Uncomplicated Alcohol Withdrawal Research Articles

Abstract- Poster

Introduction:Alcohol dependence is a prevalent health problem in India with 12-month prevalence of 2.1%. Patients with alcohol withdrawal can present with symptoms ranging from mild to severe withdrawals including withdrawal seizures and delirium tremens with significant mortality. Thus it will be beneficial to identify patients at risk for severe withdrawals for appropriate management. Previous studies have correlated drinking pattern with withdrawal severity but there are limited studies comparing social factors to the severity of withdrawal symptoms. Studies correlating age with withdrawal severity showed conflicting results- with one study showing higher severity and prolonged withdrawals in younger patients while another study showing more severity in older patients. In another study bivariate analysis showed patients who were African-American, unemployed, and homeless were more likely to develop delirium tremens. Thus we propose this study to assess financial status, legal status, employment status and social relationships in patients with complicated and uncomplicated alcohol withdrawal.Aim:To assess financial status, legal status, employment status and social relationships in patients with complicated and uncomplicated alcohol withdrawal.Methodology:Study design:hospital-based cross-sectional study.Universe of Study:All adult patients admitted to any psychiatry unit for acute management of alcohol withdrawal.Study population:Adult patients admitted to Department of Psychiatry and Drug De-addiction Centre, LadyHardinge Medical College & Smt. S. K. Hospital, New Delhi for acute management of alcohol withdrawal.Study population comprised of three groups-1. Patients with Alcohol withdrawal seizures (AWS)2. Patients with Alcohol withdrawal delirium tremens (AWDT)3. Patients with alcohol withdrawal uncomplicated (AWU)Study Duration:18 Months (November 2017 to April 2019)Data collection period:12 months (November 2017 to December 2018)During the study period, all adult patients admitted for acute management of alcohol withdrawal were assessed for inclusion in study. Those fulfilling selection criteria and willing to give consent were recruited in the study. Participants were recruited only after they were conscious, oriented and had minimal alcohol withdrawal signs/symptoms (CIWAAr <10) to ensure that they are amenable for interview. Patients were assessed for various risk factors, the social factors concerned with this study were assessed using Alcohol severity Index(ASI). Alcohol Severity Index(ASI) assessed drug and alcohol use, psychiatry and medical comorbidity and effect of alcohol use on their medical status, employment status, legal status and family relationship.Results and conclusion:The following study reveals significant differences in the legal status, financial status, employment status and social relationships among patients of complicated and uncomplicated alcohol withdrawal. However, within the two groups of complicated alcohol withdrawal, that is, alcohol withdrawal delirium tremens (AWDT) and alcohol withdrawal seizures (AWS) there were not much significant differences in the given domains assessed. The data is large and detailed results along with conclusion will be part of final presentation.

On the importance of nonionic osmotically active substances of the blood for the pathogenesis of severe alcoholic delirium

The main non-ionic osmotically active substances in blood serum are glucose and urea. The aim of the study was to study the changes in the water-osmotic state caused by non-ionic (organic) substances in patients with delirium tremens (DT) and in a state of alcohol withdrawal, and to assess their influence on the blood leukocyte composition and the clinical manifestations of the disease. A total of 747 men were examined in a state of alcohol withdrawal; of these, 450 people had manifestations of severe DT (F10.43), 213 — “classic” DT (F10.4), 84 patients had signs of alcohol withdrawal with somatic and vegetative manifestations (F10.3). To quantitatively describe the composition of leukocytes, an index equal to the neutrophil to lymphocyte ratio (NL-R) was used. We were able to mathematically describe a previously unknown quantitative relationship between the osmolarity level due to non-ionic osmotically active substances in blood serum and the NL-R values. It is expressed by the following formula: G + U = 1 mmol/L (log2 NL-R + 9.5), where G — concentration of glucose in blood serum, mmol/l; U is the concentration of urea in the blood serum, mmol/l; NL-R — neutrophil-lymphocyte index, units; 1 mmol/l — coefficient providing the required dimension of the result; log2 — logarithm with base 2; 9.5 is a constant whose size depends on the selected system of units. It was found that regular changes in blood osmolarity in patients with alcohol withdrawal and DT, both at the stage of initiation of psychosis and during the progression of the disease and the formation of severe DT, occur mainly, and maybe completely, due to non-ionic osmotically active substances. Glucose and urea have their unique role in the formation of homeostasis disorders during the development of the disease in individuals with uncomplicated alcohol withdrawal, as well as DT of varying severity.

