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K E Bremner

Publications and source records attributed to K E Bremner.

18 recordsLinked to original sources
PubMed2000

Long-term benzodiazepine therapy does not result in brain abnormalities.

Studies on the association between long-term benzodiazepine use and brain abnormalities have yielded conflicting results. The computed tomographic (CT) scans of 20 long-term users of benzodiazepine (65% men; mean age +/- SD [range], 42 +/- 12.1 years [23-59]; mean daily benzodiazepine dose [diazepam equivalents], 19.5 +/- 16.2 mg [2.5-70]; mean cumulative benzodiazepine exposure, 55.2 g [1.8-198]) were compared with 36 age- (+/-3 years) and sex-matched controls. Controls were prospectively recruited from 96 patients attending a neurology clinic and were interviewed to screen for alcohol and substance use disorders and other conditions possibly leading to brain atrophy. Three neuroradiologists blindly assessed each CT scan for atrophy and measured ventricles (V1, V2, V3), sulci, fissures, cisterns, and folia. Reliability among observers ranged from 0.92 to <0.1, in which case deleting one observer increased all reliabilities to >0.45. No difference in atrophy was found between benzodiazepine users and controls. V1 measures were significantly higher for benzodiazepine users than for controls (mean +/- SD, 12.1 +/- 1.3 vs. 11.1 +/- 2.0;p = 0.02), but measures of third and fourth largest sulci were significantly higher in controls than in benzodiazepine users. Right third and fourth largest sulci (mean +/- SD), respectively, were the following: controls, 0.72 +/- 0.4 and 0.74 +/- 0.7; benzodiazepine users, 0.51 +/- 0.3 and 0.46 +/- 0.3 (p < 0.02). Left third and fourth largest sulci, respectively, were the following: controls, 0.77 +/- 0.6 and 0.65 +/-0.3; benzodiazepine users, 0.53 +/- 0.3 and 0.5 +/- 0.3 (p < 0.02). Long-term benzodiazepine therapy does not result in brain abnormalities that can be demonstrated on CT scans.

Adult↗
PubMed2000

Variations in response to citalopram in men and women with alcohol dependence.

OBJECTIVE: To examine the differential effects of citalopram on alcohol consumption in nondepressed women and men with mild to moderate alcohol dependence. DESIGN: Prospective, placebo-controlled study. PARTICIPANTS: Sixty-one subjects (34 men and 27 women). INTERVENTIONS: After a 2-week baseline, subjects were randomly assigned to 12 weeks of citalopram (40 mg per day) (n = 15 women, 16 men) or placebo (n = 12 women, 18 men). All received brief standard psychosocial interventions. OUTCOME MEASURES: Alcohol Dependence Scale, Montgomery-Asberg Depression Scale, Michigan Alcohol Screening Test, State-Trait Anxiety Inventory and daily alcohol intake. RESULTS: Pretreatment sex differences were evident in alcohol consumption, alcohol dependence, alcohol-related problems and on anxiety and depression measures. After treatment, analyses of covariance with depression and anxiety scores as covariates revealed a differential benefit of citalopram for men. Men receiving citalopram reduced average drinks per day by 44%, whereas women exhibited a 27% decrease (p < 0.05). CONCLUSIONS: Men may benefit more than women from citalopram in the treatment of alcohol dependence. These findings highlight the importance of examining sex as a significant variable in evaluating response to pharmacotherapy.

Adult↗
PubMed1998

Safety of ipsapirone treatment compared with lorazepam: discontinuation effects.

OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.

Adult↗
PubMed1997

Using fuzzy logic to predict response to citalopram in alcohol dependence.

