Effect of add-on amantadine to clonidine on opioid withdrawal symptoms in opioid-dependent patients detoxified with buprenorphine: a randomized controlled trial

ABSTRACT

Objective

This research aimed to assess the effectiveness of combination therapy with amantadine and clonidine against clonidine alone on subjective opioid withdrawal symptoms in patients treated with buprenorphine.

Methods and Materials

Patients were recruited from outpatient addiction treatment centers for this double-blind, randomized control trial. They were divided into two groups randomly assigned to receive either clonidine (0.15–0.3 mg/day) or clonidine with amantadine (100–200 mg/day). We assessed withdrawal symptoms with the Subjective Opiate Withdrawal Scale (SOWS) on the first day of admission and 3, 7, 14, and 21 days afterward.

Results

Forty-three patients completed the trial in each group. The impact of adding-on amantadine on the mean SOWS compared to control was significant (p < .001) at any time of the study period. However, there were no significant differences in mean SOWS within groups during follow-up (p > .05). Also, there were no significant differences in mean SOWS between the two groups during follow-up time (day 3rd, 7th, 14th, and 21st) (p > .05).

Conclusion

Amantadine and clonidine combined treatment would result in fewer opioid withdrawal symptoms than clonidine alone, with a decrease commencing on the third day.

KEYWORDS:

• Amantadine
• clonidine
• buprenorphine
• opioid withdrawal syndrome

Acknowledgments

The authors would like to express their gratitude to the study staff at the investigative center and the study participants and their families.

Consent to participate

All patients consented to participate in the study. Signed consent forms are available from the authors.

Disclosure statement

• No potential conflict of interest was reported by the author(s).

Ethics approval and consent statement

This trial is registered with the Iranian Clinical Trials Registry (IRCT20090801002266N15) and was authorized by the Isfahan University of Medical Sciences ethics committee (IR.MUI.MED.REC.1399.1147).

Primary funding

This study revealed that when amantadine is combined with clonidine, it better manages opioid withdrawal symptoms than clonidine alone.

Data availability statement

The corresponding author, Arezoo Safari had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.