1	Bringing AWS Treatment Into Focus Paolo B. DePetrillo, M.D. Mark K. McDonough, M Ed.
2	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
3	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
4	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
5	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
6	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
7	Prioritizing AWS Symptoms
8	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.
9	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)
10	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 > 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).
11	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
12	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
13	Therapy of Type B Withdrawal
14	Therapy of Type B Withdrawal
15	Therapy of Type B Withdrawal
16	Therapy of Type B Withdrawal
17	Therapy of Type C Withdrawal
18	Therapy of Type C Withdrawal
19	Therapy of Type C Withdrawal
20	Therapy of Type C Withdrawal
21	Therapy of Type C Withdrawal
22	References Zilker T. Alkoholentzugssyndrom und Delirium tremens. Diagnose und Therapie. MMW Fortschr Med 1999 Aug 19;141(33):26-30. Myrick H, Brady KT, Malcolm R. Divalproex in the treatment of alcohol withdrawal. Am J Drug Alcohol Abuse. 2000 Feb;26(1):155-60. Tiecks FP; Einhaupl KM. Behandlungsalternativen des Alkoholdelirs. [Treatment alternatives of alcohol withdrawal delirium] Nervenarzt 1994 Apr;65(4):213-9. Isbell H, Fraser HF, Wikler A, Belleville RE, Eisenman AJ. An experimental study of the etiology of “Rum Fits” and “Delirium Tremens.” Q J Stud Alc. 1955;16:1-33. Mendelson JH, La Dou J. Experimentally induced chronic intoxication and withdrawal in alcoholics. Q J Stud Alc. 1964;Supp 2:1-39. De Witte P. The role of neurotransmitters in alcohol dependence: animal research. Alcohol Alcohol Suppl. 1996 Mar;1:13-6. 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 Sep;139(1-2):34-43.
23	More References Linnoila M. Neurotransmitters and alcoholism: methodological issues. Adv Alcohol Subst Abuse. 1988;7(3-4):17-24. Kumari M, Ticku MK. Regulation of NMDA receptors by ethanol. Prog Drug Res. 2000;54:152-89. Lovinger DM. 5-HT3 receptors and the neural actions of alcohols: an increasingly exciting topic. Neurochem Int. 1999 Aug;35(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-Jun;34(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 Feb;22(1):3-9. Fitzgerald LW, Nestler EJ. Molecular and cellular adaptations in signal transduction pathways following ethanol exposure. Clin Neurosci. 1995;3(3):165-73.
24	More Information Alcohol Withdrawal Treatment Manual P.B. DePetrillo and M.K. McDonough http/www.sagetalk.com/ Resources and Information E-mail: info@sagetalk.com