Refractory Schizophrenia Patients Research Articles

M161. NEURAL CHANGES INDUCED BY ELECTROCONVULSIVE THERAPY (ECT) IN SCHIZOPHRENIA PATIENTS: A SYSTEMATIC REVIEW

BackgroundDespite the remarkable progress of antipsychotic drugs, electroconvulsive therapy (ECT) remains a potent treatment option for schizophrenia. However, the underlying neural mechanism of ECT effect on schizophrenia remains unclear. For this reason, we reviewed literature which investigated structural and functional brain changes after ECT in schizophrenia patients.MethodsWe searched the PubMed, EMBASE, Cochrane Reviews database to search for eligible articles. Following medical subject headings (MeSH) terms were used: ECT AND schizophrenia AND (MRI OR MRS OR PET OR SPECT OR NIRS OR DTI).ResultsThirteen studies were eligible for the reviewing process. Of them, three studies investigated the effect of ECT upon volumetric changes of cerebral regions; 4 studies on the effect of ECT upon functional brain activities; three studies using magnetic resonance spectroscopy (MRS); and another three studies investigating blood flow changes. Medial temporal lobe (MTL) structures seemed to be increased after ECT sessions in schizophrenia patients, as in major depressive disorder (MDD) patients. Insula and left dorsolateral prefrontal cortex (DLFPC) is other potential neural substrates that might be disease specific for ECT induced changes in schizophrenia. Outcomes of functional imaging seemed to vary among studies, with divergent region of interests (ROI). MRS study results suggests the ratio of left prefrontal NAA/Cr might be increase after adequate ECT sessions. Studies investigating effect of ECT upon cerebral blood flow largely varied among studies with mixed results.DiscussionDespite the treatment effect of ECT in schizophrenia patients, there have been only a handful of studies investigating the biological mechanisms underlying ECT. Of them, the effect of ECT in schizophrenia seemed also to be mediated by structural volume increases in the MTL region (as in MDD), and the insula and left DLPFC might be other potential neural substrates of ECT effect in schizophrenia patients. Future studies are needed to validate the neural mechanisms that underlie the effect of ECT in schizophrenia, which might help to aid in tailoring treatment plans for refractory schizophrenia patients.

Verbal learning deficits associated with increased anticholinergic burden are attenuated with targeted cognitive training in treatment refractory schizophrenia patients

Targeted cognitive training (TCT) has been reported to improve verbal learning deficits in patients with schizophrenia (SZ). Despite positive findings, it is not clear whether demographic factors and clinical characteristics contribute to the success of TCT on an individual basis. Medication-associated anticholinergic burden has been shown to impact TCT-associated verbal learning gains in SZ outpatients, but the role of anticholinergic medication burden on TCT gains in treatment refractory SZ patients has not been described. In this study, SZ patients mandated to a locked residential rehabilitation center were randomized to treatment as usual (TAU; n=22) or a course of TAU augmented with TCT (n=24). Anticholinergic medication burden was calculated from medication data at baseline and follow-up using the Anticholinergic Cognitive Burden (ACB) Scale. MATRICS Consensus Cognitive Battery Verbal Learning domain scores were used as the primary outcome variable. The TAU and TCT groups were matched in ACB at baseline and follow-up. While baseline ACB was not associated with verbal learning in either group, increases in ACB over the course of the study were significantly associated with deterioration of verbal learning in the TAU group (r=−0.51, p=0.02). This was not seen in subjects randomized to TCT (r=−0.13, p=0.62). Our results suggest that TCT may blunt anticholinergic medication burden associated reduction in verbal learning in severely disabled SZ inpatients.

Targeted cognitive training improves auditory and verbal outcomes among treatment refractory schizophrenia patients mandated to residential care

Computerized targeted cognitive training (TCT) of auditory processing has been shown to improve verbal learning in several clinical trials of schizophrenia outpatients. Less is known, however, about the effectiveness of this promising intervention in more chronic, treatment-refractory patients who are treated in non-academic settings. This study aimed to determine whether TCT improves auditory processing, verbal learning, and clinical symptoms in SZ patients mandated to receive care at a locked residential rehabilitation center. Secondarily, potential factors that moderate TCT's effectiveness including age, symptom severity, antipsychotic medication load, and duration of illness were examined. Schizophrenia patients were randomized to treatment as usual (TAU; n = 22) or TAU augmented with TCT (TAU + TCT; n = 24). Outcomes included a measure of auditory perception (Word-In-Noise test, WIN), verbal learning domain scores from the MATRICS Consensus Cognitive Battery (MCCB), and clinical symptoms (Scale for the Assessment of Positive Symptoms, SAPS; Scale for the Assessment of Negative Symptoms, SANS). TCT produced significant improvements in auditory perception (d = 0.67) and verbal learning (d = 0.65); exploratory analyses revealed a statistically significant reduction in auditory hallucinations (d = −0.64). TCT's effects were only weakly, and mostly non-significantly, moderated by age, clinical symptoms, medication, and illness duration. These findings indicate that even highly symptomatic, functionally disabled patients with chronic illness benefit from this emerging treatment. Ongoing studies will examine the predictive utility of neurophysiological biomarkers and other characteristics assessed at baseline.

