Nutrition and alcohol neurotoxicity.
Author Manzo L; Locatelli C; Candura SM; Costa LG
Abstract Neurological complications of alcoholism such as Wernicke-Korsakoff syndrome and polyneuropathy often originate from interactive factors involving direct nervous system toxicity of ethanol and nutrient deficiencies associated to heavy drinking. Not all patients are equally susceptible to these disorders and a genetic predisposition to thiamine deficiency has been described in subjects with Wernicke's encephalopathy. At moderate alcohol dosages, nutrient abnormalities may be marginal, inducing no obvious manifestations until other neurotoxic agents are absorbed. Examples are presented illustrating the interaction of ethanol and styrene on brain glutathione metabolism in rats, and cases of methanol poisoning in alcoholics. In these patients, ethanol-induced folate deficiency can potentiate visual toxicity of methanol due to impairment of the folate-dependent pathway involved in formate detoxication. The notion that nutritional deficiencies and ethanol toxicity may act synergistically in the nervous system outlines the importance of adequate nutritional strategies in the treatment of alcoholism and also indicates that methodological flaws may result during experimental studies from failure to control for nutritional variables.
Mechanisms of ethanol-drug-nutrition interactions.
Author Lieber CS Address Alcohol Research and Treatment Center, VA Medical Center, Bronx, NY 10468. Source J Toxicol Clin Toxicol, 32: 6, 1994, 631-81
Abstract Mechanisms of the toxicologic manifestations of ethanol abuse are reviewed. Hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive hepatic generation of nicotinamide adenine dinucleotide and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) pathway, the microsomal ethanol-oxidizing system, which involves a specific cytochrome P450. It generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications and carcinogens. The contribution of gastric alcohol dehydrogenase to the first pass metabolism of ethanol and alcohol-drug interactions is now recognized. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and beta-carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other supernutrients include polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human primates. Thus, a better understanding of the pathology induced by ethanol has now generated improved prospects for therapy.
ALCOHOL AND ALDEHYDE DEHYDROGENASE POLYMORPHISMS AND ALCOHOLISM.
Thomasson HR, Crabb DW, Edenberg HJ, Li TK:
Behavior Genetics 1993; 23(2):131-6.
Summary: The alcohol-flush reaction occurs in Asians who inherit the mutant
ALDH2*2 allele that produces an inactive aldehyde dehydrogenase enzyme. In these
individuals, high blood acetaldehyde levels are believed to be the cause of the
unpleasant symptoms that follow drinking. We measured the alcohol elimination
rates and intensity of flushing in Chinese subjects in whom the alcohol
dehydrogenase ADH2 and ALDH2 genotypes were determined. We also correlated ADH2,
ADH3, and ALDH2 genotypes with drinking behavior in 100 Chinese men. We
discovered that ADH2*2 and ADH3*1, alleles that encode the high activity forms
of alcohol dehydrogenase, as well as the mutant ALDH2*2 allele were less
frequent in alcoholics than in controls. The presence of ALDH2*2 was associated
with slower alcohol metabolism and the most intense flushing. In those
homozygous for ALDH2*1, the presence of two ADH2*2 alleles correlated with
slightly faster alcohol metabolism and more intense flushing, although a great
deal of variability in the latter was noted. [References: 25]
GENETIC MODELS IN THE STUDY OF ALCOHOLISM AND SUBSTANCE ABUSE MECHANISMS. George FR: Progress in Neuro-Psychopharmacology & Biological Psychiatry 1993; 17(3):345-61.
Summary: 1. Vulnerability to substance abuse is an important emerging issue.
Some related factors are the relationship between propensity to self-administer
a drug and neurosensitivity to that drug; similarities and differences between
various models of drug seeking behavior; and the commonality of drug-seeking
behavior across drugs and genotypes, that is, whether reinforcement from and
abuse of alcohol and other drugs define variations within a single behavioral
phenomenon, or whether reinforcement and abuse must be individually defined for
each substance involved. 2. Findings related to these issues are now being
obtained from the areas of pharmacogenetics and operant drug
self-administration. 3. The results indicate that reinforcement from alcohol and
other drugs is only moderately related to preference for alcohol and other
drugs. In addition, neurosensitivity to drugs appears to have little influence
on whether that drug will come to serve as a positive reinforcer for any given
individual or animal. Indeed, the critical factor appears to be the individual
organism's innate propensity to find a particular drug reinforcing. 4. Initial
findings also show that genotypic patterns of reinforcement from ethanol appear
to correlate highly with patterns of reinforcement from cocaine and opiates. 5.
From these findings it is concluded that there exist important genetic
determinants of drug reinforced behavior; reinforcement is an important and
independent effect of several psychoactive drugs; and drug seeking behaviors
maintained by ethanol, cocaine and opiates may have at least some common
biological determinants. [References: 53]
Schuckit MA, Hesselbrock V: ALCOHOL DEPENDENCE AND ANXIETY DISORDERS: WHAT IS THE RELATIONSHIP? American Journal of Psychiatry 1994; 151(12):1723-34.
Summary: OBJECTIVE: In this critical review the authors evaluate the
literature regarding the relationship between lifelong DSM-III-R anxiety
disorders and alcohol dependence. Many alcohol-dependent individuals demonstrate
severe anxiety symptoms in the context of acute or protracted abstinence
syndromes, but it is unclear whether these anxiety conditions are independent
psychiatric disorders or temporary syndromes likely to disappear on their own.
METHODS: Reports since 1975 describing the relationship between alcoholism and
anxiety disorders were reviewed to determine whether 1) lifelong anxiety
disorders are unusually prevalent among alcohol-dependent individuals, 2)
children of alcoholics are more likely to develop anxiety disorders than
comparison populations, 3) anxiety syndromes are likely to disappear with
abstinence, 4) the rate of alcohol dependence among subjects with lifelong
anxiety disorders is higher than normal, 5) there is familial crossover between
alcohol dependence and anxiety disorders, and 6) alcoholism is often preceded by
anxiety disorders in groups from the general population studied prospectively.
