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Die Angst ist ein ganz zentrales Phanomen, vieler Patienten, die an einer Erkrankung aus dem schizophrenen Formenkreis leiden. Unterschiedliche psychopathologische Phanomene konnen Angst auslosen, nur selten konnen Wahngebaude auch angstlindernd wirken. Neben unmittelbaren krankheitsbedingten ideologischen Modellen fur die Angst kann diese auch durch andere Faktoren entstehen: Das immer noch gefurchtete Setting der Behandlung in einem Psychiatrischen Krankenhaus, eventuell im Unterbringungsbereich, die Angst vor der Behandlung, vor Nebenwirkungen, die Angst vor Stigmatisierung durch andere, die Angst also, einer wenig geschatzten Minderheit anzugehoren.

Background: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. Methods: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. Findings: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0·37, [95% CI 0·24-0·57]), olanzapine (HR 0·28 [0·18-0·43]), quetiapine (HR 0·52 [0·35-0·76]), and ziprasidone (HR 0·51 [0·32-0·81]). However, symptom reductions were virtually the same in all the groups, at around 60%. Interpretation: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement. Funding: AstraZeneca, Pfizer, Sanofi-Aventis. © 2008 Elsevier Ltd. All rights reserved.

The management of acute episodes in schizophrenia is frequently initiated in the psychiatric emergency department and requires rapid intervention to relieve distress and psychiatric symptoms. Both non-pharmacological and pharmacological interventions are needed to calm the patient and prevent potential harm to the patient or others. Treatment is a step-by-step process including management of behavioral symptomatology, diagnosis of potential organic causes, and evaluation of potential substance abuse. Better care is delivered if predefined standard operating procedures are adopted systematically. The ultimate goal of treatment is to establish a therapeutic alliance with the patient. Atypical antipsychotics given orally are recommended as a first-line treatment. As the treatment endpoint is calmness rather than sleep, a non-sedative antipsychotic agent is usually preferred. Drug tolerance is a major issue for the patient. Amisulpride is an effective atypical antipsychotic agent in this context. The optimal dose is 800 mg/day, which is effective on positive and negative symptoms and can be given from the first day with a low risk of extrapyramidal symptoms. Since drug–drug interactions are limited, agitation and anxiety may be controlled by short-term adjunctive therapy with benzodiazepines. In conclusion, amisulpride is an appropriate first-line treatment for the management of acute psychosis.

We conducted a prospective, open study in schizophrenia patients treated with second-generation antipsychotics in order to investigate the risk for elevation of liver enzymes and its correlation to antipsychotic-induced weight gain. Body mass index, serum transaminases, plasma serum levels of the antipsychotic used, and blood cell counts were measured weekly during the first 6 weeks of treatment and monthly thereafter. A considerable proportion of subjects showed an increase beyond normal levels of at least one of the measured transaminases. In all but one case, the elevation of liver enzymes was transient. We found a statistically significant correlation between weight gain and liver enzyme elevation. The group of patients that had gained at least 7% of the baseline body weight showed significantly higher increases of transaminases as compared with those who had gained less than 7% weight. We conclude that antipsychotic-induced elevation of liver enzymes is mostly transient and could be associated with weight gain.

Although second-generation antipsychotics have notabLe benefits as compared to typical antipsychotics, their use has been associated with metaboLic disturbances, such as alterations of glucose homeostasis. It is still being debated whether this is a class effect of second-generation antipsychotics. We conducted a prospective, open study comparing body weight, parameters of insuLin resistance in schizophrenia patients treated with either clozapine ( n = 10) or amisuLpride ( n = 12). All parameters were assessed monthly over a period of 12 to 16 weeks. Body mass index (BMI), fasting serum insulin Levels and the Homeostasis Model Assessment (HOMA) index for insulin resistance increased significantly in patients treated with clozapine. None of these parameters increased significantly in patients treated with amisulpride. This study indicates that treatment with clozapine appears to have a higher risk to Lead to metabolic disturbances than amisupride.

