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Home , Disulfiram, Ondansetron, Ritanserin

and Craving

Robert M. Swift, M.D., Ph.D.

The use of medications as an adjunct to treatment is based on the premise that craving and other manifestations of alcoholism are mediated by neurobiological mechanisms. Three of the four medications approved in the United States or Europe for treating alcoholism are reported to reduce craving; these include (ReVia™), , and tiapride. The remaining , disulfiram (Antabuse®), may also possess some anticraving activity. Additional medications that have been investigated include , which has not been shown to decrease craving or drinking levels in humans, and , which shows promise for treating early onset alcoholics, who generally respond poorly to psychosocial treatment alone. Use of anticraving medications in combination (e.g., naltrexone plus acamprosate) may enhance their effectiveness. Future studies should address such issues as optimal dosing regimens and the development of strategies to enhance patient compliance. KEY WORDS: AOD (alcohol and other drug) craving; anti alcohol craving agents; alcohol withdrawal agents; drug therapy; neurobiological theory; alcohol cue; disulfiram; naltrexone; calcium acetylhomotaurinate; ; uptake inhibitors; ; treatment outcome; reinforcement; ; patient assessment; literature review

riteria for defining alcoholism Results of craving research are often tions (i.e., pharmacotherapy) to improve vary widely. Most definitions difficult to interpret, because the subjec- the effectiveness of psychosocial alco- Cof include tive nature of craving makes it difficult holism treatment (Litten et al. 1996; the following descriptors: a compulsion to assess and quantify. Also, the quality Swift 1999). Alcoholism pharma- to seek and consume alcohol, a loss of and intensity of craving may vary cotherapy is based on the premise that control over consumption after begin- according to personal characteristics as alcohol use is mediated through spe- ning a drinking session, and a strong well as environmental circumstances or likelihood of relapse during or after experimental conditions. Nevertheless, withdrawal.1 These manifestations may phenomena associated with craving ROBERT M. SWIFT, M.D., PH.D., is an be accompanied by a conscious desire may have important implications for associate professor in the Department of or urge to consume alcohol (i.e., crav- preventing and treating alcoholism. Psychiatry and Human Behavior at Brown ing). Craving can occur spontaneously, For example, high levels of craving are University and associate chief of staff for or it can be elicited by internal or exter- associated with increased probability research and education at the Providence nal stimuli, known as cues (see sidebar of relapse, particularly during the early Veterans Administration Medical Center by Tiffany on p. 216 ). Internal cues stages of the posttreatment period (Anton in Providence, Rhode Island. may include emotional states (e.g., anx- et al. 1996). In addition, treatments iety) or symptoms of acute alcohol that reduce craving have been shown to 1Symptoms of acute withdrawal (e.g., tremors, agi- withdrawal. External cues may include reduce subsequent alcohol use (Monti tation, and seizures) may occur following cessation exposure to alcohol-related environ- et al. 1993).2 or reduction of heavy drinking. ments or objects (e.g., bottles of alco- In the past decade there has been 2Craving alone is neither necessary nor sufficient holic beverages or advertisements). increasing interest in the use of medica- for relapse.

