Alcohol related disorders osmanali

Presenter

Dr Mohd Osman Ali, MBBS, DPM
CONSULTANT PSYCHIATRIST
dr_osmanali@yahoo.com

Scheme of
presentation
PART - A
• Epidemiology
• Etiology

• Chemistry and
Pharmacokinetics
• Pharmacodynamic
s

PART - B

PART – C

• Effects on the
body systems and
disorders
• Diagnostic tools
• Co-morbid
conditions
• Course and
prognosis

• Intervention
• Dexofication
• Maintenance treatment
/Rehabilitation
• Relapse prevention
• Psychosocial
approaches
• Pharmacological
approaches

ETIOLOGY OF ALCOHOL RELATED
DISORDERS
•Biological theories– genetic
factors
•Psychological theories
•Sociocultural theories
• Psychodynamic theories

Nature Vs Nurture-- Genetic factors are responsible for
approximately 60 percent of the proportion of risk for
alcoholism, while environmental factors are responsible
for the remaining 40 percent of the variance
genetic factors
enviromental factors

• the decision to drink,
• the development of
temporary alcoholrelated difficulties in
the teenage years
and the 20s,
• and the
development of
alcohol dependence.
the factors that influence the
decision to drink or those that
contribute to temporary problems
might be different from
those that add to the risk for the
severe, recurring problems of
alcohol dependence

it is postulated that different factors may be
more or less important at different stages of
the process.
•Thus, drug availability, social
acceptability, and peer pressures may be the
major determinants of initial experimentation
with a drug,
•but other factors, such as personality and
individual biology, probably are more
important in how the effects of a given drug
are perceived

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T GENETIC FACTORS
H Four lines of evidence for genetic
E factors
Close family members have a fourfold
O
increased risk.
 The identical twin of an alcoholic person
R
is at higher risk than is a fraternal twin.
I
 Adopted-away children of alcoholics
have a fourfold increased risk for
E
alcoholism even if not raised by alcoholics.
S
studies in animals support the
importance of a variety of genes in the use
of alcohol

• In a review of population-based twin studies of
alcohol dependence published since 1992,
heritability estimates ranged between 0.52 and 0.64,
with no substantial sex difference (Kendler 2001 ).
• The majority of adoption studies have shown an
excess of alcohol dependence in adopted-away
offspring of biological parents (McGue 1994 )
• One study conducted in Sweden using data from
temperance board registration showed that the
estimate of the genetic contribution to risk of the
disorder was stable across four birth cohorts over a
50-year period, despite a rapidly changing social
environment(Kendler et al. 1997 ).

• Despite evidence that a genetic factor is influential in the
transmission of alcohol dependence, exactly how risk of
the disorder is transmitted remains unknown
• Alcohol dependence appears to be a polygenic disorder
with multiple genes acting either in additive or
interactive ways.
• Two molecular genetic approaches that have been used
to identify the genes that influence risk of alcohol
dependence are
– candidate gene studies --are population-level
investigations in which genetic loci that code for
proteins thought to be important in the etiology of
the disorder are examined in samples of unrelated
individuals.
– linkage studies -- Individuals from families that
manifest the disorder are examined genetically.

Candidate gene studies
• variant forms of the alcohol-metabolizing enzymes
alcohol dehydrogenase (ADH) and aldehyde
dehydrogenase (ALDH) (Gelernter 1995 ).

– There is, in fact, evidence that a variant that
greatly reduces or eliminates ALDH function
(occurring mostly in Asian populations) is
protective against alcohol dependence, and
ADH variants that increase function may also
be protective (Thomasson et al. 1991 ).
• Genes encoding proteins in the serotonergic and
opioidergic neurotransmitter systems have also been
targeted as candidate genes for alcohol dependence--have failed provide convincing evidence

Linkage studies
• the Collaborative Study on the Genetics of Alcoholism
(COGA),
– includes more than 9,000 adults and nearly 1,500 children

and adolescents. A genomic scan of the COGA samples
showed that chromosomes 1 and 7 each have a region
containing one or more genes that increase risk of alcohol
dependence (Hesselbrock et al. 2001 ).
– In addition, COGA found evidence for a “protective factor”
on chromosome 4 (Reich et al. 1998 ).

• A linkage study has also been reported from a sample of
152 subjects belonging to extended pedigrees in a
southwestern American-Indian tribe (Long et al. 1998 ).
– A genome-wide scan was performed on 172 sibling
pairs from this sample.
– Evidence for linkage to alcohol dependence was
obtained for regions on chromosomes 4 and 11.

reflects a range of separate
characteristics, each of which affects the
vulnerability toward alcoholism
• ALCOHOL METABOLISING ENZYMES,
• IMPULSIVITY AND DISINHIBITION,
• ADDITIONAL PSYCHIATRIC DISORDERS,
• AND A LOW RESPONSE TO ALCOHOL
• *Nurnberger JI Jr, Bierut LJ: Seeking the connections: Alcoholism and our genes. Sci Am.
•

•

•

2007;296(4):46
Dick DM, Bierut L, Hinrichs A, Fox L, Bucholz KK: The role of GABRA2 in risk for conduct
disorder and alcohol and drug dependence across developmental stages. Behav Genet.
2006;36:577
Soyka M, Preuss U, Hesselbrock V, Zill P, Koller G: GABA-A2 receptor subunit gene
(GABRA2) polymorphisms and risk for alcohol dependence. J Psychiatric Research.
2008;42:184.
D'Onofrio BM, Slutske WS, Turkheimer E, Emery RE, Harden KP: Intergenerational
transmission of childhood conduct problems: A children of twins study. Arch Gen
Psychiatry. 2007;64:820.

Alcohol metabolizing enzymes
VARIATIONS IN ADH
• chromosome 4
• Additional genes that
impact the forms of ADH1B
and ADH1C,
• which are more prevalent
among Asian, black, and
Jewish individuals,
contribute to a slight increased rate
of breakdown of alcohol, with a
possible modest increase in
acetaldehyde.
This appears to have a modest
protective effect for alcohol use

VARIATIONS ALDH
• on chromosome 12

• The most relevant isoenzyme is
the low Km ALDH2 located in the
mitochondria of cells,
• and the gene responsible for the
ALDH2*2 polymorphism is seen
in approximately 50 percent of
Japanese, Chinese, and Korean
individuals..

VARIATIONS ALDH
ALDH2*2, 2*1 Heterozygotes
ALDH2*2, 2*2 homozygote
• they inherit a disulfiram (or
Antabuse)–like aversive
reaction to alcohol
• because the enzyme
cannot metabolize low to
moderate levels of
acetaldehyde
– The resulting alcoholism
risk is close to zero.

• have a mild to modest facial
flush after drinking, a higher
heart rate, and a moderately
more intense (although not more
aversive) response to alcohol.
• the level of protection is much
less for that seen for
homozygotes.
– if a person develops alcohol
dependence, he or she carries
higher risks for acetaldehyderelated damage to the brain,
liver, pancreas, and testes.

Impulsivity and disinhibition
• these characteristics are seen at
– a higher prevalence among alcoholics,
– are observed in a substantial minority of
their children,
Extreme impulsivity and disinhibition
characterize individuals with the Antisocial personality
disorder
who are both more likely to drink heavily and less likely
to demonstrate self-control when under the influence
of alcohol

and appear to reflect the action of a
range of genes,
including those coding for GABAAα 2
and CHRM2 receptors.

Additional psychiatric disorders
(schizophrenia and bipolar disorder)
• the poor judgment that can be seen in both of these major
psychiatric disorders
• and the impulsive state in mania.
• Some of the relationship might also occur as an individual
attempts to moderate
– his or her psychiatric symptoms
– or the side effects of medications
risk operates through genes
that enhance the vulnerability to several psychiatric
disorders.
And might relate to an overlap of genes responsible
for the predisposition toward substance-related
problems and those that impact on schizophrenia
and bipolar disorder

A low response(LR) to alcohol
• Because many young drinkers consume alcohol for
the intoxication effect, the need for higher doses to
achieve the desired effect leads them to drink larger
quantities.
• This subsequently affects their choice of friends to
those who are heavy drinkers, alters what they expect
from drinking, and enhances the alcoholism risk
Preliminary data have identified the potential
contribution of genes for
the serotonin transporter,
GABAAα 6 receptors,
potassium channels
and components of the second
messenger systems.

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• STRESS AND ALCOHOL INTAKE
• ONE’S EXPECTATIONS REGARDING
WHAT ALCOHOL WILL DO TO
THEM
• THE PERCEIVED PATTERN OF
DRINKING AMONG PEERS
• PERSONALITY FACTORS
• OTHER FACTORS
– Excitement
– Boasting of capacity to drink
– Young – symbol of rebellion against
the oppressive older generation
– An excuse for bad behavior

Stress and alcohol intake
The tension-reducing effects of alcohol may be modest
and most likely to be noted in light-to-moderate
drinkers.
• the strength of the interaction and the direction of the correlation is not so
obvious.
– retrospective studies-- higher stress is associated with more frequent
and heavier drinking, as well as alcohol-related problems such as
arguments and missed work
– prospective studies-- often indicate little or no impact of stress on any
particular day regarding the alcohol use pattern on that same day or in
the subsequent 48 hours.
–

At higher doses and especially at falling blood alcohol levels, most
objective measures of muscle tension and psychological feelings of
nervousness are increased (not diminished).

Veenstra MY, Lemmens PHHM, Friesema IHM, Garretsen HFL, Knottnerus JA: Literature overview of the
relationship between life-events and alcohol use in the general population. Alcohol Alcohol. 2006;41:455.

One's expectations
regarding what alcohol will
do to them( Behavioral
theory)

• Sense of well being
• Self confidence
• social interactions,
• Approval of friends
• Relation to celebration and high living
• sexual performance,
• terminating noxious states such as
pain, anxiety, or depression
• Alleviation of withdrawal symptoms

and subsequent reinforcement after
alcohol intake
•all contribute to the decision to drink again after the first
experience with alcohol and to continue to imbibe despite
problems.
•These issues are important in efforts to modify drinking
behaviors in the general population

• the paraphernalia (needles, bottles, cigarette packs) and
behaviors associated with substance use can become
secondary reinforcers, as well as cues signaling availability of
the substance, and in their presence, craving or a desire to
experience the effects increases.
• withdrawal phenomena can be conditioned (in the Pavlovian
or classic sense) to environmental or interoceptive stimuli.
– For a long time after withdrawal (from opioids, nicotine, or
alcohol), the addict exposed to environmental stimuli previously
linked with substance use or withdrawal may experience conditioned
withdrawal, conditioned craving, or both.

• The most intense craving is elicited by conditions associated
with the availability or use of the substance, such as
watching someone else use heroin or light a cigarette or
being offered some drug by a friend.

