Successful treatment of severe alcohol withdrawal delirium with very high-dose diazepam (260-480 mg) administration.

INTRODUCTION: Alcohol withdrawal delirium, commonly known as "delirium tremens (DT)", is the most severe clinical condition of alcohol withdrawal syndrome (AWS). Symptoms of DT include changes in consciousness and cognitive and perceptual impairments that fluctuate during the day. Treatment includes general support, such as helping the patient to re-orientate, close monitoring of vital signs and adequate hydration, and symptomatic treatment for agitation, autonomic instability, and hallucinations. In symptomatic treatment of DT, benzodiazepines are most commonly preferred due to their GABA-ergic effects. Diazepam, a benzodiazepine, has a faster onset of action than other benzodiazepines when administered intravenously (iv) and effectively controls symptoms. Although low doses of diazepam usually relieve DT symptoms, very high doses may be required in some patients. This case series discusses patients receiving high doses of diazepam to relieve DT symptoms. CASE REPORT: Four male patients aged from 43 to 57 years who regularly consumed alcohol with a daily average of 20-100 standard drinks and developed DT afterwards and were followed up in the intensive care unit are presented. In these patients, the symptoms of DT were relieved, and somnolence was achieved with the administration of very high-dose IV diazepam (260-480 mg/day), contrary to routine treatment doses. All patients were successfully treated and discharged without any morbidity. CONCLUSION: Severe AWS can potentially result in death otherwise managed quickly and adequately. Diazepam is a suitable agent for severe AWS or DT treatment. Clinicians should keep in mind that high-dose diazepam treatment may be required in the treatment of DT that develops after a long-term and high amount of alcohol consumption. Publications reporting the need for very high doses of diazepam in DT are limited and usually published long ago; in this context, our findings are significant. The evidence is often based on case reports and uncontrolled studies, so controlled trials are needed to determine optimal treatment doses in severe DT.

Clinical Effects of Cannabis Use in First-Episode Acute Psychotic Patients.

Introduction: Cannabis is the most widely used illegal psychoactive substance worldwide. Although there are clinical studies examining the differences between psychotic symptoms emerging after cannabis use and non-cannabis-related psychotic symptoms, data are limited in the scientific literature. We aimed to investigate the effects of cannabis use on psychotic symptoms and compare the cognitive function differences between the cannabis-user and non-user groups. Methods: First-episode psychotic patients were included in the study and divided into two groups based on cannabis use. Participants with cannabis use and without cannabis use were compared in terms of socio-demographic factors, psychotic symptoms, cognitive functions, and childhood trauma. All patients were assessed twice, during recruitment and after treatment for psychotic symptoms. Results: A total of 38 patients comprising of 18 patients with a history of cannabis use and 20 patients without a history of cannabis use were included. There were significant correlations between cannabis use, and living apart from family and family history of substance abuse. Negative psychotic symptoms were higher in the non-user group. The negative psychotic symptoms improved more significantly after treatment in the non-user group. There was a significant correlation between cannabis use and Stroop Color-Word Test scores. Conclusion: Our results give us a chance to argue that psychosis has different features in people with and without a history of cannabis use. These two phenomena could differ in many ways, so different prevention strategies and treatment options should be considered.

Smart Multiplex Point-of-Care Platform for Simultaneous Drug Monitoring.

Recently, illicit drug use has become more widespread and is linked to problems with crime and public health. These drugs disrupt consciousness, affecting perceptions and feelings. Combining stimulants and depressants to suppress the effect of drugs has become the most common reason for drug overdose deaths. On-site platforms for illicit-drug detection have gained an important role in dealing, without any excess equipment, long process, and training, with drug abuse and drug trafficking. Consequently, the development of rapid, sensitive, noninvasive, and reliable multiplex drug-detecting platforms has become a major necessity. In this study, a multiplex laser-scribed graphene (LSG) sensing platform with one counter, one reference, and three working electrodes was developed for rapid and sensitive electrochemical detection of amphetamine (AMP), cocaine (COC), and benzodiazepine (BZD) simultaneously in saliva samples. The multidetection sensing system was combined with a custom-made potentiostat to achieve a complete point-of-care (POC) platform. Smartphone integration was achieved by a customized application to operate, display, and send data. To the best of our knowledge, this is the first multiplex LSG-based electrochemical platform designed for illicit-drug detection with a custom-made potentiostat device to build a complete POC platform. Each working electrode was optimized with standard solutions of AMP, COC, and BZD in the concentration range of 1.0 pg/mL-500 ng/mL. The detection limit of each illicit drug was calculated as 4.3 ng/mL for AMP, 9.7 ng/mL for BZD, and 9.0 ng/mL for COC. Healthy and MET (methamphetamine) patient saliva samples were used for the clinical study. The multiplex LSG sensor was able to detect target analytes in real saliva samples successfully. This multiplex detection device serves the role of a practical and affordable alternative to conventional drug-detection methods by combining multiple drug detections in one portable platform.

