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Antipsychotic drugs were originally developed to treat the positive symptoms of schizophrenia (e.g., delusions, hallucinations). Nowadays, antipsychotic drugs are also commonly used in the treatment of geriatric patients, especially those suffering from dementia. When treating behavioural symptoms of dementia, the use of antipsychotic drugs should not be first choice and when they do present the best treatment option, they should not be used long-term. Patients suffering from schizophrenia, on the other hand, may require long-term treatment with antipsychotic drugs in order to avoid relapse. In the following, the use of antipsychotic drugs in the treatment of schizophrenia and behavioural symptoms in dementia according to the respective treatment guidelines will be explained. In addition, the pharmacological receptor profiles of frequently used antipsychotic drugs (e.g., risperidone, haloperidol, quetiapine, aripiprazole) are presented and the expected adverse drug reactions, such as extrapyramidal symptoms and hyperprolactinemia, are explained. Treatment options of the most common adverse drug reactions associated with antipsychotic drugs are also presented., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Keine Finanzielle Interessenkonflikte JS: Teilnahme an 2 von Otsuka/Lundbeck gesponsorten Fortbildungsveranstaltungen. ST: Vortragshonorare von Janssen-Cilag GmbH, Otsuka/Lundbeck, Recordati Pharmka GmbH und Servier. Advisory Board Tätigkeiten bei Otsuka und Janssen-Cilag GmbH. DD: Vortragshonorar von Aristo Pharma. HBM: Teilnahme an einer von Livanova gesponsorten Fortbildungsveranstaltung. HBM wird unterstützt vom PRACTIS-Clinician Scientist Programm der Medizinische Hochschule Hannover, gefördert durch die Deutsche Forschungsgemeinschaft (DFG – Deutsche Forschungsgemeinschaft, ME3696/3-1) – Projekt-ID 413617135., (Thieme. All rights reserved.)

Background: Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation., Objective: To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia., Material and Methods: Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia., Results: Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the "side effect" of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance., Conclusion: New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.

Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge This case-study deals with the often difficult differential diagnosis of Asperger syndrome and a clinical high risk state of psychosis, in particular as indicated by attenuated psychotic symptoms, as well as with its therapeutic implications. The presented case is a 10-year old girl, who has not been diagnosed with an autism spectrum disorder before being referred to a specialized center for early detection of psychosis due to possible hallucinatory experiences and delusional ideas. We demonstrate how to perform a context-sensitive differential diagnosis to distinguish between specific interests as well as related behaviors and unusual thought content as well as perceptive abnormalities, between paranoid ideas and biased interpretations of the behaviors of others typical for autism, and between disorganized symptoms and autistic unusual communication and social behavior. The resulting dual diagnoses in our case-study formed the basis for a complex differential indication, which considered both the increased stress vulnerability associated with an increased risk for the development of psychosis as well as the rigid thinking style associated with autism. Our case-report shows that such a precise differential indication can lead to stabilization over the long-term, even in patients with dual diagnoses.

Objective Augmentation of antidepressants with atypical antipsychotics is used in depressive patients with non-response to antidepressants. We investigated the utility of this strategy.Methods Systematic computer-based search in the online library Pubmed for randomized placebo-controlled double-blind trials (RCT) from the years 1990 to 2011.Results We found 14 RCT about augmentation of antidepressants with atypical antipsychotics in depressive patients with non-response to antidepressants. Trials examined olanzapine, risperidone, quetiapine and aripiprazole.Conclusions Augmentation of antidepressants with atypical antipsychotics is an alternative to the augmentation with lithium in unipolar depressive patients with non-response to antidepressants. But treatment with atypical antipsychotics as opposed to placebo increases the risk of non-compliance due to side-effects of medication. Augmentation of antidepressants with atypical antipsychotics in unipolar depression is an off-label therapy in Germany except for the augmentation with extended-release quetiapine. Knowledge about treatment strategies regarding augmentation of antidepressants with atypical antipsychotics can increase the chance of a successful treatment, but interactions and side-effects should be considered., (© Georg Thieme Verlag KG Stuttgart · New York.)

