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1.
PLoS One ; 19(4): e0300511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38598465

RESUMO

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Humanos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Análise Custo-Benefício , Índia , Farmacogenética , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética
2.
Int J Neuropsychopharmacol ; 27(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629703

RESUMO

The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors, apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine, and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at the highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/farmacologia , Humanos , Animais , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Ínsulas Olfatórias/efeitos dos fármacos , Ínsulas Olfatórias/metabolismo , Neurogênese/efeitos dos fármacos
3.
BMC Psychiatry ; 24(1): 248, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566016

RESUMO

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/diagnóstico , Esquizofrenia Resistente ao Tratamento , Receptores de Glutamato/uso terapêutico , Ácido Glutâmico , Antipsicóticos/efeitos adversos
4.
Br J Psychiatry ; 224(5): 164-169, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38652060

RESUMO

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.


Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia Resistente ao Tratamento , Humanos , Clozapina/efeitos adversos , Clozapina/uso terapêutico , Masculino , Feminino , Adulto , Antipsicóticos/efeitos adversos , Estudos Longitudinais , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia Resistente ao Tratamento/tratamento farmacológico , Esquizofrenia Resistente ao Tratamento/genética , Pessoa de Meia-Idade , Comportamento Compulsivo/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/induzido quimicamente , Esquizofrenia/tratamento farmacológico
5.
CNS Neurosci Ther ; 30(4): e14713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38615362

RESUMO

AIMS: We aimed to evaluate the potential of a novel selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator, LT-102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. METHODS: The activity of LT-102 was examined by Ca2+ influx assays and patch-clamp in rat primary hippocampal neurons. The structure of the complex was determined by X-ray crystallography. The selectivity of LT-102 was evaluated by hERG tail current recording and kinase-inhibition assays. The electrophysiological characterization of LT-102 was characterized by patch-clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. RESULTS: LT-102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT-102 facilitated long-term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine-induced mouse model. Additionally, LT-102 treatment increased the protein level of brain-derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. CONCLUSION: We conclude that LT-102 ameliorates cognitive impairments in a phencyclidine-induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS.


Assuntos
Disfunção Cognitiva , Propionatos , Esquizofrenia , Animais , Camundongos , Ratos , Fenciclidina , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Isoxazóis
6.
Riv Psichiatr ; 59(2): 75-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651776

RESUMO

Treatment with long-acting injection (LAI) antipsychotics, such as paliperidone palmitate, has improved the quality of life in terms of symptoms and prevention of relapses in patients with schizophrenia. Although there are plenty of evidences about the efficacy and safety of paliperidone palmitate 3-monthly injection (PP3M) in adults with schizophrenia, literature appears lacking about the use of LAIs during pregnancy. We hereby describe the clinical case of a pregnant woman affected by schizophrenia (DSM-5-TR), taking pharmacological treatment of PP3M. Considering the inadequate evidence regarding the use of PP3M in pregnancy in agreement with the patient, we switched PP3M to an oral therapy with aripiprazole. The switch to oral aripiprazole allowed the patient to improve her sense of autonomy and strengthen the therapeutic relationship. To our knowledge, this is the first case report monitoring an entire pregnancy of a women affected by schizophrenia in treatment with PP3M injection and oral aripiprazole. No obstetrical or fetal complications were reported. As the research in this field is very demanding, it would be precipitous to derive final conclusions from the current case report, but we hope to build a growing number of data that would allow us to make more appropriate and safe therapeutic choices in such a vulnerable phase as the peripartum.


Assuntos
Antipsicóticos , Aripiprazol , Preparações de Ação Retardada , Palmitato de Paliperidona , Complicações na Gravidez , Esquizofrenia , Humanos , Feminino , Aripiprazol/administração & dosagem , Aripiprazol/uso terapêutico , Palmitato de Paliperidona/administração & dosagem , Palmitato de Paliperidona/uso terapêutico , Gravidez , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Administração Oral , Complicações na Gravidez/tratamento farmacológico , Substituição de Medicamentos , Injeções Intramusculares
8.
Psychopharmacol Bull ; 54(2): 15-27, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38601834