PHENOBARBITAL VS BENZODIAZEPINES FOR ALCOHOL WITHDRAWAL MANAGEMENT IN MEDICAL ICU: PRELIMINARY RESULTS OF PRE-POST PROTOCOL STUDY

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: Phenobarbital (PB) has been suggested as an alternative to benzodiazepines (BZD) for alcohol withdrawal (AW) management. Few studies have examined the efficacy of different PB regimens for the management of AW in the medical intensive care unit (ICU). METHODS: Retrospective, pre-post protocol, cohort study for patients with AW syndrome admitted to the medical ICU at Cleveland Clinic, Fairview Hospital, during the period from January 2019 through April 2021. Historically a symptom-triggered BZD based protocol utilizing CIWA-Ar has been employed. In September 2020, a PB-based protocol was implemented for AW management. The protocol included PB 260 mg intravenous (IV) followed by 130 mg IV repeated doses every 15 - 30 minutes as needed up to a total of 15 mg/kg (ideal body weight) to maintain CIWA-Ar score below 10. We included adult patients who were admitted to medical ICU primarily for AW management. We excluded patients intubated before ICU admission or the presence of a serious medical or surgical diagnosis that would have otherwise dictated admission to the ICU. The primary outcome is ICU length of stay (LOS). Secondary outcomes include hospital LOS, intubation rate, the number of adjunctive agents, medication side effects, requirement for sitter, restraining, ICU readmission and mortality rate. RESULTS: A total of 270 patients were screened, of which only 62 patients with AW were enrolled, 15 in the PB arm and 47 in the BZD arm. Overall, 32% of all patients presented as uncomplicated AW, 42% as delirium tremens, and 13% as AW seizure. No significant differences in basic characteristics between arms were observed. Compared to BZD arm, patients who received PB had significant shorter ICU LOS (median [IQR], 28 hours [24 – 37] vs 59 hours [34 – 115]; P=<.001) and hospital LOS (median [IQR] 4 days [3 – 5] vs 6 days [4 – 10]; P=.006). PB arm required less number of adjunctive agents to control AW (1 [0 – 1] vs 3 [2 – 4]; p=<.001) including less utilization of dexmedetomidine (1 [7%] vs 22 [47%]; p=<.001). None of the patients in the PB arm required restraint use (0 vs 27 [57%]; p=<.001). No significant difference between arms with regards to medication side effects, sitter requirement, ICU readmission, intubation rate, and mortality rate. CONCLUSIONS: The initial findings from our study are suggesting that our proposed PB-AW management protocol is associated with shorter ICU and hospital LOS. It may be considered as an effective and safe alternative to BZD. CLINICAL IMPLICATIONS: Our results will help in evolving AW management guidelines in ICU. DISCLOSURES: No relevant relationships by Saira Afzal, source=Web Response No relevant relationships by BASSEL AKBIK, source=Web Response No relevant relationships by Dina alayan, source=Web Response No relevant relationships by Sura Alqaisi, source=Web Response No relevant relationships by Mahmoud Alwakeel, source=Web Response No relevant relationships by Ellen Immler, source=Web Response No relevant relationships by Talha Saleem, source=Web Response No relevant relationships by Xiaofeng Wang, source=Web Response

