1. The use of Topiramate in
Alcohol withdrawal and
dependence
A presentation
by Edward
Gomm

2. Reasons and Methods
 Personal interest
 Substance abuse clinic
 Drinking in media
 Methods
 Textbooks
 Medline/Cochrane Library searches
 Drug Clinic/personal correspondence

3. Alcohol dependence
syndrome - Key elements
 Desire or compulsion to drink
 Salience of drinking/ Neglect
 Increased tolerance
 Withdrawal symptoms - relieved by further
drinking
 Difficulty controlling drinking
 Narrowing of repertoire
 Reinstatement after abstinence

4. The withdrawal state
 Severity related to size of dependence and
quantity habitually consumed.
 Mild symptoms include: mood disturbances
(anxiety, depression), sweating, tremor,
nausea, vomiting, raised pulse, hyperaucusis
and raised BP.
 Severe symptoms: “Delerium tremens”,
hallucinations, seizures (grand mal).

5. Alcohol Detoxification
 May be managed in out-patient.
 Acute detox - Benzodiazapine
indicated.Day Diazepam Chlordiazepoxide
1 15mg, qd 30mg,qd
2 10mg,qd 30mg,td
3 10mg,td 20mg,bd
4 5mg,qd 10mg,bd
5 5mg,td 10mg,bd
6 5mg,bd 10mg,nocte
7 5mg,nocte

6. Dependence Syndrome -
Relapse Prevention
 Psychological therapy e.g Motivational
interviewing.
 Pharmacological:
 Disulfiram (Antabuse)
 Acamprosate (Campral)
 Others - not licensed for alcohol dependence
(Naltrexone, SSRIs, Buspirone, Ondansetron)
 Both should be incorporated into
comprehensive treatment program.

7. Problems with current
medications
 Benzodiazepine
 Potential for abuse
 Potential for respiratory depression
 Disulfiram:
 Inappropriate for: CV or respiratory
disease, hepatic or renal impairment,
diabetes, epilepsy, and pregnant or
breastfeeding women.
 Requires commitment and/or supervision.
 Drug interactions.

8.  Acamprosate
 Relatively safe, but should not be
prescribed to hepatic/renal impairment or
pregnant/breastfeeding women.
 UK trial showed little benefit over Placebo
(Chick et al,2000).
 Naltrexone:
 Potential liver toxicity
 Problem with opioid analgesia

9. Topiramate
(Topamax)
 From naturally occurring sulfamate
fructopyranose.
 Anticonvulsant used to prevent epileptic seizures
 Multiple actions:
 Blocks VgNa+
and VgCa2+
channels
 Inhibits carbonic anhydrase
 Inhibits activity of AMPA and kainate subtypes of
glutamate receptors
 Facillitates GABAergic neurotransmission
Reproduced from
www.drugs.com

10. Mechanism in preventing alcohol
dependence
Reproduced from Ait-Daoud et al, 2006

11. Mechanism in withdrawal
 May reduce the over-activity of the
sympathetic NS and neuronal
hyperactivity seen in withdrawal.
 As effective as Lorazepam in treating
withdrawal (Choi et al, 2005).

12. Evidence
 Only one RCT- Johnson et al, Lancet 2003.
 Method:
 12 wk, double blind, placebo controlled trial
 Recruited 150 alcohol dependants (DSM-IV criteria).
 Received daily 300mg oral topiramate or placebo, with
weekly compliance therapy
 Results - compared to placebo.
 2.88 fewer drinks per day
 3.10 fewer drinks per drinking day
 27.6% fewer heavy drinking days
 26.2 more days abstinent
 Reduction in plasma gama-glutamyl transferase

13. Benefits
 Good pharmacological profile.
 Quick absorption (within 2hrs)
 Not affected by food consumption
 Poor plasma protein binding
 Could be used in withdrawal AND dependence
syndrome.
 Seizure protection
 Not addictive.
 No adverse reaction if alcohol consumed.

14. Conclusion
 Current medication is limited.
 Can be abused
 Can interact with other medication
 Do not treat withdrawal and dependence
syndrome together.
 Topiramate may be used in withdrawal and
relapse prevention.
 Initial trials indicate it is effective at preventing
relapse.
 Further investigation is required.

15. Reflection - Strengths and
Weaknesses.
 Limitations:
 Only focused on one drug
 Psychological therapy also crucial
 Learning:
 Details of alcohol dependence
 Refined literature searching/presentation skills
 The importance of exploration of possible new
roles for current medications

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alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer
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Chick J, Howlett H, Morgan M Y, and Ritson B (2000) United Kingdom Multicentre
Acamprosate Study (UKMAS): a 6-month prospective study of
acamprosate versus placebo in preventing relapse after withdrawal
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Choi E. A, Ki S. W, Kim S. E, Kim J. W, and Park, J. K. (2005). The efficacy and safety of
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Hamid Ghodse (2002). Drugs and addictive behaviour; a guide to treatment. 3rd Edition. Cambridge
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