RESUMO

The study aimed to assess Rivastigmine augmentation on positive and negative symptoms (PNSs), general psychopathology, and quality of life in patients with chronic Schizophrenia. A double-blind, parallel-design, randomized, placebo-controlled trial of 60 schizophrenia patients was conducted. Intervention group received rivastigmine 3 mg/day + Treatment as Usual (TAU) and the control group: TAU + placebo. Negative and positive symptoms, general psychopathology; and quality of life were measured using Positive and Negative Symptom Scale (PANSS) and Manchester Short Assessment of Quality of Life (MANSA). T-test, ANOVA, and the general univariate linear model tests were used for the analyses. Out of 60 participants, 52 (86.6%) were male. At baseline, no significant relationship was found for demographic and clinical characteristics between intervention and control groups. Between-group analysis indicated that all outcome measures PNSs, general psychopathology symptoms, and QoL score in rivastigmine group was significantly improved (p = 0.001). According to within-group analysis, a significant association was found between Rivastigmine and placebo groups in PNSs (p < 0.05). Rivastigmine augmentation improved PNSs and psychopathology in schizophrenia patients. However, no significant association found for improving the life quality after 8 weeks treatment.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Masculino , Feminino , Esquizofrenia/tratamento farmacológico , Rivastigmina/farmacologia , Rivastigmina/uso terapêutico , Qualidade de Vida , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Quimioterapia Combinada , Método Duplo-Cego
9.
Psychopharmacol Bull ; 54(2): 46-50, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38601835

RESUMO

Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely, clozapine remains underutilized.


Assuntos
Antipsicóticos , Clozapina , Discinesia Induzida por Medicamentos , Esquizofrenia , Humanos , Clozapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Antipsicóticos/farmacologia
10.
J Psychiatr Res ; 173: 302-308, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38560960

RESUMO

Post-schizophrenic depression (PSD) increases the morbidity, mortality, and health burden in patients with schizophrenia. However, treatment of PSD is challenging due to the lack of substantial evidence of standard clinical practice. This study was aimed at comparing the efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination (OFC) in PSD. This was a randomized controlled trial conducted in sixty patients with PSD fulfilling the eligibility criteria. Recruited patients were randomized to receive either amisulpride at low dose (i.e., 100-300 mg/day) or OFC (5/10 mg + 20 mg) for eight weeks. The Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression-Severity (CGI-S) and serum BDNF levels were assessed at baseline and after eight weeks of treatment. The change in the CDSS scores from baseline over eight weeks was significant in both the amisulpride and OFC groups. However, the changes were not significant when compared between the groups. Similarly, the changes in CGI-S scores and serum BDNF levels were significant in each group; but non-significant between the groups. A significant negative correlation was found between the changes in the CDSS scores and the serum BDNF levels in each group. No significant adverse events were noted in either group. Thus, to conclude, low-dose amisulpride can be a potential monotherapy in PSD with a favourable clinical outcome and safety profile (ClinicalTrials.gov ID: NCT04876521).


Assuntos
Antipsicóticos , Fluoxetina , Esquizofrenia , Humanos , Amissulprida/efeitos adversos , Antipsicóticos/uso terapêutico , Sulpirida/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo , Depressão/tratamento farmacológico , Depressão/etiologia , Benzodiazepinas , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , Resultado do Tratamento , Combinação de Medicamentos
11.
BMC Psychiatry ; 24(1): 244, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566055

RESUMO

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.


Assuntos
Transtorno Bipolar , Esquizofrenia , Humanos , Analgésicos Opioides/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Dor , Padrões de Prática Médica , Prescrições , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Estados Unidos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
12.
Expert Rev Neurother ; 24(4): 325-332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38445396