Exclusion criteria of the DSM-IV-TR and ICD-10 do prevent dual diagnoses of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). However, inattention, impulsivity and hyperactivity are amongst the most frequent associated symptoms of ASD. Psychopathological, neuropsychological, brain imaging and genetic studies suggest possible pathophysiological links between ASD and ADHD. Thus, standard diagnostic procedures for both disorders should assess the presence of potential comorbid symptoms of the other disorder. Treatment strategies for ADHD symptoms in the context of ASD overlap with those for patients with ADHD, but lower dosages and slower titration might be recommendable.

A delusion of parasitosis can be idiopathic or due to different somatic or psychiatric disorders. We report on a 48-year-old man who suffered from imagined animals in his nose. A somatic cause could not be found so that we diagnosed an idiopathic delusion of parasitosis. Later, Wegener's granulomatosis, a rare form of autoimmune induced vasculitis, was diagnosed. It was treated successfully with immunosuppressiva. The psychotic symptoms which remitted under risperidone did not return after finishing the neuroleptic medication., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The enzyme system cytochrome P450 plays a central role in the metabolism of drugs in the human body. The enzyme CYP2D6 is important for the metabolism of psychoactive agents. Genetic changes in the CYP2D6 gene can lead to reduced or absent activity., Methods: We report on a 37-year-old female patient who was given risperidone to treat an acute delusional disorder. Despite receiving a very low dose, the patient suffered from an intoxication. We inferred that an excessively raised plasma level of risperidone may result from a pharmacologically relevant disorder of metabolism., Results: The molecular genetic investigation revealed a compound heterozygous mutation in the CYP2D6 gene and thus documented a genetic predisposition as a "poor [non]metabolizer"., Conclusions: In intoxications with psychoactive agents, the presence of an enzyme defect in the P450 system should be considered as an additional possible cause.

Objective: We investigated the change of antipsychotic treatment of elderly persons with dementia after several publications indicated an association between use of antipsychotics and cerebrovascular events in this population., Methods: Twice a year, the complete medication, age, diagnosis and gender of all inpatients in 30 German psychiatric sites is collected anonymously in a data base for statistical analysis., Results: The treatment changed for the benefit of Quetiapine and Haloperidol. The use of both Risperidone and Olanzapine decreased markedly., Conclusion: The antipsychotic treatment changed due to critical publication. But, the evidence for the risk profile is still a matter of debate.

Objective: Considerable debate exists regarding differing prevalence rates of co-morbid bipolar disorder in children and adolescents with ADHD in Germany as compared to the US., Methods: Described in this case report are the assessment of and treatment procedure for a 14-year old boy with hyperkinetic conduct disorder and co-morbid hypomanic episode, as well as different possible interpretations of symptoms., Conclusions: Further studies of children and adolescents with ADHD and coexisting impulsive-aggressive behaviour are needed. Important in practice is a precise differentiation of symptoms with regard to co-morbid bipolar disorder.

Objective: Turner syndrome encompasses several chromosomal abnormalities and includes a typical clinical manifestation. While common somatic symptoms are often described, neuropsychiatric alterations are rare and not frequently mentioned in the literature., Method: In this paper, we report on a subject with Turner syndrome who also showed psychotic symptoms., Conclusions: The theoretical background and the relevance of this observation are discussed. Furthermore, this article briefly reviews existing reports on Turner syndrome and psychosis and presents neuropsychiatric changes in patients with Turner syndrome.

Objective: In comparison to metabolic syndrome, edema seems to be a rare occurrence in antipsychotic treatment., Method: In this paper, we report on two subjects with psychotic disorders who were found to have peripheral edema during olanzapine therapy., Discussion: The theoretical background and the relevance of this observation are examined. Furthermore, edema as a side effect of antipsychotic treatment is reviewed. In particular, the importance of olanzapine, a commonly used neuroleptic drug, as a possible causative substance is evaluated.

