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DISULFIRAM Comparative Studies
andExperiences from Clinical Practice
Dr. Avinash De Sousa
State government aided hospital.
Private psychiatric set up – nursing home. Out patient private practice.
Private general hospital with a large psychiatric set up.
My work in India
No major research available on long term management till last five years.
Few doctors interested in specializing in addiction medicine.
Indian culture and alcohol dependence.
Alcohol Dependence in India
Cheaper alternative to Naltrexone, Acamprosate and Topiramate.
Alcoholism is a very rampant problems and most patients are the sole bread winners.
Abstinence is very important for work.
Lack of aided psychiatric services.
Disulfiram in India
Though cheaper – few psychiatrists are comfortable with usage.
Side effects are rare – hepatotoxicity or neuropathy.
Complicated alcohol withdrawals are common in our practice.
Disulfiram induced confusion or psychosis.
Disulfiram in India
The Indian Studies Three open randomized trials (2004-2008)
Naltrexone VS DisulfiramAcamprosate VS DisulfiramTopiramate VS Disulfiram
Conditions in the study were similar to routine clinical practice in India.
All patients – underwent detoxification. Randomized but open study.
Inclusion Criteria
Age between 18-65 years. DSM-IV criteria for alcohol dependence. All had a stable and supportive family
environment. One responsible family member. Importance of supervised Disulfiram
therapy
Exclusion Criteria
Other substance use disorders other than Nicotine Dependence.
Any co-morbid psychiatric disorder.
Any medical condition that would interfere with compliance.
Elevated liver functions. Previous treatment with the 2 drugs of
the study.
Methodology
Subjects informed about the study and the drugs involved.
Need for a family member to be present on regular follow up.
Importance of psychoeducation in Disulfiram therapy.
Procedure & Assessments
Addiction Severity Index. Severity of Alcohol Dependence Scale.
Scale to measure the 3 parameters of craving frequency, duration and intensity – (Anton).
Baseline liver function tests. Calendar to record alcohol consumption.
Dose of medication used 50mg of Naltrexone once a day. 250mg of Disulfiram once a day. 666mg of Acamprosate thrice daily. 50mg Topiramate thrice daily.
NTX and DSF taken as a single daily dose in the morning after breakfast with a family member to observe that the patient takes the medicine.
Follow ups
Weekly for the first 3 months. Fortnightly till the end of the study. Transport paid by us – other incentive
offered.
Supportive group psychotherapy – once a week – less structured than in a classical de-addiction programme – emphasis on compliance.
Additional medications
Sertraline 50-100mg and Escitalopram 5-10mg in case of depression. Duloxetine 20-40mg per day in the
Topiramate study.
Zolpidem 5-10mg at night in case of insomnia.
No benzodiazepines were prescribed.
Outcome measures Accumulated days of abstinence.
Days until the first relapse (defined as consuming more than 5 alcoholic drinks or 40gm alcohol in 24 hours).
Outcome Measures
Craving measures.
GGT measured every 3 months.
Discontinuation of treatment.