RESUMO

INTRODUCTION: Paliperidone Palmitate is the only antipsychotic that has been developed in three different intramuscular long-acting injectable (LAI) dosing regimen: monthly (PP1M), quarterly (PP3M), and from 2020 also twice-yearly (PP6M). The latter was approved for the maintenance treatment of adults with schizophrenia and clinically stabilized with PP1M or PP3M. AREAS COVERED: Data from studies evaluating efficacy in the maintenance treatment of schizophrenia with PP6M are reviewed. Since no post-marketing safety studies are currently available, data from spontaneous reporting system databases, FAERS and Eudravigilance, are analyzed and the reported treatment-emergent adverse events of PP6M are discussed. EXPERT OPINION: The efficacy of PP6M is comparable to that of PP3M in terms of relapses prevention in patients with schizophrenia previously stabilized on PP3M or PP1M. Also, the maintenance of clinical efficacy in the long term has been demonstrated. Data from pharmacovigilance analyses, as well as from phase 3 studies, show that PP6M is generally well tolerated, consistently with PP3M safety data. PP6M allows a longer dosing interval than any other LAI antipsychotics, potentially reducing nonadherence and disease relapses. In future, an increase in the prescription rates of PP6M is expected and real-world efficacy and tolerability studies will be conducted.


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Humanos , Palmitato de Paliperidona/uso terapêutico , Palmitato de Paliperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento , Recidiva
13.
Arch Psychiatr Nurs ; 48: 13-19, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38453277

RESUMO

OBJECTIVES: The goal of this quality improvement project (QIP) was to increase awareness of the serious medical consequences of clozapine-associated constipation to front line nursing staff and patients with schizophrenia. METHODS: The QIP was developed iteratively by psychiatric nurses, psychiatrists and pharmacists with input from patients. The processes involved a literature review, development of educational materials for staff and patients, and the creation of a daily bowel movements log (BML). Implementation involved review of the BML at treatment team meetings, and deployment of pharmacological and non-pharmacological interventions to resolve constipation and increase awareness and knowledge of this clinical concern. OUTCOMES: The initial pilot screened for symptoms of constipation in patients receiving clozapine and non-clozapine antipsychotic agents and intervening as necessary during multidisciplinary team meetings. Patients benefited from relief of constipation and improved bowel habits. Staff benefited from improved knowledge and making requisite changes in workflow and practice. Feedback allowed refinements to be made to the educational materials for patients and staff. Since full implementation, bowel habits are routinely monitored, and interventions are reviewed for effectiveness. Staff satisfaction with this QIP is reflected in answers to a structured questionnaire and in patient reports (n = 50). CONCLUSIONS: Clozapine, the only approved and efficacious medication for treatment-resistant schizophrenia is significantly underutilized. Medically consequential constipation can be a serious barrier to retention of patients benefiting from clozapine. Increased awareness and use of educational materials for patients and staff, routine monitoring of bowel habits combined with pharmacological and non-pharmacological interventions can successfully address this clinical problem.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/efeitos adversos , Melhoria de Qualidade , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/diagnóstico
14.
Psychopharmacol Bull ; 54(1): 40-42, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38449476

RESUMO

Here, authors report on an interesting case of early-onset of schizophrenia where adjunctive pregabalin alleviated risperidone-induced pseudoparkinsonism, helped with insomnia and agitation and boosted antipsychotic response with great tolerability. We wager that gabapentenoids can be a viable option in the niche of psychopharmacotherapy of schizophrenia in CAP population.


Assuntos
Antipsicóticos , Esquizofrenia , Adolescente , Humanos , Risperidona/efeitos adversos , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Pregabalina/uso terapêutico
15.
BMC Psychiatry ; 24(1): 173, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429778

RESUMO

BACKGROUND: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. METHODS: The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. RESULTS: Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05). CONCLUSION: The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.


Assuntos
Esquizofrenia , Humanos , Masculino , Cognição , Inflamação , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 2 da Matriz/química , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/química
16.
Ann Palliat Med ; 13(2): 433-439, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38509645

RESUMO

BACKGROUND: Palliative psychiatry is an emerging field that suggests a role for palliative interventions in the management of severe and persistent mental illness (SPMI). Current literature describes using a palliative approach for patients with severe anorexia nervosa. To our knowledge, this is the first case report describing end-of-life care in a patient with treatment-refractory catatonic schizophrenia. CASE DESCRIPTION: We describe the case of a 49-year-old man with schizophrenia and severe chronic agitated/malignant catatonia who was hospitalized for ten months. Multiple treatment trials including medication such as neuroleptics and benzodiazepines, electroconvulsive therapy, and empiric interventions such as intravenous immunoglobulins were either not tolerated or did not result in clinically significant improvement. The patient continued to intermittently require intubation and sedation to control intractable behavioral and psychiatric disturbances. Ultimately, with collaboration of psychiatry, neurology, ethics, intensive care, and palliative care teams, the patient's parents decided to forgo further diagnostic testing and life-sustaining treatments. The patient died weeks later of aspiration pneumonia with good symptom control. CONCLUSIONS: This case permits discussion of palliative interventions in patients with SPMI such as treatment-refractory psychotic disorders who likely cannot achieve a quality of life that is acceptable to them. Here, it can be justified to prioritize relief of suffering and prevention of further burdensome interventions over treatment of the SPMI symptoms such as catatonia and even over keeping the patient alive.