All states of confusion with acute onset and alteration of thinking, perception and awareness are defined as "delirium". Delirium is a common problem in older patients admitted to the hospital. It is combined with a negative prognosis and complications (falls, infections, etc.). Diagnosis and management need special efforts. Delirium is mostly associated with an underlying disease. In the elderly patient, nearly every disease can be accompanied by delirium, and the fragile older patient is especially affected.Delirium should be evaluated using a systematic approach according to frequency and impact of possible causes. An accurate diagnosis can be challenging. Symptoms have to be distinguished from other cerebral alterations, such as preexisting dementia or depression. Due to the high prevalence, one should always be aware to the presence of delirium.With the treatment of the identified disease, there is generally a reduction of delirium. Often medical intervention in the acute state is necessary to prevent further alteration of the patient. Beside an adequate medical strategy, it is important to create a safe environment for the affected patient. The article gives suggestions for a systematic diagnostic and therapeutic strategy of delirium.

Sotos syndrome, or cerebral gigantism, is a rare genetic syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial gestalt and learning difficulties. It is caused by mutations or deletions of the NSD-1 gene. Most cases are sporadic. Apart from a number of physical abnormalities that are commonly present, a high prevalence of cognitive, emotional and behavioural problems in children with Sotos syndrome can be assumed. However, there has been almost no literature about psychiatric symptoms in adults with Sotos syndrome so far; one case of psychosis was reported. In the present case, the authors present psychopathological features of an adult patient with Sotos syndrom who developed - among other things - psychotic symptoms.

22q11.2 deletion is the most common microdeletion in humans and one of the most important risk factors for schizophrenia. Nevertheless, case reports of children or adolescents with 22q11.2 deletion and schizophrenia are very rare. After a review of the current knowledge about physical, developmental, behavioural and psychiatric problems in 22q11.2 deletion, the case of a 12;10-year-old boy with schizophrenia and the microdeletion is reported. About three years after the first symptoms, and only after medication with several neuroleptics, the patient reached his pre-morbid functioning level under treatment with risperidone. Under medication with clozapine he had experienced a single event of seizures which were due to hypocalcemia. This case report illustrates the importance of serum calcium controls at regular intervals for patients with 22q11.2 deletion and schizophrenia who are on neuroleptic medication. Ideally, children and adolescents with the deletion and co-morbid psychiatric problems should be treated in child and adolescent psychiatry units specialized in problems associated with the deletion. A good cooperation with other medical services is absolutely necessary.

Background and Objective: Up to 90% of the patients with dementia develop behavioral and psychological symptoms during the course of their illness. Since 1999 the atypical neuroleptic risperidone is the only drug approved by the German authorities for the treatment of aggressive behavior or psychotic symptoms of dementia, which was defined in March 2004 with respect to severe chronic aggressive behavior, endangering themselves or others, or impoverishing psychotic symptoms. This prospective investigation was aimed at detecting therapeutic efficacy and the tolerability of risperidone after changing from low-potency neuroleptics in patients, for whom the broader indications before March 2004 were still valid., Patients and Methods: Symptoms, activities of daily living and caregivers" burden were documented for 6 weeks in 111 demented patients with chronic aggressive behavior and psychotic symptoms., Results: Marked improvements of psychotic symptoms, aggressiveness, other behavioral disorders and activities of daily living were observed. Furthermore, a substantial reduction of caregivers' burden was noted. The treatment with risperidone was well tolerated. No patient died and no cerebrovascular events were observed., Conclusion: Changing the treatment of demented patients from low-potency neuroleptics to risperidone led to marked improvement of symptoms and to a substantial decrease of caregivers' burden.

In patients with bipolar disorder antipsychotics are frequently used for the treatment of acute manic episodes, either in monotherapy, in addition to a mood stabilizer or in patients refractory to lithium or other mood stabilizers. However, a number of studies demonstrated that the use of conventional neuroleptics is restricted -- particularly for long-term treatment and relapse prevention in bipolar disorder -- due to their side effect profile and their potential to induce or worsen depressive symptoms. In contrast, atypical antipsychotics have a better tolerability profile and fewer extrapyramidal side effects. A number of clinical studies showed that the atypical antipsychotic risperidone was effective and well tolerated in the treatment of bipolar mania. This was reported both for the treatment of acute episodes and for the maintenance therapy. Recent data suggest that risperidone can be used effectively either in addition to or even instead of a mood stabilizer. This review summarizes the available literature on risperidone in the treatment of bipolar disorders.

