Alcohol related disorders osmanali

Alcohol Related Disorders

Presenter

Dr Mohd Osman Ali, MBBS, DPMCONSULTANT PSYCHIATRIST

[email protected]

mailto:[email protected]

PART - A• Epidemiology • Etiology• Chemistry and

Pharmacokinetics• Pharmacodynamic

s

Scheme of presentation

PART - B• Effects on the

body systems and disorders

• Diagnostic tools• Co-morbid

conditions• Course and

prognosis

PART – C• 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

genetic factorsenviromental factors

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

• the decision to drink, • the development of

temporary alcohol-related 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

BIOLOGICAL

THEORIES

GENETIC FACTORS Four lines of evidence for genetic factors

Close family members have a fourfold increased risk.

The identical twin of an alcoholic person is at higher risk than is a fraternal twin.

Adopted-away children of alcoholics have a fourfold increased risk for alcoholism even if not raised by alcoholics.

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.

VARIATIONS IN ADH• 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

• chromosome 4• Additional genes that

impact the forms of ADH1B and ADH1C,

• which are more prevalent among Asian, black, and Jewish individuals,

Alcohol metabolizing enzymes

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

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.

ALDH2*2, 2*1 Heterozygotes

• 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 acetaldehyde-related damage to the brain, liver, pancreas, and testes.

VARIATIONS ALDH

Impulsivity and disinhibition• these characteristics are seen at

– a higher prevalence among alcoholics, – are observed in a substantial minority of their

children,

and appear to reflect the action of a range of genes,

including those coding for GABAAα 2

and CHRM2 receptors.

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

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.

• 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

PSYCHOLOGICAL

THEORIES

Stress and alcohol intake

• 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).

The tension-reducing effects of alcohol may be modest and most likely to be noted in light-to-moderate drinkers.

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

•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

and subsequent reinforcement after alcohol intake

• 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.

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

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

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.

PSYCHODYNAMIC

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

(inability to deal with reality)

THEORIES

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.

SOCIOCULTURAL

• 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.

THEORIES

- • 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.

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

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

Alcoholic beverages and Standard drink

1/3 sachet arrack

CongenersComponents of alcoholic

beverages other than alcohol. (consist of combinations of methanol, butanol, aldehydes, phenols, tannins, lead, cobalt, iron, and other substances) result from method of production

responsible for much of the characteristic taste of the beverage

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)

•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

Distribution

• 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

ALCOHOL ACETALDEHYDE ACETATEADH ALDH

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

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

in both the liver cell cytosol and mitochondria

•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.

liver (90%) through oxidationOne drink in an hour 15 mg/dLAlso induces microsomal enzymes

Excretion

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

the lungs

kidneys,

sweatConcentation exhaled in air is about0.05% of blood concentration

PHARMACODYNAMICSwhat 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 second-messenger 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

Chronic alcoholism• During withdrawal state

– glutamate overexcitement—neuronal damage(exctotoxicity) (fig 2-35, 36,fig 9-46to 9-56)

– GABA deficiency

Proteomics and alcoholismPeroxiredoxin, 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.

•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

Cellular membrane effects

Gupta S, Kulhara P. Cellular and molecular mechanisms of drug dependence: An overview and update. Indian J Psychiatry 2007;49:85-90

Neuro chemical effects of alcohol

• 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 DA-activating effect.

Glycine and strychnine alter extracellular dopamine levels in the NAc, probably via GlyR stimulation and blockade

Adenosine, neurosteroids, and acetylcholine.

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

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

Reward circuitry/neurobiology of addiction

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• 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

Abuse

Addiction

Dependence

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 effectsAnd 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 cross-tolerance 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 architecturre—impaired• 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 asleep.