INTRODUCTION: The prediction of patient response to new pharmacotherapies for alcohol dependence has usually not been successful with standard statistical techniques. We hypothesized that fuzzy logic, a qualitative computational approach, could predict response to 40 mg/day citalopram and 40 mg/day citalopram with a brief psychosocial intervention in alcohol-dependent patients. METHODS: Two data sets were formed with patients from our studies who received 40 mg/day citalopram alone (n = 34) or 40 mg/day citalopram and a brief psychosocial intervention (n = 28). The output variable, "response," was the percentage decrease in alcohol intake from baseline. Input variables included age, gender, baseline alcohol intake, and levels of anxiety, depression, alcohol dependence, and alcohol-related problems. RESULTS: A fuzzy rulebase was created from the data of 26 randomly chosen patients who received 40 mg/day citalopram and was used to predict the responses of the remaining eight patients. Eight rules related response with depression, anxiety, alcohol dependence, alcohol-related problems, age, and baseline alcohol intake. The average magnitude of the error in the predictions (RMSE) was 2.6 with a bias (ME) of 0.6. Predicted and actual response correlated (r = 0.99; p < 0.001). A fuzzy rulebase was created from the data of 28 randomly chosen patients who received 40 mg/day citalopram and a brief psychosocial intervention and was used to predict the responses of the remaining five patients. Six rules related response with age, anxiety, depression, alcohol dependence, and baseline alcohol intake with good predictive performance (RMSE = 6.4; ME = -1.5; r = 0.96; p < 0.01). CONCLUSIONS: This study indicates that fuzzy logic modeling can predict response to pharmacotherapies for alcohol dependence.

Alcoholism↗
PubMed1997

Pharmacotherapy of late life mood disorders.

The pharmacotherapy of elderly patients with affective illnesses presents clinicians with a number of challenges. Changes associated with normal aging, as well as concomitant medical illnesses and their treatment, can affect the pharmacokinetics and pharmacodynamics of psychotropic drugs. Furthermore, the relative paucity of controlled trials with elderly patients necessitates a reliance on studies done on younger populations, which may be inappropriate. This review attempts to highlight how knowledge of the effects of aging on pharmacokinetics and pharmacodynamics can help clinicians optimize therapy for their older patients with affective disorders.

Aged↗
PubMed1997

Long-acting injectable bromocriptine does not reduce relapse in alcoholics.

Dopamine is one of several neurotransmitters that may mediate alcohol intake and dependence. A randomized, double-blind, placebo-controlled international, multicentre study was conducted to assess the effects of a long-acting injectable preparation of bromocriptine, a dopamine agonist, (Parlodel-LAR) in reducing relapse in 366 moderately/severely dependent alcoholics (DSM-III-R), drinking approximately 200 g alcohol (14.5 standard drinks) per day. After detoxification they were randomized to receive six monthly injections of bromocriptine 25 mg (n = 120), bromocriptine 50 mg (n = 124), placebo (n = 122). Brief psychosocial treatment was allowed. At 6 months there were no significant differences between treatment groups in rates of relapse to any drinking or to drinking > or = 5 days per month and > or = 3 drinks per day. Pre-treatment alcohol intake did not determine response. Efficacy ratings by subjects and investigators and adverse events, reported by 51% of subjects, did not differ between treatments. The results of this large study, in which compliance was enhanced by Parlodel-LAR, do not indicate that bromocriptine is efficacious in the maintenance of abstinence or reduced drinking. Possible reasons for the discrepancy between these conclusions and those of some previous clinical trials, in which bromocriptine was reported to reduce symptoms of alcohol withdrawal and dependence, are discussed.

Adolescent↗
PubMed1996

Research strategies to assess pharmacotherapies for alcoholism.

1. The development and implementation of standardized basic and clinical research strategies is necessary for the discovery and testing of new and effective pharmacotherapies for alcohol dependence. While many animal studies have indicated the involvement of central serotonin, endogenous opioids and dopamine, their exact mechanisms of action have not been fully discerned. One problem is the use of various animal models, making it difficult to compare or replicate results from different laboratories. 2. Once a drug appears to decrease alcohol intake in animals, assessing its effects in humans can be even more challenging. 3. Most drugs were developed and may be even registered for another indication, so Phase I trials must be repeated in heavy alcohol users in case the drug has behavioural, pharmacokinetic or pharmacodynamic interactions with alcohol. 4. Phase II trials, assessing the effects of the drug on alcohol intake, are usually radically different from the animal models: most are long (> 6 months), use varied designs, and accept only abstinence as successful outcome. Moderately dependent alcoholics, who comprise the majority of patients, prefer a goal of nonhazardous drinking. 5. In Phase III multicentre trials, especially international ones, it is almost impossible to control for potentially confounding variables, such as patient characteristics and concomitant psychosocial treatment. 6. Also, research in pharmacotherapies for alcoholism is influenced by external factors such as sources of funding and other resources. Thus, this methodical progression from Phase I to Phase III clinical trials is often abbreviated. 7. The authors developed a brief early Phase II clinical paradigm to assess pharmacotherapies for moderately dependent alcoholics, and conducted 3 studies with the serotonin uptake inhibitors, citalopram and fluoxetine, and a serotonin antagonist, ritanserin. This paradigm, which includes a short (1 to 2 weeks) outpatient phase and two experimental drinking sessions, measures alcohol intake, desire to drink, alcohol's subjective effects, and intoxication. While it may have limited relevance to a goal of abstinence, it is efficient and economical to screen drug effects on alcohol intake and suggest mechanisms (desire to drink, subjective effects). It is also the only human model concordant with results in animals. 8. Development of new pharmacotherapies for alcoholism may benefit from acceptance of both abstinence and moderation of drinking as acceptable treatment goals.