Pharmacological treatment of schizophrenia often requires careful dosage titration to achieve satisfactory symptom control whilst minimising the risk of adverse effects. Relapses requiring hospitalisation are an important potential source of additional cost for the health service and any inadequate symptom control increases the indirect costs of schizophrenia relating to, for example, the need for sheltered accommodation or intensive social services support. The availability of generic drugs is widely regarded as an opportunity to reduce expenditure on drug costs and deploy limited resources more widely and effectively. However, generic drugs may differ from branded drugs in their formulation and may not show precise bioequivalence with the branded product. This may have consequences for the pharmacokinetic profile of the generic drug. A higher maximum plasma concentration (C(max)) could lead to increased or emergent adverse effects, whereas a decreased absorption or minimum plasma concentration (C(min)) may result in a reduced therapeutic effect. For example, plasma levels of clozapine are critical to therapeutic response. Symptom aggravation occurred in approximately 10% of patients switched from branded to generic clozapine in a small, randomised, crossover study. Patients with schizophrenia may also show suspicion and hostility regarding their treatment. This may result in unwillingness to take an unfamiliar medication and decreased compliance, thus increasing the risk of a relapse. Thus, great care should be taken by psychiatrists when switching patients with schizophrenia from branded to generic antipsychotic drugs; this entails monitoring clinical outcome closely and adjusting the treatment in case of symptom aggravation or emergence of adverse effects.

Background: The aim of this study was to compare glucose metabolism in patients with schizophrenia receiving olanzapine with that in control subjects. Method: We conducted a prospective, controlled, open study comparing body weight, fat mass, and indices of insulin resistance/ sensitivity in 10 olanzapine-treated patients with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a group of 10 mentally and physically healthy volunteers. Weight, fat mass, and indices of insulin resistance/sensitivity were assessed over individual 8-week observation periods from November 1997 to October 1999. Results: Fasting serum glucose and fasting serum insulin increased significantly in the olanzapine-treated patients (p = .008 for glucose and p = .006 for insulin). The homeostasis model assessment (HOMA) index for beta cell function did not change significantly in the olanzapine-treated patients, whereas the HOMA index for insulin resistance did increase (p = .006). In the control group, these parameters were stable. A significant increase in body weight (p = .001) and body fat (p = .004) was seen in patients treated with olanzapine, while the control group showed no significant changes. Conclusion: This study indicates that the disturbances in glucose homeostasis during antipsychotic treatment with olanzapine are mainly due to insulin resistance. However, beta cell function remains unaltered in olanzapine-treated patients. We conclude that treatment with some second-generation antipsychotic drugs may lead to insulin resistance.

The importance of antipsychotics in the treatment of schizophrenia has been documented in numerous clinical trials. In addition to its established superiority over other antipsychotics in treatment-resistant patients, clozapine has been consistently shown to improve psychopathology and other psychosocial outcome variables in patients with schizophrenia. To determine whether the course of the illness has an influence on response and side-effects to clozapine, we directly contrasted first- and multiple-episode patients with schizophrenia, who had histories of failing response to traditional antipsychotics, during the acute treatment phase. Thirty-nine first-episode patients with schizophrenia and 56 patients who had suffered from at least two episodes of this illness were investigated. Severity of illness and clinical improvement were rated by means of the CGI Scale. Vital signs were recorded weekly. Side-effects were regularly assessed with the UKU Side Effect Rating Scale. Compliance was regularly assessed by clinical interviews and plasma level monitoring. By using comparable mean clozapine doses, the number of treatment responders was similar in both groups (first-episode patients, 51.3%; multiple-episode patients, 46.4%). However, we found a negative association between age and response rate. With regard to side-effects, we could not find any significant difference between groups. Altogether, response and side-effects to clozapine treatment do not seem to be determined by the chronicity of the disorder.

Background Despite the fact that the efficacy of antipsychotic treatment in patients with schizophrenia has been demonstrated in numerous double-blind studies, placebo-controlled studies are still commonly performed. Although much is known about the opinions of professionals concerning this issue, so far nothing is known about the opinions of patients who are most affected by the realization of placebo-controlled clinical trials. Method In a cross-sectional study from June 2000 to January 2001, 100 inpatients and outpatients with ICD-10 schizophrenia or schizophreniform disorder were investigated by using a questionnaire specifically developed to survey patients' attitudes concerning possible participation in placebo-controlled clinical trials. Psychopathology and side effects were physician-rated. Results 56% of patients would not be willing to participate in a placebo-controlled clinical trial. On the other hand, only about 16% of the patients are against clinical trials in principle. Gender, treatment, severity of psychopathology (Positive and Negative Syndrome Scale), adverse events (UKU Side Effect Rating Scale), and attitude toward medication (Drug Attitude Inventory) had no statistically significant influence on the decision. Most of the patients (76%) stated that they would not lose trust in their physician if asked to participate in a placebo-controlled clinical trial. Conclusion The opinions and fears of patients who are most affected by the debate need to be considered when deciding whether a placebo-controlled clinical trial is necessary.

