Pharmacotherapies for alcohol abuse. Withdrawal and treatment

Pharmacologic management of alcoholism is only one part of the management of both alcohol dependence and withdrawal, which also includes the provision of a calm, quiet environment; reassurance; ongoing reassessment; attention to fluid and electrolyte disorders; treatment of coexisting addictions and common medical, surgical, and psychiatric comorbidities; and referral for ongoing psychosocial and medical treatment. For further discussion of these topics, the reader is referred to previously published sources. A survey of alcoholism treatment programs revealed that although benzodiazepines were the most commonly used drugs, standardized monitoring of patients' withdrawal severity was not common practice, and a significant minority of clinicians were using a variety of other drugs, some not known to prevent or treat the complications of withdrawal. Treatment should be based on the available evidence (Working Group on Pharmacological Management of Alcohol Withdrawal: American Society of Addiction Medicine Committee on Practice Guidelines: Pharmacological management of alcohol withdrawal: An evidence-based practice guideline. Unpublished draft, 1997). Patients with significant symptoms, patients with complications such as seizures or delirium tremens, and patients at higher risk for complications of alcohol withdrawal should receive benzodiazepines, particularly chlordiazepoxide, diazepam, or lorazepam, because of their safety and documented efficacy in preventing and treating the most serious complications of alcohol withdrawal. These drugs may be dosed on a fixed schedule for a predetermined number of doses on a tapering schedule over several days, or they may be administered by front-loading. An alternative approach for selected patients without seizures or acute comorbidity is symptom-triggered therapy, which individualizes treatment and decreases the duration and dose of medication administration. With either of the regimens, patients should have their withdrawal severity monitored until symptoms are resolving. Once withdrawal from alcohol is safely completed, the focus should turn to helping to prevent relapse. Disulfiram may be useful in highly motivated subsets of patients and when compliance-enhancing strategies are used. Naltrexone is useful in the broader population of patients entering treatment for alcohol dependence. These pharmacologic interventions should be given in the context of ongoing psychosocial support. There is substantial evidence that pharmacologic management of alcohol abuse and dependence is effective. As would be predicted from alcohol's myriad cellular effects, no panacea exists for alcoholism. For alcohol withdrawal, however, although treatment regimens have only recently been refined, evidence for effective treatment of symptoms and prevention of complications with benzodiazepines has been available for decades. Within the last decade, effective treatments, including naltrexone, have been shown to reduce alcohol intake in alcohol-dependent persons. Given the prevalence and cost of alcohol-related problems, all effective therapies (including pharmacologic treatments) should be considered to treat alcohol abuse and dependence.     

Depressive symptoms associated with gonadotropin-releasing hormone agonists

The gonadotropin-releasing hormone (GnRH) agonists are a relatively new class of drugs that are potentially effective in treating disorders that are aggravated either by estrogen or testosterone. GnRH agonists are effective in the treatment of endometriosis, as well as other disorders, such as advanced prostrate cancer, precocious puberty and uterine leiomyomata. While the GnRH agonists reduce the extent of the endometrial lesions and the occurrence of pelvic pain associated with endometriosis, these agents are associated with physical and psychiatric side effects. The adverse effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. Preliminary results of a prospective, double-blind placebo-controlled study and an open label trial indicates that depressive mood symptoms increase in women treated with GnRH agonist therapy for endometriosis. Additional evidence suggest that sertraline effectively manages depressive mood symptoms associated with GnRH agonist therapy. The reason for the decline in mood on GnRH agonists is postulated to be associated with the decline in estrogen levels. Effective treatment strategies for depressive mood symptoms in women on GnRH agonists therapy may offer insight into the mechanisms of action of estrogen on mood.     

A study of the relationship between home care services and hospital readmission of patients with congestive heart failure

Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.     

Ectopic eruption of maxillary first permanent molars in children with cleft lip

The main aims of therapy for inflammatory bowel disease (Crohn disease) in children and adolescents are (1) the induction and maintenance of remission, (2) the correction of nutrient deficits and (3) the restoration of growth and maturation. These goals are reached with the use of a combination of therapeutic methods, including pharmacologic agents, nutritional and psychological support, and surgical intervention. The commonly used drugs sulfasalazine, corticosteroids and metronidazole have all been shown to be safe and efficacious when given to children. Newer steroid preparations that are rapidly degraded either in the target tissue or elsewhere are being studied. Of these, budesonide currently shows promise as an efficacious drug with few side effects, but its use in children needs further study. Newer 5-amino-salicylate preparations such as Asacol have been shown to be effective in children, but the number of patients studied is small. Immunomodulatory drugs such as azathioprine and 6-mercaptopurine appear to be safe and efficacious for children; cyclosporine has been used infrequently to treat refractory Crohn disease in children. The use of other agents such as methotrexate, tacrolimus, monoclonal antibodies to cytokines, antibiotics and specific dietary products such as fish oils have not been intensively studied in children with Crohn disease. Nutritional therapy remains a mainstay of treatment because it corrects nutritional deficits, replaces losses and stimulates growth.     

