Detoxification Strategies for Polysubstance Abuse and Anticraving Medication

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Detoxification Strategies for Polysubstance Abuse
and Anti-craving Medication

• Mark Publicker, MD FASAM
• Medical Director
• Mercy Recovery Center

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Addiction

• A chronic but treatable brain disease
  characterized by
• loss of control
• compulsive use
• use despite known harm
• relapse

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Definition

• Addiction is a cycle of spiraling dysregulation
  of brain reward systems that progressively
  increases, resulting in compulsive drug use and a
  loss of control over drug taking.
• George Koob

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Pathophysiology

• Neural circuitry of reward and brain reward
  thresholds
• Tolerance
• Altered hedonic tone
• Sensitization
• Activation of HPA axis
• Genetic predisposition

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Neuroadaptation

• Drugs change the brains balance
• The brain has mechanisms to oppose this change
• The balancing action overshoots
• The stronger the drug, the higher the dosage and
  the longer the use, the more the opposing change

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Opponent process theory
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Allostasis

• Change to new, vulnerable state
• Deficit states inhibition of brain reward
  circuitry
• Altered hedonic tone (Koob)
• Reward thresholds increase
• Opponent process theory
• Counteradaptive hedonic dysregulation

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Alcohol detoxification

• Benzodiazepines treatment of choice
• Upregulate GABA tone
• Decrease risk of seizures
• Chlordiazepoxide (Librium)
• Lorazepam (Ativan)
• Oxazepam (Serax)
• Diazepam (Valium)

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Alcohol detoxificationAdjunctive medications

• Trazodone
• Beta-blockers
• Alpha-2 agonists
• Magnesium Sulfate
• Vitamins

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Alcohol withdrawal seizures

• No routine role for most anti-convulsants
• Topiramate
• Pre-existing epilepsy

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Benzodiazepine detoxification

• Phenobarbital loading and taper
• Valproic Acid (Depakote)
• Carbemazepine (Tegretol)

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Opioid Addiction

• Maine highest national prevalence for opioid
  addiction
• Epidemiology young,female
• High rate of IVDA

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Methadone

• Good abstinence rates 70-80
• Blocks craving
• Blocks euphoria
• Normalization of HPA axis
• Normalization of limbic function

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Opioid detoxification

• Alpha-2 agonists clonidine,guanfacine
• NSAIDS
• Benzodiazepines
• Phenothiazines
• Trazodone
• Bentyl
• Imodium

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Buprenorphine - Partial agonist

• New treatment for opioid dependence
• Alternative to methadone maintenance therapy
• Can be prescribed by office-based physicians
• Increases access to effective treatment
• Mainstreams treatment of addictive disorders

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Buprenorphine

• Novel opioid with both opioid and anti-opioid
  effects
• Long duration of action gt24 hours
• High affinity for the mu opioid receptor
• Slow dissociation from the opioid receptor

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Beneficial effects

• Blocks craving
• Blocks opiate withdrawal
• Does not produce a high
• Blocks the effects of abused opioids
• Increases treatment retention
• Less physical dependence than methadone and
  therefore easier withdrawal

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Buprenorphorine bioavailability

• Good parenteral bioavailability
• Poor oral bioavailability
• Fair sublingual bioavailability

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Naloxone

• Poor oral bioavailability
• Will not precipitate withdrawal
• Added in 41 ratio

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Induction - risk of withdrawal

• May precipitate withdrawal in opioid dependent
  patients
• Related to timing and type of opioid
• Avoided if patient is in mild to moderate
  withdrawal at time of induction
• If switching from methadone, dose should be no
  higher than 30 mg to minimize risk of
  precipitated withdrawal

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Use in opioid withdrawal

• Effective in producing comfortable withdrawal
• Best if tapered over 30 days
• Withdrawal not an effective treatment in opioid
  dependence

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Cocaine

• No physical withdrawal
• Alcohol plus cocaine -Cocaethylene
• Benzodiazepines
• Topiramate
• Bupropion

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Naltrexone

• Alcohol produces its positive reinforcing effects
  through the opioid system
• Pure opioid antagonist
• Effective in treatment of alcoholism and opiate
  addiction
• Blocks cue-triggered craving
• Blocks the high and increases the negatives

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Naltrexone

• Naltrexone can decrease
• The percentage of days spent drinking
• The amount of alcohol consumed on a drinking
  occasion
• Relapse to excessive and destructive drinking

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Naltrexone

• Great majority of studies show significant
  benefit over placebo
• Antidepressant studies under 50 response
• Works best in patients who have strong craving
  and strong family history
• These patients seem to have a gene variant
  causing increased b-endorphin sensitivity
• Without naltrexone this group did poorly in
  studies
• Genomic differences translate into different
  treatment responses

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Naltrexone

• Oral (Revia) and soon an injectable depot
  formulation (Vivitrol)
• Primary drug-drug interaction Opioids
• Challenges
• Side effects (nausea in small percentage)
• Adherence
• Physician awareness and knowledge
• Integration with psychosocial treatment
• Optimal duration of treatment unknown

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Acamprosate (Campral)

• NMDA receptor antagonist
• Glutamatergic (excitatory) system
• Blocks craving particularly context and
  stress-related cues
• Use in detoxified patients engaged in active
  psychosocial treatment
• Doubles abstinence rates
• Additive with naltrexone (Combine Study)

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Acamprosate

• No liver metabolism or toxicity
• No drug-drug interactions
• Greater rates of complete abstinence
• Longer times to first drink
• May be neuroprotective
• Challenge three time a day dosing

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Conclusions

• Addiction is a treatable brain disease
• Research is edifying the biological mechanisms
  involved

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Conclusions

• Increased understanding of neurobiology is
  allowing for the development of effective,
  targeted pharmacotherapies
• State of the art, evidenced-based treatment must
  integrate behavioral and medical therapies to
  produce the best outcomes.