Pattern of alcohol withdrawal syndrome and its clinical correlates

Introduction and Aim: Management strategies of Alcohol Withdrawal Syndrome could be optimized if patients with greater risk are identified early and treated aggressively. Studying the pattern and predictors of alcohol withdrawal syndrome was the main objective of our study.&#x0D; &#x0D; Materials and Methods: A total of 100 consenting male patients in the age group of 18-60 years diagnosed with alcohol dependence and uncomplicated alcohol withdrawal undergoing in-patient detoxification in tertiary care center in north India were included in the study. A semi structured proforma was used to collect socio-demographic data, Alcohol Use Disorders Identification Test (AUDIT) was used as screening tool and Clinical Institute Withdrawal Assessmentfor Alcohol-revised (CIWA- Ar) was used to assess severity of withdrawal.&#x0D; &#x0D; Results: Symptoms like difficulty in orientation, seizures and hallucinations were relatively specific for severe AWS, while tremors and anxiety were common to all the patients and were non-specific for predicting severity of AWS. The severity of AWS symptoms correlated significantly with increasing age, duration of alcohol use and AUDIT score.&#x0D; &#x0D; Conclusion:We concluded that increasing age, longer duration of alcohol use, higher AUDIT score and symptoms related to hallucinations, orientation and seizure are linked to severe alcohol withdrawal. Prior knowledge of these predictors will help to identify the patients at risk of severe alcohol withdrawal so that individual care can be enhanced.

Clinical and metabolic predictors for delirium tremens

To search for objective diagnostic criteria for the development of delirium tremens (DT) based on physiological and metabolic parameters. The total number of patients was 506, including 393 patients with DT and 113 patients with uncomplicated alcohol withdrawal syndrome (UAWS). Twenty clinical and metabolic indicators were analyzed statistically using comparison of means, logistic regression and ROC-analysis. Hyponatremia, thrombocytopenia and tachycardia are most prognostically significant indicators, changes in which are observed in the development of DT. These indicators can serve as the basis for objective diagnosis of alcohol withdrawal syndrome complicated by delirium.

A Study of Patterns of Platelet Counts in Alcohol Withdrawal.

Aims:This study aimed to evaluate the patterns of platelet counts during the course of alcohol withdrawal and its relationship if any with liver enzymes.Methodology:Forty consecutive patients, with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-fourth edition, Text Revision criteria, willing for a 10-day inpatient detoxification program and presenting within 12 h of the last consumption of alcohol were recruited in the study. Details about the diagnosis and alcohol consumption patterns were assessed with a detailed psychiatric interview. After admission, routine investigations (complete blood counts [CBCs] and liver function tests) were sent and records were kept. CBC was sent for platelet counts on the 2nd, 4th, 6th, 8th, and the 10th day of alcohol withdrawal.Results:Nearly 40% of the patients developed delirium tremens (DT group) and rest had an uncomplicated alcohol withdrawal (ND group). Platelet counts at baseline and all the 4 days of collection were significantly lower in DT group than the ND group. Platelet counts increased gradually from baseline till 10th day of alcohol withdrawal, mean increase in platelet counts being 88.61 ± 11.60% (median: 61.11%, range [23.41–391.23%]). Platelet counts in 63% of the patients showed a drop on the 4th day of withdrawal before rising till the 10th day of alcohol withdrawal. Platelet counts were not affected by liver enzymes or other alcohol consumption patterns.Conclusions:Transient thrombocytopenia and reverse thrombocytosis during alcohol withdrawal are associated with an initial drop in platelet counts. The synchrony between the drop and the onset of DT needs to be evaluated.

A Randomized Comparison of Lorazepam and Chlordiazepoxide in Patients With Uncomplicated Alcohol withdrawal

A Randomized Comparison of Lorazepam and Chlordiazepoxide in Patients With Uncomplicated Alcohol withdrawal

A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome

BackgroundAlcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. MethodsSixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. ResultsBoth baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. ConclusionThe present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative.

Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in Medically Ill Inpatients: A New Scale for the Prediction of Complicated Alcohol Withdrawal Syndrome.

