Severity Of Alcohol Withdrawal Symptoms Research Articles

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder

ABSTRACT Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms. Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY). Methods: At postnatal day 32, parallel groups of 12–24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior. Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832). Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

Quantitative electroencephalographic analysis of delirium tremens development following alcohol-withdrawal seizure based on a small number of male cases.

Seizures and delirium tremens (DTs) are recognized as severe alcohol-withdrawal symptoms. Prolonged admission and serious complications associated with alcohol withdrawal are responsible for increased costs and use of medical and social resources. This study investigated the predictive value of quantitative electroencephalography (QEEG) for developing alcohol-related DTs after alcohol-withdrawal seizure (AWS). We compared differences in QEEG in patients after AWS (n = 13). QEEG was performed in the intensive care unit within 48 h of admission, including in age- and sex-matched healthy controls. We also investigated the prognostic value of QEEG for the development of alcohol DTs after AWS in a retrospective, case-control study. The spectral power of each band frequency and the ratio of the theta to alpha band (TAR) in the electroencephalogram were analyzed using iSyncBrain® (iMediSync, Inc., Korea). The beta frequency and the alpha frequency band power were significantly higher and lower, respectively, in patients than in age- and sex-matched healthy controls. In AWS patients with DTs, the relative beta-3 power was lower, particularly in the left frontal area, and the TAR was significantly higher in the central channel than in those without DTs. Quantitative EEG showed neuronal excitability and decreased cognitive activities characteristic of AWS associated with alcohol-withdrawal state, and we demonstrated that quantitative EEG might be a helpful tool for detecting patients at a high risk of developing DTs during an alcohol-dependence period.

The Effectiveness of Non-Benzodiazepine, Non-Barbiturate Medications for Alcohol Withdrawal Syndrome: A Rapid Systematic Review.

There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS. We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT. Thirty-four RCTs were included. Gabapentin (n=6), carbamazepine (n=5), baclofen (n=5), valproate (n=3), clonidine/lofexidine (n=3) and acamprosate (n=2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a 'moderate' level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was 'low' for carbamazepine, baclofen and valproate and 'very low' for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable. Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.

Gabapentin for Alcohol-Related Disorders: Critical Appraisal of the Symptom-Driven Approach.

Gabapentin, available as gabapentin and as the prodrug gabapentin enacarbil, is an approved treatment for partial seizures, postherpetic neuralgia, and the restless legs syndrome. Gabapentin has been studied for diverse off-label indications, including alcohol use disorder (AUD). Meta-analyses of randomized controlled trials (RCTs) suggest that gabapentin reduces the severity of alcohol withdrawal symptoms (AWS) as well as the percentage of heavy drinking days in persons with AUD; however, the magnitude of benefit is small, and no benefits are apparent for other drinking outcomes. Furthermore, a recent, large RCT found an extended-release formulation of gabapentin enacarbil ineffective for a wide range of drinking and other outcomes in patients with AUD. Some research suggests that gabapentin may improve drinking outcomes specifically in AUD patients with higher levels of AWS; this may be a result of gabapentin-associated reduction in AWS, precluding AWS-triggered continued drinking. In this context, a recent, large RCT found that gabapentin reduced heavy drinking and increased abstinence, and that these findings were apparent only in patients with higher levels of AWS during the 2 weeks before randomization; disconcertingly, gabapentin appeared to worsen drinking outcomes in the patients with low AWS. Whereas these findings support the conjecture that gabapentin could be considered indicated in AUD patients with high AWS, problems with this RCT and with its findings limit the applicability of the findings to everyday clinical practice. These problems are discussed in detail. It is concluded that, in line with the recommendations of a recent treatment guideline, gabapentin may be considered for patients with AUD only if first line drugs such as naltrexone and acamprosate cannot be used. It may also be worth examining benefits with gabapentin in AUD associated with chronic pain, anxiety, and chronic insomnia because gabapentin is suggested to attenuate these syndromes.

Alcohol withdrawal management during the Covid-19 lockdown in Kerala.

The lockdown declared to prevent the spread of Covid 19 in India created unforeseen problems, including severe alcohol withdrawal symptoms and the need to manage them. The state of Kerala in India saw suicide deaths by six affected individuals, prompting the state government to instruct government doctors to prescribe alcohol to addicts. The local medical association approached the courts against this. These events raise interesting ethical issues discussed here. Keywords: alcohol withdrawal, prescribing alcohol, Covid 19, ethics of alcohol prescription.

Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2.

