients with schizophrenia--a meta-analysis of randomized clinical trials.

OBJECTIVE: To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. METHOD: Multiple-treatments meta-analysis model. RESULTS: On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12-1.63, quetiapine, ES 0.75; 95% CI: 0.00-1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14-1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00-0.74, olanzapine, ES 0.31; 95%CI: 0.02-0.59, quetiapine, ES 0.34; 95% CI: 0.03-0.64, and FGAs, ES 0.51; 95% CI: 0.18-0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04-0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06-1.58, olanzapine, ES 0.81; 95% CI: 0.07-1.55, quetiapine, ES 0.76; 95% CI: 0.02-1.51, ziprasidone, ES 0.90; 95% CI: 0.14-1.67, and FGAs, ES 0.83; 95% CI: 0.08-1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02-1.91, and quetiapine, ES 0.36; 95% CI: 0.01-0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06-0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01-0.50, and clozapine, ES 0.44; 95% CI: 0.06-0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04-0.78, and clozapine, ES 0.44; 95% CI: 0.05-0.83, performed poorer on visuospatial skill compared to olanzapine. CONCLUSION: The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.

Effects of sertindole on cognition in clozapine-treated schizophrenia patients.

OBJECTIVE: To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial. METHOD: A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. RESULTS: Participants displayed substantial cognitive deficits, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative Syndrome (PANSS) subscales, Global Assessment of Functioning subscale (GAF-F) and Clinical Global Impression (CGI) with 20 neurocognitive indices was conducted, but no significant correlations were found. Second, we tested change from baseline to endpoint for the PANSS, GAF-F, and CGI, vs. the concomitant changes in cognitive test performance, and found no significant correlations. CONCLUSION: The clozapine-treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect on cognition of augmenting clozapine treatment with another antipsychotic drug.

Five-year follow-up during antipsychotic treatment: efficacy, safety, functional and social outcome.

OBJECTIVE: Explore the long-term course of schizophrenia and related disorders. METHOD: Naturalistic study of 225 patients initially treated with risperidone (monotherapy or in combination with other psychotropic drugs) over 5 years. RESULTS: Stable symptomatology and side effects were observed. Clinician GAF scores were 55-61, but patients' self-ratings were higher. Clinician and patient CGI scores were at the same level. Annual in-patient days decreased but days in sheltered accommodations increased still more. Only 12% of the patients studied or worked full-time. One in four had no social contacts except with staff. Eight patients died during the 5 years. CONCLUSION: The findings underline the chronicity and seriousness of psychotic disorders in terms of social outcome and, indirectly, the low quality of life of this group of persons. Patients were generally well aware of their illness and able to sort out symptoms from drug side effects. This opens for more active involvement of patients in monitoring their own treatment.

Nicotine use and its correlates in patients with psychosis.

OBJECTIVE: To examine nicotine use and its correlates among psychotic patients. METHOD: Longitudinal naturalistic study of 176 patients, diagnosed with schizophrenia or schizophrenia-related psychotic disorders, and treated with risperidone at study entry. Levels of nicotine use (smoking, snuffing) were measured along with other relevant ratings and measurements (symptoms, drug treatment, side effects, weight, cognitive functions and outcome) at baseline and once yearly for 5 years. RESULTS: Nicotine use was twice as common as in the general population. Only few nicotine users had started after onset of psychoses. We could not find any differences among nicotine users and non-users in diagnosis, symptoms, side effects, weight, cognitive functions, personality and outcome, cross-sectionally and longitudinally, ruling against the 'self-medication' hypothesis. CONCLUSION: A parsimonious interpretation of the findings is that patients suffering from psychosis fail to desist from nicotine rather than experience significant positive effects of the usage.

Clinical decision-making during 5 years of antipsychotic treatment.

OBJECTIVE: Explore how clinicians select drug treatment based on symptoms, side effects and patient factors, including patient participation in the process, and the association between these factors and attitudes towards drugs. METHOD: A cohort of 166 patients initially treated with risperidone was followed with yearly assessments over 5 years. At the end of the study, 101 patients were evaluated of whom 58 were still treated with risperidone. RESULTS: More women than men remained in the study, and on the initial medication. The most common reason for medication switch was lack of efficacy. Clinicians and patients agreed well in their global ratings of medication effects and side effects. Robust associations between switch decisions and patient characteristics including symptoms and side effects could not be identified. The effects of switches were rated as better by the clinicians than by the patients. Negative drug attitudes were associated with pronounced positive symptoms (threshold effect), whereas the corresponding association with 'lack of judgment and insight' was linear over the whole range. CONCLUSION: The decision-making process appears to have many unknown components, and may benefit from more active patient involvement by using structured clinician and patient rating scales for monitoring the treatment. Such shared decision-making may improve compliance.

