The Value of Desmethylclozapine and Serum CRP in Clozapine Toxicity: A Case Report

Clozapine, an atypical antipsychotic, has proved to be superior to other antipsychotics in treating patients with refractory schizophrenia. An increased plasma clozapine level above the therapeutic window may be associated with serious adverse events including paralytic ileus. Clozapine toxicity may occur in association with infection or after drug overdose. In a medical emergency situation, differentiating between a toxic clozapine ingestion and an infection-induced toxicity might be hindered by associated CNS changes and by the clozapine modulation of the inflammatory process. This may delay prompt initiation of a tailored treatment strategy. Here, we report a case of paralytic ileus developed within the context of clozapine toxicity. Although the underlying cause of toxicity was not clinically obvious, giving antimicrobial therapy resulted in an improvement in the patient's clinical condition. This report indicates the value of serum levels of C-reactive protein and desmethylclozapine, major metabolite of clozapine, in the treatment of aetiologically unclear clozapine toxicity

Do routine outcome monitoring results translate to clinical practice? A cross-sectional study in patients with a psychotic disorder

Background: The use of Routine Outcome Monitoring (ROM) in mental health care has increased widely during the past decade. Little is known, however, on the implementation and applicability of ROM outcome in daily clinical practice. In the Netherlands, an extensive ROM-protocol for patients with psychotic disorders has been implemented over the last years (ROM-Phamous). The current study investigated to what extent ROM results translate to daily clinical practice. Therefore, we investigated whether clinical problems as identified with ROM were detected and used in the treatment of patients with psychotic disorders. Methods: Out of the ROM database of 2010 (n = 1040), a random sample of 100 patients diagnosed with a psychotic disorder was drawn. ROM-data used in this study included a physical examination, laboratory tests, interviews and self-report questionnaires. Based on these data, the prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors was determined. Next, we investigated whether these problems, as identified with ROM, were reflected in the treatment plans of patients, as an indication of the use of ROM in clinical practice. Results: The sample consisted of 63 males and 37 females. The mean age was 44 and the mean duration of illness was 17.7 years. The prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors ranged from 11 to 86 %. In the majority of cases, problems as identified with ROM were not reflected in the treatment plans of patients. Conclusions: We found a substantial discrepancy between the ROM measurements and the treatment plans, i.e. low rates of detection of symptoms, psychosocial problems and cardiovascular risk factors in the treatment plans, even though these problems were identified with ROM. The opposite occurred as well, where problems were reflected in the treatment plans but not identified with ROM. Thus, ROM and daily clinical practice appear to be two separate processes, whereas ideally they should be integrated. Strong efforts should be made to integrate ROM and consequent treatment activities. Such integration may help to provide patients with adequate and customized care and simultaneously minimize under-and over-treatment

Abnormal connectivity between attentional, language and auditory networks in schizophrenia

Brain circuits involved in language processing have been suggested to be compromised in patients with schizophrenia. This does not only include regions subserving language production and perception, but also auditory processing and attention. We investigated resting state network connectivity of auditory, language and attention networks of patients with schizophrenia and hypothesized that patients would show reduced connectivity. Patients with schizophrenia (n=45) and healthy controls (n=30) underwent a resting state fMRI scan. Independent components analysis was used to identify networks of the auditory cortex, left inferior frontal language regions and the anterior cingulate region, associated with attention. The time courses of the components where correlated with each other, the correlations were transformed by a Fisher's Z transformation, and compared between groups. In patients with schizophrenia, we observed decreased connectivity between the auditory and language networks. Conversely, patients showed increased connectivity between the attention and language network compared to controls. There was no relationship with severity of symptoms such as auditory hallucinations. The decreased connectivity between auditory and language processing areas observed in schizophrenia patients is consistent with earlier research and may underlie language processing difficulties. Altered anterior cingulate connectivity in patients may be a correlate of habitual suppression of unintended speech, or of excessive attention to internally generated speech. This altered connectivity pattern appears to be present independent of symptom severity, and may be suggestive of a trait, rather than a state characteristic. (C) 2011 Elsevier B.V. All rights reserved

