DISULFIRAM Comparative Studies and Experiences from Clinical Practice

1. DISULFIRAM Comparative StudiesandExperiences from Clinical Practice Dr. Avinash De Sousa

2. My work in India • State government aided hospital. • Private psychiatric set up – nursing home. • Out patient private practice. • Private general hospital with a large psychiatric set up.

4. Alcohol Dependence 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.

6. Disulfiram 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.

7. 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.

9. The Indian Studies • Three open randomized trials (2004-2008) Naltrexone VS Disulfiram Acamprosate VS Disulfiram Topiramate VS Disulfiram • Conditions in the study were similar to routine clinical practice in India. • All patients – underwent detoxification. • Randomized but open study.

10. 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

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Additional medications • Sertraline 50-100mg and • Escitalopram5-10mg 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.

17. 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).

18. Outcome Measures • Craving measures. • GGT measured every 3 months. • Discontinuation of treatment. • Drop out from the study

19. DisulfiramVSNaltrexone(Alcohol & Alcoholism 2004 ; 39(6) : 528-531)

20. Clinical Variables at start

21. Clinical Variables at start

22. Outcomes at the end of 1 year

23. Outcomes at the end of 1 year

24. DisulfiramVSAcamprosate(Alcohol & Alcoholism 2005 ; 40(6) : 545-548)

25. Clinical Variables at start

26. Clinical Variables at start

27. Outcomes at the end of 1 year

28. Outcomes at the end of 1 year

29. DisulfiramVSTopiramate( J Subs Abuse Treatment 2008; 34 : 460-463)

30. Clinical Variables at start

31. Clinical Variables at start

32. Outcomes at the end of 1 year

33. Outcomes at the end of 1 year

34. 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.

35. Other studies done by us • 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) • Disulfiramsuperior to Naltrexone in female alcoholics. (unpublished work)

36. Studies in progress • 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)

37. Other pivotal studies • The Helsinki Disulfiram study. • Disulfiram superior to Acamprosate. • OLITA Study. • Other small but important studies.

38. 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.

42. Other issues in Disulfiram therapy • Incorporating Disulfiram into psychotherapy. • Disulfiram in patients with comorbid psychiatric disorders. • Where does Disulfiram stand today in the modern pharmacotherapy of alcoholism.

43. Conclusions • Disulfiram is a treatment option that cannot be ignored. • Psychiatrists worldwide need to be trained. • Oral DisulfiramVS Long acting Naltrexone or Naltrexone implants • Effective compliance monitoring.

44. Acknowledgements • 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.