Alcohol use disorder (AUD) is characterized by repetitive and uncontrolled intake of alcohol with severe consequences for affected individuals, their families and society as a whole. Numerous studies have implicated brain-derived neurotrophic factor (BDNF) activity in the neurobiology underlying AUD. The BDNF signaling mechanism is complex and depends on two receptor systems, TrkB and p75NTR, which appear to have opposite effects on alcohol seeking behavior in animal models. We recently discovered that the sortilin-related receptor SorCS2 forms complexes with both TrkB and p75NTR and is important for BDNF activity in the developing and adult CNS. Moreover, the SORCS2 gene was recently identified as the top association signal for severity of alcohol withdrawal symptoms. Hence, we speculated that SorCS2 deficient mice would have an altered response to alcohol. The role of SorCS2 in the acute and adapted response to alcohol was therefore investigated by comparing SorCS2 knockout (Sorcs2−/−) mice to wild type (WT) mice in three paradigms modeling alcohol sensitivity and consumption; alcohol-induced conditioned place preference, two-bottle choice test as well as the behavioral response to alcohol withdrawal. We found that, when compared to the WT mice, (I) Sorcs2−/− mice displayed complete lack of alcohol-induced place preference, (II) when given free choice between water and alcohol, Sorcs2−/− mice consumed less alcohol, and (III) Sorcs2−/− mice showed no handling-induced convulsion in response to alcohol withdrawal following extended alcohol exposure. Taken together, these results show that lack of the alcohol withdrawal risk gene Sorcs2 results in abnormal behavioral response to alcohol in mice. Consequently, SorCS2 may play an important role in the molecular pathways underlying AUD and complications associated with alcohol withdrawal.

Are short-acting or long-acting benzodiazepines more effective in decreasing the severity of alcohol withdrawal symptoms?

Are short-acting or long-acting benzodiazepines more effective in decreasing the severity of alcohol withdrawal symptoms?

TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years.

To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence. The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for. At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival. An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender. We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.

Medications for alcohol use disorders: An overview.

Patients who suffer from alcohol use disorders (AUDs) usually go through various socio-behavioral and pathophysiological changes that take place in the brain and other organs. Recently, consumption of unhealthy food and excess alcohol along with a sedentary lifestyle has become a norm in both developed and developing countries. Despite the beneficial effects of moderate alcohol consumption, chronic and/or excessive alcohol intake is reported to negatively affect the brain, liver and other organs, resulting in cell death, organ damage/failure and death. The most effective therapy for alcoholism and alcohol related comorbidities is alcohol abstinence, however, chronic alcoholic patients cannot stop drinking alcohol. Therefore, targeted therapies are urgently needed to treat such populations. Patients who suffer from alcoholism and/or alcohol abuse experience harmful effects and changes that occur in the brain and other organs. Upon stopping alcohol consumption, alcoholic patients experience acute withdrawal symptoms followed by a protracted abstinence syndrome resulting in the risk of relapse to heavy drinking. For the past few decades, several drugs have been available for the treatment of AUDs. These drugs include medications to reduce or stop severe alcohol withdrawal symptoms during alcohol detoxification as well as recovery medications to reduce alcohol craving and support abstinence. However, there is no drug that completely antagonizes the adverse effects of excessive amounts of alcohol. This review summarizes the drugs which are available and approved by the FDA and their mechanisms of action as well as the medications that are under various phases of preclinical and clinical trials. In addition, the repurposing of the FDA approved drugs, such as anticonvulsants, antipsychotics, antidepressants and other medications, to prevent alcoholism and treat AUDs and their potential target mechanisms are summarized.

Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process. Nine groups of 8-10 students participated in a 2.5-hour simulation event that included an alcohol withdrawal seizure, team meeting, and discharge of the patient. Students recognized the importance of all the professional roles and how each professional benefits patient care. Before the simulation, students thought they were prepared to care for patients experiencing alcohol withdrawal; however, the crisis of an alcohol seizure decreased the student's ability to perform skills and communicate effectively. These findings suggest that new nurses and social workers may not be prepared to care for the acute alcohol withdrawal patient.

Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats.

Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. Alcohol-dependent patients (N=39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24hours after the last drink and after 2weeks of abstinence. MRI and MRS data of healthy controls (N=34) were acquired once. Our thorough quality criteria resulted in N=15 available spectra from the first and of N=21 from the second measurement in patients, and of N=19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60hours of withdrawal, and 3weeks of abstinence. In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.

Treatment of Alcohol Withdrawal Syndrome with and without Dexmedetomidine.