RESULTS: The interaction between alcohol use and anxiety disorders is complex.
The available data, while imperfect, do not prove a close relationship between
life-long anxiety disorders and alcohol dependence. Further, prospective studies
of children of alcoholics and individuals from the general population do not
indicate a high rate of anxiety disorders preceding alcohol dependence.
CONCLUSIONS: The high rates of comorbidity in some studies likely reflect a
mixture of true anxiety disorders among alcoholics at a rate equal to or
slightly higher than that for the general population, along with temporary, but
at times severe, substance-induced anxiety syndromes. [References: 111]
Gianoulakis C, de Waele JP: GENETICS OF ALCOHOLISM: ROLE OF THE ENDOGENOUS OPIOID SYSTEM. Metabolic Brain Disease 1994; 9(2):105-31.
Summary: At the present time alcoholism is recognized as a metabolic disease
exhibiting the clinical features of craving for alcohol, loss of control over
drinking, tolerance and physical dependence on alcohol, while both
epidemiological and experimental studies have demonstrated that genetic factors
may be important in determining whether an individual has a high or low
vulnerability to develop alcoholism. Evidence also indicates that alcoholism is
not characterized by a single gene single allele inheritance. Instead it seems
that multiple genes and environmental factors interact to increase or decrease
an individual's vulnerability to become an alcoholic. Current research is aimed
at investigating whether certain behavioral, physiological and biochemical
markers are highly associated with the incidence of alcoholism. Among the
biochemical markers currently under investigation is the endogenous opioid
system and its implication in mediating the reinforcing effects of ethanol. It
is the objective of this manuscript to review current research on: (a) the
interactions of ethanol with the endogenous opioid system at the molecular
level; (b) the existence of genetically determined differences in the response
of the endogenous opioid system to ethanol between subjects at high and low risk
for excessive ethanol consumption, as well as between lines of animals showing
preference or aversion for ethanol solutions; (c) the decrease of alcohol
consumption following pretreatment with opioid antagonists; and (d) the possible
use of specific opioid receptor antagonists together with behavioral therapy to
modify drinking behavior, to control craving and to prevent relapse.
ALCOHOL CONSUMPTION, ALCOHOL ABUSE AND ALCOHOL DEPENDENCE. THE UNITED STATES AS AN EXAMPLE. Addiction 1994; 89(11):1357-65.
Summary: This paper presents national estimates of alcohol consumption and DSM-IV alcohol abuse and dependence in the United States. Fifty-two percent of the adults surveyed were classified as current drinkers and nearly 9.0% met criteria for DSM-IV alcohol abuse or dependence. Greater percentages of males and whites were classified as current drinkers and as alcohol abusers or dependent, compared with females and non-whites, respectively. There is a need for future epidemiological research to collect better data on drinking patterns as an aid to interpreting socio-demographic differentials and to estimate more precisely the association between alcohol consumption and abuse and dependence in multivariate statistical environments. The critical need to examine the unprecedented reversal of the abuse-to-dependence ratio resulting from the application of the DSM-IV classification is emphasized. The role of future longitudinal alcohol epidemiological research in elucidating the initiation and maintenance of consumption patterns and alcohol use disorders is stressed.
Gunning WB, Pattiselanno SE, van der Stelt O, Wiers RW: CHILDREN OF ALCOHOLICS. PREDICTORS FOR PSYCHOPATHOLOGY AND ADDICTION. Acta Paediatrica 1994; Supplement. 404:7-8.
Summary: Children of alcoholics have a higher risk of psychopathology and alcoholism. Therefore, in 1993 the Amsterdam Institute for Addiction Research initiated a study on vulnerability markers and risk factors in children of alcoholics, aimed at identifying predictors for the development of psychopathology and addiction in children of alcoholics. This article provides a summary of the background, rationales and aims of the study. With more specific and sensitive biological vulnerability markers that indicate risk status, more effective preventive interventions might become available. The biochemical part of the study aims at answering the question whether adenylate cyclase is a vulnerability marker for alcoholism. The psychophysiological part is directed at event-related potentials during task performance to clarify the nature of the brain and cognitive functions that may underlie or relate to vulnerability to alcoholism. The third part, the psychological component, aims at possible psychological mechanisms of enhanced risk of addition in children of alcoholics as well as the relationship with childhood psychopathology. [References: 21]
Littleton J, Little H: CONCEPTS OF ETHANOL DEPENDENCE. Addiction 1994; 89(11):1397-412.
Summary: Alcohol dependence is considered to be divisible into two types
(although the divisions between these are indistinct). These are psychological
dependence, in which the rewarding effects of alcohol play a primary role, and
chemical dependence, in which adaptive changes in the brain initiate punishing
effects on withdrawal of alcohol, and suppression of these becomes the primary
motive for using the drug. The neurochemical basis for the rewarding effects of
alcohol may be the potentiation of GABA at GABAA receptors (causing relaxation)
and release of dopamine from mesolimbic neurones (causing euphoria). The
adaptive changes which cause the alcohol withdrawal syndrome are not known for
certain, but alterations in GABAA receptors, NMDA receptors and voltage-operated
calcium channels all have a claim. However, it is distinctly doubtful whether
these all contribute to the negatively reinforcing effects of alcohol that are
important in chemical dependence, although they may be important in other
pathological effects of alcohol abuse. Current research badly needs better
communication between basic scientists and clinicians to establish research
goals and to improve current models. [References: 75]
Abbott L, Nadler J, Rude RK: MAGNESIUM DEFICIENCY IN ALCOHOLISM: POSSIBLE CONTRIBUTION TO OSTEOPOROSIS AND CARDIOVASCULAR DISEASE IN ALCOHOLICS. Alcoholism, Clinical & Experimental Research 1994; 18(5):1076-82.