The perceived pattern
of drinking among
peers.
overestimate the usual amounts of
alcohol consumed by their friends.
they may overestimate the amount of
drinking that is
acceptable, healthy, and safe,
engage in subsequent heavier drinking
themselves.

Personality factors
pathological scores on personality tests
• are often seen during intoxication, withdrawal,
and early recovery,
• many of these characteristics have not been
found to predate alcoholism, and most disappear
with abstinence.

Also, prospective studies of
children of alcoholics who
themselves have no cooccurring disorders usually
document high risks mostly
for alcoholism.

Addictive personality-- present in
the majority of alcoholics and
associated with a propensity to lack
control of intake of a wide range of
substances and foods.
most studies have not been able to
document

Feske U, Tarter RE, Kirisci L, Pilkonis PA: Borderline personality and substance use in women. Am
J Addict. 2006;15:131.

Antisocial personality–
the extreme levels of impulsivity
seen in the 15 to 20 percent of
alcoholic men with antisocial
personality disorder
as these people have high risks
for criminality, violence, and
multiple substance
dependencies.

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• deal with self-punitive harsh superegos
• and to decrease unconscious stress levels.
• Reflection of disturbed ego function
(inability to deal with reality)

Classic psychoanalytical theory
•hypothesizes that at least some alcoholic people may
have become fixated at the oral stage of development
•and use alcohol to relieve their frustrations by taking the
substance by mouth.

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•THE NEIGHBORHOOD IN WHICH ONE LIVES
•A PERSON'S INCOME (AND THUS, THE MONEY
AVAILABLE TO BUY ALCOHOL)
• AND THE PERSON'S EDUCATION AND RELIGIOUS
BELIEFS
•ATTIDUDE OF FAMILY MEMBERS.
• often based on extrapolations from social groups that
have high and low rates of alcoholism.
• often depend on stereotypes that tend to be
erroneous, and there are prominent exceptions to these
rules.
• Jews-- It has been hypothesized that ethnic groups, such
as Jews, who introduce children to modest levels of
drinking in a family atmosphere and eschew drunkenness
have low rates of alcoholism.
• Irish men or some Native American tribes-- have high
rates of abstention but have a tradition of drinking to the
point of drunkenness among drinkers.

Although living in a lower socioeconomic
neighborhood is associated with a higher risk
for heavier drinking in general,
the probability of being a current modest
drinker actually increases with levels of
education and income

although difficult to study, it is likely that cultural attitudes toward
drinking, drunkenness, and personal responsibility for consequences
are important contributors to the rates of alcohol-related problems
in a society

Codependence
•used to designate the behavioral patterns of family members who have been
significantly affected by another family member's substance use or addiction.

Enabling and Denial
•one of the first, and more agreed on, characteristics of codependence or
coaddiction.
•because of the social pressures for protecting and supporting family members
•or because of pathological interdependencies, or both,
•unwillingness to accept the notion of addiction as a disease.
•The family members continue to behave as if the substance-using behavior were
voluntary and willful (if not actually spiteful) and the user cares more for alcohol and
drugs than for family members.
•addicts, in an effort to deny loss of control over drugs and to shift the focus of
concern away from their use, often try to place the responsibility for such use on
other family members, who often seem willing to accept some or all of it.

?? Addiction is a brain diseae

World Health Organization schematic model of drug use and dependence. (From
Edwards G, Arif A, Hodgson R. Nemenclature and classification of drug-and alcohol-related problems. A
WHO memorandum. Bull WHO. 1981;99:225

CHEMISTRY
AND

PHARMACOKINETICS
what body does to
the alcohol

•Alcoholic beverages
and Standard drinks
•Absorption
•Distribution
•Excretion
•Metabolism

C2H5OH

Alcoholic beverages
and Standard drink
BEVERAGE

%
OF
ALCOHOL

ONE STANDARD
DRINK DEFINED AS
CONTAINING 10 TO
12 G OF ETHANOL

BEER

3.6

12 OZ/ 330 ML

TABLE WINE

12

5 OZ/ 150 ML

80-PROOF SPIRITS

40

1.5 OZ/ 30 ML

Congeners
Components of alcoholic
beverages other than
alcohol. (consist of combinations of
methanol, butanol, aldehydes, phenols, t
annins, lead, cobalt, iron, and other
substances) result from method of

production

responsible for much of the
characteristic taste of the
beverage

1/3 sachet
arrack

Absorption

• well absorbed through the mucosal lining of the
digestive tract in the mouth, esophagus, and
stomach (10%)
• The most prominent area of uptake, (90%)
however, is in the proximal small intestine,
– which is also the site of absorption of many
of the B vitamins.
• Faster absorption
– from the digestive tract occurs on an empty
stomach
– and if alcohol is taken as a carbonated
beverage.
– with beverages containing 15 to 30 percent
alcohol (30 to 60 proof).
– slower drinking it
• if the concentration of alcohol in the stomach
becomes too high, mucus is secreted, and the
pyloric valve closes (pylorospasm)

Distribution

•enters the bloodstream rapidly and
distributed throughout the body
• Peak blood concentration of alcohol is
reached in 30 to 90 minutes and usually in 45
to 60 minutes
•one drink) is likely to raise the blood alcohol
level by approximately 15 to 20 mg/dL For an
average 70-kg (155 lb) person who has an average amount of
body fat

•Because alcohol is uniformly dissolved in the
body's water, tissues containing a high
proportion of water receive a high
concentration of alcohol.
•Metabolism of alcohol follows zero order
kinetics
• Acute tolerance or the Mallenby effect– The intoxicating effects are greater when the blood alcohol concentration is rising
than when it is falling or this reason, the rate of absorption bears directly on the
intoxication response

Metabolism
in the cytosol of liver

liver (90%) through oxidation
One drink in an hour 15 mg/dL
Also induces microsomal enzymes

although at high blood-alcohol levels,
down in the microsomes of the liver's
smooth endoplasmic reticulum (the
microsomal ethanol oxidizing system
[MEOS]).

ALCOHOL

ADH

in both the liver cell cytosol and
mitochondria

ACETALDEHYDE

the usual rate-limiting metabolic
step,
occurring relatively slowly because
of the liver's need to handle the
produced hydrogen ions through
the actions of a cofactor that is in
relatively short supply,
nicotinamide adenine dinucleotide
(NAD).
Women have low ADH content

ALDH

ACETATE

•This step occurs rapidly, so that the
average person does not have
substantial levels of acetaldehyde after
drinking.
•while low levels of ALDH can be both
stimulating and reinforcing,
• at high levels this substance can
release histamines and catecholamines
• that

contribute to rapid changes in
blood pressure along with nausea and
vomiting.

Excretion

Between 2 and 10 percent of the
alcohol is excreted unchanged through

Concentation exhaled in air is about
0.05% of blood concentration

sweat

the lungs

kidneys,

PHARMACODYNAMICS
what alcohol does to the body
•Alcohol effects ( acute and chronic),
•Celllualar membrane ffects
•Neurochemical effects

•reward circuitry/neurobiology of
addiction
•The mesolimbic dopamine circuit as the final
common pathway of reward
•The reactive reward system: reward from the
bottom up
•The reflective reward system: reward from top
down
•Turning reward into goal directed behavior: output
of reward system

Alcohol effects
• Pharmacology of alcohol – is still poorly characterized and its mechanism
of action is still thought to be somewhat nonspecific, since alcohol can
have effect on a wide variety of neurotransmitter system causes acute
and chronic changes
– No single molecular target has been identified as the mediator for the effects
of alcohol.
– Alcohol enhances inhibition and reduces excitation which may explain its
characterization as “depressant” of CNS neuronal functioning------ these
effects may thus explain some of its intoxicating, amnestic and ataxic effects

• Alcohols reinforcing effects are theoretically mediated by its effects
specifically a mesolimbic reward circuitry.
– This include not only actions at GABA and glutamate synapse and receptors
but also direct or indirect actions at opiate and cannabinoid synapses and
receptors

• recent research focuses on the effects of substances on the secondmessenger system and on gene regulation.

• Receptors have various effector mechanisms,
which are broadly of four types:
–
–
–
–

G protein-coupled receptors (Gs, Gi, Gq and G13)
Receptors with intrinsic ion channels
Enzymatic receptors
Receptors regulating gene expression

• The diversity of drug receptors now forces a
consideration of changes in the actual structure
of the receptor molecule or changes in the
distribution of these molecules on the surface
of the neuron.
• Drugs of abuse also have long-term effects
resulting from the expression of genes activated
as a consequence of the action of the drug.

• Alcohol enhances stress hormones such as CRF and
neuropeptide Y

Proteomics and alcoholism
Peroxiredoxin, creatine kinase, fatty acid binding protein
are some of the proteins that are upregulated in chronic
alcoholic patients.
Synuclein, tubulin and enolases are downregulated.
These proteins are associated with the neurodegeneration
in chronic alcoholism and some of these overlap with the
changes in Alzheimer's disease.
Chronic alcoholism
• During withdrawal state
– glutamate overexcitement—
neuronal damage(exctotoxicity)
(fig 2-35, 36,fig 9-46to 9-56)
– GABA deficiency

Cellular membrane effects
•alcohol produces its effects by intercalating itself into
membranes and, thus, increasing fluidity of the membranes
with short-term use.
•With long-term use, however, the theory hypothesizes that
the membranes become rigid or stiff.
•Alters the state of membrane lipids
•Activity of membrane bound enzymes like Na K ATPase and
adenyl cyclase altered
•The activity and translocation of channel enzyme proteins
in the membrane could be affected by alcohol through PKA
and PKC alteration in the state of phosphorylation
Gupta S, Kulhara P. Cellular and molecular mechanisms of drug
dependence: An overview and update. Indian J Psychiatry 2007;49:8590

Neuro chemical effects of alcohol

Alcohol action at cannabinoid
receptors (presynaptic)
• Cannabinoid antagonists such as
Rimonabant, which blocks CB1
receptors, can reduce craving in
animals dependent upon
alcohol, its is in testing for this
use in patients with alcoholism

• Dopamine-- on the pleasure centers
in the ventral tegmental area of the
brain. Alcohol acutely increases
dopamine and its metabolites.
chronic drinking changes dopamine
receptor numbers and
sensitivity.(implicated in tolerance)

Serotonin-- increase in the concentration of serotonin in
the synapse and up regulates serotonin receptors.
Low levels of cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF
HIAA) have been associated with alcoholism especially with
rapid onset, aggressiveness and severe impulsivity.
Specific serotonin reuptake inhibitors (SSRIs)-citalopram and
fluoxetine are reported to decrease alcohol consumption.

Glycine receptors (GlyR) –
in the NAc might act as targets for alcohol in its mesolimbic DAactivating effect.
Glycine and strychnine alter extracellular dopamine levels in the
NAc, probably via GlyR stimulation and blockade

Adenosine, neurosteroids, and acetylcholine.