Case Report: Augmentation with Blonanserin for a Schizophrenia Patient with Insufficient Response to Clozapine

Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.

S.19.03 - Influence of exercise in combination with clozapine and other antipsychotics in chronic refractory schizophrenia patients

The purpose of this paper was to evaluate the effects of the longitudinal single differential (LSD), the longitudinal double differential (LDD) and the normal double differential (NDD) spatial filters, the electrode shape, the inter-electrode distance (IED) on non-Gaussianity and non-linearity levels of simulated surface EMG (sEMG) signals when the maximum voluntary contraction (MVC) varied from 10% to 100% by a step of 10%. The effects of recruitment range thresholds (RR), the firing rate (FR) strategy and the peak firing rate (PFR) of motor units were also considered.A cylindrical multilayer model of the volume conductor and a model of motor unit (MU) recruitment and firing rate were used to simulate sEMG signals in a pool of 120 MUs for 5 s. Firstly, the stationarity of sEMG signals was tested by the runs, the reverse arrangements (RA) and the modified reverse arrangements (MRA) tests. Then the non-Gaussianity was characterised with bicoherence and kurtosis, and non-linearity levels was evaluated with linearity test.The kurtosis analysis showed that the sEMG signals detected by the LSD filter were the most Gaussian and those detected by the NDD filter were the least Gaussian. In addition, the sEMG signals detected by the LSD filter were the most linear. For a given filter, the sEMG signals detected by using rectangular electrodes were more Gaussian and more linear than that detected with circular electrodes. Moreover, the sEMG signals are less non-Gaussian and more linear with reverse onion-skin firing rate strategy than those with onion-skin strategy. The levels of sEMG signal Gaussianity and linearity increased with the increase of the IED, RR and PFR.

A False Case of Clozapine-Resistant Schizophrenia

One of the subjects that most concerns physicians is treatment-resistance. About 30%–60% of schizophrenia patients do not respond adequately to antipsychotic treatment and are known as refractory schizophrenia patients. Clozapine has been the drug of choice in such cases. However, approximately 30% of them do not respond to clozapine either. Here, we describe a patient with an initial diagnosis of refractory schizophrenia who had a history of dramatic aggressiveness. However, in this case, “refractoriness” was a wrong diagnosis. A case of psychosis secondary to epilepsy had been treated as schizophrenia for almost 20 years. Reports like this one are important because they remind us of how a thorough investigation can lead to the correct diagnosis and improve the patient's prognosis.

Research of mood stabilizer applied ints schizophrenia

Objective To explore the validity of mood stabilizers to refractory schizophrenia patients who had accepted Clozapine therapy but without any efficacy.Methods 33 cases of Clozapine with no significant difference in age and gender were divided into three groups.On the basis of the reduction of Clozapine in each group,they were given Sodium valpreato,Carbamazepine and Lithium carbonate treatment respectively.Results In the end of the 8th weekend,15 cases' (45.4%) Positive and Negative Syndrome Scale (PASS) decreased≥20% and 9 cases (27.2%) decreased≥50%.TESS scores had no significant difference before and after treatment.Conclusion The combination of mood stabilizers has a certain effect to patients who had Key words: Mood stabilizer; Clozapine; Refractory schizophrenia

Risperidone augmentation for schizophrenia partially responsive to clozapine: A double-blind, placebo-controlled trial

Rationale Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. Objectives To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. Methods We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. Results Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly ( β = − 3.3079, p = 0.047). Conclusions Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.

Comment on “Tardive Dyskinesia Circa 2006”