Costs of schizophrenia during 5 years.

OBJECTIVE: To explore the direct and indirect costs in a cohort of 225 risperidone-treated patients with schizophrenia followed up annually during 5 years. METHOD: Data on costs for medication, hospitalization, sheltered living and productivity losses, as well as degree of social isolation, were collected. RESULTS: The direct costs were dominated by hospitalization and sheltered living expenses, while drug costs only represented 7% of the direct costs. Indirect costs represented 43% of the total costs during the 5 years. About 12% worked full-time, and 12% worked part-time, implying large productivity losses. As a consequence of the national mental health care reform, a substantial shift of costs from hospital care to sheltered living took place on the national level, but the reduction of hospital days for the study patients over time was much larger suggesting that the switch from first to second generation compounds was therapeutically successful. A high degree of social isolation was seen, with more than 20% being completely without social contacts and 30% seeing friends/relatives less often than once a week. CONCLUSION: The economic costs of schizophrenia are high and driven by the need for assisted living and hospitalizations, together with productivity losses. In addition, the intangible costs, such as social contacts, are also high.

Weight development in patients treated with risperidone: a 5-year naturalistic study.

OBJECTIVE: To examine annual weight-development in a sample of 215 psychotic patients treated with risperidone over 5 years. METHOD: Naturalistic longitudinal study. RESULTS: The sample was more obese than the general population at baseline, but also increased much more in mean body mass index over approximately the same time period, while patients off medication seemed to remain weight stable. Excessive weight gain (>7%) was experienced by 40.2% and was weakly associated with weight at baseline (beta = -0.2%; P = 0.02), while independent of gender, symptoms, years of illness, prolactin levels and nicotine consumption. In patients with complete weight data (n = 87), approximately 72% (3.4 +/- 8.3 kg) of the observed 5 years weight gain (4.7 +/- 11.6 kg) had been accumulated after 2 years. CONCLUSION: Antipsychotic drug treatment resulted in significant weight gain, which levelled off over time. Unfortunately, few significant predictors of adverse weight development could be identified, leaving little guidance for clinical decision making regarding this specific side-effect.

Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders.

OBJECTIVE: To investigate prolactin levels and related side effects in 128 men and 90 women initially treated with risperidone. METHOD: Patients initially treated with risperidone were followed over 5 years, during which 45% were switched to other antipsychotic drugs. RESULTS: Initially, prolactin levels were fivefold the norm in women, and threefold in men. Diagnosis did not affect the prolactin level if adjustment for sex, current age, and age at onset of psychosis was applied. Prolactin levels did not correlate significantly neither with any Positive and Negative Symptom Scale item or subscale, nor with side effects. Drugs other than risperidone were not associated with high prolactin levels. For patients on continuous monotherapy risperidone treatment, there was a marked linear reduction of prolactin level over all 5 years. CONCLUSION: Risperidone induces a higher prolactin elevation than other atypical antipsychotics, but the effect adapts over time. Prolactin was not associated with expected side effects (e.g. sexual, mental, or weight gain).

Treatment costs and clinical outcome for first episode schizophrenia patients: a 3-year follow-up of the Swedish "Parachute Project" and two comparison groups.

OBJECTIVE: To evaluate "need-specific treatment" of first episode schizophrenia syndrome patients. METHOD: Sixty-one consecutive first episode schizophrenia syndrome patients were followed over 3 years. They were compared with a Historical "treatment as usual" group (n = 41) and a Prospective group from a high quality social and biological psychiatry centre (n = 25). RESULTS: Symptomatic and functional outcome was significantly better compared with the Historical group and equal with the Prospective group. During the first year, the direct costs for in- and out-patient care per patient in the Parachute project were less than half of those in the Prospective group. CONCLUSION: The study confirms the feasibility, clinically and economically, with a large scale application of "need-specific treatments" for first episode psychotic patients.

Schizophrenia, neighbourhood, and crime.

OBJECTIVE: To investigate the relationship between the prevalence of schizophrenia and measures of social deprivation in varying areas in the city of Malmö. METHOD: A case-finding study of schizophrenia was combined with a victimization survey. Data was factor-analysed and visualized using geographical information system software. RESULTS: The schizophrenic patients lived predominantly in socially disorganized areas characterized by high levels of disorder, fear of crime and victimization. The local prevalence of schizophrenia covaried significantly with all indices of social disorganization. In addition, a significant but weak association was obtained between prevalence of schizophrenia and fear of specific persons in the neighbourhood. CONCLUSION: In spite of enormous changes in social conditions, psychiatric knowledge and organization of treatment, and political ambitions, schizophrenic patients still aggregate in socially deprived areas. This segregation may result in worsening of the illness as well as increasing the social disorganization in the local domicile.