Medical treatment of migraine: from mechanisms of action to contraindications

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).     

Behavioral analysis of the saccharin deprivation effect in rats.

The deprivation effect (DE)--an increase in the level of free-choice consumption of alcohol after a period of forced abstinence--may reflect relapselike drinking and be relevant for modeling alcohol abuse. However, the behavioral mechanisms of the DE are unclear. In these experiments, rats had unlimited free-choice access to water and saccharin-containing solutions and underwent repeated episodes of saccharin deprivation. It was found that DE magnitude correlates positively with the deprivation phase duration, expression of the DE is highly context dependent, and the DE can be prevented by extinguishing response to the saccharin-associated stimuli. Thus, DE procedures may be useful for studying the effects of continued exposure to stimuli associated with various primary reinforcers such as drugs of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dual dopamine/serotonin releasers: Potential treatment agents for stimulant addiction.

"Agonist therapy" for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g., monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability because of activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs is to add in serotonin (5-HT) releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This article addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, the authors briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, the authors discuss data demonstrating that 5HT release can dampen DA-mediated stimulant effects, and the "antistimulant" role of 5-HT2C receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, the authors discuss recently published data with PAL-287, a novel nonamphetamine DA/5-HT releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions, as well as for obesity, attention-deficit disorder, and depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adolescent alcohol expectancies in relation to personal and parental drinking patterns.

Increased expectations of positive effects of alcohol have been associated with severity of drinking across a variety of abusing and nonabusing adult populations. Although alcohol expectancies have been examined among high school adolescents, no study has examined expectancies of identified adolescent abusers in treatment. This study investigated whether adolescent alcohol abusers in treatment expect significantly more reinforcement from alcohol than do nonabusing peers and whether expectancies vary as a function of exposure to parental alcohol abuse. The adolescent version of the Alcohol Expectancy Questionnaire (Christiansen, Goldman, & Inn, 1982) was completed by 116 abusing and nonabusing adolescents. Results indicate that adolescent alcohol abusers expect significantly more reinforcement from alcohol than do demographically comparable nonabusing peers. Adolescents with an alcohol-abusing parent reported expecting more cognitive and motor enhancement from drinking than did adolescents without a family history of abuse. Thus, both personal alcohol use and parental alcohol use are related to adolescent alcohol expectancies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treating obsessive-compulsive disorder among substance abusers: A guide.

Explores psychotherapeutic and pharmacologic approaches for the treatment of obsessive–compulsive disorder (OCD), and explains how these interventions can be integrated into a substance abuse treatment plan. Behavior therapy is the most effective treatment for OCD, using an exposure and response prevention paradigm. Five steps are recommended for treating substance abusers with OCD: (1) psychodiagnostic assessment, (2) assessment of symptom type and severity, (3) psychoeducational therapy, (4) developing a hierarchy of anxiety-evoking stimuli, and (5) treating OCD patients with exposure and response prevention. Four heterocyclic drugs with potent serotonin-reuptake inhibitor properties (clomipramine, fluoxetine, fluvoxamine, and sertraline) have also shown consistent effectiveness in reducing OCD symptoms. A case example is provided of a 37-yr-old male substance abuser seeking therapy for contamination fears and washing rituals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use and abuse of over-the-counter analgesic agents

Pain and discomfort in everyday life are often treated with over-the-counter (OTC) analgesic medications. These drugs are remarkably safe, but serious side effects can occur. Up to 70% of the population in Western countries uses analgesics regularly, primarily for headaches, other specific pains and febrile illness. It is not known whether the patterns of use are consistent with good pain management practices. OTC analgesics are also widely used to treat dysphoric mood states and sleep disturbances, and high levels of OTC analgesic medication use are associated with psychiatric illness, particularly depressive symptoms, and the use of alcohol, nicotine and caffeine. More than 4 g per day of acetylsalicylic acid (ASA) or acetaminophen over long periods is considered abuse. People using excessive amounts of OTC analgesics may need more effective treatments for chronic pain, depression or dysthymia. The possibility that these drugs have subtle reinforcing properties needs to be investigated. Certainly phenacetin, which was taken off the market in the 1970s, had intoxicating effects. A better understanding of patterns of use is needed to determine the extent of problem use of OTC analgesics, and whether health could be improved by educating people about the appropriate use of these drugs.     

Review of alcohol problems in ethnic minority groups.

