Dr. Avinash De Sousa. State government aided hospital. Private psychiatric set up – nursing...

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