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

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

• Van Reen E, Jenni OG, Carskadon MA: Effects of alcohol on sleep and the sleep electroencephalogram in healthy young women. Alcohol Clin Exp Res. 2006;30:974

Alcohol intoxication

•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

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

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

Level Likely Impairment20–30 mg/dL Slowed motor performance and decreased thinking ability

30–80 mg/dL Increases in motor and cognitive problems80–200 mg/dL Increases in incoordination and judgment errors

Mood lability Deterioration in cognition

200–300 mg/dL Nystagmus, marked slurring of speech, and alcoholic blackouts

>300 mg/dL Impaired vital signs and possible death

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 sedative-hypnotic drugs, and feeling fatigued

• injection of an antipsychotic drug, such as haloperidol (Haldol), is useful for controlling assaultiveness.

Blackout • 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

•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.

95 percent --mild or moderate symptoms,

for 3 to 5 percent-- convulsions or delirium.(each <1 percent)

Conditions that may predispose to, or aggravate, withdrawal symptoms include

fatigue, malnutrition, physical illness, and depression

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-IV-TR.

• 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

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.

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.

•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.

Severe alcohol withdrawal --convulsions (rum fits)

•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

• 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.

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

Drug Therapy for Alcohol Intoxication and Withdrawal

Clinical Problem Drug Route Dosage CommentTremulousness and mild to moderate

agitation

Chlordiazepoxide Oral 25–100 mg every 4–6 hr

Initial dose can be repeated every 2 hr

until patient is calm; subsequent

doses must be individualized and

titrated

Diazepam Oral 5–20 mg every 4–6 hr

Hallucinosis Lorazepam Oral 2–10 mg every 4–6 hr

Extreme agitation Chlordiazepoxide Intravenous 0.5 mg/kg at 12.5 mg/min

Give until patient is calm; subsequent

doses must be individualized and

titrated

Withdrawal seizures

Diazepam Intravenous 0.15 mg/kg at 2.5 mg/min

Delirium tremens Lorazepam Intravenous 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

The key to diagnosis of alcohol abuse and dependence -- heavy and repetitive use of alcohol to the point of developing recurrent problems.

• Quantity and frequency of alcohol intake,– while useful, are often not sufficient to establish the threshold– because of the large variation in the amounts of alcohol

required for problems across men versus women, larger versus smaller individuals, and older versus younger people.

• Repetitive problems – Emphasis is placed on this-- a person keeps using despite

problems.– This, in turn, predicts the probability that a return to drinking

is likely to be associated with the re-establishment of problems.

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

Dependence has been defined as a cluster of behavioral, cognitive and physiological phenomena that develop after repeated substance use

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.

•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.

THREE PROCESSES

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 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 motivation to seek out alcohol

The drinking patterns are often associated with certain behaviors:

• the inability to cut down or stopdrinking;

• 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

• 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.

Abuse and harmful use

• 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.

DSM IV Vs ICD-10

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

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

Heavy drinking vs reduced risk drinking

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

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.

Developmentally limited alcoholism• 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 Conditionspsychiatric 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

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

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 withdrawal-related 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

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.

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.

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

Alcohol-Induced Persisting Dementia

• Poorly studied• heterogeneous • long-term

cognitive problem•Global decreases in intellectual functioning,

•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.

increased size of the brain ventricles

shrinkage of the cerebral sulci,

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 severe deficiency of the B vitamin thiamine.

• higher risk those with genetically influenced transketolase deficiency.

historically subdivided into • Wernicke's encephalopathy • and Korsakoff's syndrome

Other nutritional disorders associated with alcoholism

• Peripheral neuropathy• Cerebellar degeneration• Ambylopia• Marchiafava– Bignami disease• Central pontine myelinosis

• 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 alcohol-related 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

• 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).

WERNICKE'S ENCEPHALOPATHY KORSAKOFF'S SYNDROME

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 encephalopathyCardiovascular diseases Cardiomyopathy with potential cardiogenic emboli and cerebrovascular disease Arrhythmias and abnormal blood pressure leading to cerebrovascular diseaseHematological 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 hypertensionRespiratory depression and associated hypoxiaToxic 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 HypophosphatemiaIncreased 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

• The initial step in diagnosis is to screen first for dependence– 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. • 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

• 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– 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

• 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

• 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.

