Opioid Addiction in Medical Practice:

• Prevalence: Increasing cases due to both illegal drug use and prescribed opioid addiction.
• Definition: Opioid addiction or dependence syndrome involves compulsive drug use despite harm.
  • Examples: Continued opioid injecting despite overdoses or infections, excessive or unsanctioned use leading to impairment and accidents.
• Chronic Disease: Addiction is chronic, with a relapsing and remitting pattern, significant long-term morbidity, and increased mortality risk.

Opioid Substitution Therapy (OST)

Benefits of OST:

• Drugs Used: Methadone, among others.
• Evidence Base: Substantial evidence supports OST in improving physical and social health outcomes.
  • Improvements:
    • Reduces drug-related crimes.
    • Decreases blood-borne viral transmission.
    • Lowers overall mortality rates.

Harm Reduction:

• Approach: OST reduces harm rather than maintaining addiction.
• Global Recognition: Methadone is included in the World Health Organization’s Essential Medicines List for treating opioid addiction due to its effectiveness.

Key Points for Medical Practitioners

1. Diagnosis and Patient Identification:
   • Apply diagnostic criteria based on history, examination, and urine drug testing.
   • Access patient records through confidential communication with local health departments.
2. Patient Suitability for OST:
   • Not all opioid-addicted patients are suitable for OST.
   • Consider alternative therapies such as abstinence-focused programs, behavioral interventions, and self-directed interventions.
3. Indications for OST:
   • Brief Treatment: For opioid withdrawal during crisis intervention.
   • Prolonged Maintenance Therapy: Correlates with better long-term outcomes like remission and recovery.
4. Management of Withdrawal:
   • Short-term Prescribing: Use of opioid substitutes like buprenorphine in reducing doses, supervised daily or in inpatient settings.
   • Post-treatment Care: General health review, relapse prevention counseling, and overdose prevention education.
5. Maintenance Therapy:
   • Methadone maintenance programs offer long-term rehabilitation.
   • Address barriers such as low numbers of prescribers and patient costs.
6. Potential Problems and Risks:
   • Adverse Effects: Increased risk during methadone’s induction period.
   • Drug Interactions: Risk with illicit drugs and certain prescription drugs.
   • Diversion Risk: Assess risk in group households and consider accidental exposure to children.
   • Occupational Considerations: Some industries prohibit opioid use, and OST poses risks for driving, especially during dose adjustment.
7. Special Circumstances:
   • Considerations for inpatient care, pain management, pregnancy, and travel, especially overseas.

Assessing suitability for opioid substitution therapy:

• Requirements
  • Addiction to opioids
  • Ongoing risk of opioid-related harms
  • Other treatment options ineffective or unsuitable
  • Capacity for informed consent
  • Circumstances appropriate (e.g. able to access
  • pharmacy and take opioid substitution therapy)
• Contraindications
  • Proven or likely sensitivity (or allergy) to some form of opioid substitution therapy
  • Pregnancy generally excludes treatment with buprenorphine with naloxone, and naltrexone
  • Active current alcohol dependence (e.g. daily drinking)
  • QTc prolongation syndrome with methadone – especially when combined with conditions or other drugs which prolong the QTc interval
  • Travel to some countries where opioid substitution
  • therapy is not sanctioned

Alternative Therapies:

• Abstinence-focused programs.
• Behavioral interventions (e.g., contingency management).
• Self-directed interventions (e.g., Narcotics Anonymous).

Management of Withdrawal

Short-term Prescribing:

• Method: Reducing doses of an opioid substitute, supervised daily or in an inpatient detox unit for about a week.
• Objective: Manage acute opioid withdrawal symptoms.
• Post-treatment Care:
  • General health review.
  • Relapse prevention counseling.
  • Medical counseling about overdose prevention, especially after periods of abstinence.

Maintenance Therapy

Long-term Rehabilitation:

• Programs: Methadone maintenance programs have proven efficacy.
• Barriers: Low numbers of prescribers and patient costs.

Pharmacotherapy

Methadone

Methadone Syrup:

• Concentration: 5 mg/mL.
• Formulations: Available with or without added ethanol and sorbitol.
• Indication: heroin use
• Administration:
  • Full agonist at the mu opioid receptor (Can overdose on it)
  • t1/2 12-47hrs
  • Usual dose 60-120mg
  • Long term use 2-5yrs
  • Start slow & ­ slowly every 3-4 days by 5-10mg
  • When wanting to cease: ¯ dose by up to 10% every 2 weeks
• Advantages:
  • Preferred by many patients due to its full agonist properties.
  • Syrup formulation is useful for supervised dispensing as liquid cannot be concealed under the tongue.
  • Approved for use in pregnancy.
  • Metabolism does not produce active metabolites, making it safer for patients with liver or renal impairment.
• Bioavailability: Approximately 70% oral bioavailability compared to parenteral formulation.
• Special Considerations:
  • Requires a 30% dose reduction when ‘nil orally’ restrictions apply.
  • Higher opioid analgesic doses may be needed for acute pain management due to tolerance while maintaining regular methadone dosing.