Glutamate in dorsolateral prefrontal cortex and auditory verbal hallucinations in patients with schizophrenia:A (1)H MRS study

Purpose: Glutamatergic models of psychosis propose that dysfunction of N-methyl-D-aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate + glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy (H-1 MRS) to calculate their association with AVH. Methods: Sixty-seven patients with schizophrenia and thirty healthy control participants (HC) underwent magnetic resonance spectroscopy (MRS) to estimate levels of Glx in the white matter of the left prefrontal lobe. The spectrum was estimated from an 8 mm(3) voxel placed in the left lateral prefrontal region, belonging to both the cingulum and forceps minor. Patients with lifetime AVH (AVH group; n = 45) and patients without lifetime AVH were compared (NoAVH group; n = 22) to control participants. Results: Levels of Glx were significantly different between the groups (F(2,94) = 5.27, p = 0.007). Planned comparisons showed that higher Glx levels were found in control participants than in the total patient group (p = 0.010). However, patients with lifetime AVH had higher levels of Glx compared to patients without lifetime AVH (p = 0.019). Creatin levels were similar in all three groups. We found no association between Gix and the severity of symptoms (item P3 of the PANSS or PANSS positive subscale). Conclusion: The higher Glx levels in patients with lifetime AVH as compared to patients without lifetime AVH suggest a mediating role for Glx in AVH. Our results are consistent with a previous study that found similar decreased levels of Glx in patients with schizophrenia, and increased levels in an AVH group as compared to a NoAVH group. The role of the glutamatergic system deserves further investigation, for example in different brain regions and in relation to clinical variables

The development and evaluation of a computerized decision aid for the treatment of psychotic disorders

Abstract Background Routinely monitoring of symptoms and medical needs can improve the diagnostics and treatment of medical problems, including psychiatric. However, several studies show that few clinicians use Routine Outcome Monitoring (ROM) in their daily work. We describe the development and first evaluation of a ROM based computerized clinical decision aid, Treatment-E-Assist (TREAT) for the treatment of psychotic disorders. The goal is to generate personalized treatment recommendations, based on international guidelines combined with outcomes of mental and physical health acquired through ROM. We present a pilot study aimed to assess the feasibility of this computerized clinical decision aid in daily clinical practice by evaluating clinicians’ experiences with the system. Methods Clinical decision algorithms were developed based on international schizophrenia treatment guidelines and the input of multidisciplinary expert panels from multiple psychiatric institutes. Yearly obtained diagnostic (ROM) information of patients was presented to treating clinicians combined with treatment suggestions generated by the algorithms of TREAT. In this pilot study 6 clinicians and 16 patients of Lentis Psychiatric Institute used the application. Clinicians were interviewed and asked to fill out self-report questionnaires evaluating their opinions about ROM and the effectiveness of TREAT. Results Six clinicians and 16 patients with psychotic disorders participated in the pilot study. The clinicians were psychiatrists, physicians and nurse-practitioners which all worked at least 8 years in mental health care of which at least 3 years treating patients with psychotic illnesses. All Clinicians found TREAT easy to use and would like to continue using the application. They reported that TREAT offered support in using diagnostic ROM information when drafting the treatment plans, by creating more awareness of current treatment options. Conclusion This article presents a pilot study on the implementation of a computerized clinical decision aid linking routine outcome monitoring to clinical guidelines in order to generate personalized treatment advice. TREAT was found to be feasible for daily clinical practice and effective based on this first evaluation by clinicians. However, adjustments have to be made to the system and algorithms of the application. The ultimate goal is to provide appropriate evidence based care for patients with severe mental illnesses

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia:meta-analysis of controlled trials

Background: Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. Objectives: To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Methods: Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I-2 tests. Results: For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline-posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. Conclusions: The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of studies as yet with tDCS. More research is needed to establish moderator variables that may affect response to neurostimulation and to optimize treatment parameters in order to achieve stable and durable (and thus clinically relevant) effects