This article reviews recent research on alcohol use and alcohol problems among Black Americans, Hispanic Americans, and American Indians. Strengths and weaknesses of conventional research methods and lacunae in current information are examined. To date, no studies have systematically documented variations in drinking styles and factors that promote or maintain alcohol abuse. Each minority group is heterogeneous in its drinking patterns; drinking problems; and psychological, medical, and social consequences of alcohol abuse. Collectively, these factors have important implications for evaluating programs to treat minority persons. The author suggests that future research adopt multidisciplinary approaches to more fully characterize ethnopharmacological profiles of alcohol use and abuse among these ethnic minorities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reasons for drinking, alcohol use, and alcoholism among Mexican Americans and non-Hispanic Whites.

Estimated associations of subjective reasons for drinking with heavy drinking (HD), frequent drinking (FD), and alcohol abuse or dependence (AAOD). Respondents were 725 Mexican-American and 915 non-Hispanic White community residents who reported drinking at least once in the 6 mo before being interviewed. Each reason for drinking and number of reasons given for drinking were associated with HD, FD, or AAOD. However, multivariate models suggested that different reasons may be associated with different types of alcohol involvement. Cultural differences in alcohol involvement were typically not accounted for by cultural differences in reasons for drinking. Drinking to cheer up or to loosen up around people and drinking to induce sleep had different associations with HD and AAOD in different cultural groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory association and personality as predictors of alcohol use: mediation and moderator effects

We investigated the nature of the effects of memory associations on alcohol use and abuse. First, we determined if effects of memory associations on drinking problems are mediated entirely through the frequency of alcohol consumption or, alternatively, if such effects are more direct. Second, personality traits were assessed to evaluate whether they were confounded with memory association in their effects or whether they might moderate the effects of memory associations on alcohol use and abuse. The results showed that memory association measures directly and independently predicted alcohol consumption; these measures indirectly predicted problems from drinking, including drunk driving. None of the assessed personality variables moderated the predictive effects of memory association. The results are consistent with the view that memory associations influence behavior through cognitive processes that are not affected by personality traits or by cognitions emanating from such traits.     

Central stimulants in adults with AD/HD. Can they be abused?]

As early as in 1979, abuse was observed when adults with MBD were treated with psychostimulants. In a study from 1981, five patients (19%) had been stimulated or excited. It was concluded that there was no reason to believe that adults with MBD were immune from stimulant abuse problems. In subsequent studies, it has been the rule to exclude patients who abuse alcohol or drugs. Obviously, there has been agreement that treatment implies a considerable risk of abuse of stimulants. However, nobody has systematically studied the frequency of psychostimulant abuse in subjects with AD/HD with and without abuse of alcohol and drugs, neither during the study nor at follow-up. There has been some attempts at using pemoline, a stimulant which cannot be abused. However, the mental and physical complications have been severe. Some preliminary studies indicate that stimulants can be used to treat alcoholics and substance abusers with concurrent AD/HD. Before such treatment can be recommended, the observations should be confirmed in controlled studies with representative materials, and the patients should be followed over a long period of time. It seems that stimulants are not an appropriate treatment for subjects with psychopathic personality and antisocial behaviour.     

Role of cytosolic calcium balance on cell injury in cultured bovine aortic endothelial cells during hypoxia and reoxygenation]

The integration of pharmacological therapies for comorbid disorders requires an acceptance of independence and interactions of respective addictive and psychiatric disorders. At the same time, alcohol and other drugs induce psychiatric states that are indistinguishable from psychiatric disorders. On the other hand, while psychiatric disorders do not induce addictive use of alcohol and drugs, they do pose vulnerabilities to the development of addictive disorders. Generally, the treatment of comorbid disorders begins with abstinence and evaluation of the effects of alcohol and other drugs in contributing to the psychiatric picture. In the case of comorbid disorders, stabilization and standard treatments can be employed with certain cautions, namely, to avoid the use of addicting medications such as benzodiazepines and opiates beyond the detoxification stage. High potency neuroleptics and antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) can be used to treat continuing psychiatric states after the exclusionary criteria in DSM-IV for substance-related disorders have been applied to the clinical case. If the psychiatric symptoms clear with sustained abstinence, little or no medications may be required. Specific treatment of the addictive disorders will often determine the extent that addictive disorders are responsible for psychiatric symptomatology. Alternatively, treatment of the psychiatric disorder will enhance compliance with addiction treatment.     