Objective: Therapeutic drug monitoring (TDM) has been established at BKH Augsburg (psychiatric district hospital) since January 2001. According to Olanzapine product information the following illustration shows the evaluation (n = 216) of various parameters of the TDM requirements of Olanzapine., Methods: Items examined include "classification according to diagnoses", "reason for requirement", "severity of disease", "therapeutic effect" and "side-effects". In addition, serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating Scale), age, height and weight of patients will be presented., Results: Clearly sick patients, 52 % of them between 20 and 30 years old, were less compliant and achieved only a moderate therapeutic effect., Conclusions: TDM is mainly assessed to control compliance. However, more specific and more personalized TDM would be more useful.

In this case-study the case of a 76-year old white male with the diagnosis of beginning dementia and psychotic symptoms, who ingested 200 mg of diphenhydramin in suicidal intention, is presented. After a 3 days period in an internal medicine ward, in which he showed only mild anticholinergic symptoms, the patient was transferred to the psychiatric hospital. Here he showed more severe anticholinergic symptoms, including EEG-changes, for a prolonged period of two weeks time. This case helps to show the relevance of closer observation and EEG-controls in gerontopsychiatric patients even after the ingestion of a comparatively low dose of antihistaminics.

Objective: This research examines how successful recommended longterm medical treatment of schizophrenic patients is following their discharge from inpatient treatment by evaluating the yearly rehospitalization rates., Methods: The sample consisted of 76 patients with schizophrenia who were admitted for the first time into Bezirkskrankenhaus Augsburg within a year. The recommended long-term medical treatment with conventional or atypical antipsychotics of patients after discharge and the one year rehospitalization rate depending on the medical treatment at time of discharge were examined., Results: After discharge from hospital more than 50 % of the observed patients were treated with atypical antipsychotics like olanzapine, risperidone or amisupride. Only 9 % were discharged with conventional neuroleptics. 38 % of the 76 observed patients had to be readmitted., Conclusions: This research shows that the beneficial properties of modern atypical antipsychotics are less favourable on a lower rehospitalization rate than expected.

Background: Within the last decade therapeutic approaches to tic disorders are reflected in many new studies. The advent of novel neuroleptics and the more sophisticated behavioural therapeutic techniques may give new hope to children and adolescents with tic disorders., Objective: Hence, the progress in the field should be explored to find out the state of the art., Method: A critical review of the empirically based literature and practical experience., Results: Worldwide, drug treatment with clonidine and (from the group of novel antipsychotics) risperidone show the broadest empirical basis while in Europe benzamides have a good empirical clinical background. Behaviour therapy presents more and more helpful empirical data., Conclusions: Risperidone may become the first-line drug in treatment of tic disorders and behaviour therapy might be increasingly used within a multimodal treatment program.

The term bipolar disorder is no longer limited to the classical manic-depressive condition, but now subsumes a wide spectrum of illnesses. As a consequence of this expansion of the classification systems, the therapeutic utility of lithium and other mood stabilizing agents has to be defined anew. The majority treatment recommendations differentiate, symptom-related, between euphoric mania, mixed conditions, mania with psychotic symptoms and rapid cycling manic episodes. Current acute treatment includes, in addition to lithium, in particular carbamazepine and valproate, but also newer antiepileptic drugs such as lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone. Due to the high suicidal risk, patients with bipolar depression often need to be given an antidepressant as well. It must, however, be remembered that in patients with rapid cycling, antidepressants may re-trigger mania.

Objective: The aim of this study was to evaluate the effects of atypical antipsychotics on cognitive function in schizophrenic patients under clinical routine conditions., Method: Schizophrenic patients (n = 78) were evaluated on neuropsychological tests of attention, short-term- and working memory, learning, long-term memory (retention) and executive function. Data were analyzed according to medication, severity of illness and age., Results: We observed that treatment with atypical antipsychotics compared to conventional neuroleptics was significantly associated with a more favorable effect on cognitive function. Especially in short-term memory and retention a clear advantage of atypical antipsychotics could be seen., Conclusion: Results from this study suggest that even under clinical routine conditions atypical antipsychotics have an advantage on cognitive function when compared with conventional neuroleptics.

