Antiepileptic Oxcarbazepine Research Articles

Freezing degradation of the anticonvulsant oxcarbazepine by bromate in water ice under sunlight irradiation

Ice plays a crucial role in contaminant transformation in seasonally ice-covered waters. In this study, the characteristics and mechanisms of an emerging contaminant oxcarbazepine (OXC) degradation by a disinfection by-product bromate (BrO3–) in ice were explored via combined experiments and theoretical calculations. Results showed that 74.0 % and 86.4 % of OXC was degraded by BrO3– in ice after 140 min in dark and 120 min under solar irradiation, respectively, while the reaction was negligible in water. The oxidation-reduction potential of BrO3– solution at 1000 μmol L−1 was 56.9 % higher than that at 50 μmol L−1. The oxidation-reduction potential of BrO3– solution at pH 2 was 14.8 %–109.5 % higher than those at other pH values. Enhanced OXC degradation by BrO3– in ice could be attributed to increased BrO3– oxidation capacity resulting from locally elevated BrO3– and H+ concentrations. Hypobromous acid (HOBr), •OH, and Br• generated by direct photolysis under solar irradiation further promoted the OXC degradation in ice. Br• formed by the direct photolysis of accumulated HOBr under solar irradiation caused the generation of bromine-containing degradation products. Bromine-containing degradation products possessed higher potential toxicities, which could contribute to increase the secondary pollution of water environment.

Development and Validation of a Highly Sensitive and Rapid LC-MS3 Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring

A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS3) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, v:v) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS3 method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing–Bablok regression coefficients and Bland–Altman plots showed that the developed LC–MS3 method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS3 method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.

Forced normalization in epilepsy: Myth or reality?

It was Landolt working in the Swiss Epilepsy Centre who first described the phenomenon of Forced Normalization in 1953. He observed that in patients with intractable epilepsy exposed to the then new drug, ethosuximide, the seizures became controlled, but there emerged a range of psychiatric symptoms. The EEG at this time was relatively or completely normal, leading Landolt to comment on the “paradoxical nature” of the relationship between seizures and behaviour. Tellenbach, described this phenomenon as “the alternative psychosis of epilepsy”. Wolf in his extensive review described how Forced Normalization was reported with every anti-epileptic drug developed, the condition being reviewed extensively in the eponymous book edited by Trimble & Schmitz. Forced Normalization has been described in the last two decades with novel AEDs, levetiracetam, lacosamide; however, the risk of alternative psychosis and forced normalization seems to be particularly low with the new anticonvulsants oxcarbazepine, eslicarbazepine, gabapentin and pregabalin. Despite many years of research, Forced Normalization remains a controversial entity in neuropsychiatry. Many case series and reports point to its presence as a phenomenon in clinical practice when a new AED is introduced in patient management and seizures cease. Yet, very little by way of prospective research or clinical trial attention as been paid to this condition, which indeed could help one distinguish, perhaps, strong from weak AEDs. In this talk we will examine the myth and reality of Forced Normalization in epilepsy, the contemporary relevance of the phenomenon in drug development and clinical practice, and indeed its future application.

Hot Melt Coating: Development and Optimization of Controlled Release Formulation and Process of Oxcarbazepine

Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system for anti-epileptic drug Oxcarbazepine. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of solid lipid material and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus on HMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization (by CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Psychotropic drug-induced hyponatremia: results from a drug surveillance program\u2013an update

Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of < 130 mmol/l) and often induced by drugs including psychotropic drugs. AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicenter drug surveillance program that assesses severe or unusual adverse drug reactions (ADRs) occurring during treatment with psychotropic drugs. This study presents data from 462,661 psychiatric inpatients treated in participating hospitals between 1993 and 2016 and serves as an update of a previous contribution by Letmaier et al. (JAMA 15(6):739–748, 2012). A total of 210 cases of HN were observed affecting 0.05% of patients. 57.1% of cases presented symptomatically; 19.0% presented with severe symptoms (e.g., seizures, vomiting). HN occurred after a median of 7 days following the first dose or dose increase. Incidence of HN was highest among the two antiepileptic drugs oxcarbazepine (1.661% of patients treated) and carbamazepine (0.169%), followed by selective serotonin-norepinephrine reuptake inhibitors (SSNRIs, 0.088%) and selective serotonin reuptake inhibitors (0.071%). Antipsychotic drugs, tricyclic antidepressants, and mirtazapine exhibited a significantly lower incidence of HN. The risk of HN was 16–42 times higher among patients concomitantly treated with other potentially HN-inducing drugs such as diuretic drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and proton pump inhibitors. Female SSNRI-users aged ≥ 65 years concomitantly using other HN-inducing drugs were the population subgroup with the highest risk of developing HN. The identification of high-risk drug combinations and vulnerable patient subgroups represents a significant step in the improvement of drug safety and facilitates the implementation of precautionary measures.