The prevalence of alcohol use disorders (AUDs) among hospitalized medically ill patients exceeds 40%. Most AUD patients experience uncomplicated alcohol withdrawal syndrome (AWS), requiring only supportive medical intervention, while complicated AWS occurs in up to 20% of cases (i.e. seizures, delirium tremens). We aimed to prospectively test and validate the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), a new tool to identify patients at risk for developing complicated AWS, in medically ill hospitalized patients. We prospectively considered all subjects hospitalized to selected general medicine and surgery units over a 12-month period. Participants were assessed independently and blindly on a daily basis with PAWSS, Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) and clinical monitoring throughout their admission to determine the presence and severity of AWS. Four hundred and three patients were enrolled in the study. Patients were grouped by PAWSS score: Group A (PAWSS < 4; considered at low risk for complicated AWS); Group B (PAWSS ≥ 4; considered at high risk for complicated AWS). The results of this study suggest that, using a PAWSS cutoff of 4, the tool's sensitivity for identifying complicated AWS is 93.1% (95%CI[77.2, 99.2%]), specificity is 99.5% (95%CI[98.1, 99.9%]), positive predictive value is 93.1% and negative predictive value is 99.5%; and has excellent inter-rater reliability with Lin's concordance coefficient of 0.963 (95% CI [0.936, 0.979]). PAWSS has excellent psychometric characteristics and predictive value among medically ill hospitalized patients, helping clinicians identify those at risk for complicated AWS and allowing for prevention and timely treatment of complicated AWS.

A Comparative Study of Fixed Tapering Dose Regimen versus Symptom-triggered Regimen of Lorazepam for Alcohol Detoxification

The study aimed at comparing the fixed tapering dose and the symptom-triggered regimens of lorazepam for alcohol detoxification. We carried out a prospective, randomized, double blind controlled trial involving 63 consecutive consenting male patients admitted with diagnosis of uncomplicated alcohol withdrawal. The patients were randomized into two groups based on the type of lorazepam dosage: symptom-triggered (n = 33) and fixed tapering dose regimens (n = 30). Alcohol withdrawal symptoms were rated on CIWA-Ar (Clinical Institute Withdrawal Assessment - Alcohol revised). The main outcome measures were the total amount and duration of lorazepam treatment and the incidence of adverse events or complications. The mean lorazepam dose administered in the symptom-triggered group was significantly lower than in the fixed tapering dose group (9.5 versus 19.9 mg, P < 0.001) and for a significantly shorter duration of time (47.8 versus 146 h, P < 0.001) with more significant results for higher initial CIWA-Ar scores. There were no significant differences between both the groups in terms of the incidence of complications like seizures or delirium tremens. Symptom-triggered lorazepam treatment for alcohol withdrawal resulted in administration of lower total doses of medication for a shorter duration of treatment and was as safe as the fixed tapering dose.

Clinical manifestations of complicated alcohol withdrawal and uncomplicated alcohol withdrawal: a comparative study

Substantial variability exists in the evolution of symptoms during alcohol withdrawal. This study is an endeavour to compare the distinction between complicated and uncomplicated alcohol withdrawal syndrome (AWS) with regards to their clinical manifestations. This study was a prospective hospital-based comparative study conducted at the Central Institute of Psychiatry, India. The total sample consisted of 60 male patients of alcohol dependence syndrome who had taken their last drink within 6 h before admission. Measures such as socio-demographic and clinical data sheet, Windsor Clinic Alcohol Withdrawal Assessment Scale and AWS Scale were applied on selected patients. Patients with complicated withdrawal syndrome had symptoms such as withdrawal seizures, delirium tremens along with psychological symptoms. While patients having uncomplicated withdrawal syndrome predominantly showed psychological symptoms such as anxiety, restlessness and agitation accompanied by tremor. Anxiety, tremor and agitation are th...