Background A cross-sectional study was conducted in patients with schizophrenia who regularly attended an outpatient clinic to examine the impact of psychopathology, side effects, and sociodemographic factors on attitudes toward antipsychotics. Method Sixty patients with a schizophrenic disorder according to ICD-10 criteria who had a duration of illness over 1 year and whose discharge from an inpatient unit had been at least 6 weeks earlier were investigated. Apart from the registration of demographic data, various rating scales were used: the Positive and Negative Syndrome Scale, the St. Hans Rating Scale for Extrapyramidal Syndromes, the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale, and the Drug Attitude Inventory (DAI). Results Generally, the aspects describing a positive attitude toward antipsychotics on the DAI received a higher degree of assent than those characterizing a negative drug attitude. However, employment status correlated with a poorer global medication attitude on the DAI, and positive symptoms and sedation correlated with greater negative feelings on the DAI subjective negative feelings subscale. Conclusion Our results suggest that special attention should be paid to patients who experience positive symptoms or sedation and to those with relative absence of symptoms, who are therefore tempted to stop taking medication.

Objective: Despite the demonstrated efficacy of antipsychotics the relapse rate among patients with schizophrenia remains high. One major reason for this is non-compliance. In this article we review different factors influencing compliance and discuss possibilities to enhance compliance among schizophrenic patients. Method: This review is based on a systematic literature search in Medline. Results: We summarize the four main factors (patient-, environment-, physician- and treatment-related) that influence compliance and discuss possible measures to enhance compliance. Next to many other variables discussed in more detail, it is crucial to ensure a positive doctor–patient relationship and to provide sufficient information about the benefit/risk ratio of the medication as well as about the illness itself to build up and sustain compliance. Significant others should be included into the therapeutic alliance whenever possible. Conclusion: Despite many published reports on compliance, it remains to be a problem of eminent clinical relevance. Clinicians must not underestimate it in order to optimize the treatment of patients with schizophrenia.

Despite the fact that most antipsychotics have only been formally evaluated for the treatment of schizophreniform disorder, schizophrenia, mania, and schizoaffective disorder (defined as "classical indications"), antipsychotics are widely used for the treatment of a broad range of symptoms and disorders. In this study, 173 patients who were having their prescriptions for antipsychotics filled at local pharmacies were interviewed. In 115 patients (66.5%), an antipsychotic was prescribed for off-label indications. Patients most often stated that they took antipsychotics as a tranquilizer or an anxiolytic. Neither gender, education, duration of treatment, nor efficacy of treatment showed an influence on the prescription practices for antipsychotics. In contrast, family status and side effects showed a significant influence. A classical indication was more often found in married and widowed patients than in unmarried or divorced ones. Patients in whom antipsychotics were prescribed for the treatment of schizophrenia, schizophreniform disorder, mania, or schizoaffective disorder experienced side effects more often than others. Age was also important for the indication of antipsychotics. Classical indications of antipsychotics were most often found in patients aged 30 to 49 years. In older patients (49-70 years), antipsychotics were almost exclusively used for off-label indications. In classical indications, clozapine was used more frequently (50%) than other antipsychotics. Melperone was primarily prescribed for off-label use.

The current state of the art of the pharmacological treatment of schizophrenia, and a review of the latest findings in antipsychotic drug development are presented. A first step in optimising treatment is an increase in the awareness and implementation of existing treatment standards. The introduction of clozapine challenges the view that all antipsychotics are of similar efficacy; the drug has an established superiority over some of the traditional antipsychotics in treatment-resistant patients. Newer agents such as zotepine, risperidone, quetiapine, olanzapine and sertindole, which have a lower risk of producing extrapyramidal motor symptoms, have been developed in the wake of clozapine. While it is still common to switch nonresponding patients to an antipsychotic of a different chemical class, clozapine treatment remains the only strategy based on sound scientific evidence in these patients, although the novel antipsychotics give rise to hope. Alternatively, combination treatment with benzodiazepines, lithium or an anticonvulsant has been employed. If treatment with a depot antipsychotic is planned, it is advisable to start a patient on the oral form of the same drug in order to obtain dose requirements and tolerability information of the drug in that patient. Long term maintenance therapy is crucial and continuous monitoring for the development of adverse effects essential.

Neuroleptic induced akathisia (NIA) is a common and distressing side effect of antipsychotic treatment. Incidence rates are reported to be between 25% and 75%, depending on criteria used for diagnosis. The results of our four week prospective naturalistic study are based on the assessment of 73 inpatients, which were started on antipsychotic medication in one of the inpatient units of the Department of Psychiatry. NIA was rated with the Hillside Akathisia Scale. Assuming that both, objective as well subjective phenomena are necessary for a valid diagnosis of NIA, we calculated an incidence rate of 22.4%. 75% of all NIA cases occurred within the first three days of antipsychotic treatment. When attempting to determine risk factors for the development of NIA, we found a significant influence of dose increase in the first days of treatment.