Objective: The effectiveness of atypical antipsychotic agents in the treatment of acute schizophrenic episodes is still a subject of controversial debate. The objective, therefore, was to investigate the efficacy and tolerability of an initial therapy with the atypical antipsychotic agent risperidone in acutely exacerbated patients under the conditions of clinical practice. A sub-analysis was performed to show if highly agitated and aggressive patients may profit from an initial risperidone therapy as well., Material and Methods: In a still ongoing prospective multicentre observational trial, schizophrenic patients with acute exacerbations treated with risperidone within 24 hours of in-patient admission were observed for six weeks. Patients showing a total score of > or = 15 in the items "excitement", "hostility" and "uncooperativeness" of the Positive and Negative Syndrome Scale (PANSS) were defined as highly agitated patients. Evaluation of efficacy was carried out according to a modified PANSS, the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS)., Results: 1,117 patients were evaluated. An improvement of all parameters was shown in the whole study group (51 % males, age 39.8 + 14.3 years, paranoid schizophrenia in 70.1 % of cases) and in particular in the subgroup of highly agitated patients. In these patients (n = 163), a greater improvement of symptoms was observed. Only in 4,1 % of cases was risperidone discontinued because of side effects. At the end of the observation, the mean dosage was 5.1 mg/day in both groups. More than 50 % of the patients were finally treated with a risperidone monotherapy., Conclusion: The initial acute treatment with risperidone proves to be effective and safe even for highly agitated schizophrenic patients under the conditions of clinical practice.

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.

The olfactory delusional syndrome belongs to the rare delusional diseases. It is characterized by the persuasion of bothering other people by sending out an odour. This case report is about a 52 year old male suffering of alcoholism in addition. Aspects of this special comorbidity are discussed. Neuroleptic treatment with Risperidone led to a partial remission of the delusional syndrome.

The treatment of severe depression represents a difficult task in the daily psychiatric practice. In certain cases, augmentation therapies in order to improve the efficacy of SSRIs can be useful. Recently, it has become possible to use atypical antipsychotics for SSRI augmentation. This option adds to the existing strategies in the treatment of depression and primary systematic studies show encouraging results. In this review, the possibility of a SSRI augmentation by additionally administering risperidone or olanzapine is critically discussed.

Despite definite indication for psychopharmacologic intervention, severe and persistent symptoms of aggressive and self-injurious behaviour still remain a therapeutic challenge. As recent research has demonstrated, not only the dopaminergic and serotonergic but also the endogenous opiate system plays a role in the pathogenesis of self-injurious behaviour. Nevertheless, the efficacy of classical neuroleptics as well as opiate antagonists is questioned. In open and controlled studies, the administration of the atypical neuroleptic risperidone (a serotonin 2A-dopamine D2 antagonist) was associated with a long-term effect in reducing self-injuries. In our clinical trial, 20 mentally retarded adults presenting with severe self-injurious and aggressive behaviour were administered risperidone over a follow-up period of 35 months. Clinical efficacy was measured with the Disability Assessment Schedule (DAS), conducted in a home for people with mental retardation. In 17 patients, a significant reduction in self-injurious behaviour is shown. Besides, there was a significant overall clinical improvement in behaviour.

The treatment of aggressive symptoms in schizophrenic patients is a relevant clinical problem. We systematically review the efficacy of the different atypical neuroleptics on acute or persistent aggressive symptoms also regarding methodological problems. Currently typical neuroleptics are still first choice in treating acute aggressive symptoms, while risperidone and olanzapine could be alternatives. In persistent aggression clozapin shows the best specific results. Typical depot neuroleptics should be considered in cases when medication compliance is a problem.

There is evidence for the occurrence of psychopathological symptoms in the adult form of myotonic dystrophy such as disturbance of concentration and memory, chronic depression, disturbed social behaviour, mental retardation, and hypersomnia. In this report we present a patient suffering from multisystemic myotonic myopathy without a cytosine-thymine-guanine [corrected] repeat expansion on chromosome 19q13.3 and schizophrenia. In this patient, a severe increase of creatine kinase (CK) occurred during treatment with olanzapine and amisulpride. The following risperidone medication was well tolerated without side effects. Susceptibility for malignant hyperthermia was detected by a positive in vitro contracture test. The occurrence of elevated muscle enzymes during treatment with atypical neuroleptics is suspicious as a possible side effect of neuroleptic medication and muscle disease.