Drug Interactions and Risks:

• Smoking: Potential for toxicity if patients suddenly stop smoking.
• QTc Prolongation: Risk increases at higher doses (e.g., >100 mg daily) and in those with other risk factors.

Naltrexone

• Formulation: 50 mg tablet.
• Usage:
  • Listed on the PBS for alcohol dependence.
  • Used off-label for opioid addiction to maintain opioid abstinence.
  • Not recommended for rapid opioid detoxification.
• Cost: Up to approximately $180 per month (not listed on the PBS for opioid addiction).
• Efficacy:
  • Effective for alcohol dependence.
  • Less impressive evidence for opioid addiction.

Implant and Depot Formulations:

• Implant Formulations: Available but not approved by the Therapeutic Goods Administration (TGA).
• Depot Formulation: Available in the USA for alcohol dependence and can be used for opioid addiction.

Patient Considerations:

• Minority Usage: Only a minority of patients seek this ‘antagonist’ treatment.
• Adherence Strategy: Recommended to prescribe with an adherence strategy involving the patient’s spouse or other reminders.
• Comparative Efficacy:
  • Opioid substitution therapy with an agonist has primary (rewarding) and secondary (avoidance of withdrawal) reinforcing efficacy.
  • Patients are more likely to remember to take agonist treatments due to their reinforcing effects.

Buprenorphine with naloxone (Suboxone Sublingual Film)

Sublingual buprenorphine products PBS-listed for opiate dependence

	Formulation	Strengths available
Single-ingredient
buprenorphine (Subutex)	tablet	400 micrograms 2 mg 8 mg
Combination
buprenorphine–naloxone (Suboxone)	tablet	2 mg / 0.5 mg 8 mg / 2 mg
buprenorphine–naloxone (Suboxone Sublingual Film)	film	2 mg / 0.5 mg 8mg / 2 mg

Less Potential for Abuse in Supervised Dosing Settings:

• Sublingual film formulation designed for easier supervision.
• Reduces chances of patients removing the dose from the mouth.
• Faster dissolution under the tongue compared to sublingual tablets.
• Adheres quickly to the oral mucosa, deterring removal and misuse.
• Effective supervision diminishes opportunities for misuse and diversion.

History of Buprenorphine Use for Opiate Dependence:

• Partial opioid agonist with high affinity for the µ-receptor.
• Reduces craving and blocks effects of full opioid agonists.
• Lower overdose risk compared to methadone, but can cause fatal overdose with other sedatives.
• Individual preference and program factors should determine treatment selection.
• Poorly absorbed if swallowed; effective when administered sublingually.

Naloxone Component:

• Discourages injection of buprenorphine.
• Poorly absorbed sublingually/orally but effective if injected, causing withdrawal symptoms in opioid-dependent individuals.

Buprenorphine Sublingual Tablets:

• Initially PBS listed in 2001 but associated with high rates of diversion and abuse.
• Buprenorphine-with-naloxone sublingual tablets (Suboxone) PBS listed in 2006; less abused than single-ingredient tablets.

Alternative to Buprenorphine-with-Naloxone Tablets for Unsupervised Dosing:

• No data suggesting sublingual film is less likely to be abused than combination tablets when unsupervised.
• Naloxone reduces but does not eliminate buprenorphine abuse.

Vigilance for Intravenous Misuse:

• Risk of post-injection thrombosis and serious local reactions.
• Potentially serious acute hepatitis reported with injection of sublingual buprenorphine tablets.

Possible Film-Specific Adverse Reactions:

• Commonly causes withdrawal symptoms if not dosed carefully.
• Oral mucosal erythema, glossodynia, oral hypo-aesthesia, stomatitis, toothache, and coated tongue reported in a safety study.

Dose Adjustment:

• Monitor closely when switching between sublingual film and tablets.
• Bioavailability of buprenorphine with naloxone sublingual film is about 20% greater than tablets.

Starting Buprenorphine-with-Naloxone Sublingual Film:

• Assess opioid dependency, last opioid use, type of opioid dependence, likelihood of concurrent use, medical conditions, and use of other drugs.
• Start dosing after early signs of withdrawal appear.
• Recommended starting dose: 6–8 mg on day 1, with adjustments in subsequent days.

