Bringing AWS Treatment Into Focus

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Bringing AWS Treatment Into Focus

• Paolo B. DePetrillo, M.D.
• Mark K. McDonough, M Ed.

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Rational Pharmacotherapy of AWS

• Use of the Type Indicator to assess and evaluate
  response to therapy
• Drug classes to be discussed
• Benzodiazepines
• Anticonvulsants
• Sympatholytics
• Neuroleptics

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Why no Protocol?

• AWS is dynamic and therapy should be dynamic
• AWS symptoms vary widely from patient to patient
• some factors age, gender, medical and
  psychiatric co-morbidities, history of previous
  withdrawal, other drug use
• Response to treatment is also variable
• it is important to consider each symptom cluster
  independently.
• following a rigid medication protocol results in
  some patients receiving agents they do not need,
  and leaves others with uncontrolled symptoms

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General Scheme for Use of Type Indicator in AWS

• 1. Assess patient with TI
• 2. Prioritize and treat symptoms
• 3. Repeat 1 and 2 until target symptoms have
  resolved

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Dynamic Individualized Therapy

• Dynamic
• patient is evaluated for treatment response
  before additional therapy is given
• Individualized
• symptom clusters, their order of presentation,
  and their severity all vary widely from patient
  to patient
• treatment is based on the emergence of specific
  symptom clusters over time
• Therapy
• to reduce each Type score

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Dynamic Individualized Therapy in Practice

• Patient is evaluated for presence of symptom
  clusters (Types A, B, and C) with the Type
  Indicator
• Therapy is ordered for the treatment of specific
  symptoms present
• Patient is re-evaluated with the Type Indicator
• Therapy is adjusted based on response to prior
  therapy

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Prioritizing AWS Symptoms

• Treat lowest level symptoms first
• A, then B, then C except in emergencies
• Typical Emergencies
• Severe Type B symptoms, such as severe
  hypertension, tachycardia
• Severe Type C symptoms (alcohol withdrawal
  delirium) including agitation that poses a danger
  to patient or others
• Re-administer Type Indicator to assess response

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Benzodiazepines in AWS Treatment

• Benzodiazepines are useful primarily for treating
  the least medically serious AWS symptoms (Type A)
• Benzodiazepines have never been proven effective
  for the control of severe hypertension in AWS,
  nor in any other context
• There is no evidence that treatment with
  benzodiazepines prevents the emergence of AWS
  delirium
• Benzodiazepines have been shown to be associated
  with delirium and cognitive disruption.

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Therapy of Type A Withdrawal

• Therapeutic objectives
• Treat until patient is alert or easily aroused
  but has no Type A symptoms
• Useful agents
• Benzodiazepines
• Anti-convulsants
• Carbamazepine (Tegretol)
• Valproic acid (Depakote)

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Therapy of Type A Withdrawal

• When to use benzodiazepines
• Type A symptoms present mild Type B symptoms
• Short-acting (lorazepam) vs long-acting (diazepam
  or chlordiazepoxide (Librium)
• Use short-acting if age gt 55, liver disease
• Use an alternative to benzodiazepines such as
  carbamazepine or valproic acid if
• Patient has risk factors for atypical AWS, such
  as history of severe head injury, alcoholic
  dementia, impairment of judgement due to other
  psychiatric condition, delirium (unless emergent
  sedation required).

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Therapy of Type A Withdrawal

• Common errors in use of benzodiazepine therapy of
  AWS
• Continuing therapy with these agents to treat
  elevated blood pressure and/or heart rate if
  patient is already sedated (sleepy but arousable)
• Use of these agents to treat AWS-related delirium
• Commencing therapy with these agents in the
  presence of elevated blood alcohol levels
• Use of these agents to treat disinhibited
  behaviors

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Therapy of Type B Withdrawal

• Therapeutic objectives
• Reduce Type B symptoms by attenuating the effects
  of elevated levels of circulating catecholamines
  (adrenalin) on cardiovascular system
• Useful agents
• Clonidine - alpha-2 adrenergic agonist which
  decreases central nervous system sympathetic
  output
• Sympatholytics (directly block effects of
  adrenalin)
• Propranolol - beta blocker
• Atenolol - beta-blocker
• Labetalol - alpha and beta blocker

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Therapy of Type B Withdrawal

• When to use sympatholytics
• Type A symptoms have responded to therapy but
  Type B symptoms persist or increase
• Emergency treatment of severe Type B symptoms
• Choosing a sympatholytic
• Clonidine
• Available for oral or dermal use
• Long duration of action
• Good first choice for uncomplicated Type B
  symptoms in absence of contraindications

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Therapy of Type B Withdrawal

• Choosing a sympatholytic
• Atenolol
• Orally available sympatholytic
• Useful in older patients where sedation from
  clonidine might be problematic
• If not contraindicated, useful in patients with
  history of angina
• Propranolol
• alternative to atenolol since available in IV
  form
• Sedating, so may be useful in patients with
  severe Type B symptoms associated with Type C
  symptoms