Studies suggest that dexmedetomidine-an intravenous central-acting α2-adrenergic agonist that effectively reduces anxiety among critically ill patients-is being used in patients with severe alcohol withdrawal. However, evidence supporting its use is limited, and it is not approved for this indication. To assess the effect of dexmedetomidine on severe alcohol withdrawal symptoms and to compare its use with benzodiazepines alone. A retrospective, cohort study of 77 patients admitted to the adult medical intensive care unit with severe alcohol withdrawal between January 1, 2009, and October 31, 2013. The difference in lorazepam equivalents and Clinical Institute Withdrawal Assessment for Alcohol scores in the 24 hours before and after initiation of dexmedetomidine therapy. The frequency of dexmedetomidine use increased dramatically between 2009 and 2013 (16.7% vs 82.4%; p = 0.01). Initiation of dexmedetomidine therapy was associated with significant improvements in Clinical Institute Withdrawal Assessment for Alcohol scores over corresponding 24-hour intervals (14.5 vs 8.5; p < 0.01). Benzodiazepine use also decreased, but the difference was not statistically significant at 24 hours (p = 0.10). Dexmedetomidine was well tolerated, requiring discontinuation of therapy in only 4 patients (10.5%). Dexmedetomidine use was also associated with significantly longer hospitalizations (p < 0.01). Dexmedetomidine initiation was associated with a reduction in short-term alcohol withdrawal symptoms in patients in the intensive care unit, with only a few patients experiencing adverse events. However, its use was also associated with longer hospitalizations. Further research is necessary to evaluate whether dexmedetomidine is efficacious or cost-effective in severe alcohol withdrawal.

Plasticity of hippocampal subfield volume cornu ammonis 2+3 over the course of withdrawal in patients with alcohol dependence.

Research focusing on plasticity has shown adult neurogenesis in hippocampal subfields. Chronic alcoholism is associated with decreased plasticity and reduced whole hippocampal volume that could contribute to neuropsychiatric characteristics and outcome of the disease. To investigate the effect of alcohol abstinence on neuronal plasticity measured as longitudinal volume change in distinct hippocampal subfields. We acquired high-resolution structural images of 42 patients addicted to alcohol and 32 healthy control participants. Patients and control participants were both scanned twice, once after withdrawal and 2 weeks later. Volumes of hippocampal subfields cornu ammonis (CA) 2+3, CA4+dentate gyrus, and subiculum were determined with a user-independent segmentation method. We found plasticity effects in bilateral CA2+3 in patients addicted to alcohol. Compared with healthy control participants, patients had lower CA2+3 volume at pretest (t31 = -0.73, P = .47) and showed a significant normalization of gray matter volume 2 weeks later. Pretest CA2+3 (t31 = -3.93, P < .001) volume was negatively associated with years of regular alcohol consumption (r42 = -0.32, P < .05) and more severe alcohol-withdrawal symptoms (r38 = -0.35, P < .05). Patients with stronger withdrawal symptoms displayed the largest volume increase of CA2+3 (r38 = 0.55, P < .001). The observed normalization of the bilateral hippocampal CA2+3 volume deficit matches animal data, showing a strong increase of hippocampal neurogenesis after cessation of alcohol consumption, and fits the reported increase of patients' cognitive function within a few months of alcohol abstinence. The role of CA3 in pattern separation and completion is also critical for formation of hallucinations, which constitute a severe symptom of the withdrawal syndrome. The study adds further biological arguments from structural brain research to abstain from alcohol.

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Introduction: Benzodiazepines (BZD) are initially used for treatment of alcohol withdrawal. Phenobarbital (PB) is a barbiturate agent that has also been used in managing alcohol withdrawal symptoms, especially refractory to BZD. However, limited data is available in critically ill patients. The purpose of our study is to describe our institution’s experience with adjunctive PB use in managing severe alcohol withdrawal in the intensive care unit (ICU). Hypothesis: PB can be safely used adjunctively with BZD in managing severe alcohol withdrawal symptoms in the ICU. Methods: A retrospective review was performed for patients who received PB for severe alcohol withdrawal admitted to the medical ICU from July 2011 to February 2012. Patients were managed with the medical ICU severe alcohol withdrawal protocol which utilizes a step-wise approach with BZD and PB. IRB approval was granted. Data were collected on demographics, time to symptom control, medication doses, ventilator days, ICU length of stay and adverse effects of PB. Results: Of the 28 patients analyzed, the mean values for medication requirements were as follows: average amount of PB administered = 1086 mg + 390 mg, cumulative dose of lorazepam administered in the first 24 hours of protocol initiation = 209 mg + 145 mg and duration of continuous sedative infusions = 97 + 59.8 hours. The average time to symptom control was 1.4 + 0.7 hours. The majority of patients (18/28) requiring mechanical ventilation were for reasons unrelated to PB. Average duration of mechanical ventilation was 5.7 + 2.1 days and average ICU length of stay was 7.9 + 2.4 days. Complications of PB included respiratory failure requiring intubation in 2/28 (7.1%) and hypotension in 3/28 (10.7%) of the study population. Conclusions: PB when used adjunctively with BZD was able to control severe alcohol withdrawal symptoms in the ICU with minimal complications. PB may have a potential role for managing severe alcohol withdrawal symptoms in critically ill patients that are not adequately controlled with BZD. Continued work is directed at comparing outcomes before and after PB use in the medical ICU.