How Do Cannabis and Synthetic Cannabinoids Affect Neurocognitive Functions? / Esrar ve Sentetik Kannabinoidler Nörobilissel Islevleri Nasil Etkiler?

OBJECTIVE: In this study, the losses of neurocognitive function caused by the use of cannabis and synthetic cannabinoid were studied on specific cognitive areas (attention and working memory, executive functions, visuospatial perception, learning and memory, planning and problem solving, word naming) and were described in comparision with healthy controls (control group). METHOD: In this study, while 52 participants who applied to Ege University Faculty of Medicine Department of Mental Health and Mental Disorders Drug Addiction Treatment Center Clinic between March 2015 - February 2017 and used cannabis at least for one year in the past and 51 participants who used synthetic cannabinoids for at least one year in the past were participant groups with a history of substance use; 57 staff/student of Ege University with no history of any substance use were participants of the control group. The research sample consisted of 160 participants. The sample group consisted of 160 men aged 18-35, and also 16 participants aged 36-54 were involved in the study in order to observe neuropsychological functions that changed with age. Stroop Test for attention area, Raven Standart Progressive Matrices Test for executive functions area, Line Orientation Test and Cancellation Test for visuospatial perception area, Serial Digit Learning Test and Öktem Verbal Memory Progresses Scale for learning and memory area, The Tower of London Test for planning and problem solving skill, Boston Naming Test for word naming area were used. RESULTS: In this study, while the lowest perfomance on the ability of focused attention, visuospatial cognition, visual scanning, orientation, sustained attention, general ability, short-term memory, learning, long-term memory, word naming was shown by the participants with a history of synthetic cannabis use, the participants with a history of cannabis use had the lowest performance on the ability of response rate, perseveration, conceptualizing, abstract thinking, changing sets, recognition. Participants' history of substance use did not affect the ability of planning and problem solving. CONCLUSION: In conclusion, this study suggests that the addition of cognitive rehabilitation programs to medical and psychosocial improvement studies carried out in the field of addiction will increase the success.

The Effects of the Addiction Programme of Probation on Treatment Motivation, Abstinence and Quality of Life: a Comparative Study with Motivational Interviewing and Individual Intervention.

INTRODUCTION: The aim of this study is to evaluate the effectiveness of Addiction Programme of Probation (APP) created by the Substance Abuse Treatment Commission of Ministry of Health. METHODS: The sample was consisted of probationers who were referred to Ege University by probation offices in February 2010. Literate probationers aged above 18, who fulfilled the SCID-I criteria for substance dependence, or had positive urine sample for illegal drugs were included. The probationers were allocated respectively to three treatment groups: APP (n=28); Motivational Interviewing (MI; n=30); Individual Intervention (II; n=30). The effectiveness of the treatment modalities was assessed by the State Anxiety Inventory; the WHO Quality of Life-Brief form; the Treatment Motivation Questionnaire. Visual analogue and Likert-type scales were used to assess the sense of the importance and the readiness of quitting drugs also the levels of craving. Urine toxicological analyses were performed fortnightly. RESULTS: The APP increased the readiness of quitting drugs. The MI increased both the sense of importance and readiness of quitting drugs, decreased the frequency and severity of craving. The II improved the mental and physical health, increased the confidence in treatment also readiness of quitting drugs. Additionally, II decreased the level of anxiety, the severity, frequency and duration of craving. There was a significant decrease in positive urine samples of all groups. CONCLUSION: Because of changing only "the level of being ready to quit substance abuse", APP is considered as an inadequate program compared with MI and II.

[Severity of Alcohol Dependence Questionnaire: Validity and Reliability of the Turkish Version]. / Alkol Bagimliligi Siddeti Ölçegi: Türkçe Formunun Geçerlik ve Güvenirligi.