Vol. 23, No. 3, 1999 207 cific neurobiological and behavioral mechanisms that initiate and maintain The Role of Neurons and Neurotransmitters drinking. Several medications have The ends of adjacent nerve cells, or neurons, are generally separated from demonstrated their ability to reduce one another by microscopic gaps called synapses. Most neurons communi- alcohol consumption in humans, and cate with one another by releasing chemicals called neurotransmitters, several of these drugs are reported to which cross the synapse and attach to a receptor protein on the receiving reduce alcohol craving. Researchers can neuron. Each binds preferentially to a single family of reasonably conclude that medications receptor subtypes, each of which may then stimulate, inhibit, or modulate a which reduce craving may be effective specific physiological function. A single neuron generally releases only one in alcoholism treatment. or a few types of neurotransmitters but may contain several types of recep- tors. A neurotransmitter released into a synapse is usually quickly removed Assessing and Measuring by chemical degradation or by transporter molecules that carry the neuro- Craving transmitter back into the neuron that released it. The function of a neuro- transmitter can be increased or mimicked by drugs, medications, or other chemical agents (i.e., ) or decreased, inhibited, or reversed by other Because craving is a subjective phe- agents (i.e., antagonists). nomenon, researchers commonly assess its intensity based on the self-reports of study participants.3 The simplest craving The Neurobiology 1996). Reinforcement of AOD use is assessments are single-item questionnaires. of Craving associated with release of the neuro- In the most basic approach, the subject transmitter dopamine in a brain region responds to a question (such as, “How Research during the past decade has called the nucleus accumbens (Roberts much do you desire alcohol right now?”) expanded our knowledge of the brain and Koob 1997) (see textbox above). by selecting one of three to five statements mechanisms that mediate the use of Long-term exposure to alcohol can lead that indicate increasing levels of intensity alcohol and other drugs (AODs). Alcohol to compulsive use that characterizes (e.g., from “not at all” to “very much”). may be consumed for its rewarding dependence (Roberts and Koob 1997). In some studies the patient rates his or effects, which are sometimes consciously Following repeated administration her craving on a visual analog scale (VAS). perceived as a pleasurable state (e.g., of alcohol, the brain attempts to restore In this approach, the patient places a mark the effects of mild alcohol intoxica- normal function through physiological on a line that is approximately 4 inches tion), or as relief from a painful or adjustments (i.e., counteradaptations) long and divided into arbitrary units uncomfortable state (e.g., amelioration that tend to reduce alcohol’s initial beginning with zero. The reliability of of withdrawal symptoms). Repeated sedating effects (Roberts and Koob 1997). single-item craving assessments is variable. exposure to a rewarding stimulus increases When a person terminates a prolonged Multi-item questionnaires include the the probability that a person will con- drinking session, these counteradapta- Obsessive Compulsive Drinking Scale tinue to seek, approach, and maintain tions are unopposed, resulting in signs (Anton et al. 1995), which contains 14 contact with the particular stimulus. and symptoms of acute withdrawal. questions, each rated on a scale from 0 to Stated simply, a person who finds alco- During this period, craving may represent 4, and the Alcohol Urge Questionnaire, hol use rewarding may subsequently a desire to self-medicate the anxiety which contains 8 statements rated from drink more often and in larger quanti- and hyperexcitability that accompany 1 to 7 (Bohn et al. 1995). ties. This process is referred to as posi- this state. Craving is sometimes assessed by tive reinforcement when its goal is to Certain manifestations of counter- measuring certain physiological changes attain a pleasurable state and is referred adaptation, presumably involving per- thought to accompany craving, such as to as negative reinforcement when its sistent dopamine dysregulation in the changes in heart rate, blood pressure, goal is to ameliorate an unpleasant state nucleus accumbens, can prolong vul- salivation, and sweat gland activity. Finally, (Roberts and Koob 1997).4 nerability to craving long after the acute craving can be assessed by directly AODs may activate the same neuro- symptoms of withdrawal have subsided. observing a subject’s drinking behavior. biological mechanisms that respond to This mechanism may account for the Behavioral measurements may include conventional reinforcers, such as food ability of cues, such as the sight, sound, number of drinks consumed, time and sexual activity (Di Chiara et al. or smell of alcohol, to trigger relapse elapsed between cue exposure and initia- years after an alcoholic has stopped tion of drinking (i.e., latency), and time drinking (Roberts and Koob 1997). elapsed between commencement and 4Research suggests that in some alcoholics an aver- The processes involved in completion of drinking. sive state may result from inherited deficiencies in include complex interactions among serotonin or other neurotransmitters; this state may several neurotransmitters in addition to 3This section presents a brief overview. For more detail, initially be alleviated by self-medication with alco- see the article in this issue by Drobes and Thomas, hol but will actually worsen from long-term, con- dopamine (see table, p. 209). For exam- pp. 179–186. tinued consumption (Roberts and Koob 1997). ple, peptides may mediate some