Effects of antiepileptic drugs on serum lipids profile among young adult Sudanese patient with epilepsy at Aljazeera State

consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy, several studies have reported that the patients commonly used antiepileptic drugs like phenytoin, and carbamazepine increase serum total Cholesterol, High Density Lipoproteins Cholesterol (HDL-C) Low Density lipoprotein Cholesterol ( LDL-C ) levels and Triglyceride (TG) .The aim of this study to assess and compare serum lipid profile of young adult patients treated by anti-epileptic drugs (phenytoin, oxcarbazepine and valproic acid) . Materials and Methods a cross-sectional study was conducted in Aljazeera state. Epileptic patients were of recruited. and taking antiepileptic drugs for more than six months and on regular follow up; approximately 120 patients on commonly used antiepileptic drugs (40 on phenytoin, 40 on oxcarbazepine, 40 on valproic Acid). Age and sex matching 40 controls were taken. our results show significant difference in the of mean TC, TG, HDL, and LDL-C levels in the group receiving phenytoin for more than six months when compared with control group P value (0.00) for all lipid profile. Also significant difference between the mean of TC, TG, HDL-C and LDL-C levels in the group receiving oxcarbazepine for more than six months when compared with control P value (0.00 ) for all lipid profile. From the present study we concluded that CYP enzyme inducer anti-epileptic medicines like phenytoin and oxcarbazepine is strongly associated with increased levels of TC, LDL-C, HDL-C and TG, where asvalproate showed no significant change. Therefore, the serum cholesterol level should be regularly monitored in patients undergoing. Therapy with inducer anti-epileptic medicines.

Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice

BackgroundDue to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice.Materials and methodsAs a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry.ResultsSotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study.ConclusionSotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine.

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.

Pre- and Post-Treatment with Novel Antiepileptic Drug Oxcarbazepine Exerts Neuroprotective Effect in the Hippocampus in a Gerbil Model of Transient Global Cerebral Ischemia.

Oxcarbazepine, an antiepileptic drug, has been reported to modulate voltage-dependent sodium channels, and it is commonly used in epilepsy treatment. In this study, we investigated the neuroprotective effect of oxcarbazepine in the hippocampus after transient ischemia in gerbils. Gerbils randomly received oxcarbazepine 100 or 200 mg/kg before and after transient ischemia. We examined its neuroprotective effect in the cornu ammonis 1 subfield of the gerbil hippocampus at 5 days after transient ischemia by using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-Jade B histofluorescence staining for neuroprotection, and by using glial fibrillary protein and ionized calcium-binding adapter molecule 1 immunohistochemistry for reaction of astrocytes and microglia, respectively. Pre- and post-treatment with 200 mg/kg of oxcarbazepine, but not 100 mg/kg of oxcarbazepine, protected pyramidal neurons of the cornu ammonis 1 subfield from transient ischemic damage. In addition, pre- and post-treatment with oxcarbazepine (200 mg/kg) significantly ameliorated astrocytes and microglia activation in the ischemic cornu ammonis 1 subfield. In brief, our current results indicate that post-treatment as well as pre-treatment with 200 mg/kg of oxcarbazepine can protect neurons from ischemic insults via attenuation of the glia reaction.

Alternative Psychoses and Forced Normalization after Seizure Control by Anticonvulsants with Special Consideration of the New Anticonvulsants

