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Treatment resistant schizophrenia

Shiva Shanker Reddy Mukku, P T Sivakumar, Mathew Varghese
Clozapine is the first second generation antipsychotic with different receptor profile of action. Clozapine is the most efficacious drug for the treatment of psychotic disorder and is the drug of choice in treatment resistant schizophrenia. Clozapine is used in elderly patients infrequently owing to its adverse effects profile and tolerability. There is paucity of literature with respect to clozapine use in late life. In this narrative review, we discuss clozapine use in elderly and challenges associated with its use...
March 3, 2018: Asian Journal of Psychiatry
Noriko Kudo, Hidenaga Yamamori, Tamaki Ishima, Kiyotaka Nemoto, Yuka Yasuda, Michiko Fujimoto, Hirotsugu Azechi, Tomihisa Niitsu, Shusuke Numata, Manabu Ikeda, Masaomi Iyo, Tetsuro Ohmori, Masaki Fukunaga, Yoshiyuki Watanabe, Kenji Hashimoto, Ryota Hashimoto
Background: An imbalance in the inflammatory tumor necrosis factor (TNF) system, including soluble tumor necrosis factor receptor 2 (sTNFR2), may contribute to the pathophysiology of schizophrenia. Methods: We measured the plasma levels of sTNFR2 in 256 healthy controls and 250 patients with schizophrenia including antipsychotic drug-free patients and treatment-resistant patients. We also explored the possible association between plasma sTNFR2 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS-Ⅲ), the Wechsler Memory Scale-Revised (WMS-R), and the Rey Auditory Verbal Learning Test (AVLT)...
February 24, 2018: International Journal of Neuropsychopharmacology
Sohag N Sanghani, Georgios Petrides, Charles H Kellner
PURPOSE OF REVIEW: ECT remains an important, yet underutilized, treatment for schizophrenia. Recent research shows that medication-resistant patients with schizophrenia, including those resistant to clozapine, respond well to ECT augmentation. The purpose of this article is to review recent studies of the use of ECT in the treatment of schizophrenia. RECENT FINDINGS: We performed an electronic database search for articles on ECT and schizophrenia, published in 2017...
March 9, 2018: Current Opinion in Psychiatry
Cristian Mena, Alfonso Gonzalez-Valderrama, Barbara Iruretagoyena, Juan Undurraga, Nicolas A Crossley
BACKGROUND: Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences...
March 8, 2018: Schizophrenia Research
Kristen Thien, Meghan Bowtell, Scott Eaton, Melissa Bardell-Williams, Linglee Downey, Aswin Ratheesh, Patrick McGorry, Brian O'Donoghue
BACKGROUND: The superior efficacy of clozapine in treatment resistant schizophrenia has been clearly demonstrated, yet there are often delays in the commencement of clozapine. In this study, we aimed to determine; the proportion of young people with a first episode of psychosis (FEP) who would be considered eligible for clozapine treatment, the theoretical delay in commencing clozapine and to compare the outcomes of those treated with clozapine to those who were eligible but not treated with clozapine...
March 8, 2018: Schizophrenia Research
Marion Psomiades, Marine Mondino, Clara Fonteneau, Remy Bation, Frederic Haesebaert, Marie-Françoise Suaud-Chagny, Jerome Brunelin
Auditory verbal hallucinations (AVH) in patients with schizophrenia are linked to abnormalities within a large cerebral network including frontal and temporal regions. Whilst abnormalities of frontal speech production and temporal speech perception regions have been extensively studied, alterations of the dorsolateral prefrontal cortex (DLPFC), a region critically involved in the pathophysiology of schizophrenia, have rarely been studied in relation to AVH. Using 1.5 T proton magnetic resonance spectroscopy, this study examined the relationship between right and left DLPFCs N-AcetylAspartate (NAA) levels and the severity of AVH in patients with schizophrenia...
March 7, 2018: Scientific Reports
Adam Carlbo, Hanna Persic Claesson, Sture Åström
INTRODUCTION: Schizophrenia is a common disease with a high risk of comorbidity in both psychiatric and somatic diseases. Physical activity is proven effective in reducing symptoms of schizophrenia and increasing overall health. Still it is not used systematically in the care of persons with schizophrenia. AIM: The aim of this study is to describe nurses' experience, including personal motivation, in using physical activity as complementary treatment in patients with schizophrenia...
March 5, 2018: Issues in Mental Health Nursing
Kevin J Li, Ronald J Gurrera, Lynn E Delisi
Clozapine has been shown to be the most efficacious therapy for treatment resistant schizophrenia, estimated at one third of all schizophrenia cases. There is significant morbidity and mortality associated with clozapine including risk of agranulocytosis, aspiration pneumonia, bowel ischemia, myocarditis, seizures, and weight gain. Here we present a case of a 62-year-old man with chronic paranoid schizophrenia refractory to numerous antipsychotics who was started on clozapine therapy during an acute inpatient psychiatric admission...
March 1, 2018: Schizophrenia Research
Bunta Yoshimura, Shinji Sakamoto, Kojiro Sato, Manabu Takaki, Norihito Yamada
AIM: Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy...