Successful Use of Oxazepam in the Treatment of Delirium Tremens

To the Editor: Delirium tremens is a manifestation of alcohol withdrawal syndrome that occurs in about 5% of patients and has a high mortality rate.1 The withdrawal state involves reduced brain γ-aminobutyric acid (GABA) levels and GABA receptor sensitivity and activation of glutamate systems, which leads to neuronal overactivity in the absence of alcohol.2,3 Longer-acting benzodiazepines such as diazepam with active metabolites are preferred over shorter-acting ones for detoxification because they are associated with a lesser chance of recurrent withdrawal.4 Benzodiazepines with a short half-life (eg, oxazepam and lorazepam) have potential benefit for patients with liver disease, which is a common comorbid medical condition in alcohol-dependent individuals. The efficacy and safety of the short-acting benzodiazepine oxazepam in alcohol withdrawal–related delirium are not clear. To our knowledge, this is the only case reported in the literature of the use of oxazepam in the treatment of delirium tremens. Case report. Mr A, a 42-year-old man, presented to the psychiatric emergency services with a 15-year history of alcohol use. He met DSM-IV-TR criteria for alcohol dependence with a history suggestive of craving, tolerance, salience, loss of control, and withdrawal symptoms for the past 5 years. After being abstinent from alcohol for 4 days, he had developed symptoms characterized by disorientation to time, place, and person; tactile hallucinations; severe tremulousness; and autonomic instability signs. On the day of admission in July 2010, the patient’s Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar)5 score was 42, corresponding to severe withdrawal. Mr A did not have a history of seizures, loss of consciousness, or significant head injury. Neurologic examination revealed no focal deficits, and there were no signs or symptoms suggestive of neuroinfection. Computed tomographic scanning of the brain was normal except for mild cerebral atrophy. Biochemical investigations revealed abnormal liver function values, while the results of other tests including sugar levels, renal function parameters, and electrolyte levels were within normal range. In view of the patient’s liver function values, we started treatment with the shorter-acting benzodiazepine oxazepam 90 mg/d in 3 divided doses of 30 mg each, with the dose tapered every 3 days. With tapering doses of oxazepam, Mr A showed improvement, with reduction of CIWA-Ar score to less than 10 by the fifth day. In this case, oxazepam, which is a shorter-acting benzodiazepine, was used to treat delirium tremens. Most benzodiazepines have active metabolites, and hence their duration of action seems to exceed their plasma half-life.4 Oxazepam has no cytochrome P450 interactions and no active metabolites. It does not have initial euphoric effects because of its slow resorption, and therefore there is less risk of misuse. The half-life of oxazepam is 4–10 hours, and it has a better therapeutic window compared to other short-acting agents. Oxazepam has been used in the treatment of uncomplicated alcohol withdrawal syndrome.6 Safety data on the use of oxazepam in medical emergencies such as delirium tremens would be of benefit in cases with associated impaired liver functioning. The outcome of this case, as well as the pharmacokinetics of oxazepam, suggests that it may be a good alternative to lorazepam for patients with significant comorbid hepatic illnesses.

A Randomized, Double-Blind Comparison of Lorazepam and Chlordiazepoxide in Patients With Uncomplicated Alcohol Withdrawal

For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries. One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward. One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug. With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal.