Advice for Patients:

• Place film under the tongue until completely dissolved.
• Do not swallow, chew, or move the film.
• Avoid eating or drinking until the film is dissolved.
• Do not inject; causes withdrawal symptoms if injected while receiving other opioids.
• Be cautious with benzodiazepines and alcohol due to increased drowsiness risk.
• Inform doctors about all other medicines being taken.

Appearance:

• Paper-thin, orange-colored rectangular strip.
• Available strengths: 2 mg / 0.5mg and 8mg / 2 mg.
• Identifiable by a white ink imprint: ‘N2’ and ‘N8’.
• Enclosed in sachets, with 28 films per carton.

Both methadone & suboxone are safe in pregnancy – but need dose adjustment

When treating acute general pain issues in those with opioid dependence

1. Continue usual dose
2. Follow pain ladder
3. Split doses
4. May require ­ doses
5. Consider alternatives: nerve blocks, ketamine, gabapentin

Harm Minimisation Strategies for IVDU

1. Needle and Syringe Programs (NSPs):

• Clean needle and syringe distribution to reduce blood-borne infections.
• Safe disposal of used needles and syringes.
• Locations include pharmacies, community health centers, and mobile services.

2. Opioid Substitution Therapy (OST):

• Methadone Maintenance Treatment (MMT).
• Buprenorphine (Suboxone) programs.
• Available through specialized clinics, some general practitioners (GPs), and pharmacies.

3. Supervised Injecting Facilities (SIFs):

• Medically Supervised Injecting Centre (MSIC) in Kings Cross, Sydney.
• Provides a safe environment for injecting under medical supervision.
• Offers health services and support to drug users.

4. Drug Education and Outreach:

• Community education programs by organizations such as Harm Reduction Australia.
• Peer outreach programs to provide education and support.
• Online resources and helplines for information and assistance.

5. Access to Health Services:

• Free or low-cost healthcare services, including mental health and addiction treatment.
• Regular health check-ups and vaccinations (e.g., hepatitis B vaccination).
• Treatment for infections and wound care related to drug use.

6. Overdose Prevention Programs:

• Naloxone distribution programs (e.g., take-home naloxone kits).
• Training for drug users, families, and service providers on naloxone use.
• Available through pharmacies, NSPs, and community health organizations.

7. Counseling and Support Services:

• Individual and group counseling for substance use and mental health issues.
• Support services for housing, employment, and social reintegration.
• Services provided by organizations like Turning Point and Headspace.

8. Legal and Policy Interventions:

• Decriminalization of small amounts of drugs for personal use in some jurisdictions.
• Supportive policies for harm reduction approaches over punitive measures.
• Drug diversion programs to direct individuals to treatment instead of the criminal justice system.

9. Community-Based Programs:

• Local community health centers offering harm reduction services.
• Programs like the Australian Injecting & Illicit Drug Users League (AIVL) that provide peer support.
• Community education and support initiatives.

10. Psychosocial Interventions:

• Cognitive-behavioral therapy (CBT) and other evidence-based therapies.
• Motivational interviewing and enhancement therapy.
• Services available through public health systems and private providers.

11. Addressing Social Determinants:

• Social support services to address poverty, unemployment, and lack of education.
• Comprehensive programs to improve housing, employment, and education opportunities.
• Initiatives by government and non-profit organizations to support vulnerable populations.

Acute Opioid Overdose

Specific opiates:

• Dextropropxyphene: 10 mg/kg will cause symptoms, >20 mg/kg will cause CNS depression, seizures and cardiac dysrhythmias (sodium channel blockade).
• Methadone and oxycodone: QT prolongation (torsades is rare), prolonged toxicity which can last >24 hours.
• Pethidine: Repeated doses increase the risk of seizures and it can also precipitate serotonin toxicity.
• Heroin toxicity lasts approximately 6 hours.
• Controlled release preparations can result in respiratory depression up to 12 hours post ingestion.

CLINICAL FEATURES

• Clinical features:
  • CNS and respiratory depression with miosis is the classic toxidrome.
  • Bradycardia is common unless hypoxia or hypercarbia are present.
  • Complications include: 
    • Aspiration pneumonia
    • hypothermia
    • skin necrosis
    • rhabdomyolysis
    • compartment syndrome
    • hypoxic brain injury

MANAGEMENT

Resuscitation: appropriate use of naloxone can prevent intubation

Electrolytes and Acid-base: respiratory acidosis

Specific Therapy

• naloxone: titrated doses until reversal of respiratory depression -> may require an infusion
• dose: 0.4-2mg IV/IM/SC -> 1-10mcg/kg/hr

Underlying Cause

• addiction counselling/ psychiatric review