Back to table of contents Previous article Next article Letters to the EditorFull AccessComment on “Tardive Dyskinesia Circa 2006”ROBERT A. ROSENHECK M.D.,ROBERT A. ROSENHECK M.D.Search for more papers by this author,Published Online:1 Jan 2007https://doi.org/10.1176/ajp.2007.164.1.170AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Risk assessment of tardive dyskinesia might be further strengthened by considering its severity and impact on quality of life. Descriptive data from two clinical trials (1 , 2) are used to illustrate the relationship of Quality of Life Interview ratings and tardive dyskinesia levels documented by combined average scores on the three global ratings of the Abnormal Involuntary Movement Scale. Using 1,275 ratings from 423 refractory schizophrenia patients (1) and observations when no tardive dyskinesia was present as a reference point (mean Quality of Life Interview score=43.3 [SD=17.1]), mild tardive dyskinesia was associated with a 3.6-point lower (–8%) mean Quality of Life Interview rating, and moderate tardive dyskinesia was associated with a 6.9-point lower (–16%) mean Quality of Life Interview rating. After multivariate adjustment for differences in concurrent symptoms (total Positive and Negative Syndrome Scale scores), differences in adjusted means reversed direction. Adverse effects of tardive dyskinesia on ratings of quality of life were thus not independent of the effect of symptom severity in this cohort. Data from another trial (2) included 826 observations from 309 patients with schizophrenia. As compared with observations when no tardive dyskinesia was present (mean Quality of Life Interview score=47.2 [SD=16.7]), mild tardive dyskinesia was associated with a 4.0-point lower (–8%) average Quality of Life Interview rating, and moderate tardive dyskinesia was associated with a 2.2-point (–4.5%) lower rating. After adjusting for symptoms of schizophrenia and other neurological side effects, these differences were reduced only slightly to 3.6- and 1.8-point lower ratings (–7.4% and –3.6%, respectively). These data show average net reduction of quality of life associated with mild or moderate tardive dyskinesia ranging from 0% (based on the risk-adjusted analyses in the first cohort) to –16% (without adjustment). John M. Kane, M.D., (3) suggests a 3%–5% annual incidence of tardive dyskinesia in patients with first generation antipsychotics and 1% with newer medications. The attributable risk of tardive dyskinesia because of first generation antipsychotics would thus be 2%–4% per year. Multiplying the attributable risk by the reductions in quality of life estimated above, one can calculate average annual tardive dyskinesia-related reductions in quality of life attributable to first generation antipsychotics. This risk would be estimated to range from 0% (based on the risk-adjusted analysis of the first cohort) to a maximum of –0.64% (i.e., 0.04 attributable risk of tardive dyskinesia multiplied by –16% reduction in Quality of Life Interview scores). These analyses are limited, however, by the absence of data on severe tardive dyskinesia. An upper bound estimate of the average risk of decline in Quality of Life Interview scores because of mild or moderate tardive dyskinesia with first generation antipsychotics may thus be less than 1%. Clinical decision making must be based on individual patient circumstances and preferences, rather than on average risk calculations. However, side effect risks are central to antipsychotic treatment decisions, and it may be informative to use quantitative methods to evaluate their net effects on measures of well-being.West Haven, Conn.

Comment on "Tardive Dyskinesia Circa 2006"

Back to table of contents Previous article Next article Letters to the EditorFull AccessComment on “Tardive Dyskinesia Circa 2006”ROBERT A. ROSENHECK M.D.,ROBERT A. ROSENHECK M.D.Search for more papers by this author,Published Online:1 Jan 2007https://doi.org/10.1176/ajp.2007.164.1.170AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Risk assessment of tardive dyskinesia might be further strengthened by considering its severity and impact on quality of life. Descriptive data from two clinical trials (1 , 2) are used to illustrate the relationship of Quality of Life Interview ratings and tardive dyskinesia levels documented by combined average scores on the three global ratings of the Abnormal Involuntary Movement Scale. Using 1,275 ratings from 423 refractory schizophrenia patients (1) and observations when no tardive dyskinesia was present as a reference point (mean Quality of Life Interview score=43.3 [SD=17.1]), mild tardive dyskinesia was associated with a 3.6-point lower (–8%) mean Quality of Life Interview rating, and moderate tardive dyskinesia was associated with a 6.9-point lower (–16%) mean Quality of Life Interview rating. After multivariate adjustment for differences in concurrent symptoms (total Positive and Negative Syndrome Scale scores), differences in adjusted means reversed direction. Adverse effects of tardive dyskinesia on ratings of quality of life were thus not independent of the effect of symptom severity in this cohort. Data from another trial (2) included 826 observations from 309 patients with schizophrenia. As compared with observations when no tardive dyskinesia was present (mean Quality of Life Interview score=47.2 [SD=16.7]), mild tardive dyskinesia was associated with a 4.0-point lower (–8%) average Quality of Life Interview rating, and moderate tardive dyskinesia was associated with a 2.2-point (–4.5%) lower rating. After adjusting for symptoms of schizophrenia and other neurological side effects, these differences were reduced only slightly to 3.6- and 1.8-point lower ratings (–7.4% and –3.6%, respectively). These data show average net reduction of quality of life associated with mild or moderate tardive dyskinesia ranging from 0% (based on the risk-adjusted analyses in the first cohort) to –16% (without adjustment). John M. Kane, M.D., (3) suggests a 3%–5% annual incidence of tardive dyskinesia in patients with first generation antipsychotics and 1% with newer medications. The attributable risk of tardive dyskinesia because of first generation antipsychotics would thus be 2%–4% per year. Multiplying the attributable risk by the reductions in quality of life estimated above, one can calculate average annual tardive dyskinesia-related reductions in quality of life attributable to first generation antipsychotics. This risk would be estimated to range from 0% (based on the risk-adjusted analysis of the first cohort) to a maximum of –0.64% (i.e., 0.04 attributable risk of tardive dyskinesia multiplied by –16% reduction in Quality of Life Interview scores). These analyses are limited, however, by the absence of data on severe tardive dyskinesia. An upper bound estimate of the average risk of decline in Quality of Life Interview scores because of mild or moderate tardive dyskinesia with first generation antipsychotics may thus be less than 1%. Clinical decision making must be based on individual patient circumstances and preferences, rather than on average risk calculations. However, side effect risks are central to antipsychotic treatment decisions, and it may be informative to use quantitative methods to evaluate their net effects on measures of well-being.West Haven, Conn.