208 Alcohol Research & Health Medications and Alcohol Craving

of alcohol’s rewarding effects (e.g., eupho- not been approved for use in the patients who maintain total abstinence ria), and serotonin may help regulate United States. Additional medications (Hughes and Cook 1997). Disulfiram’s overall motivational and appetitive are used empirically by clinicians to effects on craving have not been specif- behaviors. In addition, both of the above- treat alcohol dependence, and several ically evaluated. However, disulfiram mentioned neurotransmitters influence other agents are being developed. has been shown to interfere with the dopamine activity in the nucleus accum- of dopamine (Rogers et bens. These interactions are further reg- Disulfiram al. 1979), potentially influencing the ulated by a balance between excitatory development of craving. neurotransmitters (e.g., glutamate) and Disulfiram interferes with the metabolism inhibitory neurotransmitters (e.g., of alcohol by the , permitting a Opioid Antagonists gamma-aminobutyric acid [GABA]). toxic breakdown product of alcohol to accumulate in the bloodstream. Alcohol Because opioid peptides stimulate consumption following disulfiram dopamine release in the nucleus accum- Medications To Treat treatment results in unpleasant symp- bens, medications that block opioid Alcohol Dependence toms, such as , palpitations, activity may block the reinforcing effects and Craving difficulty breathing, headache, and of alcohol. Naltrexone, an opioid antag- . Recent reviews of placebo- onist used (under the brand name Four medications are currently mar- controlled clinical trials with disulfiram Trexan®) to treat heroin addiction, has keted for treating alcohol dependence. have failed to confirm the drug’s efficacy been approved for treating alcoholism. Two of them—disulfiram (Antabuse®) in alcoholism treatment (Hughes and In a randomized, placebo-controlled and naltrexone (ReVia™)—have been Cook 1997). As an adjunct to psychoso- (Volpicelli et al. 1992), approved for this purpose by the Food cial therapy, disulfiram may decrease patients who received 50 milligrams and Drug Administration in the United the quantity (Chick et al. 1992) and (mg) of naltrexone per day5 reduced States. The two other medications— frequency (Chick et al. 1992; Fuller et acamprosate (Geerlings et al. 1997) and al. 1986) of drinking among recovering 5Fifty mg/day is standard dose of naltrexone for tiapride—are used in various European alcoholics, but the medication does not clinical treatment of opioid dependence (Volpicelli countries, although these drugs have appear to increase the proportion of et al. 1992).

Presumed Major Functions of Some Specific Neurotransmitters Involved in Alcohol-Related Behaviors and Alcoholism

Neurotransmitter General Function Alcohol-Related Function Dopamine Regulates motivation, reinforcement, Mediates reinforcement of alcohol consumption and fine movement coordination

Serotonin Regulates bodily rhythms, appetite, May influence alcohol consumption, intoxication,

sexual behavior, emotional states, and development of tolerance through 5HT1 sleep, attention, and motivation receptors; may contribute to withdrawal symptoms

and reinforcement through 5HT2 receptors; and may modulate dopamine release through 5HT3 receptors, thereby increasing alcohol’s rewarding effects (see dopamine)

GammaÐaminobutyric acid Serves as the primary inhibitory May contribute to intoxication and sedation; (GABA) neurotransmitter in the brain inhibition of GABA function following drinking cessation may contribute to acute withdrawal symptoms

Glutumate Serves as the major excitatory May contribute to acute withdrawal symptoms; neurotransmitter in the brain inhibition of glutamate function following drinking cessation may contribute to intoxication and sedation

Opioid peptides Regulates various functions as well Contributes to reinforcement of alcohol consump- (including beta-endorphin) as produces -like effects, tion, possibly through interaction with dopamine including pain relief and mood elevation

NOTE: The effects of the extensive and complex interactions among these neurotransmitters are not fully understood.

