Şizofrenide Mevcut Tedaviye Yardımcı Olarak Rastgele, Çift Kör, Çapraz Geçişli, Plasebo Kontrollü L-Arjinin Eklenmesi
Bibliographic record
Abstract
Schizophrenia is a disabling disorder which impairs social, occupational and individual functioning. Current drug treatments for schizophrenia are only partially effective and combination/augmentation strategies are commonly applied. L-arginine is a conditionally essential amino acid that is a natural constituent of dietary proteins. L-arginine is the precursor of nitric oxide (NO), a neuromodulator which is reported to take part in learning and memory, synaptic plasticity, and neuroprotection. Nitric oxide modulates dopamine, GABA and glutamate systems, all of which have been implicated in schizophrenia. We aimed to investigate whether L-arginine add-on to current medication might improve positive, negative, cognitive and depressive symptoms associated with schizophrenia. The study was conducted at Hacettepe University Faculty of Medicine, Department of Psychiatry. Twelve patients, 18-65 years old, diagnosed with schizophrenia/schizoaffective disorder were included. The study was designed as a randomized, double blind, placebo controlled, crossover study of addition of L-arginine 3 g b.i.d as an add-on treatment to the patients usual medication. The active treatment period was 3 weeks (first phase), with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization (second phase). The assessments were done at four times: day 0 as the baseline visit, day 21 after the first phase was completed, day 26 after the washout period and day 47 after the second phase was completed. Primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) scores. Secondary efficacy measures were Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression Scale (CGI), and a neuropsychological test battery consisted of the following: Rey Auditory Verbal Learning and Memory Test, Digit Span Forward and Backward Test from the Wechsler Memory Scale?Revised Edition (WMS-R), Controlled Word Association Test and Category Fluency Test, Trail Making Test?PartA/ B, Auditory Consonant Trigram Test, Visual Reproduction subtest of the WMS-R and Rey-Osterrieth Complex Figure Test. Physical examination and assessment of vital signs were performed and safety measurements including weight measurement, laboratory investigations of hemogram, liver, renal, thyroid function tests, electrolytes and electrocardiogram were conducted at the begining and at the end of study. Abnormal Involuntry Movement Scale (AIMS), UKU Side Effect Rating Scale were employed and L-Arginine levels were measured in each visit.. Statistical analysis were done using SPSS for Windows, Version 15.0 Package Program. Mann-Whitney-U, Wilcoxon and Friedman's test were used where necessary. No difference was observed between treatment groups on primary outcome measures, namely PANSS positive, negative, general psychopathology and total scores on days 0, 21, 26 and 47. There were also no difference when clozapine taking patients (n=6) and patients using other antipsychotics were evaluated seperately. Secondary outcome measures, CGI, CDSS and neuropsychological test scores also did not display a difference between the treatment groups on days 0, 21, 26 and 47. Within group comparisons between pre- and post-treatment states revealed no differences on primary outcomes, however CGI and some neuropsychological test scores were different of which is not supportive of a consistent putative effect of L-arginine. Safety measures did not differ between groups. In this study no effects of L-arginine augmentation on antipsychotics was observed. Failure to find a difference may be associated with the lack of effects of increasing NO levels in schizophrenia but also may be related to small sample size and inadequate dosage. To provide conclusive evidence, studies need to be conducted on more homogenous groups regarding psychopathology and treatment, with increased sample sizes and with higher dose of L-arginine.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".