Assuntos
Catatonia , Psiquiatria , Esquizofrenia , Masculino , Humanos , Pessoa de Meia-Idade , Catatonia/diagnóstico , Catatonia/tratamento farmacológico , Esquizofrenia/terapia , Esquizofrenia/tratamento farmacológico , Esquizofrenia Resistente ao Tratamento , Qualidade de Vida/psicologia
17.
Expert Opin Drug Saf ; 23(4): 399-409, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467517

RESUMO

INTRODUCTION: Antipsychotics are the foundation of pharmacologic treatment for schizophrenia. There are many oral antipsychotics available and given that these medications are generally considered comparably efficacious when titrated to an adequate dose, their varied tolerability, and safety profiles become critically important for medication selection. AREAS COVERED: This paper reviews tolerability and safety considerations for first-line second-generation oral antipsychotics currently approved for the treatment of schizophrenia in the USA. Excluded from consideration are clozapine and non-oral formulations. EXPERT OPINION: Among antipsychotics, there are many differences in adverse reactions observed in clinical trials, such as variable likelihood to cause sedation vs insomnia, weight gain and abnormalities in glucose/lipid metabolism, hyperprolactinemia, potential for impact on the QT interval, and motoric adverse effects. Additional safety data that can help with medication selection include safety in pregnancy and lactation, and potential for drug-drug interactions. Ultimately, working with patients to personalize treatment by focusing on safety and individual tolerability considerations for various adverse effects can help in building a therapeutic alliance and improving patients' outcomes.


Assuntos
Antipsicóticos , Clozapina , Hiperprolactinemia , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Clozapina/uso terapêutico , Hiperprolactinemia/induzido quimicamente , Tiazóis/uso terapêutico
18.
Eur Psychiatry ; 67(1): e15, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450540

RESUMO

BACKGROUND: Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia. METHODS: This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK. RESULTS: Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%). CONCLUSION: PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.


Assuntos
Palmitato de Paliperidona , Esquizofrenia , Humanos , Palmitato de Paliperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Seguimentos , Hospitais Psiquiátricos , Recidiva
19.
BMC Psychiatry ; 24(1): 240, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553687

RESUMO

BACKGROUND: 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient's feeling of autonomy and psychiatric rehabilitation. CASE PRESENTATION: We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders- 10th Edition codes F20.0-5, F20.7-9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. CONCLUSIONS: Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. IMPACT AND IMPLICATIONS: Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Recidiva , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente
20.
J Correct Health Care ; 30(2): 71-81, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442318

RESUMO

The advantages of long-acting injectable antipsychotics (LAIs) in schizophrenia are well studied. However, forensic involvement is common in schizophrenia, and incarcerated individuals are often excluded from clinical trials. Nonadherence and oral medication diversion in forensic populations with schizophrenia, and the relationship between antipsychotic nonadherence and crime support LAI utilization in this subset of patients. Yet, federal regulations limit data generation in forensic populations. This review characterizes data on therapeutic outcomes of LAIs in correctional populations with schizophrenia-spectrum diagnoses. A search for primary literature was conducted in PubMed. Favorable effects of LAIs were observed on adherence, psychiatric symptomatology, patient satisfaction, health care costs, and frequency of criminal charges. Data were primarily retrospective and included small samples and individuals with historical versus current forensic involvement. Although limited, available literature and insights into the correctional system suggest advantages to LAI use in forensic populations. Barriers to conducting research in correctional settings must be addressed to facilitate further data generation.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Estudos Retrospectivos , Hospitalização , Resultado do Tratamento
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