Vol. 23, No. 3, 1999 209 both their drinking and craving. In the Laboratory investigations with naltrex- the time latency between presentation study, naltrexone was administered to one generally support the clinical find- and consumption of a drink, with shorter patients participating in an alcoholism ings of reduced craving in naltrexone- latency indicating increased desire to rehabilitation program that included treated subjects. In recently abstinent consume alcohol. Two such experiments group therapy, individual counseling, alcoholic patients who received either 50 using this approach were conducted in health education, and recreation. Craving mg of naltrexone daily or a placebo for which nonalcoholic drinkers consumed was assessed weekly by means of a sin- 7 days, patients who received naltrexone alcohol under observation in a public gle-item, 10-point scale with 0 indicat- were less likely to report cue-induced bar. In the first experiment, subjects were ing no craving and 9 indicating “severe” craving than patients who received the randomly assigned to receive either nal- craving. Although overall craving was trexone or a placebo for 8 consecutive low, averaging about three out of nine days under double-blind conditions for the placebo group, the craving prior to each of three 2-hour drinking reported by the subjects taking naltrex- Naltrexone was most sessions. The three sessions were sepa- one was lower over the entire 12 weeks rated by 2 to 3 weeks and occurred on of the study. Of the patients taking nal- effective in reducing the evening in which the last dose of trexone, 23 percent relapsed, compared drinking in patients naltrexone or the placebo had been with 54 percent of the patients taking administered. The experiment used a the placebo. who reported high crossover design, in which subjects In a double-blind study of 97 alco- switched from naltrexone to the holics who were administered either a levels of craving at placebo or from the placebo to naltrex- placebo or 50 mg of naltrexone daily for the time they one prior to each subsequent drinking 12 weeks, the naltrexone-treated group session. The results showed significant had increased abstinence rates as well as entered the study. increases in “latency to sip” between decreased drinking and decreased reports the first and second alcoholic drinks, of craving (O’Malley et al. 1992). All although no differences were found in participants received psychosocial treat- placebo. Among the subjects who reported the subjects’ self-reports on their urge ment consisting of either individual craving, however, the absolute intensity of to drink. A significant reduction in coping-skills/relapse-prevention therapy craving had not decreased from levels total alcohol intake also was observed or supportive therapy without a specific measured at the start of the experiment. during the naltrexone treatment com- coping component. Coping-skills therapy Craving was measured on a seven-point pared with the placebo “treatment” attempts to teach patients to identify and analog scale (Monti et al. 1999). (Davidson et al. 1996). handle situations that place them at high Another study of naltrexone’s effect In the second experiment, 51 heavy risk for relapse to drinking. This approach on laboratory-induced craving in recently beer drinkers were pretreated with includes instruction in self-monitoring detoxified, alcohol-dependent subjects either a placebo or 50 mg of naltrexone practices; rehearsal of anger and stress found that a single 50 mg dose of nal- daily, each for 7 consecutive days prior management techniques; training in social, trexone reduced craving in response to to the drinking sessions. Again, the problem-solving, and decisionmaking alcohol cues but not in response to a subjects’ latency to drinking increased skills; and development of alternative, sweetened control beverage (Rohsenow during the naltrexone period compared abstinence-oriented leisure activities. 1998). In this study, craving was assessed with the placebo. The subjects who In this clinical trial (O’Malley et al. as the urge to drink as rated on a seven- received naltrexone also consumed less 1992), self-reported craving over the point scale. alcohol, and the time they took to fin- previous week was rated on a 20-point Not all studies on naltrexone have ish one drink was increased. In this analog scale. An interaction existed shown reductions in craving. One study experiment, subjects reported less of between craving and the specific psy- conducted in persons who used both an urge to drink when they received chotherapy received. Abstinence rates alcohol and cocaine found no effects naltrexone than when they received were highest among participants receiving of naltrexone in reducing alcohol and a placebo (Davidson et al. 1999). naltrexone in combination with sup- cocaine craving. However, in this study, In a randomized, double-blind, portive psychotherapy. Among patients levels of induced alcohol craving were placebo-controlled study, Volpicelli who sampled alcohol during treatment, low (Modesto-Lowe et al. 1997). In and colleagues (1997) found no reduc- however, those who received naltrexone addition, a laboratory study that inves- tion in craving measured on a 10- and coping-skills therapy were least likely tigated the effects of four doses of nal- point scale among subjects receiving to relapse. A subsequent analysis of data trexone (ranging from 0 to 100 mg) naltrexone. However, these researchers from this study (Jaffe et al. 1996) indi- on alcohol-dependent subjects found have noted that many subjects dropped cated that naltrexone was most effective no effect on the subjects’ urge to drink out of treatment prematurely and in reducing drinking in patients who (Farren et al. 1999). that the clinical effectiveness of naltrex- reported high levels of craving at the Some researchers have suggested that one might be improved by techniques time they entered the study. craving can be assessed by determining for enhancing medication compliance.