Rating scales

C

• [need to] cut down [on drinking],

•Annoyance,

•Guilt [about drinking],

• [need for] Eye-opener,

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

clinical settings.

A G E

State markers of heavy drinking

TestRelevant Range of Results

γ-glutamyltransferase >35.0 U/LCarbohydrate-deficient transferrin >3.0%Mean corpuscular volume >91.0 µm3

Uric acid >6.4 mg/dL for men>5.0 mg/dL for women

Serum glutamic oxaloacetic transaminase (aspartate aminotransferase)

>45.0 IU/L

Serum glutamic pyruvic transaminase (alanine aminotransferase)

>45.0 IU/L

• 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

“IF 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 – 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.

How to manage co morbidities in generel

how do you manage alcohol dependence that is co-morbid with nicotine dependence

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

Factors contribute to alcohol-related 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)

A second most common comorbid disorder • Heavy drinking is likely

– 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

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.

Bipolar II disorderEvaluating 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.

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 withdrawal-related anxiety on subclinical traumatic-related 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 substance-related problems in late adolescence or adulthood

unless the child carries an additional risk factor, especially the precursor of antisocial personality disorder, conduct disorder.

other disordersmajor 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 substance-

induced 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 alcohol-related 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 pre-existing 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 courseAge 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

23–40 yr

Age at death 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 alcohol-related problems, – but that scenario is not applicable

to the other 80 to 90 percent of alcoholic men and 95 percent of alcoholic women

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Later courseTemporary 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.

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

• Fewer than half of alcoholic people ever get treatment. • 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

• Intervention • Dexofication• Maintenance

treatment /Rehabilitation – Relapse prevention

– Psychosocial approaches– Pharmacological

approaches

Part-C Mngmnt Aspects

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 disordderthe 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).

Intervention / confrontation

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

reassuring the patient •that abstinence can be achieved and that the clinician can help.

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

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 to seek help.

Detoxification

The essential first step-- thorough physical examination.

• In the absence of a serious medical disorder or combined drug dependence, severe alcohol withdrawal is unlikely.

The second step is to offer rest, adequate nutrition, and oral multiple vitamins, especially thiamine

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

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.

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.

Individual Vs group• Counseling or therapy

can be carried out in an individual or group setting;

• few data indicate that either is superior

Importance of the Family• 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)

Naltrexone • the long-acting, oral, opioid antagonist. • Naltrexone works by blocking opioid receptors in the brain and, thus, at

least indirectly, changing levels of activity of dopamine and serotonin. • The most frequent complaints involving GI upset, with a possible modest

increase in lethargy and, perhaps, the subjective report of a dampened level of interest in activities and life events.

• Naltrexone is also available in a 380 mg injection to be given once a month as Vivitrol. Oral – 30 decisions to quit Inj– one decision to quit ( less will power to repair from drinking) (fig 19-27 stephen stahl)

• Some data support the conclusion that the combination of acamprosate (666 mg three times a day) plus naltrexone (50 to 100 mg per day or three times a week) may be more effective than either drug alone, while not increasing the side effects of either drug alone. However, not all studies agree and further research will be needed.

Feeney G, Connor J, Young R, Tucker J, McPherson A: Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: A single centres experience with pharmacotherapy. Alcohol Alcohol. 2006;41:321

DisulfiramThe alcohol-sensitizing agent

• which is usually prescribed at 250 mg per day. • The goal is to place the patient in a condition in which drinking alcohol

precipitates an uncomfortable physical reaction, • However, few data convincingly prove that disulfiram is more effective

than a placebo, probably because placebo and active drug may have similar deterrent effects

• and most people stop taking the disulfiram when they resume drinking.• Many clinicians have stopped routinely prescribing the agent, partly in

recognition of the dangers associated with the drug itself, including – mood swings, rare instances of psychosis, the possibility of an increase in

peripheral neuropathies, the relatively uncommon occurrence of other significant neuropathies, and a rare but potentially fatal hepatitis.

• Moreover, patients with pre-existing heart disease, stroke, diabetes, and other conditions cannot be given disulfiram because an alcohol reaction to the disulfiram could be fatal.