Compliance is a behaviour influenced by many factors. Although many review articles state that extrapyramidal syndromes (EPS) are one of the most important reasons for noncompliance, only a few authors have investigated this question systematically. We review relevant literature on EPS and their potential influences on compliance in patients with schizophrenia. The findings are equivocal. When the available studies are compared, wide variations in study design, as well as different statistical approaches and hypotheses, become apparent. Another limiting factor in investigating the correlations between compliance and EPS is the observation that compliance will improve under study conditions. On the basis of the available literature, correlations between EPS and compliance cannot be definitively discussed. Definitions of compliance and standardised study designs are necessary to obtain comparable and meaningful data on this issue. Despite the paucity of conclusive research, adverse effects as well as compliance, and their inter-relationship, must always be considered during any type of treatment far schizophrenia.

Neuroleptic-induced extrapyramidal side effects (EPS) were evaluated in 92 patients treated with clozapine for the first time and 59 patients treated with haloperidol followed in a drug monitoring program. Side effects were measured by the Columbia University Rating Scale, the Simpson Dyskinesia Scale and the Hillside Akathisia Scale. The cumulative incidence rate for tremor was found to be 24.4% in the clozapine group and 39.3% in the haloperidol group. This did not amount to a statistically significant group difference. Bradykinesia was observed in 21.8% of the patients treated with clozapine and in 47.7% of the patients of haloperidol (P = 0.011). In the clozapine group the akathisia incidence rate was 5.6%, whereas haloperidol patients showed a higher rate of 31.7% (P = 0.005). Our results show higher incidence rates of tremor and bradykinesia during clozapine treatment than previous studies. We conclude that clozapine is not entirely free of EPS, but they are usually less severe and of a different quality than side effects induced by typical antipsychotics.

Sexual dysfunctions (SDs) occur frequently in schizophrenia patients and have a huge impact on quality of life and compliance. They are often associated with antipsychotic medication. Nicotine consumption, negative or depressive symptoms, and physical illness are also discussed as contributing factors. Data on SD in first-episode schizophrenia patients are scarce.As part of the European First Episode Schizophrenia Trial, first-episode schizophrenia patients were randomly assigned to 5 medication groups. We assessed SD by analyzing selected items from the Udvalg for Kliniske Undersugelser at baseline and at 5 following visits.Differences between antipsychotics were small for all SDs, and fairly little change in the prevalence of SDs was seen over the course of the study. A significantly larger increase of amenorrhea and galactorrhea was seen with amisulpride than with the other medications. In men, higher age, more pronounced Positive and Negative Syndrome Scale general psychopathology symptoms, and higher plasma prolactin levels predicted higher rates of erectile and ejaculatory dysfunctions. Positive and Negative Syndrome Scale negative symptoms and higher age were predictors for decreased libido.In women, higher prolactin plasma levels were identified as a predictor of amenorrhea. Positive and Negative Syndrome Scale negative symptoms predicted decreased libido.All evidence taken together underscores the influence of the disease schizophrenia itself on sexual functioning. In addition, there is a strong correlation between the prolactin-increasing properties of amisulpride and menstrual irregularities.

Anliegen: Es sollte evaluiert werden, in wieweit Patienten mit Schizophrenie oder einer schizoaffektiven Erkrankung von einem psychoedukativen, bewaltigungsorientierten Therapieprogramm profitieren konnen. Methode: Fur die Evaluation wurde ein kontrolliertes prospektives Studiendesign herangezogen. Zum Einsatz kam in der Experimentalgruppe das “Therapiemanual zur Psychoedukation und Krankheitsbewaltigung” (PKB), das neben gezielter Information uber die Erkrankung und die Pharmakotherapie Strategien vermittelt, wie Fruhwarnsignale erkannt und der Umgang mit ihnen erlernt werden konnen. Daruber hinaus werden auch Aspekte zu „gesundem“ Verhalten behandelt. Als Kontrollgruppe diente eine Patientengruppe mit supportiven Gesprachen bzw. eine Gruppe mit dem Schwerpunkt der Arbeitsrehabilitation. Um die Effekte der PKB zu evaluieren, wurden der psychopathologische Status, wissensbezogene sowie soziale Variablen zu verschiedenen Messzeitpunkten (vor der Therapie, nach Therapieende, 12 Monate nach Therapieende) erhoben. Als abhangige Variablen dienten der Wissensstand uber die Erkrankung, Rehospitalisierungen, soziale Integration und Bewaltigungsstrategien. Ergebnisse: 82 Patienten nahmen an der Studie teil. Sowohl in der Experimentalgruppe als auch in der Kontrollgruppe wurde eine signifikante Verbesserung des Allgemeinzustandes und der Psychopathologie beobachtet. Die Ergebnisse der Gruppen unterschieden sich insofern, dass in der Experimentalgruppe weniger Rehospitalisierungen im ersten Jahr nach Studienende vermerkt wurden und die Teilnehmer sich anderer Copingstrategien bedienten (signifikant weniger depressive Krankheitsverarbeitung und Bagatellisierung). Schlussfolgerungen: In der Behandlung von Schizophrenie konnen unterschiedliche Interventionen wirksam sein. Fragestellungen, welche Patienten von welcher Art der therapeutischen bzw. rehabilitativen Intervention profitieren konnen, sollten weiterhin Gegenstand intensiver Forschung sein.