Summary: Magnesium (Mg) deficiency occurs frequently in chronic alcoholism
and may contribute to the increased incidence of osteoporosis and cardiovascular
disease seen in this population. Mg deficiency is primarily due to renal
Mg-wasting and is exacerbated by dietary Mg deprivation, gastrointestinal losses
with diarrhea or vomiting, as well as concomitant use of drugs such as diuretics
and aminoglycosides. Osteoporosis is prevalent in the alcoholic population. Mg
deficiency may contribute to increased bone loss by its effects on mineral
homeostasis. In Mg depletion, there is often hypocalcemia due to impaired
parathyroid hormone (PTH) secretion, as well as renal and skeletal resistance to
PTH action. Serum concentrations of 1,25-vitamin D are also low. These changes
are seen with even mild degrees of Mg deficiency and may contribute to the
metabolic bone disease seen in chronic alcoholics. Hypomagnesemia in alcoholics
may also contribute to increased cardiovascular disease by altering platelet
function. Mg deficiency has been demonstrated to enhance platelet reactivity. In
these studies, Mg was shown to inhibit platelet aggregation against various
aggregation agents. Patients with Mg deficiency were shown to have increased
platelet aggregation that was normalized with Mg therapy. The antiplatelet
effect of Mg may be related to the finding that Mg inhibits the synthesis of
thromboxane A2 and 12-hydroxyeicosatetraenoic acid, eicosanoids thought to be
involved in platelet aggregation. Mg also inhibits the thrombin-induced Ca2+
influx in platelets, as well as stimulates synthesis of prostaglandin I2, the
potent antiaggregatory eicosanoid. Therefore, Mg deficiency may increase
platelet aggregation and cause increased hypertension and atherosclerotic
cardiovascular disease in alcoholics.
LeMarquand D, Pihl RO, Benkelfat C: SEROTONIN AND ALCOHOL INTAKE, ABUSE, AND DEPENDENCE: CLINICAL EVIDENCE. [REVIEW]. Biological Psychiatry 1994; 36(5):326-37.
Summary: A large body of literature has emerged concerning the role of the
neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of
alcohol intake and the development of alcoholism. Despite the wealth of
information, the functional significance of this neurotransmitter remains to be
fully elucidated. This paper, part one of a two-part review, summarizes the
available clinical research along two lines: the effects of alcohol on
serotonergic functioning and the effects of pharmacological manipulation of
serotonergic functioning on alcohol intake in normal (nonalcohol dependent) and
alcohol-dependent individuals. It is concluded that considerable evidence exists
to support the notion that some alcoholic individuals may have lowered central
serotonin neurotransmission. [References: 160]
Tsai G, Gastfriend DR, Coyle JT: THE GLUTAMATERGIC BASIS OF HUMAN ALCOHOLISM. American Journal of Psychiatry 1995; 152(3):332-40.
Summary: OBJECTIVE: Although alcoholism is one of the most common psychiatric
diagnoses, understanding of its pathophysiology remains poor. Accumulating
evidence suggests that neurophysiological and pathological effects of ethanol
are mediated to a considerable extent through the glutamatergic system. This
article reviews the evidence of ethanol's effects on glutamatergic transmission
and proposes a glutamatergic basis for alcoholism. METHOD: The information was
derived from original research. The authors located more than 100 articles from
psychiatry and neuroscience journals that related ethanol to glutamatergic
transmission. They critically reviewed the neurobiology of the glutamatergic
system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS:
Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting
the response of the N-methyl-D-aspartate (NMDA) receptor. Prolonged inhibition
of the NMDA receptor by ethanol results in development of supersensitivity;
acute removal of ethanol causes marked augmentation of activity of postsynaptic
neurons, such as those in the noradrenergic system, and, in the extreme,
glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as
intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff
syndrome, and fetal alcohol syndrome, can be understood as a spectrum of
consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A
host of findings support the hypothesis that the unifying mechanism of action of
ethanol in interference with glutamatergic neurotransmission, especially through
the NMDA receptor. Alcoholism may be considered another member of the expanding
family of glutamate-related neuropsychiatric disorders. These insights should
increase understanding of the biologic vulnerabilities leading to ethanol abuse
and dependence and aid development of more effective pharmacologic
interventions. [References: 78]
Levy MS: THE DISEASE CONTROVERSY AND PSYCHOTHERAPY WITH ALCOHOLICS. Journal of Psychoactive Drugs 1992; 24(3):251-6.
Summary: This article discusses conducting psychotherapy with alcoholics in
light of the controversy about whether alcoholism is a disease. The belief that
alcoholism is a disease forces many clinicians to offer abstinence from alcohol
as the only option for alcoholics who seek treatment. From this perspective, the
alcoholic must be helped to accept the idea that he or she has a disease and
that to recover from this problem, drinking must stop. Others maintain that
alcoholism may not be a disease and view alcoholic drinking as maladaptive
behavior. From this vantage point, helping the patient to control or to moderate
drinking might be considered. These two distinct paradigms lead to divergent
treatment goals, which leaves the clinician in a quandary about how best to
treat an individual who experiences a drinking problem. To resolve this dilemma,
it is suggested that the clinician who works with alcoholics entertain a
multiplicity of perspectives and should not be blinded by any one paradigm.
While control of alcohol intake must take place if such patients are to improve
their functioning, the author argues that recovery can occur either by
abstinence or through moderating drinking. [References: 42]
el-Guebaly N, Staley D, Leckie A, Koensgen S: ADULT CHILDREN OF ALCOHOLICS IN TREATMENT PROGRAMS FOR ANXIETY DISORDERS AND SUBSTANCE ABUSE. Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 1992; 37(8):544-8.
Summary: Studies of the first-degree relatives of patients with alcoholism
and anxiety disorders have identified a significant overlap of these disorders.