Alcohol Deterrents↗
PubMed1995

Effects of citalopram and a brief psycho-social intervention on alcohol intake, dependence and problems.

Citalopram (C) decreased alcohol intake and desire to drink in short-term (2-4 weeks) studies with no other treatment. We tested the long-term effects of C combined with a brief psycho-social intervention. After a 2-week baseline, mildly/moderately dependent alcoholics (35 males, 27 females) were randomized, double-blind to 12 weeks of C 40 mg/day (n = 31) or placebo (P) (n = 31) and a brief psycho-social intervention with follow-ups at 4 and 8 weeks post-treatment. Alcohol intake was monitored daily and alcohol dependence (ADS) and problems (MAST) were assessed at intake and post-treatment. During the first week, the decrease (%) from baseline daily alcoholic drinks (mean +/- SEM) was greater with C (47.9 +/- 5.1 from 6.5 +/- 0.6) than with P (26.1 +/- 4.2 from 5.8 +/- 0.4) (p < 0.01). However, the 12-week decreases with C (35.1%) and P (38.8%) were similar. There were gender differences within the C group. The males had higher MAST scores at intake (mean +/0 SEM = 10.4 +/- 0.8; n = 15) than the females (6.4 +/- 0.9, n = 16) (p < 0.01) and were slightly heavier drinkers during baseline (7.1 +/- 0.9 vs. 5.9 +/- 0.9 drinks/day, NS). The response to C was greater in males (44% decrease) than females (26%) (p < 0.05) and correlated with MAST scores (r = 0.44, p = 0.01), but not with baseline alcohol intake (r = 0.2, NS). Craving and liking for alcohol and alcohol dependence (ADS) and problems (MAST) decreased similarly with C and P (p < 0.01). Thus, the short-term effects of C were replicated but no long-term effect was detected. Tolerance to citalopram, perhaps through some adaptive neurobiological changes, may have developed. The potential therapeutic use of C as a useful pharmacological adjunct in alcoholics remains to be determined.

Adult↗
PubMed1995

Ritanserin, a central 5-HT2 antagonist, in heavy social drinkers: desire to drink, alcohol intake and related effects.

Ritanserin, a 5-HT2 receptor antagonist, decreased alcohol intake in some, but not all, animal studies and in an open clinical study. We tested the short-term effects of ritanserin in 39 (35 male, four female) heavy social drinkers (consuming at least 28 drinks/week), aged 19-63 years, who were not seeking treatment. After an intake assessment, they received placebo for 7 days in a single-blind baseline. They were then randomly assigned to one of three double-blind treatments for 14 days: ritanserin 5 mg/day (n = 12), ritanserin 10 mg/day (n = 13) or placebo (n = 14). Subjects recorded daily outpatient alcohol intake. Feelings of intoxication and interest, desire, craving and liking for alcohol were rated retrospectively at each weekly study visit. Experimental drinking sessions were conducted after baseline (EDS1) and treatment (EDS2); in each session subjects were offered 18 mini-drinks (total = six standard) and rated their desire to drink, intoxication and mood (POMS). Outpatient results: ritanserin 5 mg/day decreased desire and craving for alcohol (vs. baseline, p < 0.05) but not alcohol intake. Liking of alcohol decreased from baseline with ritanserin 10 mg/day (p = 0.01) and placebo (p = 0.05). Changes in alcohol intake from baseline with ritanserin 10 mg/day (increase, p > 0.05) and placebo (decrease, p > 0.05) were different (p < 0.05). EDS results: in EDS2, desire ratings for the first three mini-drinks were lower after ritanserin 5 mg/day than after ritanserin 10 mg/day (p < 0.05), but the decreases were not statistically significant when EDS1 desire ratings were controlled for. Ritanserin 10 mg/day increased alcohol-induced feelings of intoxication and friendliness, compared with placebo (p < 0.05). Both ritanserin 5 mg/day and 10 mg/day enhanced alcohol-induced decreases in fatigue, compared with placebo (p < 0.05). These results indicate that ritanserin may have differential effects on alcohol intake, desire, craving and liking, intoxication and some of alcohol's effects on mood. However, they suggest that ritanserin has limited efficacy in reducing alcohol intake in heavy drinkers.

