The aims of this study were to evaluate the effects of trazodone and mianserin on opioid-withdrawal symptoms in morphine-dependent mice. We used a comparative study of the effect of each drug on withdrawal symptoms in one model of acutely high-dose morphine-dependent mice, and two models (high-dose and lu-dose) of chronically morphine-dependent mice at the Tel Aviv University Sackler School of Medicine's laboratory.Trazodone, mianserin or both were given to the morphine-dependent mice together with a high dose of naloxone. Intensity of withdrawal symptoms was evaluated by tail-flick assay latencies and three behavioural measurements (rearing, jumping and grooming) in each group. Trazodone and mianserin, each separately,significantly attenuated withdrawal symptoms in all three models. However, the combined treatment of trazodone together with mianserin was not superior to each drug alone. The combination of trazodone and mianserin has no additive value to each drug alone in the control of withdrawal symptoms in opiate-dependent mice undergoing detoxification. When used in clinical settings, caution is needed in order to prevent the unknown influence of opioid-like drugs in medication-assisted detoxification programmes if complete opiate detoxification is the aim.