Reward circuitry
/neurobiology of addiction

Kalivas P, Volkow N: The neural basis of addiction: A
pathology of motivation and choice. Am J Psychiatry.
2005;162:1403

Natural high
•Natural ways to trigger mesolimbic neurons to
release dopamine
– Intellectual accomplishments
– Athletic accomplishments
– Enjoying a good symphony
– Deliver normal reinforcement to adaptive
behaviors– eating, drinking, sex
•

Inputs to the mesolimbic pathway that mediate
natural high
– The brains own morphine/heroin (edorphins)
– The brains own marijuana (anadaminde)
– The brains own nicotine (acetylcholine)
– The brains own cocaine and amphetamine (
dopamine)

Artificial high

Abuse

withdrawal

Addiction

Dependence

• By psychotropic drugs of abuse(
alcohol, opiates, stimulants,
benzodiazapine, sedative hypnotics,
hallucinogens, nicotine)
• Bypass the brains own
neurotransmitters and directly
stimulate the brains receptors in the
reward system calling dopamine release
• a drug induced reward causes such
wonderful feeling of dopamine to
postsynaptic limbic dopamine neurons
• that they furiously crave even more
drug to replenish dopamine once the
drug stop working,
• leading one to preoccupied with
finding drug and thus beginning a
various cycle of abuse, addiction,
dependence and withdrawal

• Upon repeated exposure to drugs of abuse, this
reactive rewars system pathologically
– “Learns” to trigger drug seeking behavior
– And “remembers” how to this when confronted with
internal cues such as craving and withdrawal and
external cues from the environment such as
people, places, and paraphernalia associated with
past drug use
– Modification of brain circuits by plastic changes (Fig
2-22 to 2-31) and Diabolic learning (Fig 8-6 a,b,c)
(also applies to – chronic pain, for symptoms
triggered by stress)

• The net result of these changes is that reactive
reward system hijacks the entire reward circuitry
when addiction has developed

• CSTC also involved in ADHD (Fig 17—3,4,5,6 )Impulsive
drug In ADHD
• Additional inputs for such as final decision also comes
from two areas
– The insula and sensory cortex, contributing feelings
about prior experiences of reward and punishment
– The hippocampus, providing contextual information
about the decision to be made

• When all the inputs are integrated, the final
output is either to stop the action that the
reactive reward system is triggering or let it
happen

• The reflective reward system is built and maintained over time based
upon various influences
– Neurodevelopment
– Genetics
– Experience
– Peer pressure
– Learning social rules
• Learning to benefits of suppressing current pleasure for more valuable
future gain.
• When fully developed and functioning properly, the reflective reward
system can also provide the motivation for pursuing more naturally
rewarding experiences such as
–
–
–
–
–
–

Education
Accomplishment
Recognition
Financial benefits
Career development
Enriching social and family connections

• After repetitive reward experiences with the drug,
the reward circuit becomes “addicted,” so that next
time there is an opportunity to use the drug, it is not
just the ingesting of the drug that causes dopamine
release and pleasure, the cues that predict hedonistic
pleasure already cause dopamine release
– The reward system has learned to anticipate the reward,
and that anticipation itself becomes pleasurable
– Getting the anticipatory reward is compelling action
– Reward is overvalued and hyperactive by virtue of the
diabolic learning that has occurred in reward circuits
– Synaptic plasticity changes the efficiency of the
information flow in the reactive reward circuitry to allow
its neuronal activity to preempt all contradictory input
coming from the reflective reward circuit in the prefrontal
cortex

Temptation
• Bottom up demand from the
reactive reward system
• Diabolic learning
• Short term rewards

Will power
• Top down decision making by the
reflective reward system
• virtuous learning
• Suppress short term for long term gains

Significance of reward circuitry
• Several other disorders thought to be regulated by reward
circuitry
– Sexual disorders
– Eating disorders
– Various impulse disorders such as gambling
• Psychiatric disorders where reward circuitry has a prominent role
– Disorders of impulsivity—ADHD, bipolar disorder, anxiety
disorder-OCD
– Disorders of motivation– major depression, apathy in
dementia in schizophrenia
– Use and abuse of stimulants and sedatives hypnotics in sleep
/wake disorders
• Substance abuse is good example of how the normal mechanisms
of learning are hijacked and built into brain disorder
Currently, modern diagnostic thought is concentrating on a more precise definition of
addiction for forthcoming DSM V , focusing on compulsive behavior marking a distinction
from the DSM- IV criteria for substance dependence per se (O’Brein et al. 2006)

ALCOHOL EFFECTS ON
THE BODY SYSTEMS

neuropsychaitric effects
And disorders
• Alcohol as a depressant drug
•Alcohol intoxication
•Alcohol withdrawal state
•Alcohol dependence syndrome
•Alcohol-induced conditions
•Nutritional def effects

Nonneruological effects
•Peripheral neuropathy,
• Gastrointestinal problems,
• Cerebrovascular and
cardiovascular problems,
•Blood producing system,
• cancer,
•Fetal alcohol effects,
•Other problems

Four Effects of alcohol on CNS
• Direct effects- depressant of CNS functioning highly dose
sensitive
• A series of disorders– fits, hallucinoses, delirium
tremens, which are largely due to alcohol withdrawal
• Associated nutritional defects- leading to variously to
Wernicke’s encephalopathy, Korsakoff’s
syndrome, peripheral neuropathy and perhaps cerebellar
degeneration
• Resulting end-stage liver disorder or bone marrow
suppression may ensue with their own neuropsychiatric
complications

Alcohol as a
Depressant drug

• Eg;(sedative hypnotics-benzodiazepines, barbiturates, and related
drugs
• production of somnolence and decreased
neuronal activity but not powerful in
attenuating pain.
• are physically addicting, with similar types
of withdrawal syndromes. produce similar
types of intoxications, produce crosstolerance with other depressants,
• are potentially lethal in overdose
(especially when multiple depressant
drugs are taken at the same time)
• The cortex and reticular acivity are more
sensitive--- causes slowing of reflexes
(driving dangerous)

Sleep
Impairment

Sleep latency—
decreased
Alcohol helps a person
fall asleep more quickly

Sleep architecturre—impaired
After abstinence
• Exaggerated forms of
sleep problems seen
• sleep stages might not
return to normal after
3 or more months.
• More sleep problems
associated with a
greater risk for relapse
•

• If the intake in an evening is more than one or two
drinks- Alcohol suppresses rapid eye movements
(REM sleep), and inhibits stage 4 sleep late in the
night,
– and is subsequently associated with frequent
alternations between sleep stages (sleep
fragmentation)
– as well as with more intense and disturbing
dreams late in the night as the blood alcohol level
falls.

• After heavy drinking people are likely to awaken
after several hours and have problems falling back
Van Reen E, Jenni OG, Carskadon MA: Effects
asleep.
of alcohol on sleep and the sleep
electroencephalogram in healthy young
women. Alcohol Clin Exp Res. 2006;30:974

Alcohol intoxication
The term intoxication is used for a reversible
nondependent experience with a substance
that produces impairment

•The effects of alcohol consumption are
•sensitive to dose ( measured as blood alcohol level )
•timing(rising versus declining phase), acute tolerance or the Mallenby
effect-The intoxicating effects are greater when the blood alcohol
concentration is rising than when it is falling
•and social context

Level
20–30 mg/dL

Likely Impairment
Slowed motor performance and decreased thinking ability

30–80 mg/dL
80–200 mg/dL

Increases in motor and cognitive problems
Increases in incoordination and judgment errors
Mood lability
Deterioration in cognition

200–300 mg/dL
>300 mg/dL

Nystagmus, marked slurring of speech, and alcoholic
blackouts
Impaired vital signs and possible death

The legal definition of
intoxication

80 or 100 mg ethanol per dL of blood (mg/dL) in the United States 17.4
mmol/L

Pharmacologic tolerance

•

approximately 150 mg/dL

•

One does not show significant levels of impairment in motor and mental
performance
In that range, most people without tolerance also experience nausea and
vomiting.

•

one drink

•

is likely to raise the blood alcohol level by approximately 15 to 20
mg/dL For an average 70-kg (155 lb) person who has an average amount of body fat

•

The same metabolised in an hour

Treatment of intoxication
• Gastric lavage unnecessary
• Episodes of paranoid or combative behavior may, on occasion,
require sedation with major tranquilizers, but there are obvious
hazards of involved in adding one cerebral depressant to another
• Alcohol coma is medical emergency should be managed in
hospital
• Care is needed to exclude
–
–
–
–
–

coincident head injury and its complications,
gastrointestinal bleeding,
hepatic failure,
Pneumonia
or meningitis

• Blood should be taken to confirm
– the presence of significant amounts of alcohol
– and to exclude alcoholic hypoglycemia

• If glucose containing fluids are transfused, thiamine must always
be given in case Wernick’s should be precipitated

Idiosyncratic alcohol intoxication (pathologic, complicated, atypical, and
•

•

•
•

•

paranoid alcohol intoxication; Manie a potu/ acute alcoholic paranoid state)
a severe behavioral syndrome develops rapidly after a person consumes a small
amount of alcohol that would have minimal behavioral effects on most persons
– usually described as lasting for a few hours, terminates in prolonged sleep,
– and those affected cannot recall the episodes on awakening
– it is reported to be most common in persons with high levels of anxiety.
Some persons with the disorder reportedly showed temporal lobe spiking on an
EEG after ingesting small amounts of alcohol. This condition must be
differentiated from other causes of abrupt behavioral change, such as complex
partial epilepsy.
The diagnosis is important in the forensic arena because alcohol intoxication is
not generally accepted as a reason for judging persons not responsible for their
activities.
Hypothesis–
– alcohol causes sufficient disorganization and loss of control to release
aggressive impulses.
– brain damage, particularly encephalitic or traumatic damage, predisposes
some persons to an intolerance for alcohol and thus to abnormal behavior
after they ingest only small amounts.
– Other predisposing factors may include advancing age, using sedativehypnotic drugs, and feeling fatigued
injection of an antipsychotic drug, such as haloperidol (Haldol), is useful for
controlling assaultiveness.