1. The authors report three cases of neuroleptic induced akathisia resistant to treatment with anticholinergics, benzodiazepines and betablockers. 2. All three patients were treated with Ritanserin 10 mg bid and improved rapidly and substantially. 3. Discontinuation of Ritanserin led to a recurrence of akathisia.

The aim of this study was to evaluate the effectiveness of a psycho-educational, coping-oriented therapy programme for patients with schizophrenia or schizo-affective disorder.Controlled, prospective study design. In the experimental group the Therapy Manual for Psycho-education and Coping with Illness (PKB) was used, providing targeted information on the illness, medical treatment, prodromal symptoms, and health behaviour. Controls participated in supportive dialogues or in an occupational rehabilitation programme. Psychopathology, re-hospitalisations, knowledge, functional outcome and coping strategies were assessed before, directly after and 12 months post therapy.82 patients participated. In both groups (experimental, control) a significant improvement in psychopathology and general functioning level were observed. Specific advantages for patients of the experimental group were limited to a few aspects, including rehospitalizations in the first year and certain coping strategies.In the treatment of schizophrenia different forms of psycho-social intervention (experimental, control) can be effective. Identification of subgroups profiting specially from certain types of intervention should be subject of future research.

Objective: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. Methods: Subjects were 498 patients with schizophreniform disorder or firstepisode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month followup evaluation. Results: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. Conclusion: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their firstepisode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.

Metabolic side effects have been found earlier during treatment with second-generation antipsychotics. Among those disturbances serum lipids are less investigated. We conducted a prospective, open study in schizophrenia patients in order to compare body weight and serum lipids during treatment with amisulpride, ziprasidone, clozapine or olanzapine over a period of 4 weeks. Body mass index, total cholesterol and triglycerides increased in patients treated with clozapine and olanzapine whereas high-density lipoprotein cholesterol decreased in those patients. In patients treated with amisulpride or ziprasidone, we found a decrease in body mass index and total cholesterol whereas high-density lipoprotein cholesterol increased. Our results indicate that treatment with ziprasidone and amisulpride is more favourable than treatment with clozapine and olanzapine with respect to the risk to induce weight gain and hyperlipidaemia. These results are important with regard to the increased risk for cardiovascular complications in patients with schizophrenia.

Outcome in schizophrenia is multidimensional and, thus, consists of clinical,humanitarian, rehabilitative and cost domains. Accordingly, recovery is conceptualized as the ability to function in the community, socially and vocationally, as well as being relatively free of disease–related psychopathology. The present cross–sectional study examined the relationship of premorbid functioning, psychopathology, insight, attitudes toward medication and side–effects, as well as sociodemographic factors with treatment outcomes in terms of quality of life (QOL) and psychosocial functioning among 60 regular attendees of a specialized schizophrenia outpatient clinic. Both insight into the illness as well as attitudes toward treatment indicated satisfactory compliance. Premorbid school and social functioning were positively correlated with actual employment status, and premorbid social functioning was further positively correlated with QOL and global functioning. Attitudes toward treatment were positively associated with global QOL, and with the patients' living situation. Both positive and negative symptoms as well as asthenia were negatively associated with QOL, while cognitive symptoms negatively influenced occupational functioning. Older patients lived independently and/or in a partnership more often, but had a lesser likelihood of competitive employment. Our observations suggest that subjective and functional outcomes in highly compliant patients are mainly predicted by psychopathological symptoms and unchangeable sociodemographic variables.

QTc prolongation is associated with the administration of some antipsychotics but the QTc interval is also known to vary physiologically. There is little published evidence about changes in QTc variability during treatment with antipsychotics. In this prospective investigation, we analyzed ECGs in 61 patients suffering from a schizophrenic disorder who were treated with different antipsychotics and 31 sex- and age-matched healthy controls. We found no differences in QTc intervals nor in QTc variability between patients and controls. Our results raise the question of the clinical relevance of a single ECG for diagnostics of cardiac complications in schizophrenia patients and suggest the need to conduct ECG monitoring in patients at high risk for cardiac complications during antipsychotic treatment.