OBJECTIVE: The aim of the study is to determine the validity and reliability of Turkish version of Severity of Alcohol Dependence Questionnaire (SADQ) developed by Tim Stockwell and colleagues in 1983 for the purpose of evaluating the severity of dependence in people with alcohol use disorder. METHOD: The present study was conducted with an adult sample of 200 participants with alcohol use disorder according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) who applied to Ege University Institute on Drug Abuse, Toxicology and Pharmaceutical Science. Regarding validity analysis, item-total score correlation coefficients and principal component analysis were calculated. The scale was compared with Michigan Alcoholism Screening Test (MAST). Reliability analysis was performed with internal consistency reliability and test-retest reliability. RESULTS: Considering the internal consistency reliability of scale, Cronbach's Alpha Reliability Coefficient was found to be α=0.914. Item and Total Score Correlation Coefficients of the scale items were found between 0.309 and 0.730 (p<0.01). The mean test-retest scores of the scale and its sub-dimensions were calculated with t-test for dependent groups and the difference was not statistically significant. Testretest correlation coefficient of the scale was found 0.855 (p<0.01). Exploratory factor analysis explained 70.5% of the total variance and four sub-dimensions were identified. Factor loadings of these sub-dimensions were estimated between 0.49-0.91. The correlation between SADQ and MAST was statistically significant (r=0.557, p<0.01). CONCLUSION: The results of this study suggest that the Turkish version of the SADQ with four sub-dimensions is a reliable and valid instrument in determining severity of alcohol dependence.

"Biomimetic-electrochemical-sensory-platform" for biomolecule free cocaine testing.

A biomimetic cocaine sensor was fabricated by using poly(p-phenylene) (PPP) with cyclodextrin (CD) units in the backbone and poly(ethylene glycol) (PEG) side chains (PPP-CD-g-PEG). The sensory platform was constructed by one step surface modification of glassy carbon electrode with PPP-CD-g-PEG by drop coating. The electrochemical measurements are based on the formation of CD-cocaine inclusion complex on the surface resulting in a significant decrease in electron transfer capacity of the selected redox probe. The changes in the surface features due to cocaine binding were explored via electrochemical techniques such as differential pulse voltammetry, cyclic voltammetry and electrochemical impedance spectrometry. The sensor exhibited linearity in the range of 25-200 nM cocaine, LOD was calculated as 28.62 nM (n = 5) according to 3Sb/m formula. Finally, the sensory platform was successfully applied for the cocaine analysis in synthetic urine samples and correlated with the chromatographic method.

Mental health, suicidality and hopelessness among university students in Turkey.

Psychological symptoms of university students can affect perceptions of physical and mental health and can influence the emergence of suicidal behavior. We investigated the association among psychological symptoms, suicidal thoughts, perceptions of physical and mental health in university students. 4330 students at Onsekiz Mart University completed an internet-based questionnaire. 15.1% of the students reported suicidal thoughts at least once in their lifetime. The severity of mental symptoms was found to increase with a decrease in perceived physical and mental health. 28.2% of the students had depression, 33.1% had anxiety. This research aims to contribute to the extensive body of work done regarding the mental health, suicidal thoughts and hopelessness among university students.

An aptamer folding-based sensory platform decorated with nanoparticles for simple cocaine testing.

The consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD). For the fabrication of AFSD, QDs were initially immobilized onto the poly-L-lysine coated µ-well surfaces. Then, the AuNP-aptamer conjugates were bound to the QDs. The addition of cocaine or BE caused a change in the aptamer structure which induced the close interaction of AuNPs with the QDs. Hence, quenching of the fluorescence of QDs was observed depending on the analyte amount. The linearity of cocaine and BE was 1.0-10 nM and 1.0-25 µM, respectively. Moreover, the limits of detection for cocaine and BE were calculated as 0.138 nM and 1.66 µM. The selectivity was tested by using different interfering substances (methamphetamine, bovine serum albumin, codeine, and 3-acetamidophenol). To investigate the use of AFSD in artificial urine matrix, cocaine/BE spiked samples were applied. Also, confirmatory analyses by using high performance liquid chromatography were performed. It is shown that AFSD has a good potential for testing the cocaine abuse and can be easily adapted for detection of various addictive drugs by changing the aptamer according to desired analytes. Copyright © 2016 John Wiley & Sons, Ltd.

Polypeptide with electroactive endgroups as sensing platform for the abused drug 'methamphetamine' by bioelectrochemical method.