Disulfiram Ethanol Reaction (DER)(Aldehyde syndrome)

• Due to release of histamine and catecholamines

• Flushing, burning sensation, throbbing headache, perspiration, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, postural fainting, circulatory collapse

• Duration of syndrome 1—4 hrs

Additional medications –• Topiramate (Topamax)

– has the usual GABA-boosting activity associated with treatments of seizure disorders along with an additional glutamate receptor blockade and effects on dopamine systems.

– Perhaps related to this combination of effects, several studies using about 300 mg of topiramate per day reported improvements in drinking patterns.

• Ondansetron (Zofran), – indicating a possible benefit for this medication, – particularly in early onset alcoholics with comorbid drug dependence and criminality.

• the nonbenzodiazepine antianxiety drug buspirone (BuSpar), • several selective serotonin reuptake inhibitors (SSRIs), • the GABA-B receptor agonist baclofen (Lioresal),• and antipsychotic medications in the treatment of alcoholism, although none of these medications have proven to be consistently better than placebo in controlled trials.

Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, for the COMBINE Study Research Group: Combined pharmacotherapies and behavioral interventions for alcohol dependence: The COMBINE Study: A randomized controlled trial. JAMA. 2006;295:2003.Kranzler H, Koob G, Gastfriend D, Swift R, Willenbring M: Advances in the pharmacotherapy of alcoholism: Challenging misconceptions. Alcohol Clin Exp Res. 2006;30:272.Spanagel R, Kiefer F: Drugs for relapse prevention of alcoholism: ten years of progress. Trends in Pharmacological Sciences. 2008;29:109 Gelernter J, Gueorgulieva R, Kranzler HR, Zhang H, Cramer J: Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: Results from the VA Cooperative Study. Alcohol Clin Exp Res. 2007;31:555.

Self-Help groups 12 step base alcoholic anonymous

• an approach that in many ways resembles cognitive-behavioral treatments.

• Members of AA have help available 24 hours a day,• the meetings promote developing a sober peer group,

– and participants learn that it is possible to participate in social functions without drinking,

– while also being presented with a model of recovery by observing the accomplishments of sober members of the group.

• Learning about AA often begins during inpatient or outpatient rehabilitation. – The clinician can play an important role by encouraging AA

attendance while helping patients select a group most appropriate for them.

• Some meetings are comprised – only of men or women, and others are mixed; – some are mostly attended by blue-collar men and women,

whereas others are mostly for professionals; – some groups place great emphasis on religion, and others are more

eclectic.

• Patients with coexisting psychiatric disorders may need some additional education about AA. – The clinician should remind them that some members of AA may not

understand their special need for medications and should arm the patients with ways of coping if anyone inappropriately suggests that the required medications be stopped.

» Although difficult to evaluate using double-blind controls, most studies indicate that participation in AA is associated with improved outcomes, and incorporation into treatment programs saves money

O you who have believed, indeed, intoxicants, gambling, stone alters, and divining arrows are but defilement from the work of Satan, so avoid it that you may be successful.

Satan only wants to cause between you animosity and hatred

through intoxicants and gambling and to avert you from the remembrance of Allah and from

prayer. So will you not desist?

(The Qur'an 5:90,91)

BIBILOGRAPHY

Further reading•Schuckit MA: Drug and Alcohol Abuse: A Clinical Guide to Diagnosis and Treatment. 6th ed. New York: Springer; 2006.•James Milam and Katherine Ketchum: Under the influence(1983)

Books referred•Kaplan and sadock– comprehensive textbook of psychiatry 9th ed•Kaplan and sadock– synopsis of psychiatry 10th ed •Lishman organic psychiatry 3rd ed•Stephen stalhl– essential psychopharmacology•Niraj ahuja– post graduate text book of psychiatry•Tasman– textbook of psychiatry

THANK YOU AND DISCUSSION

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Alcohol related disorders osmanali

Health & Medicine

Transcript of Alcohol related disorders osmanali