Efficacy and Safety of Pregabalin in the Treatment of Alcohol Withdrawal Syndrome: A Randomized Placebo-Controlled Trial

The objective of this study was to collect preliminary data on the efficacy and safety of pregabalin in attenuating the severity of alcohol withdrawal symptoms during detoxification treatment in alcohol dependence. Forty-two alcohol-dependent patients with an alcohol withdrawal syndrome (AWS) were included in the prospective randomized double-blind placebo-controlled trial during inpatient alcohol detoxification. For 6 days, participants either received pregabalin or placebo according to a fixed dose schedule starting with 300mg/day. Depending on the score of the AWS Scale (AWSS), diazepam was additionally administered as a rescue medication. The primary endpoint was the total amount of diazepam required from Day 2 to 6 of detoxification treatment in each of the two groups. Secondary outcome variables were the difference in AWSS and Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores between Day 2 and 6, tolerability and safety data, drop-out rates as well as changes in the neuropsychological scales. Pregabalin and placebo were equally safe and well tolerated. However, no statistically significant difference was found comparing the total amount of additional diazepam medication required in the two study groups. Pregabalin and placebo also showed similar efficacy according to alterations of scores of the AWSS, CIWA-Ar and neuropsychological scales. The frequency of adverse events and drop-outs did not differ between the both treatment groups. The study demonstrates the relative safety of pregabalin in the treatment of AWS. However, the results do not provide evidence in favor of pregabalin compared with placebo concerning its efficacy in the treatment of AWS.

Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism. The present study tested for associations between alcohol dependence and related traits and 22 single-nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM-III-R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms. No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5' end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p = 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p = 0.000006). These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

Levetiracetam for the Treatment of Alcohol Withdrawal Syndrome

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Oxazepam versus Clomethiazol in Alcohol Withdrawal Treatment

The pharmacological management of the alcohol withdrawal syndrome associated with alcohol dependence is heterogeneous; however, according to the guidelines, clomethiazol is the standard medication in Germany. Benzodiazepines offer another safe possibility of treating alcohol withdrawal. In a retrospective study, alcohol-dependent patients treated either with oxazepam (n = 141) or clomethiazol (n = 357) were assessed with respect to the course of treatment and withdrawal symptoms. The results showed that under oxazepam treatment, there were fewer days with severe alcohol withdrawal symptoms and less severe adverse events, but patients receiving clomethiazol treatment had a more severe course of alcohol dependence. Oxazepam is a safe, efficient and cheap drug for the treatment of alcohol withdrawal symptoms, but controlled studies are needed to compare its effectiveness with that of clomethiazol.

An Open Trial of Gabapentin in Acute Alcohol Withdrawal Using an Oral Loading Protocol

Anticonvulsants are increasingly being advocated for the treatment of acute alcohol withdrawal syndrome (AWS) to avoid the addictive properties of established medications. Because earlier works showed that moderate gabapentin doses were too low to clearly ameliorate severe AWS, we tested a higher gabapentin entry dose. Inpatients (n = 37) with severe alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-AR) score > or =15 points) were given gabapentin 800 mg, and if their symptom score reduced within 2 h, they were termed 'early responders' and were then treated for 2 days with 600 mg gabapentin q.i.d. (i.e. a total of 3200 mg in the first 24 h) before beginning a taper. Twenty-seven (73%) were early responders (baseline CIWA-AR improved from 17.3 +/- 2.6 to 8.0 +/- 3.6 points). In the remaining 10 patients, baseline CIWA-AR deteriorated within 2 h (from 20.1 +/- 4.6 to 21.5 +/- 4.65 points). These patients were switched to clomethiazole (n = 4) or clonazepam (n = 6), which is the usual treatment. Three of the 'early responders' worsened in the next 36 h and were then reclassified and treated as 'non-responders'. Among them, two developed an epileptic seizure. Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS.

Ramadan Fasting Triggering Koro-like Symptoms during Acute Alcohol Withdrawal: A Case Report from Oman

This article describes a case of koro-like symptoms from Oman associated with alcohol withdrawal and illustrates how the socio-cultural practices of Ramadan-fasting affected the patterning and timing of presentation of severe alcohol withdrawal symptoms. The patient was severely distressed by the delusion that his penis had been amputated. The acute anxiety involving this delusion appears to be conceptually and phenomenologically similar to koro.