• It consists of a dense amnesia for
significant events that have occurred
during a drinking episode, when at
the time outward behaviour seemed
little disoriented

Blackout

•not part of the DSM-IV-TR
• and is distinct from alcohol-induced
persisting amnestic disorder, formerly
known as Wernicke-Korsakoff
syndrome
•
•

Usually the gap extends for a period of several hours, but very occasionally it
may cover several days
Blackouts were rarely seen unless large amounts of alcohol were being
consumed, chiefly in the form of spirits

• common

phenomenon (As many as 40 percent of drinkers )
•The periods of amnesia can be particularly distressing when persons fear that they
have unknowingly harmed someone or behaved imprudently while intoxicated.
•During a blackout, persons have relatively intact remote memory but experience a
specific short-term memory deficit in which they are unable to recall events that
happened in the previous 5 or 10 minutes
• Because their other intellectual faculties are well preserved, they can perform
complicated tasks and appear normal to casual observers.
•The neurobiological mechanisms for alcoholic blackouts are now known at the
molecular level;
•alcohol blocks the consolidation of new memories into old memories, a process
that is thought to involve the hippocampus and related temporal lobe
structures.
•

Goodwill et al also noticed a fairly strong association with a prior history of head injury

• Enbloc blackouts
• Fragmentary blackout– the subject was unaware that events had been forgotten
until he was told about them later. Some time in this variety the memories might
return with the passage of time , and sometimes recall was facilitated by further
drinking
• The pathogenesis of these episodes remains uncertain. An interesting suggestion
is that they may represent the effects of ‘ state dependent learning’

Alcohol and aggression
• Variety of mechanisms
– Psychostimulant effects
– Diminished anxiety and pain perception
– And impaired inhibition

Alcohol withdrawal/abstinence state
• A substance-specific syndrome that occurs after stopping or reducing the
amount of the drug or substance that has been used regularly over a
prolonged period of time
• characterized by a group of symptoms that are the opposite of what was
initially experienced with intoxication.
• develops because the brain has adapted to the presence of a brain
depressant and cannot function adequately in the absence of the drug.

Conditions that may
predispose to, or
aggravate, withdrawal
symptoms include
fatigue,
malnutrition,
physical illness,
and depression

95 percent --mild or moderate
symptoms,
for 3 to 5 percent-- convulsions
or delirium.(each <1 percent)

6 to 8 hours

•Beginning of withdrawals
•Tremulousness

8 to 12 hours

•the psychotic and perceptual symptoms

12 to 24 hours

• peak intensity of withdrawal
•seizures

72 hours,
(3rd day)

•peak intensity of withdrawal
•DTs
•although physicians should watch for the development of DTs for the first
week of withdrawal.
•The syndrome of withdrawal sometimes skips the usual progression and,
for example, goes directly to DTs.

fourth or fifth day

•Diminishing of withdrawal

2 to 6 months after
the acute
withdrawal

•Protracted withdrawal

• The precise mechanisms
underlying these disorders are far
from clear. Where hallucinoses
and delirium tremens are
concerned several complex
factors are probably at work
• Sleep and withdrawal–
– abrupt rebound with great
excess of REM sleep.
Immediately prior to an
attack of delirium tremens,
REM sleep may occupy the
whole sleeping time
– It has been suggested that
the vivid hallucinations of
delirium tremens may
represent a ‘spilling over’ of
this active dream material
awakening life

• Hemmigsen and Kramp
(1988) suggested that
withdrawal reactions consist
essentially of two
components:
– Physical sign such as tremor
determined by the degree
of physical dependence
developed during the most
recent drinking bout
– And seizure, hallucinations
and delirium that reflect
long-term CNS dysfunction
accruing over many years of
repeated intoxication and
withdrawal

• A combination of both
factors may be operative in
some of withdrawal
phenomenon encountered

• the spectrum of symptoms can expand to include
– tremulousness
– psychotic and perceptual symptoms (e.g.,
delusions and hallucinations),
– seizures,
– and the symptoms of delirium tremens (DTs),
called alcohol withdrawal delirium in DSM-IVTR.
• Other symptoms of withdrawal include
– general irritability,
– gastrointestinal symptoms (e.g., nausea and
vomiting),
– and sympathetic autonomic hyperactivity,
including anxiety, arousal, sweating, facial
flushing, mydriasis, tachycardia, and mild
hypertension.
– Patients experiencing alcohol withdrawal are
generally alert but may startle easily.

Mild to moderate
withdrawal
Alcoholic tremor
• The classic sign of alcohol withdrawal is tremulousness, (commonly
called the “shakes” or the “jitters”)
– can be similar to either physiological tremor, with a continuous tremor of great
amplitude and of more than 8 Hz,
– or familial tremor, with bursts of tremor activity slower than 8 Hz

• The commonest withdrawal effect
• Is usually associated with general weakness, nausea and irritability.
• In mild form it can occur after a single night’s abstinence and after a
period of drinking of only several days
• In sever form it usually occurs 12– 24 hours after stopping , and only
after several weeks of continuous drinking
• Usually the disorder subsides over several hours or days, but after
several attack it may be 1 or 2 weeks before the patient is composed and
can sleep without sedation

Hallucinosis
• Approximately one quarter of tremulous patients have disordered sense
perception, ranging from transitory misperceptions of familiar objects to
illusions and hallucinations
• Hallucinations usually occur in both the visual and auditory modalities,
are generally fleeting, and emerge in clear consciousness
• The absence of disorientation , confusion and psychomotor over activity
is important in distinguishing the condition from delirium tremens
• It is usually benign condition , lasting often less than 24 hrs and rarely for
more than few days
• Tinnitus is common with auditory hallucinations, antedating their
appearance and persisting after they have cleared
• Visual disturbance in the form of blurring , flashes and spots are usually
repotted by patients with formed visual hallucinations
• The visual hallucinations are mostly of small animals such as rodents and
insects, characteristically moving rapidly on the walls, floor or ceiling
• Occassionally patients however develop hallucinations while continuing
to drink, and in these it has been suggested that thiamine deficiency may
be contributory cause (Morgan 1968)

Alcoholic hallucinoses
• Term sometimes used in a more restricted sense to
refer to the relatively rare condition in which verbal
auditory hallucinations occur alone, again in a setting
of clear consciousness
• Picture strongly resembles schizophrenia
• Sometimes the voices command the patient to do the
things against his will, and their compelling quality
may be such that he is driven to a suicide attempt or
some episode of bizarre behaviour
• Secondary delusional interpretations follow upon the
hallucinatory experiences, and the patient come to
believe firmly that he is watched, hounded or in
danger

Detoxification – rx of mild to moderate withdrawal
•

Treatment can focus on giving enough of a brain depressant
on the first day to diminish symptoms
• and then weaning the patient off the drug over the next 5
days to both diminish symptoms and minimize the
possibility of a severe withdrawal.
Any depressant, including alcohol, barbiturates, or a
benzodiazepine, can work, but most clinicians choose a
benzodiazepine for its relative safety.
•the benzodiazepine can often be decreased by almost 20
percent each subsequent day, with a resulting need for no
further medication after 4 or 5 days.
•However, the dose should be raised back to the initial
dose if the patient does not respond well to the taper.
• long acting Vs short acting chlordiazepoxide Vs Lorazepam

Other agents (propranolol and clonidine)
•do little to decrease the risk of seizures or delirium
•And have the drawback of masking the withdrawal
signs, such as tremor and elevated blood pressure, that
need to be used to monitor the severity of the withdrawal
carbamazepine
•studies have shown that carbamazepine (Tegretol) in daily
doses of 800 mg is as effective as benzodiazepines and has
the added benefit of minimal abuse liability.

A nonmedication-based program of detoxification
• saves money by avoiding medications while using social
supports.
• This less expensive regimen can be helpful for mild or
moderate withdrawal syndromes.

Severe alcohol withdrawal -convulsions (rum fits)
•1 percent or so of patients may have a single grand mal
convulsion. The rare person has multiple fits, and the peak
incidence is on the second day of withdrawal.
•Such patients require a neurological evaluation the cause of the
seizures is difficult to establish when a patient is first assessed in
the emergency room; thus, many patients with withdrawal
seizures receive anticonvulsant medications, which are then
discontinued once the cause of the seizures is recognized.

•Seizure activity in patients with known alcohol abuse histories
should still prompt clinicians to consider other causative
factors, such as head injuries, CNS infections, CNS
neoplasms, and other cerebrovascular diseases; long-term severe
alcohol abuse can result in hypoglycemia, hyponatremia, and
hypomagnesaemia—all of which can also be associated with
seizures.
•The consumption of alcohol can precipitate fits in a person suffering from
epilepsy
•Very occasionally they occur while consumption continues, presumably as a
result of transient falls in the blood alcohol content
•If a focal component exists, this is likely to be the result of trauma in addition
to alcoholism EEG is abnormal at the time of fits , but reverts to normal
thereafter. It remains in the interval between, thus discrediting the wide belief
that they represent a latent epileptic process that has been brought to light
(Victor 1966)
•but in the absence of evidence of an independent seizure disorder, those
with a single seizure do not benefit from anticonvulsant drugs.

alcohol withdrawal
delirium
• For the less than 5 percent of intoxications and withdrawals
• accompanied by severe cognitive symptoms--agitated confusion,
associated with tactile or visual hallucinations
• Untreated, DTs has a mortality rate of 20 percent, usually as a
result of an intercurrent medical illness such as pneumonia, renal
disease, hepatic insufficiency, or heart failure.
• Although withdrawal seizures commonly precede the
development of alcohol withdrawal delirium, delirium can also
appear unheralded.
• The essential feature of the syndrome is delirium occurring within
1 week after a person stops drinking or reduces the intake of
alcohol.

•

•

•
•
•

Patients with delirium are a danger to themselves and to others.
Because of the unpredictability of their behavior, patients with
delirium may be assaultive or suicidal or may act on hallucinations
or delusional thoughts as if they were genuine dangers
Because the syndrome usually develops on the third hospital day,
a patient admitted for an unrelated condition may unexpectedly
have an episode of delirium, the first sign of a previously
undiagnosed alcohol-related disorder.
Episodes of DTs usually begin in a patient's 30s or 40s after 5 to 15
years of heavy drinking, typically of the binge type.
Physical illness (e.g., hepatitis or pancreatitis) predisposes to the
syndrome; a person in good physical health rarely has DTs during
alcohol withdrawal.
The emergence of focal neurological symptoms, lateralizing
seizures, increased intracranial pressure, or evidence of skull
fractures or other indications of CNS pathology should prompt
clinicians to examine a patient for additional neurological disease.

• there is no perfect treatment. The best treatment for DTs
is prevention.
• The first key step is to ask why such a severe and relatively
uncommon withdrawal syndrome has occurred;
– the answer often relates to a concomitant medical problem
that needs immediate treatment.

• The withdrawal symptoms can then be minimized either
– through the use of benzodiazepines (in which case high doses
are sometimes required)
or through antipsychotic agents such as haloperidol (Haldol).

• Once the delirium appears, however, 50 to 100 mg of

chlordiazepoxide should be given every 4 hours orally, or
lorazepam (Ativan) should be given intravenously (IV) if oral
medication is not possible
•Antipsychotic medications that may reduce the seizure
threshold in patients should be avoided

• high-calorie, high-carbohydrate diet supplemented by
multivitamins is also important.
• Physically restraining patients with the DTs is risky; they may
fight against the restraints to a dangerous level of
exhaustion. When patients are disorderly and
uncontrollable, a seclusion room can be used.
• Dehydration, often exacerbated by diaphoresis and fever,
can be corrected with fluids given by mouth or IV.
• Nonbenzodiazepine anticonvulsant medication is not useful
in preventing or treating alcohol withdrawal convulsions,
although benzodiazepines are generally effective.
• Warm, supportive psychotherapy in the treatment of DTs is
essential. Patients are often bewildered, frightened, and
anxious because of their tumultuous symptoms, and skillful
verbal support is imperative.