One-year outcome in first episode psychosis patients in the Swedish Parachute project.

OBJECTIVE: Implementing a system designed to treat first episode psychotic (FEP) patients. METHOD: Every FEP patient (n=253) from a catchment area of 1.5 million inhabitants were asked to participate in this 5-year project. One historical (n=71) and one prospective (n=64) FEP group were used for comparisons. RESULTS: A total of 175 patients (69%) were followed up through the first year of treatment. Global Assessment of Functioning (GAF) values were significantly higher than in the historical comparison group but similar to the prospective group. Psychiatric in-patient care was lower as was prescription of neuroleptic medication. Satisfaction with care was generally high in the Parachute group. Access to a small overnight crisis home was associated with higher GAF. CONCLUSION: It is possible to successfully treat FEP patients with fewer in-patient days and less neuroleptic medication than is usually recommended, when combined with intensive psychosocial treatment and support.

On the operationalization of psychopathy: further support for a three-faceted personality oriented model.

OBJECTIVE: This study is an attempt to compare two alternative models of psychopathy (PCL-R); (i) the traditional 17-item two-factor model where the first factor describes a deceitful, manipulative and callous, unemotional dimension and the second factor describes the impulsive, irresponsible and antisocial behavioral lifestyle dimension; and (ii) a recently proposed 13-item three-factor model involving an interpersonal facet, an affective facet and a behavioral facet. METHOD: Exploratory and confirmatory factor analyses of PCL-R scores on a sample of 293 adult male violent offenders were conducted. RESULTS: The results of the exploratory factor analysis showed that the 13 items yielded three easily interpretable factors: an interpersonal factor, an affective factor and a behavioral/lifestyle factor. Through confirmatory factor analysis we showed that this model had a significantly closer fit to the data than the classical 17-item, two-factor model of the PCL-R. CONCLUSION: The study supports the three-faceted model of psychopathy.

Neuropsychological impairments in patients with schizophrenia: stability and prediction of outcome.

OBJECTIVE: To assess neuropsychological impairments among fairly young schizophrenic patients over time, and relations between impairment and symptoms, drug type and dose. METHOD: Clinical and neuropsychological data for 29 schizophrenic patients have been published earlier. Twenty of these patients were retested after 3 years using the same methods. RESULTS: The patients displayed stable impairments in most neuropsychological tests. Vocabulary and focused attention improved over time, whereas response slowness became more pronounced. Symptoms varied considerably over time. A specific pattern of neuropsychological impairments, but not measures of psychopathology, predicted clinical outcome. Patients were unable to judge their test performance. CONCLUSION: A few years after the first episode, our patients displayed a specific pattern of neuropsychological impairment, which predicted clinical outcome. One aspect of the impairment appears to be failure at self-monitoring.

Neuropsychological impairment in patients treated with depot neuroleptics: a longitudinal study.

OBJECTIVE: To assess neuropsychological impairments among chronic functional psychotic patients over time, and relations with symptoms, drug dose and side effects. METHOD: Thirty-four patients, representative of the most ill one-third of all patients with chronic functional psychoses known to the psychiatric services in a city catchment area, were assessed for clinical symptoms, drug side effects and by neuropsychological tests at study entry. They were then assessed repeatedly over 2 years. RESULTS: All patients were seriously impaired in the tests. The impairment was stable over time, in spite of substantial changes in the clinical state. The impairment was unrelated to drug and drug dose. Patients with prominent negative symptoms were most impaired and most unable to rate their performance in the tests. CONCLUSION: Patients with chronic functional psychoses do relapse often, also late in the course of the disease. Negative symptoms, marked impairments in simple neuropsychological tests and impaired self-monitoring went together.

Schizophrenia--progressive and massive decline in response readiness by episodes.

OBJECTIVE: To relate the pattern of neuropsychological impairments among schizophrenic patients to case history data and disease characteristics in a cross-sectional study of unselected patients, and to integrate these data with two previous longitudinal studies of neuropsychological impairments among schizophrenic patients. METHOD: One hundred consecutive schizophrenic patients were studied with respect to clinical case history and current symptoms, medication and neuropsychological impairment using a comprehensive computerized test battery. RESULTS: The most salient finding was a marked slowing of response readiness, linearly related to the number of previous acute episodes. The resulting deficit was far beyond what has been obtained in any other group of subjects (average -6 SD for >five episode patients). The impairments in many of the other neuropsychological parameters could to some extent be explained with reference to response slowing, with one exception--verbal short-term memory. Adjustment for important confounding factors (age, duration of illness, medication) did not change the strong negative association between response readiness and number of previous episodes. CONCLUSION: These findings, together with findings of our two previous longitudinal studies and a recent replication, prompted us to suggest that each acute schizophrenic episode inflicts damage to a set of hypothetical structures, cognitive pattern generators. We assume that these structures translate intentions to logistic programs. When damaged, delays are introduced into executive functions and corollary discharge processes will run out of phase with intentions. This model implicates new ways of looking at the generative mechanisms of the illness, and on treatment strategies.