The introduction of second-generation antipsychotics represents an important advance in the treatment of schizophrenia. Although these drugs are generally very effective, not all patients respond in the same way. Partial response with persistent positive and negative symptoms and residual symptoms may force physicians to change antipsychotic medication. As more and more second-generation antipsychotics are introduced, the need for practical guidelines on switching these medications becomes increasingly important. In this article we provide a short summary of the second-generation antipsychotics, focusing on efficacy, adverse effect profile and safety. Indications for switching antipsychotic medication are outlined, as well as recommendations when switching is disadvantageous. Three basic switching strategies (abrupt, gradual and overlapping switching) and their potential risks and benefits are described. We review the available evidence concerning techniques, problems and consequences when switching from one second-generation antipsychotic agent to another and discuss potential difficulties.

Osteoporosis is regularly mentioned as a possible consequence of treatment with prolactin-increasing antipsychotic medications, but little is known about the prevalence and the degree of loss of bone mineral density in patients suffering from schizophrenia. The authors' goals were to investigate the association between schizophrenia and a decrease in bone mineral density and to get more insight into potential underlying pathophysiological mechanisms.In a cross-sectional study, the authors used dual x-ray absorptiometry to determine bone mineral density of 75 inpatients and outpatients suffering from schizophrenia. All patients had been treated with antipsychotics for at least 1 year, and only patients between the ages of 19 and 50 were studied to exclude patients with age-related idiopathic osteoporosis.In men but not women with schizophrenia, bone mineral density was significantly lower than normal in the lumbar region. A comparison of loss of bone mineral density in male and female patients showed significant differences between the sexes. Bone mineral density showed a negative correlation with negative symptoms and Positive and Negative Syndrome Scale total score and a positive correlation with 25-hydroxy-vitamin D3 levels and body mass index in male patients. In female patients, a positive correlation between body mass index and bone mineral density was found. Exposure to prolactin-increasing antipsychotics was not related to bone mineral density.The male patients with schizophrenia in this study suffered from low bone density. This finding as well as other reports lend support to directing more attention to bone metabolism in patients with schizophrenia, although there is no universally accepted screening policy to identify individuals at high risk for osteoporosis.

ObjectiveThe present cross-sectional study examined the relationships of psychopathology, side effects, and sociodemographic factors with treatment outcomes in terms of patients' quality of life (QOL), functioning, and needs for care.MethodSixty outpatients with chronic schizophrenia who had been treated with either clozapine or olanzapine for at least 6 months were investigated.ResultsMost psychopathological symptoms as well as psychic side effects, weight gain, and female sex were associated with lower QOL, while cognitive symptoms correlated with better QOL. Female sex, cognitive symptoms, and parkinsonism negatively influenced occupational functioning, and negative symptoms determined a lesser likelihood of living independently. Age, education, depression/anxiety, negative symptoms, and psychic side effects were predictors of patients' needs for care.ConclusionOur results highlight the complex nature of patient outcomes in schizophrenia. They reemphasize the need of targeting effectiveness, i.e. both symptomatic improvement as well as drug safety, in such patients.

Background Quality of life (QOL) is now seen as a key outcome variable in schizophrenia. Factors deemed relevant in this context include severity of symptoms, antipsychotic-induced side effects, sociodemographic variables, and patients' subjective response to medication. Method In the current cross-sectional study, 80 patients with a schizophrenic disorder according to ICD-10 criteria who had a duration of illness over 1 year and whose discharge from an inpatient unit had been at least 6 weeks earlier were investigated. Apart from the registration of demographic data, various rating scales were used: the Positive and Negative Syndrome Scale (PANSS), the St. Hans Rating Scale for Extrapy-ramidal Syndromes, the UKU Side Effect Rating Scale, the Drug Attitude Inventory, and the Lancashire Quality of Life Profile. Results More than half of all patients (47/80) indicated that they were satisfied with their life in general. The specific areas of subjective dissatisfaction that were most commonly noted in the present sample concerned partnership and mental health. The depression/anxiety component of the PANSS, parkinsonism, and a negative attitude toward antipsychotic medication negatively influenced the patients' QOL, while cognitive symptoms and employment status correlated with higher QOL. Conclusion Our results highlight the importance of recognizing the complex nature of QOL in schizophrenia patients. They suggest that special attention should be paid to patients who experience anxiety and depressive symptoms or parkinsonism, to those who are unemployed, and to those with negative feelings and attitudes toward antipsychotics.