Adult↗
PubMed1995

Recent advances in geriatric psychopharmacology.

Psychopharmacotherapy of the elderly must take into account the effects of age-related changes in the structure and function of the brain and various organs. In general, older people are more sensitive than young people to both the therapeutic and toxic effects of psychotropic medications, necessitating lower doses and longer dosage intervals. This holds true for the treatment of 5 major types of psychiatric illness (depression, bipolar disorder, anxiety, psychotic disorders and dementia). The tricyclic antidepressants, although efficacious, inexpensive, and backed by 30 years of experience, are less well tolerated by the elderly than are newer antidepressants such as the selective serotonin uptake inhibitors. Problems with monoamine oxidase (MAO) inhibitors, including orthostatic hypotension and restrictions in diet and other medication use, have been overcome by the advent of reversible selective inhibitors of MAO-A, but the efficacy of these in the elderly has yet to be proven in clinical trials. Lithium remains the mainstay for the treatment of bipolar disorder. However, careful dosing and monitoring of plasma lithium concentrations are required in the elderly due to changes in pharmacokinetics and pharmacodynamics which make older patients very sensitive to the toxic effects of this medication. Similarly, age-related changes in the pharmacokinetics and pharmacodynamics of the benzodiazepines, the most frequently prescribed medications for anxiety in the elderly, result in recommendations for lower doses and preferential use of those agents metabolised by conjugation (e.g. oxazepam). Buspirone, a partial serotonin 5-HT1A-agonist which is better tolerated than benzodiazepines in the elderly, may be used as an alternative. The elderly are extremely sensitive to extrapyramidal adverse effects which the typical antipsychotics (neuroleptics) exhibit to varying extents. The selection of a suitable agent for the treatment of a psychotic disorder should be based upon the adverse effect profile of the drug and the specific symptoms and situation of the patient. The newer atypical antipsychotics, clozapine and risperidone, have yet to be well-studied in the elderly. Dementia, exemplified by Alzheimer's disease, is almost exclusively an illness of the elderly. Only one medication, tacrine, has been approved for its treatment, based on extensive basic research and positive results of several clinical trials. Its long-term benefits have yet to be determined and it has several adverse effects, including a tendency to increase liver enzymes to the extent that the medication has to be discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Serotonin-altering medications and desire, consumption and effects of alcohol-treatment implications.

The relationship between serotonin neurotransmission and alcohol consumption (AC) was first determined in preclinical studies. AC generally increases following treatments which decrease serotonin activity, and levels of 5-HT and metabolites are low in some brain regions of alcohol-preferring rats. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled trials, SUI consistently decreased short-term (2-4 weeks) AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Some subjects decreased AC by up to 60%. The effects of SUI on AC were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI decreased desire to drink and liking for alcohol, suggesting a mechanism of action, to be considered in the development of treatments to reduce AC and prevent relapse. However, while an adjunctive brief psychosocial intervention enhanced the short-term effect of a SUI, the long-term (12-week) effects of SUI and placebo were similar. Other drugs acting on the 5-HT system have been tested in humans, but results are inconclusive. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). Ritanserin, a 5-HT2 antagonist, reduced desire to drink and prevented relapse in a small (n = 5) study, and there was some indication that it reduced desire to drink and enhanced alcohol effects without reducing AC, in another study. The therapeutic potential of these medications is being studied. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for AC.

Alcohol Drinking↗
PubMed1994

Fluoxetine attenuates alcohol intake and desire to drink.