The introduction of conventional antipsychotics revolutionized the management of psychotic disorders in the 1950s. The use of these agents has been marked by several shortcomings, including their association with severe motor disturbances and their limited efficacy in treating the negative and cognitive symptoms of schizophrenia. Patients noncompliance has largely been the result of subjectively distressing extrapyramidal motor side-effects (EPMS). It was therefore necessary to develop antipsychotic drugs with selective pharmacological profiles, e.g. limbic selectivity. A defining characteristic of atypical neuroleptics is a higher ratio of serotonin receptor blockade to D2 receptor blockade. Their primary advantage is their superior side-effect profile. The implications of EPMS reduction touch several domains of pathology in schizophrenia such as short- and long-term movement disorders, noncompliance, relapse rate, negative symptoms and cognitive dysfunction. Novel antipsychotics may represent the second pharmacological revolution in the treatment of psychotic disorders. There is, however, still a need for a critical evaluation of the risk-benefit-ratio of differing atypical agents.

Beside the typical extrapyramidal motor symptoms such as rigidity, tremor, and dyskinesia, a reduction in handwriting area may occur under neuroleptic therapy. To date, the nature of the relationship between a reduction in handwriting area and striatal D2 dopamine receptor occupancy has remained unclear, and it is not known whether such a reduction also occurs under treatment with atypical neuroleptic drugs. In 23 schizophrenic patients treated with haloperidol, haloperidol decanoate, risperidone, and clozapine, the handwriting are was examined using a planimetric computer program. 123I-iodobenzamide (IBZM) single photon emission tomography (SPET) was used to measure the D2 dopamine receptor occupancy. A statistically significant correlation was found between a reduction in handwriting area and D2 dopamine receptor occupancy (r = 0.86; P < 0.0001). The curve derived from the plotted data resulted in a hyperbolic function. The regression was present regardless of whether the patients were treated with typical or atypical neuroleptic drugs.

The results of controlled studies of the efficacy of the new atypical neuroleptics in treating negative symptoms show that these antipsychotics have a more pronounced effect on negative symptoms in acute schizophrenic patients than the classical neuroleptics. Supplementary complex statistical analyses substantiate that the increased efficacy of the atypical neuroleptics in treating negative symptoms can only partially be explained by indirect effects of better extrapyramidal tolerability, better effects on productive psychotic symptoms, etc. Instead, it is due largely to the stronger direct effect of these atypical neuroleptics. Clinical studies to evaluate their efficacy in chronic schizophrenic patients with stable, predominantly negative symptoms are still mostly lacking. First results support the presumption that atypical neuroleptics have a direct effect. Parallel to the evaluation of the new atypical neuroleptics, important progress has been made in the methodology of clinical studies in this area.

Atypical neuroleptic drugs have enriched our treatment programs, especially in childhood and adolescent schizophrenia. Reviewed here is the use of atypical neuroleptics in children and adolescents with a schizophrenic disorder. The receptor binding profile and pharmacological properties, indications, side effects, clinical application, and trials of atypical neuroleptic drugs are compared to the classical neuroleptic drug haloperidol in the treatment of adolescent schizophrenia. Special attention is paid to the most common atypical neuroleptics clozapine, olanzapine and risperidone since most studies are carried out with these compounds, most often with clozapine. More clinically controlled trials have to be conducted since only one has been performed to date. The place of atypical neuroleptic drugs is discussed and further studies are necessary in order to differentiate, and eventually broaden the spectrum of the indications tested thus far.

Neurobiological research has implicated the dopamine and serotonin system in the pathogenesis of self-injurious behavior. The efficacy of antipsychotic drugs has been questioned. Opened and controlled investigations have shown risperidone is effective for reducing self-injurious behaviour in mentally retardation. We report about 3 mentally retarded patients which were given open-label risperidone for 12 weeks. They participated in a detailed assessment of behaviour symptoms at baseline and the repetitive behaviour was weekly rated with the disability assessment schedule (DAS). All three patients responded.