Forty percent of the patients in an outpatient anxiety disorder program were
adult children of alcoholics (ACOA), a proportion similar to that found in the
substance abuse program. The ACOAs in both programs were younger, had higher
co-dependency scores and were younger when they had their first psychiatric
contact than the controls. The adult children of alcoholics who had anxiety
disorders were more likely to be female and their alcoholic parents were less
likely to have had psychiatric antecedents to alcoholism. Aside from substance
abuse, similarities in sociodemographic variables and the impact of the parents'
alcoholism were noted, reinforcing the hypothesis that vulnerabilities to
anxiety disorders and alcoholism overlap.
Ziegler PP: MONITORING IMPAIRED PHYSICIANS: A TOOL FOR RELAPSE PREVENTION. Pennsylvania Medicine 1992; 95(10):38-40.
Summary: Physicians experience a broad spectrum of health problems which can disrupt their personal lives and impair their ability to function professionally. Some of these illnesses--such as alcoholism and other drug dependency, and certain psychiatric disorders--are chronic. While treatment usually results in remission of active symptoms, there is a risk of relapse if necessary steps are not followed. Therefore, the key to continued recovery and stable functioning lies in effective relapse prevention.
Wing DM: A FIELD STUDY OF COUPLES RECOVERING FROM ALCOHOLISM. Issues in Mental Health Nursing 1992; 13(4):333-48.
Summary: Effective recovery from alcoholism demands commitment from both
partners in a marriage. The focus of this qualitative study was to learn how
couples progressed through recovery and how they achieved their goals
conjointly. The Model of Recovering Alcoholics' Behavior Stages and Goal Setting
was used as the theoretical base. Twenty-eight couples participated in the
study. The author used analytic fieldwork to learn if spouses of alcoholics
conformed to the same stages as indicated by the model and to learn the
interactive effects of alcoholics' and spouses' stages. As a result, the author
developed the Model of Alcoholic Spouses' Behavior Stages and Goal Setting. The
research has implications for planning nursing care, determining when to
intervene individually versus conjointly, and identifying indicators of relapse.
Cornelius JR, Salloum IM, Cornelius MD, Perel JM, Thase ME, Ehler JG, Mann JJ: RECENT DEVELOPMENTS IN ALCOHOLISM: PHARMACOLOGICAL TREATMENT. [REVIEW].
Recent Developments in Alcoholism 1993; 11:413-27. Summary: Neurobiological
research over the past decade has greatly expanded our knowledge of alcohol's
interaction with the nervous system and promises significant improvement in
pharmacological treatment for all phases of alcoholism. Although no new
treatment has yet become standard clinical practice, over the next decade
benzodiazepine receptor antagonists and inverse agonists should improve
treatment of acute alcohol intoxication, adrenergic agents and anticonvulsants
should improve treatment of acute alcohol withdrawal, and serotonin uptake
blockers and mu opiate receptor antagonists should improve long-term treatment
of alcohol dependence. Future clinical research should reduce the current lack
of knowledge on pharmacological treatment of alcoholism in special populations
such as women, the elderly, and those with concurrent psychiatric diagnoses.
Hoffmann NG, DeHart SS, Fulkerson JA: MEDICAL CARE UTILIZATION AS A FUNCTION OF RECOVERY STATUS FOLLOWING CHEMICAL ADDICTIONS TREATMENT. Journal of Addictive Diseases 1993; 12(1):97-108.
Summary: A sample of 3,572 chemical dependency inpatients aged 25 to 82 years
were the subjects of a study to evaluate whether observed reductions in health
care costs are associated with successful recovery from alcoholism and other
drug dependence, a function of regression to the mean, or ancillary health care
during alcoholism/drug abuse treatment. The total number of hospital days were
calculated for the year prior to treatment, and one and two years
post-treatment. Utilization rates are not significantly different between
recovering and relapsed patients prior to treatment; however, the differences
between the two groups for the first and second year post-treatment are
significant. The recovery patients showed a continued low utilization rate while
the relapsed group had considerably higher utilization in both years. Recovery
status is an essential factor to consider when determining valid cost-offsets
for medical care utilization after alcoholism/drug abuse treatment.
Bohn MJ: ALCOHOLISM Psychiatric Clinics of North America 1993; 16(4):679-92.
Summary: Several medications may help improve treatment of alcoholic
patients. Medications that effectively and specifically reverse symptoms of
alcohol intoxication or coma currently are lacking. Benzodiazepines remain the
most effective medications for the treatment of alcohol withdrawal and for the
prevention of withdrawal seizures and delirium, even though the adrenergic
agents clonidine or atenolol may hasten resolution of withdrawal symptoms and
facilitate outpatient detoxification. Psychosocial rehabilitation of alcoholics
may be improved by judicious addition of the alcohol-sensitizing agents
disulfiram and carbimide, the serotonergic drugs fluoxetine and buspirone, the
opiate antagonist naltrexone, and, for primarily depressed alcoholics, tricyclic
antidepressants. As in psychosocial alcohol rehabilitation, patient-treatment
matching may improve results of pharmacotherapeutic intervention. [References:
Chappel JN: LONG-TERM RECOVERY FROM ALCOHOLISM. [REVIEW]. Psychiatric Clinics of North America 1993; 16(1):177-87.
