Substance Use and Addiction

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Substance Use and Addiction

• Presentation for Physicians and Other Health Care
  Providers
• Theda Care Behavioral Health
• March 30, 2006
• Michael M. Miller, M.D., FASAM, FAPA

2
DETOXIFICATION

• RESOLUTION OF A TOXIC STATE
• The Brain has been poisoned
• Manifestations are changes in behavior and
  changes in physiology

3
Management of Withdrawal

• Nicotine
• Alcohol
• Sedatives
• Opioids
• Stimulants
• Hallucinogens

4
Basic Principles of Detox

• Provide calm environment for the patient, to
  reduce anxiety that would amplify symptoms
  (regardless of the drug class)
• Replace the missing substance with a
  pharmaceutical that is cross-tolerant with the
  drug the patient is withdrawing from
• Stabilize the patient
• Institute a step-wise graded reduction in the
  replacement substance
• ORtrick the brain into thinking its receiving
  more of the missing substance

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Nicotine DetoxNicotine Replacement Therapy--NRT

• Transdermal
• Oral (buccal)
• Nasal
• Inhaled

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Alcohol Detox(Sedative Replacement)

• Benzodiazepines
• Other sedatives will work but have
  disadvantagesbarbiturates, ethanol, paraldehyde
• Other sedating drugs that arent cross-tolerant
  with EtOH wont work, e.g. phenothiazines
• Second generation anticonvulsants

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Opioid Detox (Opioid Replacement)

• Methadone
• Buprenorphine
• Any opioid will work but all others are
  illegal! except tramadol (Ultram)
• Clonidine (also guanfacine, lofexidine)
• Supplemental agents for symptom relief
• for anxiety, insomnia, aches, nausea, diarrhea,
  cramping, dehydration

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Stimulant Detox(Stimulant Replacement?)

• Replacement, stabilization, and graded step-wise
  reduction is not recommended for cocaine,
  amphetamine, psychostimulant (Ritalin, Adderal,
  Cylert), or designer drug (MDMD, Ecstasy)
  users
• Replacement, etc., is useful for persons with
  caffeine addiction (switch to oral tablets,
  decrease by 10 per day)

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Hallucinogen Detox(Social Detox)

• Replacement strategies do not apply
• The problem isnt withdrawal, its
  intoxication, with subsequent anxiety/panic in
  the wake of unanticipated dissociative symptoms
• Talk Down the person on a bad trip with
  psilocybin, LSD, hashish (esp. oral THC)
• Talking Down often insufficient for trips on
  PCP or Jimson weed (Datura stramonium)

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DETOXIFICATION

• RESOLUTION OF A TOXIC STATE
• INTOXICATION MANAGEMENT
• WITHDRAWAL MANAGEMENT

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TherapeuticsManagement of Intoxication
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Intoxication States Emerging Trends

• Great resource is www.nida.nih.gov, search for
  Club Drugs
• Ecstacy use BP, HR, hyperthermia, dehydration,
  acute renal failure, rhabdomyolysis,
  hyponatremia, water intoxication, hepatotoxicity,
  arrhythmia
• GBH use rapid shifts of level of arousal
  ataxia disinhibition not in UDT panels
• Ketamine or DM (Robo-tripping) effects are
  comparable to PCP

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Pediatric Addiction Medicine

• Become aware of the epidemic of misuse of
  dextromethorphan (in Robitussin DM and Coricidin
  Cough Cold) DXM or DM
• Effects vary widely and, maybe more so than for
  some agents, are based on expectation of effect
• 8-24 oz. of syrup is the intoxicating dose
• Consumers/parents are starting to know
  (www.coricidin.org)

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Intoxication Management

• For opioids naloxone
• For ethanol naloxone!
• For benzodiazepines flumazenil
• For amphetamines, hallucinogens, PCP
• consider acidification of the urine
• For cocaine anti-arrhythmics, anticonvulsants,
  antipsychotics
• For panic/anxiety talking down or/and benzos

15
Behavioral Management of Intoxication States

• Assure safety of yourself and ER staff
• Dont block egress for the paranoid patient vs.
  dont block egress for yourself!
• Minimize stimuli / inputs (extraneous
  noises/lights, lower volume/rate of speech)
• For delirious/disoriented patients, repeatedly
  provide orienting information and
  reassurancefear fuels anxiety!