Affinity-type sensors have emerged as outstanding platforms in the detection of diagnostic protein markers, nucleic acids and drugs. Thus, these novel platforms containing antibodies could be integrated into the monitoring systems for abused drugs. Herein, we established a novel detection platform for the analysis of a common illicit drug; methamphetamine (METH). Initially, a fluorescent-labeled polypeptide (EDOT-BTDA-Pala), derived from L-alanine N-carboxyanhydride (L-Ala-NCA) via ring-opening polymerization using 4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)benzo[c][1,2,5]thiadiazole-5,6-diamine (EDOT-NH2-BTDA) as initiator, was employed as a glassy carbon electrode (GCE) covering host, in order to immobilize the METH-selective antibody. Prior to the examination of analytical features, GCE/EDOT-BTDA-Pala/Antibody surface was successfully characterized in the way of electrochemical (cyclic voltammetry and electrochemical impedance spectroscopy) and microscopic techniques (scanning electron microscopy and fluorescence microscopy). As for the analytical characterization, linearity and limit of detection (LOD) were found as 10-100µg/mL with an equation of y=0.0429x-0.2347, (R2=0.996) and 13.07µg/mL, respectively. Moreover, sample application using artificial urine, saliva and serum samples spiked with METH (10, 25, 50µg/mL) were performed and LC-MS/MS system was used for further confirmation. The described platform can be adapted to monitor the other types of abused drugs by using suitably selected biorecognition elements.

Polypeptide Functional Surface for the Aptamer Immobilization: Electrochemical Cocaine Biosensing.

Electroanalytical technologies as a beneficial subject of modern analytical chemistry can play an important role for abused drug analysis which is crucial for both legal and social respects. This article reports a novel aptamer-based biosensing procedure for cocaine analysis by combining the advantages of aptamers as selective recognition elements with the well-known advantages of biosensor systems such as the possibility of miniaturization and automation, easy fabrication and modification, low cost, and sensitivity. In order to construct the aptasensor platform, first, polythiophene bearing polyalanine homopeptide side chains (PT-Pala) was electrochemically coated onto the surface of an electrode and then cocaine aptamer was attached to the polymer via covalent conjugation chemistry. The stepwise modification of the surface was confirmed by electrochemical characterization. The designed biosensing system was applied for the detection of cocaine and its metabolite, benzoylecgonine (BE), which exhibited a linear correlation in the range from 2.5 up to 10 nM and 0.5 up to 50 µM for cocaine and BE, respectively. In order to expand its practical application, the proposed method was successfully tested for the analysis of synthetic biological fluids.

[Pregabalin Dependence: A Case Report]. / Pregabalin Bagimliligi: Olgu Sunumu.

Pregabalin is a new generation antiepileptic that exerts its effect by decreasing the release of such neurotransmitters as glutamate, noradrenaline, and substance P. Pregabalin can be prescribed in Turkey at 150-600 mg to treat neuropathic pain, generalized anxiety disorder, and fibromyalgia, and as concomitant therapy in adult patients with partial epilepsy. Experimental studies have shown that pregabalin could be beneficial in the treatment of benzodiazepine dependence and withdrawal, as well as for relapse prevention in patients with alcohol dependence. Nonetheless, the number of case reports on the abuse potential of pregabalin has increased. Herein we present a patient with pregabalin dependence. The patient’s underlying alcohol and polysubstance dependence, and symptoms of generalized anxiety were thought to contribute to the development of pregabalin dependence. The patient reported that he had experienced severe withdrawal symptoms when he tried to stop using pregabalin. Bupropion and low-dose quetiapine were added to his paroxetine treatment, and pregabalin was discontinued gradually. Following this treatment the patient had not exhibited any signs of pregabalin dependence for one month. Although pregabalin is a promising drug for various psychiatric disorders, it should be used carefully in patients with a history of substance dependence.

LPG Dependence after a Suicide Attempt.

Inhalant abuse is a problem that is getting more common all around the world. The increase in prevalence of inhalant abuse escalates morbidity and mortality rates. About 22% of people using inhalant have died at their first attempt. Particularly propane, butane, or propane-butane mixture has highest mortality rates. Sudden sniffing death syndrome, cardiomyopathy, central nervous system toxicity, hematological abnormalities, kidney toxicity, and hepatocellular toxicities are the major complications of inhalant abuse. Herein we present a patient with inhalant use disorder. At the age of 19, after a stressful life event he had unsuccessfully tried to suicide by inhaling LPG (liquefied petroleum gas, a mixture of butane and propane gases). After he realized that he had hallucinations and felt better during the inhalation, he started to abuse it. He was addicted to LPG for 10 years at the time of admission. Besides being dangerous for the society security, this intense level of LPG inhalation (12 liters a day) not giving any physical harm makes this case interesting.

Valproate-associated reproductive hormone abnormalities: do bipolar men have the same risk as epileptic men?