Summary: AA has demonstrated success in steadily increasing membership, with no loss of the proportion of those with over 5 years of sobriety. It has been recognized as effective long-term treatment for alcoholism by psychiatrists and psychoanalysts experienced in treatment of the addictions. The triennial membership surveys of AA have shown stability in 1. A 50% dropout rate within the first 3 months of starting AA. Only 41% of those in the first year will remain in the Fellowship for another year. 2. Roughly equal numbers of those with less than 1 year, 1 to 5 years, and over 5 years of sobriety, with an average length of sobriety of about 4 years. 3. Members having a sponsor (85%) and belonging to a home group (88%). 4. Attendance by members of about three meetings a week, regardless of duration of sobriety. 5. Members telling their doctor that they are in AA, but not helping him or her learn about the program. The survey data also indicate that AA is changing in the following ways: 1. The number of women members has increased to more than one third the total membership. 2. An increasing number of young people, under 30 years of age, to more than one fifth the total. 3. A decreasing number of older people, over 50 years of age, to just under one fourth the total. 4. An increasing number of members who were also addicted to other drugs (46%). Psychiatrists can use these data and knowledge of AA to 1. Increase the effectiveness of referrals of alcoholic patients to AA regardless of age, sex, race, or other characteristics. All are welcome and can benefit. 2. Deal with resistance, which occurs when patients begin to make contact with AA. 3. Help alcoholic patients through the difficult first year of sobriety. 4. Encourage their alcoholic patients to use AA as a program for personal growth and development. 5. Helping dually addicted patients use AA's singleness of purpose to facilitate their recovery. 6. Cooperate with alcohol and drug treatment programs in helping patients transfer to AA and work on an effective program of recovery. 7. Work with members of the local AA Treatment Facilities and Cooperation with the Professional Community Committees in helping alcoholic patients enter and use AA. 8. Provide psychiatric treatment for AA members in ways that support and sustain their program of recovery, especially by avoiding dependence-producing medications. [References: 13]
Collins GB: CONTEMPORARY ISSUES IN THE TREATMENT OF ALCOHOL DEPENDENCE. Psychiatric Clinics of North America 1993; 16(1):33-48.
Summary: Alcoholism treatment has certainly come of age since its inception with the founding of Alcoholics Anonymous in 1935. Although AA is a "fellowship" and is not considered "treatment" per se, the growth and proliferation of professional treatment programs has spawned a significant new sector in the health care industry, with a corresponding rise in health care cost. Because the social cost due to the destructiveness of alcoholism is enormous, however, treatment appears to be a cost beneficial investment for society, both in terms of dollars expended and in terms of the lessening of human misery. Inpatient and outpatient programs appear to be effective, but simplistic comparisons are to be avoided because their populations are frequently much different, with patients with poor prognosis indicators showing up more frequently in inpatient settings. Although outpatient treatment is undeniably cheaper initially, appreciable long-term savings may not be realized because of the greater tendency for recidivism in outpatient-treated groups. Taken as a whole, studies of treatment outcome and cost effectiveness support the view that contemporary alcoholism treatment should provide multiple levels of care, with appropriate matching of patients, depending on severity and various demographic factors. This matching may be difficult to realize in actual practice because of the wide variability among alcoholic patients. Although some patient-treatment matching criteria are now in use by insurance carriers and treatment providers, the long-term efficacy of these criteria have not been tested adequately. In the end, it may evolve that the best determinant of assignment to a particular treatment level or modality might best be done by a responsible clinician exercising good judgment based on experience and training. Appropriate legal and financial accountability for this decision should be based on standards of reasonableness, consistent with criteria used in the treatment of other medical and surgical conditions. The alcoholism clinician is performing a valuable service to humanity and to society. Social policies should support this effort by making available appropriate facilities and programs for treatment, and by promoting access through destigmatization and favorable payment and reimbursement systems. [References: 38]
Marron JT: THE TWELVE STEPS. A PATHWAY TO RECOVERY. [REVIEW]. Primary Care; Clinics in Office Practice 1993; 20(1):107-19.
Summary: Alcoholics Anonymous and its 12 Steps and 12 Traditions have arisen
out of the experiences of recovery of alcoholics. It offers an important
treatment option to the clinician who sees destructive compulsive disease in his
or her practice. Despite their nonscientific, nonrational approach, AA and other
12-step programs have evolved to offer a set of attitudes, beliefs, and
behaviors that can facilitate change in this group of patients. AA is the
forerunner of the others and offers as its most important characteristics an
unconditional acceptance of the patient's alcoholism, an unshaken belief in the
concept of alcoholism as a disease, and support to foster a healthy dependence
in the alcoholic. The recovery of an alcoholic involves a fairly long initial
stage in which denial about alcoholism is broken down with slow and halting
identity change. This characteristic underscores the primitive level of ego
development in the alcoholic and the need for much continuing support,
nurturance, and tolerance. Clinicians can be an important part of this support
network by working with AA and other 12-step groups to help break down denial in
the patient and direct individuals to the appropriate program. By allying
themselves with this method and groups, clinicians will be making powerful
statements about their beliefs and attitudes toward these destructive illnesses.
Warner ML, Mooney AJ 3d: THE HOSPITAL TREATMENT OF ALCOHOLISM AND DRUG ADDICTION. Primary Care; Clinics in Office Practice 1993; 20(1):95-105.
Summary: Inpatient treatment of alcoholism is an option indicated by certain
clinical criteria. The American Society of Addiction Medicine suggests four
levels of care, and six assessment dimensions determine which level of care is
indicated. An addiction medicine physician can consult with the primary care
physician to recommend appropriate placement in difficult cases. Abstinence is a
primary goal of treatment; for without abstinence, no other recovery will be
possible. The remaining goals of recovery are detoxification, medical
evaluation, stabilization of life-threatening emotional issues, education,
identification of barriers to recovery, readjustment of behavior toward
recovery, and orientation and membership in a self-help group. Successful family
contributions can make the difference between success or failure of treatment
goals; the role the family plays in recovery is discussed. Treatment for family
members is important; the physical, emotional, and spiritual effects on family
members can be just as profound on them as they are on the alcoholic. Continuing
care maintains the link between the patient and the professional recovery
community after discharge and is appropriate for all patients. Extended care
allows for structured support of sobriety and often further progress through
psychosocial issues identified during the initial treatment phase (i.e., abuse,
molestation, unresolved grief). Extended care is indicated for patients
requiring further structured assistance in early recovery. A large variety of
treatment options are available once the decision has been made to hospitalize
the patient. [References: 29]
Chick J: ALCOHOL DEPENDENCE--AN ILLNESS WITH A TREATMENT? Addiction 1993; 88(11):1481-92.
