The current study was prospective, randomized, open label trial to compare efficacy and tolerability of clonidine and buprenorphine in different doses in treatment of opioid dependence. 0.4mg/day and 0.8mg/day doses of clonidine and 1.2mg/day and 2.4mg/day dose of buprenorphine were compared. Patients of opioid dependence fulfilling the inclusion and exclusion criteria were recruited.

In total, 100 patients were recruited in the study and out of them, 80 patients completed the detoxification in inpatient setting for two weeks. The patients were assessed using standard scales for various aspects of opioid use/dependence (ASI, SOCRATES 8D, VAS, COWS, SOWS) along with semi structured proforma for recording sociodemographic details and pattern of opioid use. Patients were also assessed for laboratory parameters like haemogram, serum electrolytes, renal function test, liver function test, ECG. All patients were screened for urine opioids at the time of admission to confirm the active opioid use and subsequently to confirm the abstinence from illicit opioid use during study period. Patients were assessed daily for two weeks during stay in the ward.

All groups were comparable on socio- demographic variables except in area of occupation which showed more unemployment in high dose buprenorphine group. Patients were comparable on other opioid related factors like type of opioid consumed by patients, age at first use of opioid, duration of regular use, money spent to procure opioid and addiction severity index in various domains except legal area. Various other items of addiction severity index and motivation level were also assessed and found were comparable at the time of inclusion into the study.

Effectiveness of drugs in controlling withdrawals was seen in all the groups. Buprenorphine high dose was found clearly superior from all other groups on day 2 to 7 on COWS and on day 2 to 4 on SOWS in controlling opioid withdrawals. No difference between two clonidine groups and clonidine high dose and buprenorphine low dose was seen on any scale. Low dose buprenorphine was found to be better than low dose clonidine on day 4 only on both the scales. High buprenorphine was found better than low dose buprenorphine for four days (day 2, 3, 6, 7) on COWS scale only. Mean withdrawals scores were not zero even at end of 2 weeks except in low dose clonidine group on COWS scale. No group was found better than other in controlling craving. In all the four groups, motivation was found to be significantly increased, especially in area of taking step.

Ancillary medicines lorazepam was used in significantly lesser doses from day 2 to 11 in high dose buprenorphine group. Majority of patients in both high dose groups were not requiring lorazepam by end of study period. Findings are again favouring high dose buprenorphine. Oral rehydration solution use was least required in buprenorphine high dose group.

Adverse effects were seen more in both high dose groups. In both clonidine groups total 4 patients developed hypotension leading to dropout from study. Dry mouth was most common side effect in clonidine group and constipation was most common disturbing side effect in buprenorphine group. Both drugs were well tolerated and none of the patients required dose reduction. No dropout was seen in buprenorphine group due to side effect.

 To conclude, both clonidine and buprenorphine are effective in controlling withdrawals. Buprenorphine in dose of 2.4mg/day is more effective than buprenorphine 1.2mg/day and clonidine. There is no advantage in using clonidine more than 0.4mg/day in controlling opioid withdrawals, rather higher dose lead to more side effects. Clonidine has disadvantage of risk of developing hypotension even at 0.4mg/day dose so, blood pressure monitoring and slow dose titration  is necessary.