Table 1 Currently available treatments for opioid withdrawal/opioid use disorder

Buprenorphine

Mu receptor partial agonist

Approved

1. Ceiling effect to prevent overdose.

2. Prevents euphoria due to partial agonism therapy.

3. Long-term injection formulation is available.

4. Naloxone conjunction prevents misuse.

1. Long term may lead to reduced libido.

2. May cause nausea and constipation.

3. Potential dependence on higher dosage.

(Gowing et al. 2017; Elkader and Sproule 2005)

Methadone

Mu receptor full agonist

Approved

1. Effective in resistant cases of opioid dependence.

2. Effective in HIV and HCV infectious states

3. Favorable prognostic outcome with history of non- compliance.

1. Close supervision for its administration is required.

2. More risk of sustaining dependence and GI related side effects.

3. Increased risk of overdose if taken in conjunction with other controlled sedatives.

(Mattick et al. 2008; Eap et al. 2002; Bell and Strang 2020)

Naltrexone

Mu receptor antagonist

Approved

1. Effective in co-existing alcohol and opioid dependence.

2. Prevents reinforcing effects of opioid use.

3. Long-term injection formulation is available.

1. Avoid in advanced liver diseases.

2. Caution in those who have underlying severe depressive illness.

(Blanco and Volkow 2019; Kleber 2007; Koehl et al. 2019)

Lofexidine

Alpha 2 receptor agonist

Approved

1. Effective in withdrawal state driven by high sympathetic flow.

2. Facilitates detoxification from opioids.

3. First FDA approved non-opioid medication.

1. May precipitate sedation, drowsiness.

2. Blood pressure monitoring required - Risk of inducing hypotension.

(McCambridge et al. 2007; Pergolizzi Jr. et al. 2019; Gerra et al. 2001; Kuszmaul et al. 2019)

Clonidine

Alpha 2 receptor agonist

Off label

1. Ameliorates withdrawal symptoms.

2. Helps in alleviating anxiety and restlessness associated with withdrawal.

1. Caution for sudden hypotension.

2. Precipitates sedation and dizziness

(Gerra et al. 2001; Kuszmaul et al. 2019)

Baclofen

GABA-B receptor agonist

Off label

1. Alleviates muscle spasms.

2. Facilitates detoxification course through muscular symptom neutralization

1. Abuse potential.

2. Sedations, drowsiness and dizziness as part of side effects

(Cousins et al. 2002; Rahimi-Movaghar et al. 2018)

Benzodiazepines

Increase effectiveness of GABA-A receptor complex

Off label

1. Rapid relief of symptoms

1. Highly addictive.

2. Severe side effects including respiratory depression.

(Stein et al. 2016; Lintzeris and Nielsen 2010)

Neural Stimulation

Stimulation of V, VII, IX, X cranial nerves

Approved

1. First FDA approved non systemic based device for alleviation of withdrawal symptoms.

2. Reduces use of medications during acute withdrawal.

3. Non-invasive, well tolerable, with no major side effects.

1. Cost-effectiveness unknown

2. Studies for long-term use are not available

(Miranda and Taca 2018; Baker and Chang 2016)