Postgraduate corner: Continuing medical education: Psychopharmacology

Byline: Chittaranjan. Andrade CME Questions A) Fibromyalgia is a poorly understod syndrome that is characterized by chronic, widespread musculoskeletal and joint pain. There are often multiple tender nodules present in specific anatomical loci, such as over the shoulders and back. Common accompanying symptoms include stiffness, fatigue, mood disturbance, and insomnia. Affected patients suffer from pain-related disability and impaired functioning in everyday life. With this background, mark True or False against each of the following statements: *Escitalopram is an approved treatment for fibromyalgia. *Duloxetine 120mg/day is more effective than duloxetine 60mg/day in the treatment of fibromyalgia. *An adequate trial of duloxetine for fibromyalgia should last at least 4-6 months. *In addition to attenuating measures of pain, duloxetine improves functional outcomes in fibromyalgia. *Fibromyalgia treatments have demonstrated efficacy in long-term as well as short-term management. B) Tamoxifen is prescribed for various indications to women with estrogen receptor-positive breast cancer. These women may require antidepressant medication for concurrent depression; or for the treatment of hot flushes and other symptoms of artificial menopause. With this background, mark True or False against each of the following statements: *Tamoxifen is metabolized by CYP3A4. *Mirtazapine should be preferred to duloxetine over depressed women who are receiving tamoxifen. C) Benzodiazepines have anxiolytic and anticonvulsant properties and are cross-tolerant with alcohol. They are therefore prescribed during alcohol withdrawal to reduce the severity of the withdrawal syndrome and to reduce the risk of withdrawal seizures. Diazepam and chlordiazepoxide are traditionally preferred for this indication because both have long half-lives of approximately 1-2 days, each; their levels in blood therefore tend to remain uniform across the course of the day, and drug withdrawal difficulties are fewer. However, they are metabolized by demethylation and hydroxylation and have active metabolites; as a result of these pharmacokinetic properties, they may accumulate, and mask or even precipitate hepatic encephalopathy in patients with alcoholic liver disease. With this background, mark True or False against each of the following statements: *For important theoretical reasons, if alcoholic liver disease is present or suspected, lorazepam should be avoided in patients who are being withdrawn from alcohol. *Clinical data exist to suggest that lorazepam may be effective in the management of uncomplicated alcohol withdrawal. View Answer CME Answers A) Fibromyalgia Answers: 1. False; 2. False; 3. False. 4. True; 5. True. *Citalopram appears ineffective in patients with fibromyalgia[sup] [1],[2] and, to judge from a PubMed search conducted on June 14, 2009, escitalopram has not been studied for this indication. Pregabalin,[sup] [3],[4] duloxetine[sup] [5],[6] and milnacipran[sup] [7],[8] are USA Food and Drug Administration-approved treatments for fibromyalgia. However, as serotonergic and noradrenergic mechanisms have both been described to mediate pain relief,[sup] [9] it is likely that most antidepressants, especially dual-acting drugs such as the tricyclic antidepressants, could be effective treatments for fibromyalgia. In other words, antidepressant efficacy against fibromyalgia could be a class action. *Short-term, randomized, double-blind, placebo-controlled clinical trials of duloxetine (60 or 120mg/day) in patients with fibromyalgia found that the 120mg/day dose was not better than the 60mg/day dose.[sup] [10],[11] A 1-year randomized controlled study also found no advantage with the higher dose.[sup] [12] For the majority of patients, therefore, 60mg/day is likely an adequate dose; whereas some patients may indeed require a higher dose, it should be kept in mind that the higher dose could increase the adverse effect burden. …

Effects of Fluoxetine, Indomethacine and Placebo on 3α, 5α Tetrahydroprogesterone (THP) Plasma Levels in Uncomplicated Alcohol Withdrawal

SummaryObjective: The purpose of this study was to investigate the effects of fluoxetine (F) and indomethacine (I), two drugs that regulate the synthesis of the GABAergic neurosteroid 3α, 5α tetrahydroprogesterone (allopregnanolone, THP) on THP plasma levels and on symptoms of anxiety and depression in alcoholics during ethanol withdrawal.Method: Patients who met DSM-IV criteria for alcohol abuse were randomly assigned to treatment with F (40 mg/day) plus misoprostol (M) (500 mg/day) or I (100 mg/day) plus M or placebo (PL) plus M. Patients were rated with the Hamilton Anxiety (14-HAS) and Depression (17-HDS) scales on days 1, 5, 7, 15 and 28 of ethanol withdrawal and with a Visual Analogue Scale for Depression (VASD) and a Visual Analogue Scale for Anxiety (VASA) on days 1, 2, 4, 5, 7, 15 and 28 of withdrawal. On the same days a plasma sample was collected to measure the concentrations of THP by means of a very sensitive gas chromatographic mass spectrometric method.Results: During withdrawal at days 1, 2, 4 and 5, THP plasma values were lower and symptoms of anxiety and depression were significantly higher compared to the late withdrawal phase at days 15 and 28. In the F or I treatment, the depression and anxiety score, measured by VASD and VASA, decreased significantly at day 5-7 whereas THP plasma levels significantly increased compared to PL condition.Conclusions: Treatment of alcohol withdrawal either with F or I reduced the extent of anxiety and depression and normalised THP plasma levels that were decreased during withdrawal.