In the case of alternative psychosis and forced normalization, the patient alternates between periods of clinically manifest seizures and normal behavior, and other periods of seizure freedom (or significant seizure reduction) accompanied by psychosis or behavioral disturbances. Unlike the clinically defined alternative psychosis, forced normalization is based on EEG findings. In clinical practice and in the literature, both terms are mostly used synonymously, and they also describe the same clinical pictures. This allowed a joint evaluation of the publications about alternative psychosis and forced normalization. Most often, these two disorders occur after seizure control by anticonvulsants. In the period of older anticonvulsants, the succinimides for the treatment of absence seizures were most often associated with the development of an alternative psychosis or forced normalization. In the era of newer anticonvulsants that started with the introduction of vigabatrin, mostly patients with intractable focal seizures were affected. In 1987 - 31 years ago - paranoid hallucinatory psychosis, triggered by vigabatrin in a patient with epilepsy was reported for the first time. In the following years, reports of alternative psychosis and forced normalization appeared to be related to most of the new anticonvulsants. A comprehensive literature search provided 66 cases with detailed information on such events. More than twice as many women were likely to be affected as compared to men; the reason for this phenomenon is unclear. In four retrospective studies, another 176 alternative events were reported but no details were given. The risk of alternative psychosis and forced normalization seems to be particularly low with the new anticonvulsants oxcarbazepine, eslicarbazepine, gabapentin and pregabalin.

X-ray diffraction, vibrational and thermal study of dibenzazepinodione, a pharmacopeial impurity of oxcarbazepine

The antiepileptic drug oxcarbazepine (OXC) was crystallized from various organic solvents, and mixtures of OXC crystals and red-orange particles were obtained. In view of the pharmaceutical relevance of OXC, this study focuses on the isolation and characterization of these red-orange crystals by structural [single crystal (SCXRD), powder X-ray diffraction (PXRD) and Hirshfeld surface analysis], vibrational [Fourier transform infrared (FT-IR), Fourier transform Raman (FT-Raman) and Density functional theory (DFT) calculations], and thermal methods of analysis [simultaneous thermogravimetry-differential thermal analysis (TG-DTA) and hot stage microscopy (HSM)]. According to SCXRD, the red-orange crystals corresponded to a recently codified impurity of OXC, referred as dibenzazepinodione (DBZ) or impurity D in the United States and European Pharmacopoeias respectively, which crystallized in the orthorhombic Pccn space group with a half-molecule in the asymmetric unit. Hirshfeld surface analysis revealed that weak intermolecular contacts played an important role in the stabilization of DBZ packing. DBZ was also characterized through its mid-infrared and Raman spectra and its vibrational bands were assigned based on DFT calculations with the hybrid B3LYP functional, coupled with the 6-311++g (d,p) basis set. The TG-DTA and HSM results shed light on the behaviour upon heating of DBZ, revealing that this impurity is an unsolvated solid with high thermal-oxidative stability, which sublimed, melted locally and decomposed above 320 °C. The obtained results demonstrated that slow crystallization of OXC from solvents such as ethanol and dimethylsulfoxide, at 20-25 °C, in the presence or absence of ambient light afforded DBZ. The X-ray pattern based on the SCXRD data for DBZ is presented as reliable reference for its identification.

Is It Necessary to Measure Thyroid Hormone Levels in Children Receiving Antiepileptic Drugs?

Purpose This article evaluates the effect of antiepileptic drugs (AEDs) on thyroid function tests in children with epilepsy. Methodology One hundred twenty children were studied, with 40 patients taking older generation AEDs Na valproate (N = 20) and carbamazepine (N = 20), 40 patients taking newer generation AEDs levetiracetam (N = 20) and oxcarbazepine (N = 20), and 40 healthy children as controls. Serum T3, T4, FT4, and thyroid-stimulating hormone (TSH) were measured. Results Patients taking Na valproate had lower T3, T4, and a higher TSH level than controls. Patients taking carbamazepine had the lowest T3, T4, and FT4 serum levels among patients receiving AEDs. Conclusion The thyroid function tests were affected by the use of Na valproate and carbamazepine compared to both the control group and the group taking newer AEDs oxcarbazepine and levetiracetam. In addition, there was no effect of levetiracetam on thyroid function test results.

Experts Search for Meds to Help Youth With DMDD

Experts Search for Meds to Help Youth With DMDD

Emerging therapies for neuropathic pain: new molecules or new indications for old treatments?

Neuropathic pain represents a highly unmet medical need because most of the available treatments have a modest efficacy or dose-limiting side effects. Hence, novel therapeutic perspectives are warranted. Many compounds acting on new pain targets are in preclinical or early clinical development. Only few clinical trials have suggested their clinical relevance in neuropathic pain. This concerns in particular NaV1.7 antagonists and angiotensin type II inhibitors. Another type of emerging drug therapy in neuropathic pain is represented by drugs largely used for other indications, such as botulinum toxin A and the antiepileptic oxcarbazepine, which have recently found to be effective in peripheral neuropathic pain. Emerging nondrug medical therapy with promising results in neuropathic pain also encompasses noninvasive brain neurostimulation techniques, such as repetitive transcranial magnetic stimulation and transcranial direct electrical stimulation. In this article, we review emerging medical treatments for neuropathic pain that are clinically available or with promising results from clinical trials.