Protracted Withdrawal
symptoms of anxiety, insomnia, and mild autonomic
overactivity in mild form
•are likely to continue for 2 to 6 months after the acute
withdrawal has disappeared
•At least theoretically, these protracted withdrawal symptoms
may enhance the probability of relapse
• no pharmacological treatment for
this syndrome appears
appropriate,
• it is possible that some of the
medications for the rehabilitation
phase, especially acamprosate
may work, at least in part, by
diminishing some of symptoms.

•It is important that the clinician
warn the patient that some level of
sleep problems or feelings of
nervousness might remain after
acute withdrawal

•and discuss cognitive and
behavioral approaches that might
be appropriate to helping the
patient feel more comfortable.

Drug Therapy for Alcohol Intoxication and Withdrawal
Clinical Problem
Drug
Tremulousness and Chlordiazepoxide
mild to moderate
agitation
Diazepam

Route
Oral
Oral

Hallucinosis

Lorazepam

Oral

Extreme agitation

Chlordiazepoxide

Intravenous

Withdrawal
seizures

Diazepam

Intravenous

Delirium tremens

Lorazepam

Intravenous

Dosage
Comment
25–100 mg every 4– Initial dose can be
6 hr
repeated every 2 hr
5–20 mg every 4–6 until patient is
calm; subsequent
hr
2–10 mg every 4–6 doses must be
individualized and
hr
titrated
0.5 mg/kg at 12.5 Give until patient is
mg/min
calm; subsequent
doses must be
0.15 mg/kg at 2.5
individualized and
mg/min
titrated
0.1 mg/kg at 2.0
mg/min

(Adapted from Koch-Weser J, Sellers EM, Kalant J. Alcohol intoxication and withdrawal. N Engl J
Med. 1976;294:757.)

Alcohol Dependence Syndrome
Body cannot function optimally unless the brain depressant is present
and where rebound (or withdrawal) symptoms develop if the depressant
drug is stopped too quickly
The key to diagnosis of alcohol abuse and dependence - heavy and repetitive use of alcohol to the point of Dependence has
developing recurrent problems.
been defined as a
• Quantity and frequency of alcohol intake,
cluster of
– while useful, are often not sufficient to establish the
behavioral, cognitive
threshold
and physiological
– because of the large variation in the amounts of alcohol
required for problems across men versus women, larger
phenomena that
versus smaller individuals, and older versus younger people.
develop after
• Repetitive problems
repeated substance
– Emphasis is placed on this-- a person keeps using despite
problems.
use
–

This, in turn, predicts the probability that a return to
drinking is likely to be associated with the re-establishment
of problems.

Tolerance
Phenomenon in which, after repeated administration, a given dose of
drug produces a decreased effect or increasingly larger doses must
be administered to obtain the effect observed with the original
dose.
THREE
PROCESSES

•Behavioral tolerance-- reflects the ability of a person to learn
through practice how to perform tasks effectively while
experiencing the effects of alcohol.
NEURO ADAPTATION
•Pharmacokinetic tolerance-- involves adaptations of the
metabolizing systems, including ADH and MEOS, to rid the body
of alcohol more rapidly.
•pharmacodynamic or cellular tolerance-- is an adaptation of the
nervous system so that it can function despite very high blood
alcohol concentrations (e.g., as much as 600 mg/dL), by resisting
the actions of alcohol on the cell.

Cross-tolerance/cross
tolerance
• Refers to the ability of
one drug to be
substituted for another,
each usually producing
the same physiologic
and psychological
effect (e.g., diazepam
and barbiturates).

if an individual takes two
depressant drugs at the
same time
• tolerance is not likely
to be observed, and
the effect of one drug
can magnify, or
potentiate, the effects
of the other, with a
potentially lethal
outcome

Craving

• classical conditioning
• and also reflect
neurochemical changes.
– On neuroimaging, when
substance-dependent subjects
see images of their preferred
drug, activation occurs in

The motivation to seek
out alcohol

• the limbic system,
• the orbitofrontal and
insular cortex,
• in the cerebellum.
– an increased number of mu
opioid receptors, especially
during early abstinence, and
these may contribute to an
enhanced intensity of craving.

The drinking patterns are often associated with certain
behaviors:
• the inability to cut down or stop
drinking;
• repeated efforts to control or reduce excessive drinking by “going
on the wagon” (periods of temporary abstinence)
• or by restricting drinking to certain times of the day;
• binges (remaining intoxicated throughout the day for at least 2
days);
• occasional consumption of a fifth of spirits (or its equivalent in
wine or beer);
• amnestic periods for events occurring while intoxicated
(blackouts);
• the continuation of drinking despite a serious physical disorder
that the person knows is exacerbated by alcohol use;
• and drinking nonbeverage alcohol, such as fuel and commercial
products containing alcohol

Abuse and harmful use
DSM IV Vs ICD-10

• Alcohol abuse is repetitive
legal, interpersonal, social,
or occupational
impairments related to
alcohol
• or the repetitive use of
relevant levels of alcohol in
hazardous situations.

• Harmful use defined as
repeated interference with
psychological and physical
health functioning.

Not surprisingly, reflecting differences in the criteria items in the two systems,
persons with harmful use are not likely to meet criteria for DSM-IV-TR abuse,
and visa versa.

Misuse usually applies to drugs prescribed by physicians that are not used
properly.

Heavy drinking vs reduced risk drinking
Heavy drinking
• Five or more drinks per day
for a month
• And four or more for a
woman
• On the road to recovery
heavy drinkers might first
reduce their drinking before
they become abstinent

• Ref; stahl 3rd

Reduced risk drinking
• 3—4 drinks/day max
drink/week
• 2—3 drinks / day (max 12
drinks / weeks)
• Avoid pathological behavior
patterns
– Avoid having more than one
drink in an hour
– Avoid drinking pattern (same
people, same location, same
time of the day)
– Avoid drinking to deal with the
problems

SUBTYPES OF ALCOHOL DEPENDENCE 1

Type A alcoholism
• the onset of alcoholism
after age 40 Few
childhood riskfactors
• tends to be associated
with less severe social
difficulties and more
subtle alcoholic signs and
symptoms,
• but a greater likelihood
of medical problems.
• May respond to
interactional
psychotherapies

Type B alcoholism
• early onset alcohol
dependence syndrome,
• A more severe
accompanied by
criminality and
dependence on other
drugs
• with an elevated risk for
a concomitant antisocial
personality disorder
• May respond to training
in coping skills


early-stage
problem
drinkers
• who do not yet
have complete
alcohol
dependence
syndromes;

affiliative
drinkers
• who tend to
drink daily in
moderate
amounts in
social settings;
and

schizoid-isolated
drinkers
•who have severe
dependence and
tend to drink in
binges and often
alone.


Gamma alcohol dependence
• which is thought to be
common in the United States
and represents the alcohol
dependence seen in those
who are active in Alcoholics
Anonymous (AA).
• This variant concerns control
problems in which persons are
unable to stop drinking once
they start.
• When drinking is terminated
as a result of ill health or lack
of money, these persons can
abstain for varying periods.

Delta alcohol dependence
• perhaps more common in
Europe than in the United
States,
• persons who are alcohol
dependent must drink a certain
amount each day but are
unaware of a lack of control.
•The alcohol use disorder may
not be discovered until a
person who must stop drinking
for some reason exhibits
withdrawal symptoms


Type I,
male-limited variety of
alcohol dependence
•

characterized by late
onset,
• more evidence of
psychological than of
physical dependence,
• and the presence of guilt
feelings.

Type II,
male-limited alcohol
dependence
• is characterized by onset at
an early age,
•spontaneous seeking of
alcohol for consumption,
•and a socially disruptive set
of behaviors when
intoxicated

Antisocial alcoholism

Negative-affect alcoholism

•

•which is more common in
women than in men;
•according to this hypothesis,
women are likely to use alcohol
for mood regulation and to help
ease social relationships.

•
•
•

Typically with a predominance
in men,
a poor prognosis,
early onset of alcohol-related
problems
and a close association with
antisocial personality disorder.

Developmentally cumulative
alcoholism

Developmentally limited
alcoholism

•with a primary tendency for
alcohol abuse that is exacerbated
with time as cultural expectations
foster increased opportunities to
drink

• with frequent bouts of consuming
large amounts of alcohol;
•the bouts become less frequent as
persons age and respond to the
increased expectations of society
about their jobs and families.

Psychological dependence
• Often occurs even with
moderate drinking
• Psychological dependence, also
referred to as habituation, is
characterized by a continuous or
intermittent craving for the
substance to avoid a dysphoric
state.
• Acutely, all substances of abuse
can change how a person feels,
often in a way perceived as
pleasurable,
• thus enhancing the drive to
continue to take the drug despite
potential consequences

Physical dependence
• that produces the withdrawal, or
an abstinence syndrome
• that characterizes some drugs of
abuse, but not others.

Alcohol Induced Conditions
alcoholism is the major
disorder
•is no evidence that the
additional psychiatric
syndromes either clearly
antedated the severe alcohol
problems
•or persisted for about 4 or
more weeks during a period
of abstinence

psychiatric syndrome is major
disorder
• meet full diagnostic criteria, not
mere isolated symptoms such as
sadness or nervousness,
• in excess of those usually
associated with intoxication or
withdrawal.
– Even if the psychiatric
symptoms are intense, they
do not indicate a separate
psychiatric syndrome if they
are noted only during
intoxication or withdrawal

ALCOHOL-INDUCED PSYCHOTIC DISORDER
• 3 percent of alcoholic people
• experience auditory hallucinations and/or paranoid
delusions
– Many of the symptoms resemble those seen in schizophrenia,
(shiz like)

• in the context of heavy drinking and withdrawal.
• they are likely to clear spontaneously within a few days
to a month of abstinence.
• The syndromes are likely to recur only if heavy alcohol
intake resumes.

Alcohl induced psychotic disorder -hallucinations
•

•

The most common hallucinations are auditory, usually voices,
but they are often unstructured.
– The voices are characteristically maligning, reproachful, or
threatening, although some patients report that the
voices are pleasant and nondisruptive.
The hallucinations usually last less than a week, but during
that week impaired reality testing is common.
– After the episode, most patients realize the hallucinatory nature
of the symptoms.

•

•
•

Hallucinations after alcohol withdrawal are considered rare,
and the syndrome is distinct from alcohol withdrawal delirium
--consider other psychotic disorders in the differential
diagnosis
The hallucinations can occur at any age, but usually appear in
persons abusing alcohol for a long time.
Alcohol withdrawal-related hallucinations are differentiated
from the hallucinations of schizophrenia by
– the temporal association with alcohol withdrawal,
– the absence ofa classic history of schizophrenia,
– and their usually short-lived duration.