210 Alcohol Research & Health Medications and Alcohol Craving

In summary, the data suggest that tion. Such medications increase the and anxiety disorders. In one such naltrexone’s beneficial effects in reduc- overall activity of serotonin in synapses study, Tollefson and colleagues (1992) ing alcohol consumption and increas- as well as agonists and antagonists at found that buspirone reduced patients’ ing abstinence may be associated with various serotonin-receptor subtypes. anxiety levels, number of days desiring the ability of the drug to block craving, Selective Serotonin Reuptake alcohol, and intensity of craving. How- including both the urge to drink and Inhibitors (SSRIs). These medications, ever, other controlled clinical studies associated physiological responses. which appear to reduce alcohol con- using buspirone have been negative. sumption in animals, augment overall Malcolm and colleagues (1992) con- Dopamine Antagonists function by interfering cluded that although buspirone com- with the removal of serotonin from the bined with psychosocial treatment may Dopamine’s role in reinforcement sug- synapse after its release (see textbox, p. help ameliorate psychiatric symptoms, gests the possibility of using dopamine 208). Some SSRIs are commonly pre- the drug’s effects on alcohol consump- antagonists to reduce alcohol consump- scribed for certain psychiatric disorders, tion are limited. tion and craving. In a double-blind, such as depression and anxiety. Several Ritanserin. An antagonist of sero- placebo-controlled laboratory study, 16 human studies on heavy drinkers found tonin 5HT2 receptors, ritanserin may subjects diagnosed with either alcohol SSRIs to reduce overall alcohol con- reduce alcohol consumption in rats abuse or alcohol dependence reported sumption by approximately 15 to 20 (Litten et al. 1996). Human studies, less craving for alcohol and consumed percent (Naranjo et al. 1994). In one however, are disappointing—for exam- less of their preferred alcoholic beverage study of 18 heavy drinkers that was ple, ritanserin was reported to reduce after receiving the dopamine antagonist conducted in a bar, the SSRI craving for alcohol in heavy social (Haldol®), a medication (Celexa®) reduced both drinking and drinkers, although it did not decrease commonly prescribed to treat severe self-reported craving for alcohol. consumption (Litten et al. 1996). psychiatric illness (Modell et al. 1993). However, studies with alcohol-depen- The effectiveness of ritanserin for The dopamine antagonist tiapride, dent patients have yielded less impres- treating alcoholism was recently tested marketed in Europe for the treatment sive results (Kranzler et al. 1995). While in a rigorous multicenter, placebo-con- of and dependence, was some alcohol-dependent subjects treated trolled clinical trial in which 423 alco- shown to be effective in increasing with SSRIs have reported decreased holics received up to 5 mg of ritanserin abstinence in a randomized, double- craving and liking for alcohol, the per day concurrently with cognitive- blind trial with more than 100 subjects reductions tend to be transient. Kabel behavioral therapy (Johnson et al. conducted in Great Britain, although and Petty (1996) report no differences 1996). All study participants signifi- craving for alcohol was not specifically in drinking outcome among severe cantly reduced their alcohol consump- assessed (Shaw et al. 1994). alcoholics (mean = 19 drinks per day) tion by the end of the 12-week study A preliminary, double-blind, placebo- who were treated with either period. However, no difference in either controlled laboratory study of the (Prozac®) or a placebo, although crav- craving or drinking level was observed recently approved medi- ing decreased significantly in fluoxetine- between the patients who had received cation olanzepine (Zyprexa®) on alco- treated subjects after 12 weeks. ritanserin and the patients who had hol-induced stimulation and cue-induced Buspirone. Several serotonergic ago- received the placebo. craving found that pretreatment with nists and antagonists were observed to Ondansetron. Through its action at olanzepine attenuated measures of reduce alcohol consumption in animals the 5HT3 receptor, serotonin helps reg- alcohol- and cue-induced craving and were tested in alcohol-dependent ulate the release of dopamine into the (Hutchison et al. 1998). Unlike tradi- humans. Buspirone (Buspar®), which is nucleus accumbens, thereby affecting tional antipsychotic dopamine antago- prescribed for anxiety, demonstrated the development of reinforcement. nists, this medication is less likely to incomplete agonistic activity at a spe- Researchers have shown 5HT3-receptor produce neurological , such cific serotonin-receptor subtype (i.e., antagonists to block dopamine release as movement disorders. the 5HT1 receptor). in animals and also to reduce alcohol The observation that buspirone consumption in rats (Litten et al. 1996). Serotonergic Medications reduces alcohol consumption in alco- In a placebo-controlled outpatient trial hol-drinking rats led to human studies with 71 socially stable, mildly alcohol- Several pharmacological agents that with nonanxious alcohol-dependent dependent men treated with the 5HT3 alter serotonergic function in the brain patients. In a study of 50 alcoholic sub- antagonist ondansetron (Zofran®), appear to reduce consumption jects in treatment, Bruno (1989) found researchers found that a low dose, but in animals (Kranzler and Anton 1994; reduced drinking, less craving, and not a high dose (0.25 versus 2.0 mg LeMarquand et al. 1994). However, in improved social and psychological twice daily), of ondansetron moderately the clinical treatment of alcohol-depen- status in patients receiving buspirone. reduced alcohol consumption. A signif- dent patients, the effects of most sero- Several controlled clinical studies icant difference between treatment tonergic medications seem to be only using buspirone have been conducted on effects was observed only after exclud- modest in reducing alcohol consump- patients with co-occurring alcoholism ing the heaviest drinkers (Sellers et al.