Prolactin is a polypeptide hormone that exists as a number of isoforms and is involved in a multitude of physiological processes. Prolactin secretion is promoted by various physiological stimuli and pathological processes and is inhibited by the action of dopamine on the lactotroph cells of the hypothalamus. Hyperprolactinaemia, an elevation of prolactin levels above the norm, is a physiological occurrence and is not of concern (including sexual dysfunction and decreased bone mineral density). Treatment of hyperprolactinaemia is usually confined to the removal of the primary cause of the disease, but several dopamine agonists have been investigated. Hyperprolactinaemia is also a side-effect of the conventional, and some of the second-generation, antipsychotics used in the treatment of schizophrenia. These agents rely on their dopamine antagonistic properties to provide their antipsychotic effects. However, this also removes the brake on prolactin secretion, leading to hyperprolactinaemia. While antipsychotic use has been linked to certain hyperprolactinaemia-related side-effects (sexual dysfunction), its link to others (decreased bone mineral density) has proved more controversial. The association of symptoms with antipsychotic use is further complicated by the fact that patients with schizophrenia can suffer from some of these symptoms because of the disease itself. In managing antipsychotic-induced hyperprolactinaemia, the initial step is to exclude other causes of hyperprolactinaemia while monitoring the occurrence of adverse effects. The physician should also engage in close consultation with the patient with regard to the benefits of the antipsychotic medication and the impact of any adverse effects. A regular risk-benefit discussion will allow the clinician to achieve optimal outcomes in each case.

Scientifically, compliance can be expressed as the ratio between an observed treatment behavior and given treatment standards. Although the factors that influence compliance often overlap or influence each other, it is possible to differentiate between factors that are related to the patient, the patient's environment, the treating clinician, and treatment itself. Although this differentiation is in some ways artificial, it may aid the practicing clinician in assessing the various reasons why a particular patient is likely to develop or has already developed compliance problems. The fact that a number of circumstances and parties are involved in the multifaceted issue of compliance makes it evident that patients must never be solely blamed for compliance problems. Despite the fact that compliance behavior is difficult to study from a methodological point of view, the scientific information available to date does provide many important leads for the engaged clinician to prevent and manage compliance problems.

The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia.The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period.A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change.In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.

The aim of this study was to evaluate the frequency and course of sexual disturbances associated with clozapine and haloperidol and their potential influence on compliance with medication regimens in patients with schizophrenia.The authors prospectively investigated 153 patients with schizophrenia who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring program.The frequency of sexual disturbances was lower in female patients than in male patients. There was no statistically significant difference between the patients taking haloperidol and those taking clozapine in the frequency of these disturbances. Clozapine plasma levels had a significant effect on diminished sexual desire and functional disturbances in male patients. Functional disturbances and diminished sexual desire did not have any influence on compliance in patients taking either haloperidol or clozapine.There was no statistically significant difference between haloperidol and clozapine in regard to their propensity to induce sexual side effects.

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon. (J Clin Psychopharmacol 1997;17:314-317).

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Es wird uber die Schwangerschaft einer 31 jahrigen Patientin, die seit ihrem 24 Lebensjahr an Schizophrenie erkrankt ist, berichtet. Die Patientin steht unter Clozapin-Dauermedikation, herkommliche Neuroleptika wurden nicht toleriert. Mit einer Tagesdosis von 100mg war die Patientin die letzten 5 Jahre vor ihrer Schwangerschaft symptomfrei. Wegen Kinderwunsch versuchte die Patientin Clozapin vor einer geplanten Schwangerschaft abzusetzen, das Wiederauftreten von Halluzinationen zwang jedoch zur Beibehaltung der Medikation. Nach eingehender medizinischer Beratung entschlos sich die Patientin zur Schwangerschaft unter Clozapin-Medikation.

The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital care. Not only treatment strategies, but also the evaluation of the syndrome, are discussed controversially. The most widely used instrument is the Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We modified the CIWA-A and translated it into German. Validity and reliability of the modified and translated scale were analysed by several psychological tests as well as different somatic measures in 31 patients. The German version appears to be a valid and reliable instrument for the assessment of alcohol withdrawal syndrome useful for clinical routine as well as treatment trials.

Clozapin ist ein Antipsychotikum, das nunmehr seit uber 30 Jahren in verschiedenen europaischen Landern und seit kurzer Zeit auch in den USA registriert ist. Die Wirksamkeit sowie gewisse Vorteile gegenuber herkommlichen Antipsychotika (v. a. im Bereich extrapyramidalmotorischer Nebenwirkungen) sind gut dokumentiert (Baldessarini u. Frankenburg 1991; Claghorn et al. 1987; Goodwin 1991; Kane et al. 1981, 1988; Meltzer et al. 1991; Naber u. Hippius 1990; Perez Urdaniz et al. 1990; Pilowsky et al. 1992).