Several serotonin uptake inhibitors, including the long-acting fluoxetine, have been found to decrease alcohol intake in moderately dependent alcoholics. While the mechanism of their effect is not fully elucidated, a previous study with citalopram indicated that decreased desire to drink may be an important factor. Therefore, we tested fluoxetine effects on alcohol intake and desire to drink in a placebo-controlled study. Subjects, recruited by advertisement, were mildly/moderately dependent alcoholics (12 male, four female, aged 19-59 years, healthy, non-depressed) who did not believe they had a drinking problem and were not requesting treatment. After a 1 week baseline they received, single-blind, 2 weeks placebo followed by 2 weeks fluoxetine 60 mg/day. As out-patients, subjects recorded daily standard drinks (13.6 g ethanol) and rated interest, desire, craving and liking for alcohol biweekly. Each out-patient period was immediately followed by a double-blind experimental drinking session. Out-patient daily drinks slightly decreased during fluoxetine to 6.6 +/- 0.9 (mean +/- S.E.M.) compared with during placebo (7.16 +/- 0.95, p = 0.07, N.S.) and baseline (7.18 +/- 1.0, p > 0.1, N.S.). Desire, interest and craving for alcohol decreased during fluoxetine vs placebo baseline (p < 0.05), but not vs placebo. Appetite loss and decrease in food intake (p < 0.01, fluoxetine vs placebo) correlated with each other (r = 0.91, p < 0.01) but neither correlated with decrease in alcohol intake (appetite: r = 0.26, N.S.; food intake: r = 0.22, N.S.). Weight loss occurred during fluoxetine (p < 0.05 vs placebo) but did not correlate with decrease in alcohol intake (r = 0.1, N.S.). In the experimental drinking sessions after placebo and fluoxetine treatments subjects rated their desire for each of 18 mini-drinks (each one-third of a standard drink) offered at 5 min intervals. Fluoxetine decreased desire to drink throughout the sessions; both mean and maximum desire ratings were lower after fluoxetine than after placebo (ANOVA, p < 0.05). Therefore, fluoxetine seems to have a robust effect on decreasing desire for alcohol. We propose that in the absence of intention by subjects to reduce drinking, their habitual drinking patterns mitigated against reduced consumption in the out-patient phase. However, fluoxetine could be a useful adjunct for patients in a treatment context who are motivated to reduce their drinking.

Adult↗
PubMed1994

Treatment of alcohol withdrawal syndrome.

Treatment of the alcohol withdrawal syndrome is the first step towards the rehabilitation of alcohol-dependent patients. The objectives of treatment are relief of symptoms, prevention of complications and a smooth transition into a long-term rehabilitation programme. Recently, progress has been made in the clinical management of the alcohol withdrawal syndrome through standardization of the assessment using the CIWA-A scale and frequent monitoring of clinical findings, recognition of the efficacy of non-pharmacological interventions (i.e. standardized supportive care) and simplification of pharmacotherapy by optimizing the use of long-acting benzodiadepines via a loading dose technique. Benzodiazepines, because of their cross-tolerance with ethanol, wide margin of safety and low potential for physical dependence and tolerance, are very effective and are the drugs of choice for the treatment of the alcohol withdrawal syndrome.

Adrenergic beta-Antagonists↗
PubMed1993

Clinical pharmacology of serotonin-altering medications for decreasing alcohol consumption.

Variations in serotonin neurotransmission influence alcohol consumption (AC). Levels of 5-HT and metabolites are low in some brain regions of alcohol preferring rats and in CSF of alcoholics. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled clinical trials, SUI have consistently decreased AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Effects were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI also decreased desire to drink and liking for alcohol, thus suggesting a mechanism for effects. Other drugs acting on the 5-HT system have been tested in humans, but results are difficult to interpret. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased alcohol craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). The therapeutic potentials of these medications are being studied. For example, SUI effects on AC were enhanced by a brief psychosocial intervention. Since SUI decrease urge to drink, they may be suitable pharmacological adjuncts in relapse prevention strategies. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for reducing AC.

Alcohol Drinking↗
PubMed1993

Behavioural correlates of alcohol intoxication.