Vol. 23, No. 3, 1999 211 1994). In a human laboratory study, not correlate with drinking behavior Summary ondansetron reduced subjective mea- (Sass et al. 1996). sures of the desire to drink alcohol mea- Acamprosate has been approved The concept of craving, although diffi- sured by VAS 1 hour after administra- in several European countries for the cult to describe, is nevertheless impor- tion of the medication and also reduced treatment of alcohol dependence (see tant to alcoholism treatment research. some of the pleasurable effects of alco- Geerlings et al. 1997) and is currently Several medications that reduce human hol consumption (Johnson et al. 1993). undergoing clinical testing in the United alcohol consumption in laboratory stud- States (Litten et al. 1996). ies and clinical trials also reduce craving Acamprosate for alcohol. However, craving is not Sedative Medications always associated with alcohol drinking, The medication acamprosate helps restore and a direct relationship does not always the balance of excitatory and inhibitory The sedative gamma-hydroxybutyrate exist between medication-induced neurotransmission in the nucleus accum- is a neurotransmitter related to GABA reductions in craving and reductions in bens (Litten et al. 1996). The drug has and was formerly administered clinically drinking. A better understanding of the been found to reduce alcohol consump- as both a hypnotic and an anesthetic. concept of craving and its relationship tion in rats trained to drink alcohol (Litten In addition, the drug may effectively to alcohol drinking may lead to a better et al. 1996). In randomized, placebo- relieve some alcohol-withdrawal symp- understanding of the neurobiology of controlled clinical trials with human toms (Litten et al. 1996). In an open, alcohol dependence and subsequently to alcoholics, acamprosate significantly multicenter trial with abstinent alco- more effective clinical interventions. increased the proportion of patients who holics, this medication reduced alcohol Future studies should address such remained continuously abstinent as well consumption and significantly reduced issues as optimal dosing regimens, match- as the duration of abstinence. Effects on craving measured by the 14-item Alcohol ing patients with appropriate medications, craving for alcohol, however, have been Craving Scale (Addolorato et al. 1996). and developing strategies to enhance more variable. However, some subjects became depen- patient compliance. In assessing craving, A 12-month multicenter study con- dent on the medication itself and more reliance should be placed on exper- ducted in France compared the effects began to take increasingly higher doses. imentally validated, multi-item ques- of 1.2 and 2 grams of acamprosate Therefore, the drug should be adminis- tionnaires, such as the Obsessive daily with that of a placebo (Paille et al. tered to alcoholics only with extreme Compulsive Drinking Scale. Ongoing 1995). While the higher acamprosate caution and close monitoring. research on the effectiveness of prescrib- dose significantly increased the propor- Excessive activity of the neurotransmit- ing medications in combination (e.g., tion of subjects who remained absti- ter has been implicated naltrexone and acamprosate) may usher nent at 6 and 12 months, no effect on in some symptoms of withdrawal, and in a new era of alcoholism pharma- alcohol craving occurred at these time medications that inhibit norepinephrine cotherapy. periods. However, the higher dose of may help alleviate withdrawal (Litten et acamprosate reduced craving at 3 al. 1996). Several medications that reduce months, when the intensity of craving norepinephrine-mediated arousal are References was much higher (Paille et al. 1995). reported to attenuate