Alpha2-adrenergic agonists for the management of opioid withdrawal

Alpha2-adrenergic agonists (Clonidine and lofexidine) were found in a systematic review (Gowing et al., 2016, 26 RCT, N=1 728) to be more effective than placebo in:

• ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95 % CI 0.18 to 0.57, 3 studies, N=148)
• increasing completion of treatment (RR 1.95, 95 % CI 1.34 to 2.84, 3 studies, N=148)

When compared to reducing doses of methadone

• duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95 % CI -1.31 to -0.83, 3 studies, N=310)
• hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95 % CI 1.19 to 3.10, 6 studies, N=464)
• no significant difference in rates of completion of withdrawal treatment were found (RR 0.85, 95 % CI 0.69 to 1.05, 9 studies, N=659)