[Using projective tests in forensic psychiatry may lead to wrong conclusions. Only empirically tested tests should be used]. / Projektiva test inom rättspsykiatrin medför risker för rättssäkerheten. Endast metoder med god empirisk förankring bör användas.

The use of projective and psychometric psychological tests at the Department of Forensic Psychiatry in Stockholm (Huddinge), Sweden, was studied for a population of 60 men, including many patients with neuropsychological disabilities and multiple psychiatric disorders. The results showed that the use of projective tests like Rorschach, Object Relations Test, and House-Tree-Person was more frequent than the use of objective psychometric tests. Neuropsychological test batteries like the Halstead-Reitan Neuropsychological Test Battery or Luria-Nebraska Neuropsychological Battery were not used. The majority of patients were, however, assessed by intelligence scales like the WAIS-R. The questionable reliability and validity of the projective tests, and the risk of subjective interpretations, raise a problem when used in a forensic setting, since the courts' decisions about a sentence to prison or psychiatric care is based on the forensic psychiatric assessment. The use of objective psychometric neuropsychological tests and personality tests is recommended.

Attention deficit hyperactivity disorder, reading disability, and personality disorders in a prison population.

Attention Deficit Hyperactivity Disorder (ADHD) has long been recognized in children, and for many the disorder persists into adulthood. There is a growing concern that the adults with ADHD who have the least favorable outcome, are among those who end up in prison. The aim of this study was to assess childhood ADHD and its persistence into adulthood among a representative sample of Norwegian prison inmates, as well as personality disorders and reading difficulties, which in previous studies have been linked to ADHD. The results indicate that persistent ADHD is very common among prison inmates. Personality disorders and reading difficulties are also common. Psychiatric comorbidity complicates the diagnosis of ADHD in adults. A greater awareness about ADHD in adults certainly is warranted, especially within the prison system because of the risk of misdiagnosing psychiatric disorders and also the risk of missing a condition possibly amenable to treatment.

Criminality and aggression among psychotic in-patients: frequency and clinical correlates.

OBJECTIVE: Violence is common among patients with psychoses. The aim of the study was to examine relations between diagnoses, crimes, demographic variables and aggressive behaviour during admission to hospital. METHOD: During 14 months 257 patients were consecutively referred to a unit with high staff/patient ratio. They were assessed for clinical symptoms at admittance and discharge. Also legal status, coercive measures, criminality and sentences were examined. RESULTS: Of the 257 patients, 38% were found in the police register and 33% had been prosecuted. Those patients committed 2525 crimes, including 292 acts of violence. Problems during admittance were related more to positive symptoms at admittance than to earlier criminality. CONCLUSION: Criminality rate is high among patients with functional psychoses. Many patients, especially women, had never been evaluated by a forensic psychiatrist. The psychiatric services have to consider the importance of preventing psychotic relapses and thereby also preventing violence and criminality.

New insights into the second generation antihistamines.

Second generation antihistamines are recognised as being highly effective treatments for allergy-based disease and are among the most frequently prescribed and safest drugs in the world. However, consideration of the therapeutic index or the benefit/risk ratio of the H1 receptor antagonists is of paramount importance when prescribing this class of compounds as they are used to treat non-life threatening conditions. There are many second generation antihistamines available and at first examination these appear to be comparable in terms of safety and efficacy. However, the newer antihistamines in fact represent a heterogeneous group of compounds, having markedly differing chemical structures, adverse effects, half-life, tissue distribution and metabolism, spectrum of antihistaminic properties, and varying degrees of anti-inflammatory effects. With regard to the latter, there is growing awareness that some of these compounds might represent useful adjunct medications in asthma therapy. In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions. Moreover, some of the second generation H1 antagonists have given cause for concern regarding their potential to cause a degree of somnolence in some individuals. It can be argued, therefore, that the present second generation grouping is too large and indistinct since this was based primarily on the concept of separating the first generation sedating compounds from nonsedating H1 antagonists. Although it is too early to talk about a third generation grouping of antihistamines, future membership of such a classification could be based on a low volume of distribution coupled with a lack of sedating effects, drug interactions and cardiotoxicity.