Alcohol is used in most cultures despite knowledge of the physical, psychological and social problems associated with its abuse. Behavioural impairment is a function of several factors, including blood alcohol concentration (BAC) and the rate of alcohol metabolism by alcohol dehydrogenase and the microsomal ethanol-oxidizing system. Their availability and activity depend upon alcohol use history, ethnicity, other drug use and gender. Adverse social consequences related to alcohol intoxication include impaired driving, acts of aggression and violence towards self and others, and various types of accidents. About 40% of all fatal traffic accidents in Canada and the US in 1986-1987 were alcohol-related. Similar statistics have been reported in the UK and Europe (e.g. Sweden). The risk of a fatal car accident increases exponentially with a driver's BAC, prompting recommendations to lower the legal BAC limit for driving and piloting aircraft. Risks of falls, drownings, and fires and burns may also be increased by alcohol intoxication. At least 22% of work-related accidents may have involved alcohol use. These data are probably conservative estimates as under-reporting of alcohol use is likely. Alcohol facilitates aggressive behaviours, but it is difficult to separate the pharmacological effect from psychosocial effects or some other common factor (e.g. low CSF levels of the serotonin metabolite 5-H1AA have been reported in alcoholics, suicide attempters, violent offenders). In addition, alcohol interacts with other drugs to increase or decrease their behavioural and therapeutic effects. An acutely high BAC inhibits the metabolism of other CNS depressants (e.g. benzodiazepines), but long-term alcohol use increases the metabolism of most drugs. A potential amethystic agent, to block or reverse alcohol's effects, has been identified in preclinical studies (Ro15-4513, an imidazobenzodiazepine). Some clinical studies indicated that naloxone, lithium, ibuprofen, zimeldine and catecholamine agonists may reduce ethanol-induced behavioural or cognitive effects but the results have not been consistently replicated. More research is needed to determine the potential clinical use of amethystic agents and other pharmacotherapies in the prevention and treatment of problem behaviours associated with alcohol abuse and intoxication.

Accidents↗
PubMed1992

Citalopram decreases desirability, liking, and consumption of alcohol in alcohol-dependent drinkers.

In previous studies serotonin uptake inhibitors such as citalopram decreased alcohol consumption in alcoholics. The mechanism of the effect is not fully understood. This study tested the hypothesis that it is mediated by changes in desire to drink and alcohol effects. After a 1-week baseline period, subjects (13 men and three women; aged 26 to 69 years; healthy, nondepressed, alcohol-dependent drinkers [mean, 6.6 drinks per day]) were randomized in a double-blind fashion to receive 40 mg/day citalopram and placebo for 1 week each, separated by a 1-week washout period. Daily standard alcoholic drinks (13.6 gm ethanol), nonalcoholic drinks, and tobacco use were recorded; evening urine samples were taken; and interest, desire, craving, and liking for alcohol were rated. Medical status, depression, and anxiety were assessed weekly, but no other treatment or advice was given. Daily alcoholic drinks significantly decreased during citalopram treatment (mean +/- SEM = 4.6 +/- 0.6) compared with placebo (5.7 +/- 0.8; p = 0.01), and the average decrease was 17.5%. Percentage of days abstinent increased during citalopram administration (27.7% +/- 5.7%) compared with placebo (15.5% +/- 3.7%; p less than 0.01). Citalopram decreased interest, desire, craving, and liking for alcohol (all p less than 0.05). There was clear internal validation of these measures in that variations in each correlated with alcohol consumption (all r greater than 0.5, p less than 0.05). Nonalcoholic drinks, self-reports of cigarettes smoked (daily smokers), and body weight did not change significantly. In experimental bar sessions, after the citalopram and placebo periods, subjects were required to consume as many of 18 minidrinks as possible (equivalent to six standard drinks) at 5-minute intervals. Subjects rated their desire for alcohol, intoxication, and mood. Citalopram had no significant effects on the desirability of alcohol or subjective feelings of intoxication. The findings indicate that serotonin uptake inhibitors may act by decreasing the urge to drink and the reinforcing effects of alcohol. Also, a naturalistic outpatient trial is a sensitive, simple, and economic procedure for detecting these drug effects.

Adult↗
PubMed1992

Eating disorders and alcohol abuse in women.

Theory and empirical evidence support a relationship between the eating disorders (anorexia nervosa and bulimia nervosa) and alcoholism. This study examines the co-prevalence and characteristics of these disorders among two populations of adult women: those presenting for treatment of alcoholism and those referred to a specialized eating disorders programme. Twenty-two of 73 females (30.1%) with alcohol problems met psychometric cut-off scores for eating disorder, while 25 of the 96 eating disorder females (26.9%) gave psychometric evidence of alcohol dependence. These rates exceed general population norms. While certain clinical and psychometric features distinguish subgroups with both disorders, the basis for co-prevalence and the implications for treatment are unknown.

Adult↗