A Case of Paroxysmal Kinesigenic Dystonia : Epilepsy Mimic

Background: We report a rare case of movement disorder Paroxysmal kinesigenic dystonia who was misdiagnosed as Epilepsy and Conversion disorder.&#x0D; Case report: A 35 -year female presented with episodic painful twisting of her Right hand and arm only when she is awake. These events were triggered by sudden movements and would last several seconds to minutes. Her symptoms were unilateral and her physical and neurological examinations were normal. Treatment with anticonvulsants Oxcarbazepine improved her symptoms.&#x0D; Conclusion: Although an uncommon movement disorder, it is important to recognize the clinical presentation of Paroxysmal kinesigenic dystonia as most patients respond very well to medical treatment.&#x0D; Bangladesh Journal of Neuroscience 2017; Vol. 33 (1): 44-46

A comparative analysis of the range of medicines applied for the cerebral palsy pharmacotherapy in Ukraine by the British National Formulary

Aim. The improvement of the range of medicines applied for the cerebral palsy treatment in Ukraine.Metthods. System analysis, marketing research, expert estimation of remedies.Results. Pharmacuetical market of Ukraine needs to be expanded by including the actual remedies for the cerebral palsy treatment: Oxcarbazepine from the antiepileptic remedies pharmacotherapeutic group and Atomoxetine from the group of the psycoanaleptics, which are being used in British lists. Four muscle relaxants, available in the British children's formulary: Xeomin, Azalyur, Bocautur and Damdrolene Sodium are absent in Ukraine.Conclusion. 34 drugs from the Ukraine State drug formulary (2016), State drug register (2016), the British children's formulary (April, 2016), and the British national formulary (April, 2016) as common objects for the study of the modern range of medicines in developed countries, were analyzed for comparative study of pharmaceutical market of remedied applied for the cerebral palsy treatment.The differential analysis by specific pharmacological groups is presented by muscle relaxants, which include 8 remedies, antiepileptic drugs – 12, psychoanaleptics – 12, and other remedies affecting nervous system – 2. To compare, antiepileptic drug Oxcarbazepine and Atomoxetine from the group of the psycoanaleptics are absent in Ukraine. Muscle relaxants: Suxamethonium, Pipekuroniyu bromide, Tolperizon, and psychoanaleptics that are not included into the British formularies: Caffeine, Vinpocetine, Mebicar, Phenybutun are used in Ukraine simultaneously

Thirteen years of oxcarbazepine exposures reported to US poison centers: 2000 to 2012.

Oxcarbazepine (OXC) is a 10-keto analogue of carbamazepine used in patients with partial and secondary generalized seizures. We evaluated ingestions of OXC reported to US poison centers for adverse effects from supratherapeutic doses and/or overdose. Retrospective analysis of data reported to National Poison Data System from single-substance OXC ingestions between January 2000 and December 2012. There were 18,867cases with a mean of 1451 exposures/year. The patients were predominantly adults with 5464 exposures in children <6 years (29%). The most commonly reported clinical effects were drowsiness (n = 4703, 25%), vomiting (n = 1559, 8%), tachycardia (n = 590, 3%), agitated (n = 342, 1.8%), hypotension (n = 178, 0.9%), electrolyte disturbance (n = 153, 0.8%), coma (n = 156, 0.8%), and seizures (n = 121, 0.6%). There were 176 patients with a major effect of which 31 involved were children and 1728 (9%) patients with moderate effects of which 300 involved were children. Five deaths were reported in adults. Intentional exposure (e.g. suicide) was the reason for exposure in 68% of patients with major effects and in all fatalities. Fifty-three percent of adults and 38% of children were managed in a health-care facility (HCF). HCF utilization levels remained consistent. Severe outcomes appear to be infrequent (<1%). Unlike other anticonvulsants OXC does not appear to be proconvulsant in overdose. Serious outcomes for OXC overdoses are unlikely in the pediatric patient. With only mild symptoms likely, observation at home may be appropriate for the majority of cases. In the adult population there appears to be few neurologic and cardiovascular complications even in the intentional exposure.