Divalproex in the Treatment of Alcohol Withdrawal

The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group × CIWA-Ar score interaction [F(8,72) = 2.57, p ≤. 01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p ≤. 001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal.

Clorazepate (Tranxene) effectiveness in the treatment of uncomplicated alcohol withdrawal. A comparison with diazepam treatment in a randomized, controlled study: B. Habrat, K. Bożejko, J. Charewicz, J. Waniek. Department of Prevention and Treatment of Substance Abuse, Institute of Psychiatry and Neurology, Al. Sobieskiego 1/9, 02–957 Warszawa, Poland

Clorazepate (Tranxene) effectiveness in the treatment of uncomplicated alcohol withdrawal. A comparison with diazepam treatment in a randomized, controlled study: B. Habrat, K. Bożejko, J. Charewicz, J. Waniek. Department of Prevention and Treatment of Substance Abuse, Institute of Psychiatry and Neurology, Al. Sobieskiego 1/9, 02–957 Warszawa, Poland

Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative study with propranolol and diazepam

Alcohol withdrawal is associated with a decrease in γ-aminobutyric acid neurotransmission. This explains the efficacy of benzodiazepines. However, an increase in adrenergic activity may also play a part in alcohol withdrawal symptoms, suggesting a potential efficacy of beta-blocking drugs. A double-blind comparative study of propranolol and diazepam was carried out in 28 patients suffering from moderate uncomplicated alcohol withdrawal. Patients were treated for 15 days with either 75 mg of propranolol or 30 mg of diazepam. The results show that both drugs at the dosages used are equipotent in reducing physical withdrawal symptoms and anxiety symptoms. This suggests that most likely the central as well as the peripheral effects determine the clinical usefulness of propranolol in the management of alcohol withdrawal. However, propranolol is ineffective in preventing major motor seizures, suggesting that different neurobiological mechanisms underlie the alcohol withdrawal symptoms. beta-blocking drugs / propranolol / alcohol withdrawal

Characterization of DSM-III-R Criteria for Uncomplicated Alcohol Withdrawal Provides an Empirical Basis for DSM-IV

The DSM-III-R criteria for uncomplicated alcohol withdrawal require the presence of coarse tremor of the hands, tongue, or eyelids plus one of a number of other clinical features. We examined the validity and other characteristics of these items in 137 patients in pure alcohol withdrawal using the reliable and valid Clinical Institute Withdrawal Assessment for Alcohol. The DSM-III-R items of hand tremor amplitude, nausea or vomiting, headache, transient hallucinations, autonomic hyperactivity (increased pulse or sweating), and anxiety correlated significantly with total score and significantly indicated clinical severity. Addition of an "agitation" item improved the correlation. The diagnostic accuracy is greater than 95% if any two or more items are present. The number of positive items, of which tremor can be one, to grade clinical severity shows that a score of 2 indicates "very mild"; 3, "mild"; 4, "moderate"; and 5, "severe.". We propose that an Alcohol Withdrawal Diagnostic Inventory and a DSM-III-R-compatible brief Clinical Institute Withdrawal Assessment for Alcohol are useful for clinical research, where graded symptom characterization is needed. Our data may be helpful in the development of criteria for DSM-IV.