Summary: Unlike some countries, Britain may have experienced a rise rather
than a fall in alcohol-related illness during a decade when consumption has not
risen. Objections to the "illness concept" may impede our vision and the range
of services we develop. It is possible to agree with objectors to the illness
concept that a unidimensional view is unhelpful; that explanations are often
only attributions; that the construct "illness" is not needed for help to be
offered, its use could undermine self-mastery, and its misuse can breach civil
rights. Learning can explain much over-drinking. However, the concept need not
imply bimodality of drinkers; the syndrome of alcohol dependence has uses and
does not imply a cause; physical and mental explanations are not incompatible;
genetic and biochemical research has promise. Developments in treatment are
still limited, but the mysteries of the free-will dilemma should not prevent us
seeing physiological, psychological and social contributants as partners rather
than rivals. [References: 82]
Tucker JA, Gladsjo JA: HELP-SEEKING AND RECOVERY BY PROBLEM DRINKERS: CHARACTERISTICS OF DRINKERS WHO ATTENDED ALCOHOLICS ANONYMOUS OR FORMAL TREATMENT OR WHO RECOVERED WITHOUT ASSISTANCE. Addictive Behaviors 1993; 18(5):529-42.
Summary: Most problem drinkers do not seek formal treatment, yet some achieve
problem resolution without it. This research investigated variables related to
help-seeking and to long-term drinking outcomes in a 3 x 2 factorial design,
using 126 problem drinkers who varied in their help-seeking history (no
assistance, A.A. only, or treatment plus A.A.) and current drinking status
(abstinent more than 6 months or engaging in problem drinking). Dependent
variables included alcohol-related negative consequences, dependence symptoms,
drinking patterns, other drug use, and demographic characteristics. Formal
treatment utilization was associated with greater psychosocial dysfunction,
especially in interpersonal relationships, and with greater nonprescribed drug
use. Alcohol dependence levels were not related to help-seeking, but higher
levels were associated with an abstinent drinking status. Abstinent subjects
also showed some evidence of greater social stability, but demographic
variables, including gender, did not otherwise differentiate the groups. These
findings suggest that help-seeking and attainment of abstinence are somewhat
independent processes, but that both relate more to the functional consequences
of problem drinking than to stable drinker characteristics.
Janssen PA: ADDICTION AND THE POTENTIAL FOR THERAPEUTIC DRUG DEVELOPMENT. [REVIEW]. EXS 1994; 71:361-70. Summary: Therapeutic drug development in alcoholism could be targeted at any of the following: direct antagonism, substitution, treatment of abstinence, enhancement of aversion, modification of biodisposition, or craving. Ritanserin is a potent, centrally acting, highly selective 5-HT1C/2 antagonist which, in addition to having a sleep-regulating and anti-depression/anti-axiety effect, displays a unique pharmacological action in several animal paradigms of substance abuse which assess drug-craving. In fact, the latter pharmacological action was demonstrated after initial clinical observations suggested an effect of ritanserin in the chronic withdrawal phase after detoxification from alcohol in patients. The results of a recent double-blind, placebo-controlled, trial indicated that ritanserin did not induce aversion to drink alcohol in normal volunteers who display social drinking, but are not suffering alcohol dependence. Currently, a full clinical development program of ritanserin in cocaine and alcohol abuse is ongoing. Three major double-blind, placebo-controlled trials in alcohol dependent patients are in progress. Patients of different severity levels, ranging from mild to very severe, are studied. The dosages of ritanserin tested (2.5 mg, 5 mg, and 10 mg o.d.) are known to be well tolerated and safe. Two trials aim for relapse prevention--clinically defined in one, biochemically defined in the other-, and one trial has improved (reduced) drinking behaviour as a therapeutic goal. This program, which involves close to 900 alcohol-dependent patients, is well under way, and is still picking up momentum. [References: 23]
O'Brien CP: TREATMENT OF ALCOHOLISM AS A CHRONIC DISORDER. EXS 1994; 71:349-59.
Summary: Alcoholism is a common disorder that tends to be chronic and
relapsing. Although there is clear evidence that treatment can be expected to
induce a period of remission or at least decreased symptoms, treatment of
alcoholism is generally regarded as unsuccessful. Alcoholism should be
approached as a chronic medical disorder such as diabetes or arthritis. Complete
abstinence is the preferred goal, but "cures" or permanent abstinence from
alcohol are rare. In this model, treatment benefits may be measured by length of
remission, reduction in alcohol use, improvement in health and enhancement of
social functioning. Treatment continues over a period of years, mainly on an
outpatient basis with increasing intensity if symptoms recur. Medications that
reduce craving for alcohol or diminish the euphoric effects of alcohol would be
very helpful in the management of this chronic disorder. Pre-clinical studies
have produced evidence for involvement of the endogenous opioid system in the
reinforcing effects of alcohol. Recent controlled clinical trials of the opiate
receptor antagonist naltrexone suggest that medications of this type may improve
the results of treatment for alcoholism. [References: 21]
Lieb RJ, Young NP: A CASE-SPECIFIC APPROACH TO THE TREATMENT OF ALCOHOLISM: THE APPLICATION OF CONTROL MASTERY THEORY TO ALCOHOLICS ANONYMOUS AND PROFESSIONAL PRACTICE. Journal of Substance Abuse Treatment 1994; 11(1):35-44.
Summary: Effective treatment of alcoholism requires adopting a
psychodynamically informed case-specific approach. Control mastery theory
provides a powerful way to understand and treat the alcoholic patient. The
theory posits that individuals hold unconscious pathogenic beliefs that
contribute to the development and maintenance of alcoholism. The primary
therapeutic goal is to create a safe atmosphere that enables patients to
disabuse themselves of their maladaptive beliefs and their attendant guilt. In
this way, patients become freer to more accurately test reality and thus more
effectively pursue normal developmental goals. The treatment of the alcoholic
patient progresses through phases, each of which poses different therapeutic
challenges. The salient therapeutic tasks addressed in this article are denial,
containing affect, relapse prevention, and Alcoholics Anonymous involvement. By
understanding the individual's unique pathogenic belief system, the therapist is
better equipped to help the patient through the generic phases and tasks of the
Miller KJ: THE CO-DEPENDENCY CONCEPT: DOES IT OFFER A SOLUTION FOR THE SPOUSES OF ALCOHOLICS? Journal of Substance Abuse Treatment 1994; 11(4):339-45.