Conditioned taste aversion is a confound in behavioral studies that report a reduction in the reinforcing effects of drugs

Pharmacologic agents with a potential to attenuate the reinforcing properties of drugs of abuse may have an important role in the treatment of drug addiction. The reduction of drug self-administration and sweet solution intake are two common animal models employed to screen for promising therapeutic agents. When these agents are effective in suppressing the behavior maintained by drugs of abuse, the cause is usually attributed to a neuronal mechanism such as the modification of neurotransmitters that subserve reinforcement. These experiments present data for an alternate interpretation which suggest that some of these agents produce a conditioned taste aversion (CTA) that acts as a confounding variable in the screening of potential therapeutic agents. Both carbamazepine and isradipine were shown to establish a CTA at doses reported to attenuate the reinforcing properties of drugs of abuse. It is concluded that CTA represents a potential experimental confound in studies of pharmacologic agents that appear to attenuate the reinforcing properties of drugs. These results suggest that screening for a CTA is necessary in any paradigm that measures the suppression of consummatory behavior in response to pharmacologic intervention.     

Decreased presynaptic sensitivity to adenosine after cocaine withdrawal

The nucleus accumbens (NAc) is a site mediating the rewarding properties of drugs of abuse, such as cocaine, amphetamine, opiates, nicotine, and alcohol (Wise and Bozarth, 1987; Koob, 1992; Samson andHarris, 1992; Woolverton and Johnson, 1992; Self and Nestler, 1995; Pontieri et al., 1996). Acute cocaine has been shown to decrease excitatory synaptic transmission mediated by the cortical afferents to the NAc (Nicola et al., 1996), but the effects of long-term cocaine treatment and withdrawal have not been explored. Here, we report that long-term (1 week) withdrawal from chronic cocaine reduced the potency of adenosine to presynaptically inhibit glutamate (Glu) release by activating adenosine A1 receptors. Adenosine A1 receptors were not desensitized, because the potency of the metabolically stable adenosine analog N6-cyclopentyl-adenosine was unchanged after chronic cocaine withdrawal. When adenosine transporters were blocked, the potency of adenosine to inhibit Glu release from naive and cocaine-withdrawn NAc slices was similar. These results suggest that one of the long-term consequences of cocaine withdrawal is an augmented uptake of adenosine. This long-lasting change expressed at the presynaptic excitatory inputs to the medium spiny output neurons in the NAc may help identify new therapeutic targets for the treatment of drug abuse.     

Balloon Therapy.

Describes a humorous approach to psychotherapy in which the patient wears balloons attached to both ears 24 hrs a day for a 1-wk period. Balloon therapy is effective in the treatment of depression, low self-confidence, social isolation and withdrawal, anxiety neuroses, sexual dysfunction, and alcohol abuse and dependence, and is particularly suited for the treatment of autistic and catatonic disorders. Points of therapeutic expertise and contraindications are outlined. (French abstract) (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cue exposure in moderation drinking: A comparison with cognitive–behavior therapy.

To date, the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal. A modification of cue exposure (CE) for moderation drinking, which incorporated priming doses of alcohol, could train participants to stop drinking after 2 to 3 drinks. This study examined the effects of modified CE within sessions, combined with directed homework practice. Nondependent problem drinkers who requested a moderation drinking goal were randomly allocated to modified CE or standard cognitive-behavior therapy (CBT) for alcohol abuse. Both interventions were delivered in 6 90-min group sessions. Eighty-one percent of eligible participants completed treatment and follow-up assessment. Over 6 months, CE produced significantly greater reductions than CBT in participants' reports of drinking frequency and consumption on each occasion. No pretreatment variables significantly predicted outcome. The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adverse effects of fertility drugs

Ovulation-induction agents are commonly used in the treatment of infertility in patients with or without ovulatory disturbances. These agents include clomifene, bromocriptine, gonadotrophin preparations and gonadotrophin-releasing hormone (GnRH) and its analogues. Each agent is associated with its own specific adverse effects. Although many of these adverse effects are benign and self-limited, some, in particular those effects associated with gonadotrophins, may be life-threatening. Commonly noted adverse effects encountered with the use of pharmacological agents to treat infertility include the following. Clomifene has been associated with hot flushes, multiple gestation, visual disturbances, cervical mucus abnormalities and luteal phase deficiency. Similarly, most of the adverse symptoms associated with bromocriptine are short-lived, such as nausea and postural hypotension. On the other hand, gonadotrophin therapy, even when used appropriately, may lead to the ovarian hyperstimulation syndrome (which is occasionally life-threatening) and a high incidence of multiple gestation. Pulsatile GnRH therapy maybe accompanied by similar adverse effects to those of gonadotrophins, but with a far lower incidence. With regards to the long term safety of these medications, the relationship between fertility drugs and epithelial ovarian cancer is controversial, and causality has yet to be proven. Indeed, a working knowledge of the many adverse effects associated with these medications is essential to any physician prescribing ovulation induction agents, in order to ensure maximum patient safety, compliance and understanding.