craving. Beta block- Additional randomized, double- ers (e.g., [Inderal®]) are a ADDOLORATO, G.; CASTELLI, E.; STEFANINI, G.F.; blind, placebo-controlled clinical studies class of norepinephrine antagonists, many CASELLA, G.; CAPUTO, F.; MARSIGLI, L.; BERNARDI, M.; AND GASBARRINI, G. An open multicentric study confirm that acamprosate increases the of which are prescribed to treat high evaluating 4-hydroxybutyric acid sodium salt in the rate and duration of abstinence in alcoholics blood pressure and symptoms of acute medium-term treatment of 179 alcohol dependent who receive concurrent psychosocial withdrawal symptoms (Gottlieb et al. subjects. GHB Study Group. Alcohol and Alcoholism therapy, but all studies have been nega- 1994). A random, double-blind, placebo- 31:341–345, 1996. tive with respect to craving, as measured controlled study (Gottlieb et al. 1994) ANTON, R.F.; MOAK, D.; AND LATHAM, P.K. The with single-item VAS. In a study using also found beta blockers to be effective Obsessive Compulsive Drinking Scale: A self rated 600 subjects, Lhuintre and colleagues in reducing alcohol craving during with- instrument for the quantification of thoughts about (1990) found more marked reductions drawal and early abstinence (to 1 year) alcohol and drinking behavior. Alcoholism: Clinical in craving among the most severe alco- as measured on a five-point scale. Alco- and Experimental Research 19:92–99, 1995. holics (i.e., those with the highest initial holics with high initial craving scores ANTON, R.F.; MOAK, D.; AND LATHAM, P.K. The craving scores) but with no difference showed the greatest reduction, and com- Obsessive Compulsive Drinking Scale: Assessing between the drug and the placebo groups. pletion of the program correlated with outcome in alcoholism treatment studies. Archives of General Psychiatry 53:225–231, 1996. In a study by Sass and colleagues (1996), improvement in both the drug and the abstinence rates improved in treated placebo groups. However, overall study BOHN, M.J.; KRAHN, D.D.; AND STAEHLER, B.A. alcoholics during a 48-week period. How- completion rates were low; thus, no Development and initial validation of a measure of drinking urges in abstinent alcoholics. Alcoholism: ever, self-reported craving by VAS showed conclusions could be drawn about long- Clinical and Experimental Research 19(3):600–606, wide variability over this period and did term relapse (Gottlieb et al. 1994). 1995.

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Vol. 23, No. 3, 1999 213 Are the latest NIAAA Research Monographs in your collection?

Each monograph presents research by noted scientists, reviews research progress, and offers a glimpse of future research in key areas. Scientists, clinicians, and others with an interest in alcohol research will find these volumes a welcome addition to their library.

Women and Alcohol: Issues for Prevention Research (No. 32) presents research on alcohol use and prevention among women. Topics include • Alcohol use across the life span • Alcohol use in the workplace • Alcohol-related birth defects • Parenting interventions for preventing children’s alcohol and other drug use • Influence of genetics, sexuality, and violent victimization on alcohol use.

Alcohol Problems and Aging (No. 33) reviews research on alcohol’s effects on the aging process and on the social, eco- nomic, and health status of older Americans. Topics include • Biological mechanisms underlying alcohol’s effects on the elderly • How alcohol affects cognition, sleep, and driving • Medical consequences of heavy drinking by the elderly • Life-context factors and late-life drinking behavior • Treatment and prevention of alcohol problems in the elderly.

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214 Alcohol Research & Health