•

Alcohol withdrawal-related hallucinations are differentiated
from the DTs
– by the presence of a clear sensorium in patients.

The treatment of
alcohol withdrawalrelated hallucinations
is much like the
treatment of DTs—
benzodiazepines,
adequate nutrition,
and fluids, if
necessary. If this
regimen fails or for
long-term cases,
antipsychotics may be
used

ALCOHOL-INDUCED MOOD DISORDER

• Eighty percent of
alcoholic people report
histories of intense
depression,
– including 30 to 40 percent
who were depressed for 2
or more weeks at a time.

• Heavy intake of alcohol
over several days
• but the intense sadness
markedly improves within
several days to 1 month
of abstinence.

Treatment
•teach the patient how to best view
and deal with the temporary
sadness through education and
cognitive-behavioral treatment,
• and to watch and wait at least 2 to
4 weeks before starting
antidepressant medications.

ALCOHOL-INDUCED ANXIETY DISORDER
Common (Up to 80 percent ) in the context of
acute and protracted alcohol withdrawal.
Have cases persist enough to meet criteria

Panic attacks
• Almost 80 percent of alcoholic people report
•during at least one acute withdrawal
episode.

Social phobia and agoraphobia

• during the first 4 weeks or so of
abstinence,
• people with severe alcohol problems
• are likely to avoid some social situations
for fear of being overwhelmed by anxiety
•their problems can at times be severe
enough to resemble agoraphobia.

Pre-existing anxiety
disorders
• Only a few pre-existing
anxiety disorders
•(e.g., panic disorder, social
phobia and posttraumatic
stress disorder [PTSD])
• have been clearly shown to
heighten the risk for later
alcoholism.

Alcohol-Induced Persisting Dementia
cognitive problem
•Global decreases in intellectual functioning,

• Poorly studied
• heterogeneous
• long-term

•recent memory difficulties are consistent with
the global cognitive impairment,
•an observation that helps to distinguish this
from alcohol-induced persisting amnestic
disorder

•Brain functioning tends to improve with
abstinence, but perhaps half of all affected
patients have long-term and even permanent
disabilities in memory and thinking
• Perhaps 50 to 70 percent of case of alcohol induced persistent demetia
• these changes appear to be partially or completely reversible during the
first year of complete abstinence.

shrinkage of
the cerebral sulci,

increased size of the brain
ventricles
Cognitive impairment and psychological evidence
• New learning capacity has been found to remain impaired after a minimum of 5 yrs
abstinence, likewise capacity for complex figure ground analysis (Brandt et al. 1983)
• Frontal dysfunction could be relevant to aspects of the personality change encountered
in alcoholics– the circumstantiality, plausibility and weakness and volition– that may
contribute significantly to relapse
• A vicious circle may often be established , with worsening cognitive status contributing to
the potentiation of the addiction
Cognitive impairment and neuropathology
• Alteration in dendritic structure
• A direct toxic action on alcohol may play a considerable role

Alcohol-Induced Persisting Amnestic
Disorder
• result of a relatively
historically subdivided into
severe deficiency of the B
•Wernicke's encephalopathy
vitamin thiamine.
•and Korsakoff's syndrome
• higher risk those with
genetically influenced
transketolase deficiency.
Other nutritional disorders
associated with alcoholism
• Peripheral neuropathy
• Cerebellar degeneration
• Ambylopia
• Marchiafava– Bignami disease
• Central pontine myelinosis

WERNICKE'S ENCEPHALOPATHY
• Also called alcoholic
encephalopathy
• A set of acute symptoms
•

with prominent ataxia
– and palsy of the sixth cranial
nerve

• tends to reverse fairly rapidly
– with vitamin supplementation
(The dosage of thiamine is
usually initiated at 100 mg by
mouth two to three times daily
and is continued for 1 to 2
weeks. In patients with alcoholrelated disorders who are
receiving IV administration of
glucose solution, it is good
practice to include 100 mg of
thiamine in each liter of the
glucose solution).
– May progress to Korsakoff syndrome

KORSAKOFF'S SYNDROME
• Chronic condition
• characterized by
– a pronounced anterograde
and retrograde amnesia
– and potential impairment in
visuospatial, abstract, and
other types of learning.
• which is permanent in at least a
partial form in perhaps 50 to 70
percent of the people affected.
–

–

The 30 percent or so of patients with
Korsakoff's syndrome who are likely to
recover fully
and the 50 percent or so who recover
partially appear to respond to 50 to 100
mg of oral thiamine a day, usually
administered for many months(3—12).

Wernick’s encephalopathy
• Represent the
neuropsychiatric
reaction to severe
thiamine deficiency
• It may be defined as a
disorder of acute onset
characterized by
nystagmus, abducens
and conjugate gaze
palsie, ataxia of gait and
global confusional state
occurring together in
various combinations

Role of enzymes
• Thiamine is important in relation
to several key enzyme systems of
the body and brain
• It is first phosphorylated ot TPP,
which acts as a coenzyme
• Transketolase which is essential
for the maintenance and synthesis
of myelin, and pyruvate
dehydrogenase complex and alpha
ketoglutarate dehydrogenase
complex, both of which play key
role in brain glucose metabolism
and energy production

Werinck’s encephalopathy and alcoholism
• Alcoholism is an important but not
exclusive cause
• It leads thiamine deficiency by several
routes
– The replacement of vitamin-containing
food by alcohol
– Impaired absorption of thiamine from the
gut
– Impairment of the storage by the liver
– Decreased phosphorylation to thiamine
pyrophosphate (TPP)
– And excessive requirement for the
metabolism of alcohol
– Patial gastrectomy appears to be a
significant risk factor (Price & Kerr 1985)

Other causes of wernick’s
encephalopathy
• Carcinoma of stomach
• Pregnancy
• Toxemia
• Pernicious anemia
• Vomiting
• Diarrhea
• Dietary deficiency
• Very occasionally the condition
has been developed in association
with anoexia nervosa (Elbes 1978;
Handler&Perkin 1982)
• Prolonged intravenous feeding,
renal dialysis, hyper emesis
gravidarum
• Severe malnutrition in chronic
schizophrenic

Subclinical Wernick’s encephalopathy
• If a substantial number of
alcoholics develop a thiamine
dependent pathology well before it
is clinically apparent, high-potency
vitamin therapy should find wider
prophylactic application
• The feasibility and desirability of
routinely supplementing alcoholic
beverages with thiamine has
indeed received
consideration(Centerwall & Criqui
1978; Weinstein 1978; Bisahai &
Bozetti 1986; Finlay-Jones 1986;
Rose & Armstrong 1988)

Treatment of wernicks
encephalopathy
• Medical emergency
• Intravenous infusion should
always be carried out slowly over
10 min on account of the risk of
anaphylactic reactions
• Travesia (1974) showed that
hypomagnesemia impaired both
the biochemical and clinical
response to treatment
• The syndrome of nicotinic acid
deficiency encephalopathy must
be kept in mind when response
has been lacking or incomplete to
the replacement of thiamine alone

Alcoholic pellagra encephalopathy
• is one diagnosis of potential interest to
psychiatrists presented with a patient
who appears to be afflicted with
Wernicke-Korsakoff syndrome but does
not respond to thiamine treatment.
• The symptoms of alcoholic pellagra
encephalopathy include
– confusion, clouding of
consciousness, myoclonus,
oppositional hypertonias, fatigue,
apathy, irritability, anorexia,
insomnia, and sometimes delirium.
• Patients suffer from a deficiency of
niacin (nicotinic acid),
• and the specific treatment is 50 mg of
niacin by mouth four times daily or 25
mg parenterally two to three times
daily.

Wernick’s
encephalopathy and
beriberi
• In epidemics of
beriberi
psychological
changes were found
to be prominent
with irritability,
depression and
disturbance of
memory

Cerebellar degeneration
• Typically is gradual evolution over several
weeks or months, after which the disorder
remains static for many years
• Ataxia of stance and gait– principal
abnormalities and mild nystagmus
• Pathological changes are restricted to the
anterior and superior aspects of the vermis
and cerebellar hemisphere. The cell loss
affects the Purkinje cells especially
• Nutritional cause rather than a direct toxic
effects of alcohol the consequence of a
combination of the effects of
ethanol, acetaldehyde, and vitamin
deficiencies.
• Treatment -- total abstinence and vitamin
supplementation

Ambylopia
• In rare cases retrobulbar neuritis may develop in
alcoholics, progressing over 1 of 2 weeks but
rarely extending to complete blindness
• Dimness of central vision, especially for red and
green, is the more common result
• As associated peripheral neuropathy is usual
• The smoking of strong pipe tobacco is often
incriminated in addition to the alcoholism, and
deficiencies of both thiamine and vitamin B12
appears to be responsible

Marchiafava– Bignami disease
• a thinning of the
corpus callosum
• Ataxia, dysarthria,
epilepsy and severe
impairment of
consciousness, or in
more slowly
progressive forms with
dementia and specific
paralysis of the limbs

Central pontine myelinosis
• An acute and often fatal
complication of alcoholism,
presenting with abtundation, bulbar
palsy, quadriplegia and loss of pain
sensation in the limbs and trunk
• Vomiting , confusion, disordered eye
movements and come are common
• Some patients show locked-in
syndrome
• Relabelled as ‘osmotic
demyelination syndrome’(Sterns et
al 1986)

Systemic diseases due to alcohol with secondary neurological complications
Liver disease
Hepatic encephalopathy
Acquired (non-Wilsonian) chronic hepatocerebral degeneration
Gastrointestinal diseases
Malabsorption syndromes
Postgastrectomy syndromes
Possible pancreatic encephalopathy
Cardiovascular diseases
Cardiomyopathy with potential cardiogenic emboli and cerebrovascular
disease
Arrhythmias and abnormal blood pressure leading to cerebrovascular disease
Hematological disorders
Anemia, leukopenia, thrombocytopenia (could possibly lead to hemorrhagic
cerebrovascular disease)
Fetal alcohol syndrome,
Myopathy
Infectious disease, especially meningitis (especially pneumococcal and
meningococcal)
Hypothermia and hyperthermia

Hypotension and hypertension
Respiratory depression and associated hypoxia
Toxic encephalopathies, including alcohol and other substances Electrolyte
imbalances leading to acute confusional states and, rarely, local neurological signs
and symptoms
Hypoglycemia
Hyperglycemia
Hyponatremia
Hypercalcemia
Hypomagnesemia
Hypophosphatemia
Increased incidence of trauma
Epidural, subdural, and intracerebral hematoma
Spinal cord injury
Posttraumatic seizure disorders
Compressive neuropathies and brachial plexus injuries (Saturday night palsies)
Posttraumatic symptomatic hydrocephalus (normal pressure hydrocephalus)
Muscle crush injuries and compartmental syndromes

(From Rubino FA. Neurologic complications of alcoholism. Psychiatr Clin North Am.
1992;15:361,

IDENTIFICATIONS IN CLINICAL
SETTINGS/ DIAGNOSTIC TOOLS
•Identification in clinical
settings
•Rating scales,
•State markers of heavy
drinking (Lab
investigations)– y glutamyl
transferase, CDT, the MCV)

Identification in clinical settings
• and the diagnosis of alcohol
dependence or abuse requires a
high index of suspicion for the
disorder in any patient.
• The average man or woman
presenting with severe and
repetitive alcohol problems is
likely to be

•

– The diagnosis centers on repetitive
serious problems with alcohol
• but does not directly focus
– on the quantities and
frequencies of alcohol intake
– or moral judgment
– Both abuse and dependence are
predictors of future problems.