Alcohol withdrawal delirium (AWD) requires treatment with an adequate sedative, anticonvulsant, and antipsychotic agent next to general intensive care measures. Optimal medication should have a rapid onset of action and the possibility of parenteral application. A specific antagonist should be available. Flunitrazepam is a benzodiazepine that fulfills all these criteria. Twenty five patients suffering from AWD (mean age 45 years) took part in an open trial and underwent treatment with infusions of flunitrazepam (concentration: 8 mg/250 ml NaCl; speed, 250 ml/hr). Psychopathological, vegetative, and vital parameters were assessed every hour. All patients survived. They were treated with a mean total dose (SD) of 83.9 (45.4) mg of flunitrazepam (1.3 mg/kg body weight), which induced sedation 13.2 (5.3) min after the initiation of intravenous treatment. The mean duration of AWD (85.1 +/- 39.4 hr) corresponded to other studies, whereas the frequency of preexisting and concomitant diseases was higher (92%) in our patients. A patient who suffered from bronchitis and had a nasopharyngeal tamponade showed severe respiratory depression after having received 4 mg of flunitrazepam. This complication remitted immediately when 0.5 mg of flumazenil was given intravenously. No epileptic manifestation was observed during the treatment or after discontinuation of flunitrazepam. Vegetative and psychopathological symptoms (tremor, sweating, hallucinations, confusion, and restlessness) remitted rapidly. Our data suggest that intravenous flunitrazepam can be an efficacious and safe alternative to traditional treatment strategies of AWD.

Animal studies show that cerebral lactate increases after electrically induced seizures. We investigated three adult psychiatric patients by means of localized proton and phosphorus magnetic resonance spectroscopy in order to evaluate if such effects can be observed after electroconvulsive therapy (ECT). None of the patients had changes in cerebral energy metabolism following ECT. Within the limitations of in-vivo spectroscopy in a clinical setting, our results suggest that if lactate production increases after ECT, this effect is either very short or increased perfusion causes an efficient efflux of cerebral lactate.

Schon kurz nach der Markteinfuhrung von Clozapin machten Norris et al. [6] auf eine vermehrte Gewichtszunahme aufmerksam. Wahrend der letzten Jahre beschrieben immer mehr Autoren diese Nebenwirkung. Bisher existiert jedoch nur eine Studie, welche den Unterschied zu Standardneuroleptika untersucht [4]. Diese Arbeitsgruppe beschreibt eine signifikant grosere Gewichtszunahme bei mit Clozapin behandelten Patienten im Vergleich zu Fluphenazin.

Context Dropout rates in randomized clinical trials of antipsychotic drugs have consistently been reported to be high, and the use of a placebo-controlled design is hypothesized to be one of the reasons for this. Objective To investigate this hypothesis in a meta-analysis of available data from pertinent clinical trials. Data Sources Comprehensive search of PubMed- and MEDLINE-listed journals. Study Selection Double-blind randomized controlled clinical trials of the second-generation antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole meeting the following criteria: unselected patient population with a diagnosis of schizophrenia or schizoaffective disorder, change in psychopathologic symptoms as the primary end point, and trial duration of 12 weeks or less. Data Extraction Sample size, mean age, baseline disease severity, dropout rate, trial design, trial duration, and publication year. Data Synthesis Thirty-one trials meeting the inclusion criteria were found, comprising 10 058 subjects. Weighted mean dropout rates in the active treatment arms were significantly higher in placebo-controlled trials (PCTs) than in active-control trials: 48.1% (PCTs) vs 28.3% (active-control trials) for second-generation antipsychotics (odds ratio, 2.34; 95% confidence interval, 1.58-3.47) and 55.4% (PCTs) vs 37.2% (active-control trials) for classical antipsychotics (odds ratio, 2.10; 95% confidence interval, 1.29-3.40). Within PCTs, attrition rates were significantly higher in the placebo arms than with second-generation antipsychotics (60.2% vs 48.1%; odds ratio, 1.63; 95% confidence interval, 1.37-1.94). Within the subset of trials in which both second-generation and classical antipsychotics were used, dropout rates were significantly higher with classical antipsychotics. Conclusions Use of a placebo-controlled design had a major effect on the dropout rates observed. Because high dropout rates affect the generalizability of such studies, it is suggested that, in addition to the PCTs, studies with alternative designs need to be considered when evaluating an antipsychotic’s clinical profile.