Naturalistic pharmacotherapy of acute episodes of schizophrenic disorders in comparison to treatment guidelines.

INTRODUCTION: This study was designed to investigate to what extent guidelines regarding the pharmacological treatment of patients suffering from schizophrenia-like psychosis are adopted in a naturalistic treatment setting. METHODS: Medical records of n=819 patients undergoing inpatient treatment for schizophrenia-like psychosis in 11 psychiatric hospitals in northwestern Germany were retrospectively analyzed and findings were compared to current schizophrenia guideline recommendations. RESULTS: The prescription rate of second generation antipsychotics increased from 47.1% on admission to 62.5% at discharge. Only half the patients (52.3%) received antipsychotic monotherapy while 47.7% took between 2 and 4 antipsychotic substances at a time. Dosage increases occurred most frequently (in 60%) within the first week of inpatient treatment, 16.6% experienced an elevation between days 15 and 29. A change within the atypical medication was found in 19.3%. Clozapine prescriptions increased throughout the treatment but were combined with other antipsychotic substances in the majority of cases. CONCLUSION: Under naturalistic conditions guideline recommendations for treatment of schizophrenia-like psychosis are adhered to only partially. Combination therapy with 2 or more antipsychotic drugs is quite common despite a clear recommendation for monotherapy.

Audiovisual integration of speech is disturbed in schizophrenia: an fMRI study.

Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.

The myelin-pathogenesis puzzle in schizophrenia: a literature review.

Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

Effects of quetiapine on cognitive functions in schizophrenic patients: a preliminary single-trial ERP analysis.

AIM: The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment. PATIENTS AND METHODS: Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements. RESULTS: Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0. DISCUSSION: The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.

The use of anticonvulsants to augment antidepressant medication.

Combination therapy that couples classical antidepressants with other psychoactive compounds is one of the major therapeutic strategies in therapy-resistant depression. The authors review reports on the antidepressive effects of the mood stabilizers carbamazepine and valproate and focus on the pharmacodynamic and clinical aspects of combining these compounds with antidepressant drugs. In addition, a pivotal study (N=10 outpatients) demonstrates the use and efficacy of a low-dose combination therapy of carbamazepine and amitriptyline. It is concluded that low-dose combination of classical antidepressants and mood stabilizers appears to be well tolerated and highly effective.

Emotion/cognition-coupling in word recognition memory of depressive patients: an event-related potential study.

Depressive patients show deficits in memory functions. However, the underlying mechanisms remain unclear. Experiments with a special emphasis on the link between emotion and cognition appear challenging. The aim of this study is to investigate the influence of the emotional content of words on memory in non-medicated depressive patients (n=11) compared with a control group (n=11) utilizing event-related brain potentials (ERPs). In a continuous word recognition paradigm brain responses to repeated items are characterized by more positive waveforms of ERPs. This recognition effect ('old/new effect') has been shown to be sensitive to parameters relevant for memory processing. For the purpose of this ERP experiment visually presented words were classified into three different categories of emotional content. The ERPs for the correctly detected 'old' (repeated) words showed an increased positivity beginning approximately 250 ms post-stimulus, concurring with a good recognition performance. In addition, old/new effect and behavioral data were sensitive to words' different emotional connotations in the control group. In contrast, the depressive patients performed worse and showed no significant old/new effect. Nevertheless, their recognition performance was also enhanced by the emotional content. Furthermore, a differential effect of the emotional content on frontal ERPs was found between groups. In contrast to the control group, a reduced old/new effect indicates a reduced working memory capacity in the moderately depressed patients. This is suggested to be partially due to changes of the emotion/cognition coupling related to ruminations with preferably negative emotional connotation. However, the emotional content also affects recognition performance in the depressive patients.

Discrepant target detection and action monitoring in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been related to altered mechanisms of action monitoring and target detection, and it has been hypothesized that hyperactive striatal-cortical circuits constitute the underlying pathophysiology. This study used event-related brain potentials (ERPs) to explore this hypothesis. A choice reaction time experiment was carried out in a group of OCD patients and a normal comparison group. The P3b component of the ERP to targets was taken as an indicator of the target-evaluation process and the response-locked error-related negativity (ERN) served as an indicator of action monitoring. We hypothesized that the OCD group would show a shortened P3b latency and an amplitude-enhanced ERN. Consistent with our expectations, the P3b latency was shorter and the ERN amplitude was higher in the OCD group. Unexpectedly, we also observed a prolonged ERN latency in the OCD group and a more posterior topography of this component. The data provide partial support for the hypothesis of a hyperactive neural network in OCD. In addition the disorder must involve pathophysiological processes that are presumably related to other aspects of its complex and heterogeneous clinical hallmarks.

Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression.

Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

[Remembering, forgetting and depression. Time-conceptual implications of affective disorders]. / Erinnerung, Vergessen und Depression. Zu zeittheoretischen Implikationen affektiver Erkrankungen.

As a consequence of reflections about the relevance of remembering and forgetting in psychiatric disorders, aspects of the psychopathology of the dimension of time in phenomenological psychiatry are represented. From the perspectives of research on consciousness, cognition and neurobiology of the temporal lobes with special emphasis on memory processes, the impact of time in depressive illness is investigated. Based on Freud's concept of "Todestrieb" (death-instinct) and "Nirvana-Prinzip" (nirvana-principle) with regard to the possible impact on a theory of forgetting--based on Michael Theunissens time-philosophical concept, which demonstrates coping of "dominance of time" i.e. intrusion of the past into the presence and the failure of these coping-processes in depressive patients--it is hypothesized, that "nirvana-energy" is a major constituent of processes for forgetting.

Oxcarbazepine in affective and schizoaffective disorders.

Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic value in affective and schizoaffective disorders had been documented in several clinical trials. As the authorities in several countries registered newer anticonvulsants with fewer side effects, their therapeutic value in psychiatric disorders was studied. Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine (OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug interactions compared to carbamazepine and other anticonvulsants. Therefore, the value of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated. We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects of OCBZ in the treatment of patients with affective and schizoaffective disorders. According to the literature, OCBZ is regarded as effective in acute mania and appears to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does not interact substantially with the cytochrome P450 enzyme system, co-administration with neuroleptics or antidepressants appears to be well tolerated in affective disorders. However, despite promising effects of OCBZ, few clinical studies have been published in the last 15 years. We conclude that further studies should validate the efficacy of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as well as limitations for this psychotropic compound.

[Oxcarbazepine in the treatment of affective and schizoaffective disorders]. / Oxcarbazepin in der Behandlung affektiver und schizoaffektiver Erkrankungen.

The therapeutic value of anticonvulsants in affective and schizoaffective disorders was documented in several clinical trials. Oxcarbazepine (OXC), a keto-derivative of carbamazepine, which appears to have a preferable side effect profile compared to carbamazepine, has also shown antimanic efficacy in affective and schizoaffective disorders in clinical studies since the early 80's, but was not further investigated regarding these indications. Therefore, the value of OXC in the treatment of affective and schizoaffective disorders requires evaluation. Literature was reviewed with regard to pharmacokinetic and pharmacodynamic characteristics of OXC, drug-drug interactions relevant in pharmacopsychiatry, and clinical effects in these disorders. According to the literature OXC is regarded effective in acute mania and appears to allow reduction of the neuroleptic medication required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to other anticonvulsants and neuroleptics. Furthermore, it appears to be well tolerated if augmented to neuroleptics or antidepressants, since OXC does not interact substantially with the cytochrome P450-enzyme-system. However, despite promising effects of OXC, few clinical studies have been published in the last 16 years. We conclude that further studies should validate the antimanic efficacy of OXC and evaluate possible pharmacopsychiatric indications as well as limitations of this psychotropic compound.

Possible use of amantadine in depression.

Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.

Lamotrigine in the treatment of confusion psychosis. A case report.

We report on the successful treatment of four patients suffering from confusion psychosis according to the classification of Leonhard. The patients did not sufficiently respond to neuroleptic treatment or mood stabilizers like carbamazepine and valproate, but improved when lamotrigine was added, showing a marked reduction in clinical signs and symptoms. The implications of these findings including the possible mechanisms involved are discussed.

Lycanthropy--psychopathological and psychodynamical aspects.