–

neatly dressed, show no signs of
severe alcohol withdrawal, have a job
and a family,
– and to complain of a variety of
physical conditions or temporary but
potentially severe psychiatric
complaints

The initial step in diagnosis is to screen first for
dependence

•

• It is interesting to note that only
about 10 to 15 percent of those with
abuse go on to dependence.
Patients should be asked about patterns of
problems
– related to accidents,
– interpersonal difficulties,
– problems at work,
– encounters with the law, and so on

• In psychiatric settings, as many as a third of the patients are
likely to have an alcohol problem that either caused or
exacerbated the presenting clinical condition.
• The next step can be to determine whether an independent
major psychiatric disorder exists.
– Thus, individuals should be evaluated using the timeline
approach to determine whether the psychiatric
symptoms are likely to have been substance induced (and
are thus temporary) or represent independent and
longer-term psychiatric disorders.
– Then, the clinical course of the psychiatric symptoms
should be monitored over the subsequent several weeks
to 1 month of abstinence to determine whether the
symptoms decrease in intensity over time

Rating scales
• the Alcohol Use Disorders Identification Test (AUDIT)
WHO_MSD_MSB_01.6a.pdf
• and the Michigan Alcohol Screening Test (MAST)Pocket_2.pdf

•simple questionnaires
•used to preliminarily survey relevant problem
areas.
•each of which uses ten items
•do not diagnose alcohol dependence but only
highlight individuals who might be especially
appropriate for a more intensive clinical
interview
Donovan DM, Kivlahan DR, SR Doyle SR, Longabaugh R, Greenfield SF: Concurrent
validity of the alcohol use disorders identification test (AUDIT) and AUDIT zones in
defining levels of severity among out-patients with alcohol dependence in the COMBINE
study. Addiction. 2006;101:1696.

c

• [need to] ut down
[on drinking],

C AGE

• Annoyance,
• Guilt [about drinking],
• [need for]

Eye-opener,

•More simple instrument
•too short to be sensitive or specific enough for many
clinical settings.

State markers of heavy drinking
Test
γ-glutamyltransferase
Carbohydrate-deficient transferrin
Mean corpuscular volume
Uric acid

Relevant Range
of Results
>35.0 U/L
>3.0%
>91.0 µm3
>6.4 mg/dL for men
>5.0 mg/dL for women
>45.0 IU/L

Serum glutamic oxaloacetic
transaminase (aspartate
aminotransferase)
Serum glutamic pyruvic transaminase >45.0 IU/L
(alanine aminotransferase)

• reflect physiological alterations likely to be observed if the
patient regularly ingests five or more drinks a day over
several weeks.
• The combination of elevated values in three or more of
these tests may enhance the sensitivity for identifying heavy
regular drinkers to over 80 percent.

Physical findings
•modest elevations in blood pressure;
•frequent bruising;
•cancer of the head, neck, or upper
digestive tract;
•an enlarged liver;
•evidence of cirrhosis;
•and symptoms consistent with
pancreatitis

γ-glutamyltransferase
• an amino acid–transporting
enzyme
• marker with a sensitivity and
specificity of 60 percent
• that is temporarily induced by
repetitive heavy drinking.
• Enzyme levels are likely to
return to normal after 2 to 4
weeks of abstinence,
• and because blood levels should
fall with abstinence, increases
of 20 percent or more can be
useful in identifying patients
who have returned to drinking
after treatment.

Deglycosylated form of the
protein transferrin ( CDT)
• this test has a sensitivity and a
specificity of 60 to 75
• With a biological half-life of
approximately 16 days, this test
can also be useful in monitoring
abstinence in alcoholics.
• Patients not identified by higher
γ-glutamyltransferase values
might still have elevations in
CDT,
– so that the combination is
better than either test alone for
identification of alcoholism and
monitoring abstinence.

Hietala J, Koivisto H, Anttila P, Niemela O: Comparison of the combined marker GGT-CDT
and the conventional laboratory markers of alcohol abuse in heavy drinkers, moderate
drinkers and abstainers. Alcohol Alcohol. 2006;41:528

The MCV
• with perhaps 50 percent
sensitivity,
• is useful when the size of
the red blood cell is 91
µm3 or more.
• The 120-day lifespan of the
red cell does not allow the
MCV to be useful as an
indicator of a return to
drinking.

uric acid
•high normal values of
(e.g., greater than 6.4
mg/dL)

liver function tests
•even mild elevations
•In aspartate
aminotransferase and
alanine aminotransferase.

COMORBID CONDITIONS
I

“ F THE STORM WITHIN GETS TOO LOUD,

I TAKE A GLASS TOO MUCH TO STUN MYSELF”
- VINCENT VON GOUGH

•Multisubstance dependence
•Antisocial personality disorder,
•Schizophrenia
•Bipolar I disorder
•Bipolar II disorder
• Major anxiety disorders,
•ADHD
•Other disorders

Temporary psychiatric
symptoms
• are common during
intoxication and
withdrawal from alcohol.
• likely to disappear after
abstinence. Or require
short term treatment
• These do not necessarily
indicate an independent
psychiatric disorder

How to manage co morbidities in generel
how do you manage alcohol dependence
that is co-morbid with nicotine
dependence

– may require long-term
support and medications
Schuckit MA: Comorbidity between substance use disorders and psychiatric
conditions. Addiction. 2006;101:76. Schuckit MA, Smith TL, Danko GP, Pierson J, Trim
R: A comparison of factors associated with substance-induced versus independent
depressions. J Stud Alcohol Drugs. 2007;68:805.

Multi substance dependence
• many alcoholics have
used other substances,
but most do not meet the
criteria for dependence
on illicit drugs.
• appears to run relatively
true within families,
without evidence of a
marked crossover with
most other
dependencies.
• 85% of alcoholic also smoke

Risk factors
• antisocial personality disorder
and also schizophrenia and
bipolar disorder.
• individuals with dependence on
opioids and stimulants
• to moderate his or her
intoxication or side effects from
the preferred drug of abuse.
• nicotine dependence, which has
long been noted to be elevated
among alcohol-dependent
individuals,

Antisocial personality disorder
impulsive, violent, risk takers who do not easily learn
or benefit from punishment.
•80 percent or more of people with ASPD develop severe
alcohol problems
•about 5 percent of alcoholic women and between 10 and
20 percent of alcoholic men have pre-existing ASPD
•more likely than the average alcohol-dependent person
to have a
• coexisting drug diagnosis,

•to be violent,
•to discontinue treatment prematurely,
•and to have a relatively poor prognosis.

Diagnosing Axis II disorder in ADS
• Symptoms of other Axis II conditions are often
observed during intoxication and withdrawal,
• but other than antisocial and perhaps borderline
personality disorders, few have been
documented to predate the alcohol
dependence.
• with these exceptions it is best to defer a
diagnosis of most additional Axis II disorders
– until at least a month of abstinence
– unless the personality syndrome clearly antedated
the alcohol use disorder.

Schizophrenia
A second most common comorbid
disorder
• Heavy drinking is likely
Factors contribute to alcoholrelated problems.
• live in inner-city areas and to
spend a great deal of time
on the streets,
• impaired judgment
associated with their
psychoses,
• Other possible mechanisms
• genetic
• and other biological
mechanisms
(e.g., related to
dopamine)

– to undercut the effectiveness
of antipsychotic medications,
– increase mood swings and
psychoses,
– and contribute to a higher
probability of repeatedly
revolving into and out of
inpatient care.

• Alcohol-related disorders are
observed in about 40 percent
of schizophrenic people being
treated in public mental
health facilities.

Bipolar I disorder
Factors contributing
• mania-related hyper excited and
impulsive states,
• with associated poor judgment,
• As with schizophrenia, it is
possible that some genetic
mechanisms might contribute
Bipolar II disorder
Evaluating alcohol related problems
• is difficult to evaluate
• because intoxication, withdrawal, and
adjustment to changes in living situations
can mimic hypomania.
• This label should be reserved only for
those with clear hypomanic episodes
antedating the alcoholism.

Treatment
•Initialshould focus on
controlling for mania or severe
depression,
•but detoxification must be
considered once the bipolar
disorder symptoms are under
control,
•and an alcohol rehabilitation
program is recommended once
the patient is more rational.

Major anxiety disorder
Panic disorder and social
phobia
• There is a small but
statistically significant
association between
independent (i.e., not
alcohol induced) panic
disorder and social
phobia and alcohol
dependence.

PTSD
• In some instances, especially
those with a delay of many
months or years between the
event and the development of
clinically significant PTSD
symptoms,
• the condition might reflect
the impact of alcohol
intoxication-related
depression and withdrawalrelated anxiety on
subclinical traumaticrelated symptoms.

Drissen M, Schulte S, Luedecke C, Schaefer I, Sutmann F: Trauma and PTSD in patients with
alcohol, drug, of dual dependence: A multicenter study. Alcohol Clin Exp Res. 2008;32:481.

ADHD
Factors hightening the risk in future
• children can be disruptive at home and school,
• many are treated with stimulant medications such
as methylphenidate (Ritalin),
this important issue is still the focus of active study, the
data to date do not clearly support a close tie between
ADHD and alcohol use disorders or other substancerelated problems in late adolescence or adulthood
unless the child carries an additional risk factor,
especially the precursor of antisocial personality
disorder, conduct disorder.

other disorders
major depressive disorder, agoraphobia,
obsessive-compulsive disorder (OCD), and
other major psychiatric diagnoses
•Debate in the literature continues about whether
these are overrepresented in the histories of
people with alcohol dependence.
•However, there is relatively little evidence of a
close link between these disorders and
alcoholism.

Alcohol and suicide
• If alcohol dependence
continues, the risk for death by
suicide
– may be 10 percent or more.