Summary: The popularity of the co-dependency concept has grown rapidly in the
alcoholism treatment field. At the same time, empirical findings gained through
scientific research have raised questions concerning the validity of the
concept. This paper discusses some of the problems that are created by the
disease model of co-dependency and highlights some alternative views that may be
more appropriate. It is argued that the field's understanding of the
alcoholic/spouse relationship and its ability to help the spouse are limited
unless other conceptualizations are seriously considered. [References: 36]
Miller WR, Kurtz E: MODELS OF ALCOHOLISM USED IN TREATMENT: CONTRASTING AA AND OTHER PERSPECTIVES WITH WHICH IT IS OFTEN CONFUSED. [REVIEW]. Journal of Studies on Alcohol 1994; 55(2):159-66.
Summary: Current popular and professional conceptions of alcoholism in the
United States blend four models that differ in their emphases and implications
and contain mutually contradictory beliefs. Elements of moral-volitional,
personality and dispositional disease models have been confused with, and
mistakenly attributed to, the essentially spiritual views of Alcoholics
Anonymous (AA). An original AA model can be distinguished from prior and
subsequent beliefs with which it has been added. Clarity regarding the essential
elements of an AA understanding of alcoholism is important both for clinicians
and for those who would undertake research on AA. [References: 46]
Khantzian EJ, Mack JE:
HOW AA WORKS AND WHY IT'S IMPORTANT FOR CLINICIANS TO UNDERSTAND.
Journal of Substance Abuse Treatment 1994; 11(2):77-92.
Summary: Alcoholism is associated with tremendous suffering, psychological
denial, and physical and emotional debilitation. Much of the suffering that
plagues alcoholics is rooted in core problems with self-regulation involving
self-governance, feeling life (affects), and self-care. Alcoholics Anonymous is
effective because it is a sophisticated group psychology that effectively
accesses, corrects, or repairs these core psychological vulnerabilities. The
traditions of storytelling, honesty, openness, and willingness to examine ("take
inventory") character defects allow people to express themselves who otherwise
do not feel or speak and help those who otherwise are deceitful (to self and
others) and would deny vulnerability and limitation to openly admit to it.
Mason BJ, Ritvo EC, Morgan RO, Salvato FR, Goldberg G, Welch B, Mantero-Atienza E:
ACETALDEHYDE ADDUCTS OF PROTEINS: DIAGNOSTIC AND PATHOGENIC IMPLICATIONS IN DISEASES CAUSED BY EXCESSIVE ALCOHOL CONSUMPTION. [REVIEW].
Scandinavian Journal of Clinical & Laboratory Investigation - Supplement 1993; 213:45-54.
Summary: Alcohol abuse and alcoholism continue to be a major threat to human health. Given their increasing incidence and the detrimental impact on society, it is actually surprising that no objective, specific indicators for the early detection of alcohol-related health problems are available. A diagnostic test for a disease involving excessive alcohol consumption should be extremely specific in order to achieve positive predictive power, and: ideally it should also be very sensitive in order to identify problem drinkers in broad screening programs. The present research indicates that such a test for alcohol abuse may be provided by measurements of covalent chemical addition products (adducts) of acetaldehyde with biologically stable macromolecules. It was recently demonstrated that proteins modified with acetaldehyde are formed in vivo and can induce an antibody response as a result of alcohol consumption. Monoclonal and polyclonal antibodies raised by immunizations against acetaldehyde-modified proteins recognize acetaldehyde adducts irrespective of the nature of the carrier protein. Use of such antibodies in sensitive two-site immunoenzymatic or immunofluorometric assays has indicated that high acetaldehyde adduct concentrations exist in the erythrocytes of alcohol abusers, in healthy volunteers after a bout of drinking, and also in alcohol consuming mothers who subsequently give birth to children with foetal alcohol effects. We have developed the first immunohistochemical techniques for the detection of acetaldehyde adducts in human tissues. The centrilobular region of the liver of alcohol abusers with an early stage of histological tissue damage was found to contain acetaldehyde-modified epitopes, whereas the adducts were more widespread in advanced liver disease. The diagnostic superiority of acetaldehyde adducts as markers of ethanol consumption is due to the fact that they represent true metabolites of ethanol and allow estimations of past alcohol consumption after the ethanol has been eliminated from the body. Investigations into the formation of acetaldehyde adducts in alcohol consumers do not only have diagnostic applications but also help to explain the pathogenesis of alcohol-induced organ damage.
Many types of hypersensitivity and immune responses are brought about by
acetaldehyde-modified proteins. In addition, such metabolites of ethanol also
aggravate liver disease through disturbed protein function and stimulation of
fibrogenesis. [References: 30]
Liberto JG, Oslin DW, Ruskin
ALCOHOLISM IN OLDER PERSONS: A REVIEW OF THE LITERATURE.
Hospital & Community Psychiatry 1992; 43(10):975-84.
Summary: Alcohol abuse and dependence in elderly persons is of growing social
concern. The most consistent findings of cross-sectional and longitudinal
studies are that the quantity and frequency of alcohol consumption is higher in
elderly men than in elderly women, as is the prevalence of alcohol-related
problems. Most studies show a decrease with age in consumption and
alcohol-related problems among heavy drinkers. Longitudinal studies show no
changes in consumption among light drinkers. Elderly persons with lower incomes
consume less alcohol than those with higher incomes. Hospitalized and outpatient
populations have more problem drinkers, and the elderly alcoholic is at greater
risk for medical and psychiatric comorbidity. About one-third to one-half of
elderly alcoholics experience the onset of problem drinking in middle or late
life. Outcomes seem to be better for those who have late-onset drinking and may
be improved for those treated in same-age rather than mixed-age groups.
Goldbloom DS, Naranjo CA, Bremner KE, Hicks LK:
EATING DISORDERS AND ALCOHOL ABUSE IN WOMEN.