OBJECTIVE: The effects of valproate on male reproductive hormones have been studied in epileptic patients and animals, but the results are inconsistent because reproductive hormone abnormalities may be independent of the use of valproate and may be due to epilepsy itself. The aim of this study was to determine if there is an association between valproate and reproductive abnormalities in men with bipolar disorder or if the association is unique to men with epilepsy. MATERIALS AND METHOD: The study included 39 male patients aged 18-50 years with a DSM-IV diagnosis of bipolar disorder (21 on lithium monotherapy and 18 on valproate monotherapy or valproate in combination with lithium therapy) and 15 male epilepsy patients on valproate monotherapy that were evaluated in terms of reproductive hormones. RESULTS: Duration of illness, duration of lithium and valproate therapy, daily dose and serum concentrations of lithium and valproate, duration of marriage, spouse's gravidity, the serum estradiol, luteinizing hormone, sex hormone-binding globulin, and free testosterone levels, and the free testosterone:luteinizing hormone ratio were not significantly different between the groups. Serum prolactin and follicle-stimulating hormone levels were significantly higher in the epilepsy patients than in the bipolar disorder patients on lithium monotherapy. CONCLUSION: The findings show that valproate did not have a negative effect on male reproductive hormones in the bipolar patients. The elevated prolactin and follicle-stimulating hormone levels observed in the epilepsy group should be attributed to epilepsy. To the best of our knowledge this is the first study to compare reproductive hormones in bipolar disorder and epilepsy patients on valproate therapy.

[Effects of valproate on male reproductive functions]. / Valproatin erkek ureme islevleri uzerine etkisi.

Valproate is an antiepileptic commonly used in the treatment of psychiatric and neurologic diseases. Some of the most frequently seen side effects affect the gastrointestinal, neurological, and hematological systems. Its side effects on reproductive functions have not been sufficiently studied. The use of valproate by females with bipolar disorder and epilepsy may cause menstrual cycle abnormalities, polycystic ovary syndrome, and hyperandrogenism. The effects on male reproductive functions have been researched only in epileptic patients and animals, and the results have been conflicting, because reproductive function abnormalities may be independent of the use of valproate and may be due to epilepsy itself. In the first part of this review reproductive function abnormalities due to epilepsy will be discussed, independent of the use of valproate or any other antiepileptic. Then, the results of research on valproate's effects on male reproductive functions (hormonal levels and sperm parameters) will be presented, including the possible underlying mechanisms of these effects, the effect of the duration of valproate use, and whether or not the effects are reversible. In the second section we review the results of animal research, which could be beneficial in assessing the effects of valproate and epilepsy.

[The role of low-dose pramipexole in the treatment of treatment-resistant bipolar depression: a case report]. / Tedaviye Dirençli Bipolar Depresif Dönemlerin Tedavisinde Düsük Doz Pramipeksolun Yeri.

Despite a wide range of various drugs, a significant proportion of depressed bipolar patients fail to respond to the treatment strategies. Novel theraupetics for bipolar depression are needed. Preliminary studies suggest that pramipexole a dopaminergic agent that has been used in the treatment of Parkinson's disease and restless leg syndrome may have antidepressant properties in unipolar and bipolar depressed patients as well as neurotrophic properties. The optimal antidepressant daily dose of pramipexole is not known. It has been suggested to be used between 0.125 to 9.0 mg/day. In double blind placebo controlled bipolar depression treatment studies, the average daily dose of pramipexole was 1.7 mg. Manic switches have been reported with depressive subjects and with subjects without any mental disorders. We report two cases of treatment resistant bipolar depression. Despite different treatment strategies and treatment adherence, the patients did not give optimal response to the treatments and continue to experience depressive relapses. They have been treated with low dose (0.5-0.75 mg/day) pramipexole augmentation successfully. The severity and the duration of the depressive episodes were decreased. No serious adverse event has been reported with pramipexole during the maintenance treatment.

Executive and verbal working memory dysfunction in first-degree relatives of patients with bipolar disorder.

The authors aimed to investigate cognitive performance of first-degree relatives of probands with bipolar disorder (BD). They hypothesized that the relatives of BD patients would have impaired performance on cognitive tests of frontal-executive functions. A neuropsychological battery was administered to 34 first-degree relatives of BD probands and 25 control subjects. Relatives showed significant impairment in verbal working memory and executive function. Verbal memory and psychomotor performances of relatives were not different from control subjects. One particular component of executive function, cognitive flexibility, was associated with family history of mood episodes with psychotic features. Verbal working memory and executive function deficits may be useful endophenotypic markers of genetic vulnerability to BD.