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Pediatric Addiction Medicine

• Alcoholinjuries, sexual assault
• Cannabisanxiety/panic
• Hallucinogensanxiety/panic
• Caffeineanxiety/panic
• Diet pills (bulimia et al.)anxiety/panic
• Cocaine and Ecstacyanxiety/panic

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TherapeuticsManagement of Withdrawal
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Keys to Withdrawal Management

• Alcohol / Sedative Withdrawal is potentially
  life-threatening
• Opioid Withdrawal is uncomfortable, but not
  dangerous
• Opioid Addicts are exquisitely sensitive to
  subjective discomforts / dont tolerate them
• Cocaine Withdrawal is insignificant
  physiologically but can be significant
  psychiatrically
• Nicotine Withdrawal is common and treatable

19
Alcohol Withdrawal Stages

• Autonomic Hyperactivity / Irritability
• Hallucinosis
• Seizures
• Delirium
• Delirium from any cause looks similar
• Dont ignore AWS in the differential
• Dont ignore other causes of delirium even in
  the face of alcohol withdrawal

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Stages of Alcohol and Sedative Withdrawal
General Signs Hallucination
Delirium Stage 1 mild no no Stage
2 moderate yes no Stage
4 severe maybe yes
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Stage One - AWS

• Stage One Begins six to eight hours after the
  last drink
• Increased Sympathetic Autonomic Nervous System
  Output
• Increase Blood Pressure, pulse rate, low grade
  elevated temp
• Diaphoresis, exaggerated startle reflex,
  headache, nausea, restlessness, easily distracted

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Stage Two - AWS

• Worsening symptoms and signs of Stage I
• Defined by presence of Hallucinosis
• Visual Auditory Tactile
• Typically starts 24 to 72 hours after last drink
• Occurs in 25 of untreated individuals
• Patient still cognitively intact

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Stage Three - AWS

• Withdrawal Seizures - 5 to 15 of untreated
  individuals
• Typically within the first 48 hours after the
  last drink
• Always Grand Mal - short duration of Tonic/Clonic
  seizure
• Occur in Salvoes
• 3 will enter Status Epilepticus

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Stage Four - AWS

• Delirium Tremens (DTs)
• Begins 48 hours to 14 days after last drink
• Profound clouding of the sensorium - ie Delirious
• Paranoid Delusions
• Mortality approximately 5
• Approximately 5 of untreated individuals will
  enter Stage four

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Alcohol/Sedative Withdrawal
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Prognosticators of Severe Withdrawal

• BAC greater than 300mg/dl
• Age greater than 35 years
• Previous AWS seizure
• Concomitant medical or surgical problem
• Abnormal liver functions
• Other drug use - especially sedatives/hypnotics

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Kindling Phenomenon

• Each subsequent withdrawal episode is worse
• medical management of AWS may prevent the
  Kindling phenomenon
• Evidence better with anticonvulsants such as
  valproic acid carbamazepine than
  benzodiazepines barbiturates in blocking
  progression of the Kindling phenomenon.

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Alcohol Withdrawal Management

• 1. Replace Sedative
• 2. Prevent Advancing to Higher Stages
• I II III IV
• Treat hallucinosis
• Consider other causes of seizures, especially if
  48 hours after falling BAC
• Manage the delirium co-morbid medical
  conditions

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Sedative Replacement

• Symptom-triggered
• Standard Assessment
• Standing Order Sets / Protocols
• Benzos (long-acting oral agents if uncomp.)
• DPH loading is passe
• Carbamazepine is effective
• Remember propofol is a true sed/hypnotic

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Standardized Assessment

• CIWA-A(r)
• Clinical Institute Withdrawal Assessment
• Addiction Research Institute (ARI), Toronto
• http//www.agingincanada.ca/CIWA.HTM
• C.I.W.A. (SEE-wah)

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Global Assessment of Withdrawal

• Nausea/Vomiting
• Tremor
• Paroxysmal Sweats
• Anxiety
• Agitation
• Tactile Disturbances
• Auditory Disturbances
• Visual Disturbances

• Headache
• Orientation/Clouding of the Sensorium
• All 0 to 7 except orientation which is
• 0-4

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Treatment

• Benzodiazepine substitution
• Long acting superior - diazepam and
  chlordiazepoxide
• Half life of Valium 20 to 50 hours
• Metabolized by hepatic oxidation and
  glucuronidation
• Lorazepam not as efficacious - more likely to
  have breakthrough symptoms.
• Safer profile in patients with hepatic
  insufficiency
• Half life 10-20 hours

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Treatment

• Valium 5mg Ativan 1mg
• Valium 5 mg one standard drink
• Lorazepam can be used PO / IM / IV
• Diazepam can be used PO/IV
• Phenobarbital may be slightly better with
  concomitant benzodiazepine misuse
• Phenobarbital 30mg Valium 10mg