December 12, 2017: Early Intervention in Psychiatry
Afaque H Khan, Samina Zaidi
We report five cases of treatment-resistant schizophrenia that presented with prominent negative and positive symptoms. They fulfill the criteria of diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). They showed lack of response despite receiving multiple trials of first and second generation psychotropic agents. We decided to give these patients a trial of clozapine to improve their negative and positive symptoms as well as their quality of life...
December 20, 2017: Curēus
Olivier Percie du Sert, Stéphane Potvin, Olivier Lipp, Laura Dellazizzo, Mélanie Laurelli, Richard Breton, Pierre Lalonde, Kingsada Phraxayavong, Kieron O'Connor, Jean-François Pelletier, Tarik Boukhalfi, Patrice Renaud, Alexandre Dumais
Schizophrenia is a chronic and severe mental illness that poses significant challenges. While many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, notably auditory verbal hallucinations (AVH), which are highly disabling. This unmet clinical need requires new innovative treatment options. Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a computerized representation of their voices...
February 24, 2018: Schizophrenia Research
Andrea de Bartolomeis, Felice Iasevoli, Federica Marmo, Elisabetta Filomena Buonaguro, Livia Avvisati, Gianmarco Latte, Carmine Tomasetti
Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action...
February 20, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Susanne Thümmler, Emmanuelle Dor, Renaud David, Graziella Leali, Michele Battista, Alexia David, Florence Askenazy, Céline Verstuyft
Background: Severe mental health disorders in children and adolescents represent a major public health problem. Despite adequate drug treatment, some patients develop pharmacoresistant disease. As a consequence, physicians are confronted with prescribing challenges, prolonged hospitalization and increased risk of adverse events, thus aggravating short-, medium-, and long-term prognosis. The majority of psychotropic treatments, particularly antipsychotics and antidepressants, are metabolized at hepatic level by cytochrome P450 (CYP), particularly by CYP3A4 and CYP2D6...
2018: Frontiers in Psychiatry
Olesya Ajnakina, Henriette Thisted Horsdal, John Lally, James H MacCabe, Robin M Murray, Christiane Gasse, Theresa Wimberley
Large-scale pharmacoepidemiological research on treatment resistance relies on accurate identification of people with treatment-resistant schizophrenia (TRS) based on data that are retrievable from administrative registers. This is usually approached by operationalising clinical treatment guidelines by using prescription and hospital admission information. We examined the accuracy of an algorithm-based definition of TRS based on clozapine prescription and/or meeting algorithm-based eligibility criteria for clozapine against a gold standard definition using case notes...
February 19, 2018: Schizophrenia Research
Lucy D Vanes, Elias Mouchlianitis, Tracy Collier, Bruno B Averbeck, Sukhi S Shergill
BACKGROUND: The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients. METHODS: In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces...
February 14, 2018: Psychological Medicine
Jibran Y Khokhar, Angela M Henricks, Emily D K Sullivan, Alan I Green
Schizophrenia is a heterogenous and severe neuropsychiatric disorder that affects nearly 1% of the population worldwide. Antipsychotic drugs are the mainstay of treatment, but not all patients with schizophrenia respond to treatment with these agents. Clozapine, the first atypical antipsychotic, is a highly effective medication for patients with schizophrenia who do not respond to other antipsychotics. Although clozapine tends not to produce extrapyramidal symptoms, other side effects of the drug (e.g., agranulocytosis, myocarditis, seizures) limit its widespread use...
2018: Advances in Pharmacology
Chieh-Hsin Lin, Ching-Hua Lin, Yue-Cune Chang, Yu-Jhen Huang, Po-Wei Chen, Hui-Ting Yang, Hsien-Yuan Lane
BACKGROUND: Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-amino acid oxidase inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine...
December 26, 2017: Biological Psychiatry
Lucy D Vanes, Elias Mouchlianitis, Tobias C Wood, Sukhi S Shergill
Widespread white matter abnormalities have been reported in schizophrenia, a disorder frequently characterised as a dysconnection syndrome. White matter connectivity in schizophrenia has been predominantly investigated using diffusion weighted imaging, with reductions in fractional anisotropy throughout the brain often interpreted as an indicator of abnormal myelination. However, diffusion weighted imaging lacks specificity and as such a number of microstructural factors besides myelin may be contributing to these results...
2018: NeuroImage: Clinical
Patricia N Moretti, Vanessa K Ota, Eduardo S Gouvea, Mariana Pedrini, Marcos L Santoro, Fernanda Talarico, Leticia M Spindola, Carolina Muniz Carvalho, Cristiano Noto, Gabriela Xavier, Elisa Brietzke, Ary Gadelha, Rodrigo Bressan, Jair Mari, Sintia Belangero
Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using failure to respond to two previous antipsychotic trials...
January 26, 2018: Molecular Neurobiology
Tanuka Datta, Allen J Solomon
Approved in 1989 for the management of treatment-resistant schizophrenia, Clozapine is a last-line atypical antipsychotic drug used with increasing frequency. In addition to its well-known side effect of agranulocytosis, this drug also carries with it rare but serious adverse cardiovascular risk of myocarditis. We present a patient on Clozapine who was admitted to the cardiology service with chest pain, ST segment elevations and elevated troponin concerning for acute myocardial infarction. Evaluation with imaging revealed decreased left ventricular function, however, no coronary artery disease was present on catheterization; findings consistent with a diagnosis of myocarditis...
January 2018: Oxford Medical Case Reports
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