• The risk for suicidal behavior
among alcohol-dependent men
and women is higher for those
who were
– younger,
– unmarried,
– have experience with illicit
substances,(multi substance)
– report a more severe course of
their alcoholism,
– and have histories of substanceinduced mood disorders

Ilgen MA, Jain A, Lucas E, Moos RH:
Substance use-disorder treatment and a
decline in attempted suicide during and
after treatment. J Stud Alcohol Drugs.
2007;68:503.
Preuss UW, Schuckit MA, Smith TL, Danko
GP, Bucholz KK, Hesselbrock MN, Hesselbrock
V, Kramer JR. Predictors and correlates of
suicide attempts over five years in 1237
alcohol dependent men and women. Am J
Psychiatry. 2003;160:56

COURSE AND PROGNOSIS
•Course In general
•Early course
•Later course— temporary
controlled drinking, Phenomenon of
spontaneous remission,

Course in general
•

•

Most alcoholics, regardless of their backgrounds, exhibit
similarities in the time course and prevalence of alcoholrelated life difficulties.
The type of beverage used--The pattern of problems does
not vary much with—beer, wine, or spirits

Young Vs Old –Older alcohol-dependent
individuals are more likely
•to have medical problems,
•to take multiple medications,
to experience more severe
withdrawal syndromes,
•and to have a less extensive social
support system.

Men Vs women—Women,
•are likely to begin drinking a bit
later than men,
•but their subsequent escalation of
symptoms is likely to be slightly
more rapid (telescoping)

alcoholic individuals with preexisting independent major
psychiatric disorders
• are likely to run the course of
their independent psychiatric
illness.
• The goal is to minimize the
symptoms of the independent
psychiatric disorder in the
hope
– that a greater level of life
stability will be associated
with a better prognosis
for the patient's alcohol
problems.

Early course
Age at first drinka
13–15 yr
Age at first intoxicationa 15–17 yr
Age at first problema

16–22 yr

Age at onset of
dependence
Age at death

23–40 yr
60 yr

Fluctuating course of —
abstention, temporary
control, alcohol problems
Spontaneous remission in —
20%
aSame as general population.

Early onset of drinking
• Patients with antisocial
personality disorder who go on
to develop alcoholism have an,
intoxication, and alcoholrelated problems,
– but that scenario is not applicable
to the other 80 to 90 percent of
alcoholic men and 95 percent of
alcoholic women

Later course
Temporary controlled
drinking
•

•

•

periods of drinking problems that
repeatedly alternate with periods of
nondrinking and subsequent alcohol
intake unassociated with problems
a common but temporary condition
for most alcoholic people. Those
who have less pervasive alcohol
problems, such as abuse, are more
likely to have long-term and even
permanent periods of control.
However, long-term continued
control is not likely once a person
meets the diagnostic criteria for
alcohol dependence. Therefore,
alcohol dependence is a good
example of a chronic relapsing
disorder

Phenomenon of spontaneous
remission.
• perhaps in response to
nonspecific events or to a crisis,
the alcoholic person promises to
abstain and keeps the promise
for an extended period.
• seen in at least 20 percent of
alcoholic people
• is most likely for alcoholics
– with fewer alcohol-related
problems,
– greater levels of life stability,
– and a more supportive
environment.

•Temporary Abstinence (going on the wagon)
•often develops in response to some
interpersonal, social, or legal crisis
•and is likely to produce only modest
withdrawal symptoms
•lasting days to months,
•are usually followed by times during which
drinking rules are established and followed, at
least temporarily .
• person use to convince him- or herself that
alcohol is not really a cause for concern after
all.

•This period of temporary control soon leads
to an escalation of alcohol intake, the
accumulation of a new set of problems, and a
subsequent crisis.
•These, in turn, precipitate a new period of
temporary abstinence, and the cycle begins
again.
•

Fewer than half of alcoholic people ever get treatment.
•

•

Favorable prognostic signs
• absence of pre-existing antisocial
personality disorder or other
substance abuse or dependence;
• good life stability including
– having a job,
– continuing close family
contacts,
– and the absence of severe
legal problems;
• and staying for the full course of
the initial outpatient or inpatient
rehabilitation (perhaps 2 to 4
weeks).
• These attributes predict about a
60 percent chance for 1 or more
years of abstinence. Most studies
agree that 1-year rates are
associated with a good chance for
continued abstinence over an
extended period

However, once there, contrary to popular belief, a majority of patients in treatment do
quite well and develop long-term, often permanent, abstinence.

if drinking continues, the alcoholic is likely to decrease his or her lifespan by 10 to 15
years as a result of many of the alcohol-related pathologies----- suicide

Part-C
Mngmnt Aspects
• Intervention
• Dexofication
• Maintenance treatment
/Rehabilitation
– Relapse prevention
– Psychosocial approaches
– Pharmacological
approaches

Addictive behaviors do not change abruptly, but through a series of stages.
Five stages in this gradual process have been proposed:
precontemplation,
contemplation,
preparation,
action,
and maintenance
•Those approaches assume that all possible efforts have been made
to optimize medical functioning and to address psychiatric
emergencies
•The best treatment programs combine specific procedures and
disciplines to meet the needs of the individual patient after a careful
assessment

In alcoholics with independent psychiatric disordder
the treatments are often applied after the psychiatric
disorder has been optimally stabilized.

Generally, integrated treatment in which the same staff can
treat both the psychiatric disorder and the addiction is more
effective than either parallel treatment (a mental health and
a specialty addiction program providing care concurrently)
or sequential treatment (treating either the addiction or the
psychiatric disorder first and then dealing with the comorbid
condition).

bringing face to face with the reality of the
disorder
• to break through feelings of the denial
• and help the patient recognize the
adverse consequences likely to occur if
he or she does not stop drinking.
• This step often involves convincing
patients that they are responsible for
their own actions
• Is a process aimed at maximising the
motivation for the treatment and
continued abstinence

Discussion of their presenting
complaint
• e.g., insomnia, difficulties with
sexual performance, feeling
stressed, depression
• can be a useful way to both show
empathy and enhance motivation
to change.
• The emphasis is then placed on
discussing how alcohol has either
created or contributed to these
problems

Intervention /
confrontation
reassuring the patient
•that abstinence can be
achieved and that the
clinician can help.
Persistent approach
• If the patient does not respond to
the first motivational interview,
– the same nonjudgmental but
persistent approach can be used
each time an alcohol-related
impairment is identified.
– It is the level of persistence as much
as interpersonal skills that often get
results.

Reaching Out to the Family
• need to learn to not protect the patient from the problems
caused by alcohol
• the family can suggest that the patient meet with people
who are themselves recovering from alcoholism, perhaps
through AA,
• relatives can attend groups that reach out to family
members, such as Al-Anon.
– Those support groups help family members and
friends see that they are not alone in their fears,
worry, and feelings of guilt.
– Members share coping strategies and help each
other find community resources.
– The groups can be useful in helping family members
rebuild their lives, even if the alcoholic person refuses
help.

to seek

Detoxification
The second step
is to offer rest, adequate
nutrition, and oral multiple
vitamins, especially thiamine
The essential first step-- thorough
physical examination.
• In the absence of a serious
medical disorder or combined
drug dependence, severe
alcohol withdrawal is unlikely.

If detoxification has been completed
and the patient is not one of the 10 to
15 percent of alcoholic persons who
have an independent mood disorder,
schizophrenia, or anxiety disorder,
little evidence favors prescribing
psychotropic medications for the
treatment of alcoholism

Rehabilitation
• an intensive period of
help-- first 2 to 4 weeks
of care
• at least 3 to 6 months
of less frequent
outpatient care.
– individual and group
counseling,
– the judicious avoidance of
psychotropic medications
unless needed for
independent disorders,
– and involvement in such
self-help groups as AA

Three major components
•continued efforts to increase and
maintain high levels of motivation
for abstinence,
•work to help the patient readjust
to a lifestyle that maximizes
functioning and decreases the risk
for drinking,
•relapse prevention.
Inpatient > out patient settings
• evidence of additional severe medical or
psychiatric syndromes,
• the absence of nearby outpatient groups
and facilities,
• and the patient's history of having failed in
outpatient care.

Relapse Prevention
• has a cognitive-behavioral base
Identifying situations with a high risk for
relapse
. when the craving for alcohol increases or when an
event or emotional state makes a return to drinking
more likely.

help the patient to develop modes of
coping he or she can use

An important part of relapse
prevention is reminding the
patient about the appropriate
attitude toward slips in which
short-term experiences with
alcohol can never be used as an
excuse for returning to regular
drinking.

Rather, recovery is a process of trial and error;
when slips occur they can be clues to help
identify high-risk situations and to develop more
appropriate coping techniques

Psychosocial approaches
•
•
•
•

Counseling
should focus on day-to-day life issues
help him or her optimize support systems and
healthy coping styles.
To optimize motivation, treatment sessions
– should explore the consequences of drinking,
– the likely future course of alcohol-related life
problems,
– and the marked improvement that can be expected
with abstinence.

•

Much time in counseling deals with
– how to build a lifestyle free of alcohol.
– Discussions cover the need for a sober peer group,
– a plan for social and recreational events without
drinking,
– and approaches for re-establishing communication
with family members and friends

Cognitive and behavioral approaches
• can form a solid base to these
counseling sessions.
• One goal is to help the patient learn
ways to cope with life stresses.
• The clinician can use role rehearsal,
modeling, and role playing while
encouraging patients to practice these
skills between sessions.
• At the same time, individuals are
encouraged to identify areas of
problems in day-to-day functioning,
paying special attention to how they
react to these challenges and the
impact that substance use might have
on the outcomes.

Psychotherapy techniques that
provoke anxiety or that
require deep insights
• have not been shown to be
beneficial during the early
phases of recovery and, at
least theoretically, may
impair efforts at maintaining
abstinence.

Importance of the Family

Individual Vs group
• Counseling or
therapy can be
carried out in an
individual or group
setting;
• few data indicate
that either is superior

• alcoholism has effect on the
significant people in the patient's
life.
• help family members and close
friends to understand more
about alcoholism and how
rehabilitation is an ongoing
process that lasts for 6 to 12
months.
• Couples and family counseling
and support groups for relatives
and friends help the people
involved

Pharmacological approaches
Acamprosate--anticraving agent
• is an analog of the aminoacid neurotransmitter taurine and structurally
resembles GABA
• antagonizes neuronal overactivity related to the excitatory
neurotransmitter glutamate, at least in part by acting as an antagonist to
NMDA receptors.
• Thus, one possibly important mechanism for this drug may be in
diminishing mild anxiety, mood swings, and other sleep difficulties
associated with the subacute and protracted withdrawal syndrome
observed after the first 4 to 5 days of alcohol abstinence.
• At the usual dose of about 2,000 mg per day the majority of studies
report modest but significantly better outcomes with active drug than
placebo
• Although there are no clear guidelines, it is reasonable to prescribe this
drug for about 6 months, during which time it is hoped an alcohol-free
lifestyle can be developed.

Interact with both glutamate system to
inhibit it and with the GABA system to
enhance it ( form of artificial alcohol)

Alcohol related disorders osmanali

Alcohol related disorders osmanali

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