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Diazepam Dosing Symptom Triggered

• 10mg diazepam if CIWA scores 6-11, or
  diastolic blood pressure 90, or pulse 100
• 20mg diazepam if CIWA scores 12-17, or
  diastolic blood pressure 100, or pulse 110
• 30mg diazepam if CIWA scores 18-23, or
  diastolic blood pressure 110, or pulse 120
• May try 2-4 mg IM lorazepam if CIWA scores higher
  or if vitals higher than above parameters

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Adjunctive Medications

• Haloperidol - use for hallucinosis or delirium.
  NOTE This is adjunctive treatment--the patient
  should still be receiving benzodiazepines
• Beta Blockers and centrally-acting alpha agonists
• PRN protracted tremors or elevated pulse
• Can mask other symptoms of withdrawal
• Dont protect against advancing of stages

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Prophylactic Replacement

• Replace sedative, assuming that 1 drink
• 5 mg p.o. diazepam
• 1 mg p.o. lorazepam
• Alsocarbamazepine may empirically lower the
  seizure risk, but it still takes 5 half-lives to
  reach steady-state (beyond period of maximum risk
  for withdrawal seizures)

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Alcohol Withdrawal Delirium

• Replace Sedative
• Frequent dosing with p.o. if possible
• Intravenous boluses of diazepam vs. continuous
  infusions of lorazepam/midazolam
• I.M. is not safe/effective, except somewhat for
  lorazepam I.M.
• Calming via benzos antipsychotics are only for
  hallucinosis / incoherence / disorientation

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ASAM Practice Guidelines

• JAMA, 278(2)144-51 July 9, 1997
• Michael F. Mayo-Smith, MD MPH, et. al.
• Archives of Internal Medicine, 1641405-12 July
  12, 2004
• Michael F. Mayo-Smith, MD MPH, et. al.

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Patient Safety

• Early recognition of A.W.S.
• Standardized Assessment of A.W.S.
• Protocols / Practice Guidelines for management of
  sedative replacement and other assessment/treatmen
  t in A.W.S.
• Wisconsin Hospital Association et al.

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Sedatives

• Barbiturates
• Benzodiazepines
• Sedative-Hypnotics (choral hydrate,
  meprobamatecarisoprodol/Soma)
• GHB (GBL, 1,4 BD)
• Propofol
• And dont forget Cl- channel agents Ambien
  (zolpidem) and Sonata (zaleplon)

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Sedative Intoxication

• Ataxia, dysarthria, nystagmus, and somnolence
• Avoid reversal agent flumazenil
• Only use in overdose if a sole benzodiazepine has
  been ingested in a non chronic user
• Main treatment is supportive
• Charcoal may be helpful
• Orogastric intubation and gastric evacuation
  maybe useful since GI motility may be slowed

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Sedative WithdrawalSymptoms Signs

• Anxiety
• Nausea
• Tremor
• Hypertension
• Tachycardia
• Hypersensitivity to stimuli
• Hyperreflexia
• Diaphoresis

• Hallucinosis
• Depersonalization
• Psychosis
• Delirium
• Seizures
• Looks like hypomania

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Sedative Withdrawal

• Similar to alcohol withdrawal--though usually not
  as dramatic or obvious and more variability
  often VS are normal
• Dependent on
• Duration of sedative use
• Daily amount of sedative use
• Half-life of sedative used

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Benzodiazepine Duration of Action

• Short-Acting (half life
• Triazolam
• Intermediate-Acting (half life 12-20 hours)
• Oxazepam Temazepam Lorazepam
• Alprazolam Estazolam
• Long-Acting (half life 100 hours)
• Diazepam Chlordiazepoxide Chlorazepate
• Clonazepam Flurazepam

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Sedative Withdrawal

• Declining serum levels correlate with emergence
  of withdrawal symptoms
• Shorter acting Bzdz withdrawal begins within 24
  hours of cessation peaks within 1 to 5 days
• Longer acting Bzdz withdrawal begins within 5
  days of cessation peaks within 1 to 9 days
• Duration of withdrawal
• 7 to 21 days for shorter acting Bzdz
• 10 to 28 days for longer acting Bzdz

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Alcohol/Sedative Withdrawal
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Tapering

• Usually SUBSTITUTE with a long-acting sedative
  and taper that, not the original agent
• Give the patient a calendar with a tapering
  schedule
• Write prescriptions that will be filled every day
  or every other day
• Write the date that the Rx is to be filled
• Use one pharmacy only discuss plan with the
  pharmacist