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Therapy of Type B Withdrawal

• Choosing a sympatholytic
• Labetalol - also has alpha-blocking effects and
  is available for IV use, making it an ideal agent
  for use in treatment of Type B symptoms
  associated with severe hypertension on an
  emergent basis

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Therapy of Type B Withdrawal

• Relative contraindications/problems in use of
  sympatholytics
• Beta-blockers are relatively contraindicated in
  presence of asthma or COPD/COLD(use clonidine if
  possible)
• May exacerbate cardiac conduction defects, hence
  obtain an EKG before use
• Use in dehydrated patients can cause severe drops
  in blood pressure
• Many other conditions in addition to AWS can
  result in Type B symptoms

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Therapy of Type C Withdrawal

• Therapeutic objectives
• Decrease the behavioral consequences of severe
  agitation without causing undue sedation or
  additional cognitive impairment
• Useful agents
• Haloperidol - moderately sedating
• Fluphenazine - least effect on seizure threshold
• Droperidol - most sedating
• Risperidone -least sedating

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Therapy of Type C Withdrawal

• When to use neuroleptics
• Emergent Type C symptoms whether or not Type A or
  Type B symptoms are present
• Choosing a neuroleptic
• Haloperidol
• Available for oral, IM or IV use
• Moderately sedating
• Droperidol
• Available for IV use
• Heavily sedating

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Therapy of Type C Withdrawal

• Choosing a neuroleptic
• Haloperidol
• Available for oral, IM or IV use
• Moderately sedating
• Droperidol
• Available for IV use
• Heavily sedating
• Extensive experience with high doses as
  antiemetic post cancer chemotherapy
• Good choice for immediate behavioral control

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Therapy of Type C Withdrawal

• Choosing a neuroleptic
• Fluphenazine
• Equipotent to haloperidol but has little effect
  on lowering seizure threshold
• May be agent of choice if patient has known
  seizure disorder
• Risperidone
• Parenteral preparation not available at this time
• Has less propensity to cause a movement disorder
• Is much less sedating at low to moderate doses
  (at high doses may be activating)
• May be ideal agent in geriatric AWS delirum

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Therapy of Type C Withdrawal

• Relative contraindications/problems in use of
  neuroleptics
• Can all cause prolonged QT interval EKG
  associated with fatal torsades de pointes
  arrhythmia, therefore, EKG is highly recommended
  before initiation of therapy
• All except maybe risperidone may exacerbate
  Parkinsons disease or be associated with
  movement disorders

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References

• Zilker T. Alkoholentzugssyndrom und Delirium
  tremens. Diagnose und Therapie. MMW Fortschr Med
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• Myrick H, Brady KT, Malcolm R. Divalproex in the
  treatment of alcohol withdrawal. Am J Drug
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• Tiecks FP Einhaupl KM. Behandlungsalternativen
  des Alkoholdelirs. Treatment alternatives of
  alcohol withdrawal delirium Nervenarzt 1994
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• Isbell H, Fraser HF, Wikler A, Belleville RE,
  Eisenman AJ. An experimental study of the
  etiology of Rum Fits and Delirium Tremens. Q
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• Mendelson JH, La Dou J. Experimentally induced
  chronic intoxication and withdrawal in
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• De Witte P. The role of neurotransmitters in
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  Alcohol Suppl. 1996 Mar113-6.
• Grobin AC, Matthews DB, Devaud LL, Morrow AL.
  The role of GABA(A) receptors in the acute and
  chronic effects of ethanol. Psychopharmacology
  (Berl). 1998 Sep139(1-2)34-43.

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More References

• Linnoila M. Neurotransmitters and alcoholism
  methodological issues. Adv Alcohol Subst Abuse.
  19887(3-4)17-24.
• Kumari M, Ticku MK. Regulation of NMDA receptors
  by ethanol. Prog Drug Res. 200054152-89.
• Lovinger DM. 5-HT3 receptors and the neural
  actions of alcohols an increasingly exciting
  topic. Neurochem Int. 1999 Aug35(2)125-30.
• Higley JD, Bennett AJ. Central nervous system
  serotonin and personality as variables
  contributing to excessive alcohol consumption in
  non-human primates. Alcohol Alcohol. 1999
  May-Jun34(3)402-18.
• Koob GF, Roberts AJ, Schulteis G, Parsons LH,
  Heyser CJ, Hyytia P, Merlo-Pich E, Weiss F.
  Neurocircuitry targets in ethanol reward and
  dependence. Alcohol Clin Exp Res. 1998
  Feb22(1)3-9.
• Fitzgerald LW, Nestler EJ. Molecular and cellular
  adaptations in signal transduction pathways
  following ethanol exposure. Clin Neurosci.
  19953(3)165-73.

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More Information

• Alcohol Withdrawal Treatment Manual
• P.B. DePetrillo and M.K. McDonough
• http/www.sagetalk.com/
• free on-line discussion of substance abuse issues
  and general information on substance abuse
  treatment
• E-mail info_at_sagetalk.com