Drop out from the study
DisulfiramVS
Naltrexone
(Alcohol & Alcoholism 2004 ; 39(6) : 528-531)
Clinical Variables at startData
(n = 50)Naltrexone (Mean ± SD)
Disulfiram(Mean ± SD)
Sev. Alc. Dep. 29 ± 5 28 ± 6A.S.I. 0.70 ± 0.14 0.71 ± 0.12
Craving score 52 ± 19 51 ± 22Serum GGT 110 ± 98 105 ± 102
Days of abstinence
15 ± 6 16 ± 10
Clinical Variables at startData
(n = 50)Naltrexone (Mean ± SD)
Disulfiram(Mean ± SD)
Days of drinking in the last 6 months
87 ± 20 87 ± 22
Typical number of drinks per
day
12.5 ± 5 12.2 ± 5.1
Outcomes at the end of 1 year
days to first alcohol use
days to first re-lapse
craving score Serum GGT0
20
40
60
80
100
120
4463
11.3
107103
119
16.3
85
NALTREXONE DISULFIRAM
Outcomes at the end of 1 year
completed the study
abstinent0
5
10
15
20
25
30
35
40
45
5049
22
48 45
NALTREXONE DISULFIRAM
DisulfiramVS
Acamprosate(Alcohol & Alcoholism 2005 ; 40(6) : 545-548)
Clinical Variables at startData
(n = 50)Acamprosate (Mean ± SD)
Disulfiram(Mean ± SD)
Sev. Alc. Dep. 27 ± 6 26 ± 4A.S.I. 0.73 ± 0.11 0.72 ± 0.13
Craving score 54 ± 18 51 ± 19Serum GGT 124 ± 86 114 ± 89
Days of abstinence
18 ± 8 21 ± 11
Clinical Variables at startData
(n = 50)Acamprosate
(Mean ± SD)Disulfiram
(Mean ± SD)
Days of drinking in the last 6
months
83 ± 17 86 ± 21
Typical number of drinks per
day
10.3 ± 4.7 11.6 ± 5.3
Outcomes at the end of 1 year
days to first alcohol use
days to first re-lapse
craving score Serum GGT0
20
40
60
80
100
120
140
48
71
10.9
79
112
123
17.2
111
ACAMPROSATE DISULFIRAM
Outcomes at the end of 1 year
COMPLETED THE STUDY
ABSTINENT0
5
10
15
20
25
30
35
40
45
50
47
23
4644
ACAMPROSATE DISULFIRAM
DisulfiramVS
Topiramate( J Subs Abuse Treatment 2008; 34 : 460-463)
Clinical Variables at startData
(n = 50)Topiramate (Mean ± SD)
Disulfiram(Mean ± SD)
Sev. Alc. Dep. 28 ± 4 26 ± 5A.S.I. 0.72 ± 0.10 0.69 ± 0.08
Craving score 53 ± 17 56 ± 16Serum GGT 109 ± 71 118 ± 66
Days of abstinence
20 ± 11 21 ± 11
Clinical Variables at startData
(n = 50)Topiramate (Mean ± SD)
Disulfiram(Mean ± SD)
Days of drinking in the last 6
months
82 ± 14 86 ± 12
Typical number of drinks per
day
9.6 ± 4.3 10.4 ± 4.4
Outcomes at the end of 1 year
days to first alcohol use
days to first re-lapse
craving score Serum GGT0
20
40
60
80
100
120
140
46
79
12.7
71
116
133
18.3
109
TOPIRAMATE DISULFIRAM
Outcomes at the end of 1 year
COMPLETED THE STUDY
ABSTINENT0
5
10
15
20
25
30
35
40
45
50
46
28
46 45
TOPIRAMATE DISULFIRAM
Discussion
All three drugs were well tolerated.
Larger studies across diverse populations of patients are needed to replicate and strengthen these results.
Family support in India is strong – exploiting this resource is a must in the successful use of Disulfiram.
Disulfiram superior to Naltrexone in elderly alcoholics.
(Journal of Pakistan Psychiatric Society 2009)
Disulfiram superior to Naltrexone in adolescent alcohol dependence patients.
(Journal of Substance Use 2006)
Disulfiram superior to Naltrexone in female alcoholics.
(unpublished work)
Other studies done by us
Disulfiram versus a Combined Naltrexone and Acamprosate regime
Does Acamprosate addition enhance Disulfiram therapy.
Disulfiram and Psychotherapy.
(All studies would be complete by 2011-2012)
Studies in progress
The Helsinki Disulfiram study.
Disulfiram superior to Acamprosate.
OLITA Study.
Other small but important studies.
Other pivotal studies
Limitations
Open studies rather than a blinded ones. Hypothetically a bias may have been introduced.
No laboratory marker used to assess compliance.
Good primary support group leading to fewer drop outs.
Stringent inclusion criteria.
Incorporating Disulfiram into psychotherapy.
Disulfiram in patients with comorbid psychiatric disorders.
Where does Disulfiram stand today in the modern pharmacotherapy of alcoholism.
Other issues in Disulfiram therapy
Disulfiram is a treatment option that cannot be ignored.
Psychiatrists worldwide need to be trained.
Oral Disulfiram VS Long acting Naltrexone or Naltrexone implants
Effective compliance monitoring.
Conclusions
The Stapleford Conference and its organizers.
My parents who have taught me most of my psychiatry.
My country that gives me enough freedom and patients who trust me fully.
Everyone here who made me feel at home.
Acknowledgements