OBJECTIVE: The imagination of being transformed into an animal or being an animal is called lycanthropy. The phenomenon is presented and psychodynamical aspects are discussed. METHOD: A literature review forms the base of this discussion of a psychopathological phenomenon. RESULTS: The lycanthropic symptomatology represents a spectrum of continuity of developmental and culture-dependent normal behaviour via partial forms to the complete picture of lycanthropy. It is observed in different mental disorders. CONCLUSION: Lycanthropy is interpreted by the authors as a delusion in the sense of the self-identity disorder defined by Scharfetter. It is mainly found in affective and schizophrenic disorders but can be a symptom of other psychiatric disorders as well. Psychodynamically this kind of delusion can be interpreted as an attempt to project suppressed affects, especially with aggressive or sexual content, into the figure of an animal. Psychotherapy and/or neuroleptic medication can be effective.

[Diagnostic steps in Alzheimer dementia before treatment with new antidimentives]. / Diagnostische Schritte bei Alzheimer-Demenz vor Therapiebeginn mit neuen Antidementiva.

The dementia of the Alzheimer type (DAT) is a chronic neurodegenerative illness. It will continue to increase because of rising life expectancy in the industrialized countries. Apart from the physicians interest to treat, there is also an economically justified interest to reduce the disease progression in this group of patients. The main intention of the treating physicians is to keep their patients independent as long as possible. Up to now Alzheimer's disease can only be treated symptomatically. The verified diagnosis of DAT still depends on the neuropathological investigation of brain tissue. Therefore the clinical diagnosis of DAT during lifetime should be supported by chemical analysis of typical changes in the cerebrospinal fluid (CSF) at an early stage. Meanwhile, several therapeutics with proven effectiveness in clinical studies are certified for the symptomatic treatment of DAT. However, these therapeutics are still relatively expansive. Due to this fact the clinical diagnosis of DAT should be supported by clinical-chemical markers before the beginning of such a treatment. In this paper we present the diagnostic steps in dementia patients, who are examined in our departments. Patients suspicious of DAT always are asked for a spinal tap in addition to other diagnostic tools. In case of a typical clinical constellation, the exclusion of a primarily vascular dementia as well as the proof of decreased A beta 1-42 peptides and an increased tau protein in CSF we recommend the new drugs for DAT as meaningful and justified therapeutics to yield optimal treatment.

[Clomethiazole as an adjuvant in the treatment of confusional psychosis]. / Clomethiazol als Adjuvans bei der Behandlung erregt-gehemmter Verwirrtheitspsychosen.

We report on the successful treatment of two female patients with the clinical features of severe confusional psychosis. The clinical picture of these cases was characterized by lability of mood, disorientation, delusions, hallucinations, misidentification of persons, severe thought disorder and impaired memory. A 55-year old female inpatient suffered from a psychotic episode with the clinical features of confusional psychosis. Medical history showed three proceeding confusional psychotic episodes. In the second case a 32-year old female inpatient suffered from a severe postpartum psychosis with the clinical features of confusional psychosis. In this case there was no clinical history of psychotic episodes. After nonresponsive treatment with neuroleptics and mood-stabilizers, both responded rapidly to additional medication with clomethiazole within a week, exhibiting a marked reduction in clinical signs and symptoms. A brief review about this delirium-like psychosis and current knowledge of therapeutic strategies is presented. We discuss clomethiazole as a possible potential adjunct in the treatment of confusional psychoses.

[Lycanthropy-zooanthropism--discussion of a psychopathological phenomenon]. / Lykanthropie/Zooanthropismus--Erörterung eines psychopathologischen Phänomens.

The belief to be transformed into an animal is named Lycanthropy. "Zooanthropismus" is the German equivalent. Three case reports raised the question how this phenomenon, in our cases to be transformed into a frog, a bee or a wolf/dog, can be interpreted in a psychopathological and diagnostic regard. Is it pathognomonic for a special disease? With the three case reports and a survey of the literature this paper deals with Lycanthropy trying to put this perhaps neglected topic back into the focus of psychiatric interest and place it in psychopathology.

[Paranoia with late onset. Psychopathology and psychodynamics]. / Paranoia mit spätem Beginn. Psychopathologie und Psychodynamik.

We report on a 70-year-old man who suffered from persecutory delusions during the last 20 years. During first visits, he showed neither cognitive impairment nor Schneiderian first rank symptoms. Inpatient and day clinic treatment as well as further outpatient therapy led to reintegration into social life and trusting relationships between the patient and the therapeutic team, although the persecutory delusions still persisted. During following years, symptoms of cognitive impairment increased gradually and neurological symptoms could be observed. We present a psychodynamic hypothesis regarding the reported psychopathology and discuss alternative diagnoses and pharmacological treatment.