Evaluation of cytochrome P450 inductions by anti-epileptic drug oxcarbazepine, 10-hydroxyoxcarbazepine, and carbamazepine using human hepatocytes and HepaRG cells

Anti-epileptic drug oxcarbazepine is structurally related to carbamazepine, but has reportedly different metabolic pathway. Auto-induction potentials of oxcarbazepine, its pharmacologically active metabolite 10-hydroxyoxcarbazepine and carbamazepine were evaluated by cytochrome P450 (CYP) 1A2, CYP2B6 and CYP3A4 mRNA levels and primary metabolic rates using human hepatocytes and HepaRG cells.For the CYP1A2 the induction potential determined as the fold change in mRNA levels was 7.2 (range: 2.3–11.5) and 10.0 (6.2–13.7) for oxcarbazepine and carbamazepine, respectively, while 10-hydroxyoxcarbazepine did not induce. The fold change in mRNA levels for CYP2B6 was 11.5 (3.2–19.3), 7.0 (2.5–10.8) and 14.8 (3.1–29.1) for oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine, respectively. The fold change for CYP3A4 induction level by oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine was 3.5 (1.2–7.4), 2.7 (0.8–5.7) and 8.3 (3.5–14.5), respectively. The data suggest lower induction potential of oxcarbazepine and 10-hydroxyoxcarbazepine relative to carbamazepine. The results in HepaRG cells showed similar trend as the human hepatocytes.After incubation for 72 h in hepatocytes and HepaRG cells, auto-induction was evident for only carbamazepine metabolism. The 10-keto group instead of double bond at C10 position is evidently a determinant factor for limited auto-induction of P450 enzymes by oxcarbazepine.

Degradation of oxcarbazepine by UV-activated persulfate oxidation: kinetics, mechanisms, and pathways.

The degradation kinetics and mechanism of the antiepileptic drug oxcarbazepine (OXC) by UV-activated persulfate oxidation were investigated in this study. Results showed that UV/persulfate (UV/PS) process appeared to be more effective in degrading OXC than UV or PS alone. The OXC degradation exhibited a pseudo-first order kinetics pattern and the degradation rate constants (k obs) were affected by initial OXC concentration, PS dosage, initial pH, and humic acid concentration to different degrees. It was found that low initial OXC concentration, high persulfate dosage, and initial pH enhanced the OXC degradation. Additionally, the presence of humic acid in the solution could greatly inhibit the degradation of OXC. Moreover, hydroxyl radical (OH•) and sulfate radical (SO4 (-)••) were identified to be responsible for OXC degradation and SO4 (-)• made the predominant contribution in this study. Finally, major intermediate products were identified and a preliminary degradation pathway was proposed. Results demonstrated that UV/PS system is a potential technology to control the water pollution caused by emerging contaminants such as OXC.

Placebo responses in patients with peripheral neuropathic pain

Abstract Background and aim Treatment responses during placebo periods in randomized clinical trials (RCTs) are quite often substantial and may impede a positive outcome of the trial. It would therefore be beneficial to gain more knowledge on factors contributing to large placebo responses in RCTs. The aim of the current study was to identify predictors of placebo responses in patients with peripheral neuropathic pain. Hypotheses We hypothesized that a high baseline pain intensity and variability will be predictive of large responses during placebo treatment. Furthermore, we hypothesized that expectation for pain relief, few prior treatments and side effects, low scores of pain catastrophizing, anxiety, depression and the personality trait neuroticism and high levels of positive emotions will be predictors of placebo responses. Methods This study is part of a randomized, double-blind, placebo-controlled, crossover study with the anticonvulsant oxcarbazepine. Pain intensity was registered at baseline and during treatment periods on a numerical rating scale (NRS, 0–10) along with expectation for pain relief (NRS), psychological measures (scores for anxiety, depression, catastrophizing, neuroticism, and positive emotions), prior treatments, and side effects. Results Multiple regression analysis with pain reduction during placebo treatment as the dependent variable and baseline pain, age, gender, and pain duration as explanatory variables was highly significant (R-squared = 0.53, p &lt; 0.001), while other explanatory variables did not reach statistical significance. Further analyses will be carried out. Conclusions Age and gender were not significant predictors of placebo responses in this study. Further results will be presented at the congress. Acknowledgements This study is part of the Innovative Medicines Initiative project EUROPAIN, www.imi.europa.eu.