British Journal of Addiction 1992; 87(6):913-9.
Summary: 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 program. 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
Mandell W, Eaton WW, Anthony JC, Garrison R:
ALCOHOLISM AND OCCUPATIONS: A REVIEW AND ANALYSIS OF 104 OCCUPATIONS.
Alcoholism, Clinical & Experimental Research 1992; 16(4):734-46.
Summary: A review of the many attempts to establish an association between
occupations and alcoholism reveals that most do not deal with data about
clinically defined alcoholism but instead use data about cirrhosis mortality,
self-reported alcohol problems, and frequent and heavy drinking. The present
study establishes an association between occupations and diagnoses of Alcohol
Dependence Disorder and Alcohol Abuse Disorder, using data from a large
population-based household interview study. Statistical adjustment using
logistic methods reveals that apparent associations between occupations and
alcohol-related disorders previously reported in the literature are due to
characteristics of those employed in various occupations. The prevalence of
alcohol dependence and abuse in two high risk industries, construction and
transportation, is confirmed. More than one in four construction laborers and
one in five skilled construction trades workers received a DIS/DSM-III diagnosis
related to alcohol abuse. In the transportation industry one in six heavy truck
drivers and material movers received an alcohol diagnosis. Analyses of the data
from individuals currently employed and not employed in their occupation reveals
reduction in risk for those who leave some occupations and increased risk for
those who leave other occupations. Evidence is presented that employment in some
occupations may be protective for Alcohol Dependence. The findings support the
view that occupation may be associated with Alcohol Dependence and Alcohol Abuse
independent of demographic variations. Previously proposed explanatory models
for associations between occupations and alcohol problems are called into
question because they do not take into account the demographic characteristics
and employment status of workers. [References: 66]
Agarwal DP, Goedde HW:
PHARMACOGENETICS OF ALCOHOL METABOLISM AND ALCOHOLISM.
Pharmacogenetics 1992; 2(2):48-62.
Summary: The pharmacogenetic differences among individuals in their capacity
to metabolize ingested alcohol are possibly responsible for the large
inter-individual and inter-ethnic variations observed in the outcome of alcohol
use and misuse. Based on results of adoption, twin, and family studies it is now
widely accepted that the vulnerability to alcoholism is determined by genetic
factors as well as by environment. There is a constant search for biological
markers and specific genes which could identify individuals genetically
predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for
alcoholism have been suggested including the alcohol metabolizing enzymes,
alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH
exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a
variant beta 2 subunit instead of the usual beta 1 subunit, differs
substantially from the usual form in its kinetic properties and is found more
frequently among the Japanese, Chinese and other Mongoloid populations than in
Caucasoids and Negroids. A widely prevalent genetic polymorphism has been
observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive
ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show
this isozyme abnormality. These metabolic polymorphisms seem to contribute to
differences in the in vivo elimination rate of ethanol and acetaldehyde, and may
explain differences in alcohol-related behaviour and its disease outcome. Taken
together, Orientals who possess an atypical ALDH2 gene are more sensitive to
acute responses to alcohol, tend to be discouraged from drinking alcohol, and
consequently are at lower risk of developing alcohol-related disorders. However,
more work is needed to support these findings. Recent advances in molecular
genetics have made it possible to analyze directly the human genome. This may
help in a better understanding of the complex genetic and environmental factors
in alcohol abuse by providing prospects for identification of gene loci which
may be responsible for predisposition to, and protection from, alcoholism.
Krahn D, Kurth C, Demitrack M, Drewnowski A:
THE RELATIONSHIP OF DIETING SEVERITY AND BULIMIC BEHAVIORS TO ALCOHOL AND OTHER DRUG USE IN YOUNG WOMEN.
Journal of Substance Abuse 1992; 4(4):341-53.
Summary: Patients with bulimia nervosa frequently have problems with
alcoholism and other substance abuse. The goal of this study was to assess
whether this relationship between eating abnormalities and substance abuse
extends to subthreshold levels of dieting and substance use. A self-administered
questionnaire assessing dieting and substance use (alcohol, cigarettes, and
marijuana) was completed by 1,796 women prior to their freshman year in college.
Using a scale derived from DSM-III-R criteria for bulimia nervosa and previous
research in this population, subjects were categorized as nondieters, casual,
intense, severe, at-risk or bulimic dieters. The relationship between the
dieting-severity category and frequency and intensity of alcohol use and
frequency of marijuana and cigarette use was assessed. DSM-III-R criteria for
bulimia nervosa were met by 1.6% of the women. Only 13.8% of these women were
nondieters. Increasing dieting severity was positively associated with
increasing prevalence of alcohol, cigarette, and marijuana use and with
increasing frequency and intensity of alcohol use. The bulimic and at-risk
dieters were similar in their alcohol and drug use. The relationship between
eating disorders and alcoholism and other substance abuse noted in clinical
populations extends in a continuous, graded manner to subthreshold levels of
dieting and substance use behaviors. Dieting-related attitudes and behaviors in
young women may be related to increased susceptibility to alcohol and drug
Shane SR, Flink EB:
MAGNESIUM DEFICIENCY IN ALCOHOL ADDICTION AND WITHDRAWAL.
Magnesium & Trace Elements 1991; 10(2-4):263-8.
Summary: The earliest description of clinical magnesium deficiency was reported in 1934. In 1954, Flink reported alcoholism as a cause of magnesium deficiency. This has been confirmed by low serum and tissue levels, balance studies, low exchangeable 28Mg and parenteral Mg retention tests. Alcohol causes urinary Mg wastage, but other mechanisms related to alcoholism contribute to the magnesium deficiency including malnutrition, gastrointestinal losses, phosphate deficiency, acidosis and/or alkalosis, vitamin D deficiency and free fatty acidemia associated with alcohol withdrawal. Mg replacement therapy is recommended to prevent some of the serious sequelae of magnesium deficiency. [References: 42]