49
Substitution Agents

• Usually phenobarbital or clonazepam
• Use clonazepam for alprazolam
• Phenobarbital best to use when
• High dose of sedatives
• Unknown or erratic use
• Phenobarbital intoxication not well liked
• Once steady state achieved, negligible inter-dose
  serum level variation

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Tapering with or without Substitution

• Phenobarbital on initial dose for two days
• If no signs of withdrawal or intoxication begin
  taper on day 3
• Taper over about a 20 day period
• Reduce dose by 30-60mg per day
• Final 25 make smaller daily dose reductions
• Benzodiazepine tapering
• Provide daily amount in divided doses
• About 25 reduction per week of starting dose or
  about 1mg clonazepam per week which ever is
  less
• Final 25 of reduction can/should be slower 10
  every week

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Substitution Dose Conversions

• Phenobarbital 30mg
• Diazepam 10mg
• Chlordiazepoxide 25mg
• Clonazepam 2mg
• Flurazepam 15mg
• Lorazepam 2mg
• Oxazepam 10mg
• Temazepam 15mg

• Triazolam 0.25mg
• Butalbital 100mg
• Meprobamate 400mg
• Carisoprodol 700mg
• Chloral Hydrate 500mg

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Prescriptions

• Write amount to be dispensed out in English and
  draw a box around this
• Write zero refills
• Date prescription todays date 10/21/04 but then
  write fill only on 10/23/04
• Number prescriptions in chronological order
• Make photostat copies of your prescriptions
• If patients make accusations regarding the
  pharmacist refer them to the state pharmacy board

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Adjunctive Withdrawal Management

• Carbamazepine
• 100mg every 6 hours
• 100mg every 8 hours if weight less than 100pounds
• 200mg every 8 hours if weight more than 220pounds
• Baseline CBC and hepatic panel
• Divalproex
• 250mg every 6 hours
• 250mg every 8 hours if weight less than 100pounds
• 500mg every 8 hours if weight more than 220pounds
• On fourth day check pre-dose serum level

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Adjunctive Withdrawal Management

• Once therapeutic on anti-convulsant begin taper
  of sedative dose
• 75 pretreatment dose on day one
• 50 pretreatment dose on day two
• 25 pretreatment dose on day three
• On day four give no further sedatives
• Continue anticonvulsant between 30 to 60 days
  then taper over 4 to 8 days
• Recheck hepatic panel and CBC at 1 to 3 week
  intervals for Carbamazepine

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Sedative Tolerance Test

• Pentobarbital 200mg initially then 100mg every
  one hour
• Assess for signs of intoxication
• Convert to phenobarbital at a conversion of
  pentobarbital 100mg Phenobarbital 30mg
• Pentobarbital hard to find
• Need to design a different sedative taper test

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Stimulants

• Cocaine
• Amphetamines
• Methamphetamine
• Dextroamphetamine
• Amphetamine sulfate
• Methylated amphetamines
• (designer drugs)
• MDMAEcstasy
• MDA, DOM, STP
• Psychostimulants
• --Methylphenidate (Ritalin)
• -- Pemoline (Cylert)

• Ephedrine/Pseudo-ephedrine
• Phenylpropanolamine
• Amphetamine Congeners
• Benzphetamine
• Diethylpropion
• Fenfluramine
• Phentermine
• Phenmetrazine
• Phendimetrazine
• Mazindol

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Absorption Metabolism

• Cocaine half-life 40 to 60 minutes
• Cocaethylene intermediate active metabolite
  when ethanol used concurrently
• Amphetamine half-life 6 to 12 hours
• Methylphenidate half-life 2 hours

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Intoxication

• Psychosis mainly amphetamines
• Paranoid ideation with well formed delusional
  structure
• Hallucinosis
• Stereotyped behavior
• Can persist for days
• Hyperpyrexia
• Seizure Activity
• Vasoconstriction

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Stimulant Intoxication Management

• Hypertension/Tachycardia
• Phentolamine if hypertensive urgency/emergency
• 5-10mg every 10minutes
• Avoid Beta Blockers since may lead to unopposed
  alpha adrenergic activity
• Avoid Calcium Channel Blockers
• Anxiety/Agitation
• Lorazepam
• Psychosis
• Haloperidol

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Stimulant Intoxication Management

• Seizures
• Diazepam
• Phenytoin
• Hyperthermia
• Cooling techniques
• Elimination
• Acidification with ammonium chloride may help in
  select cases of acute amphetamine overdose

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Cocaine Withdrawal

• Phase one Crash
• Initial - Intense dysphoria craving
• Middle Desire to sleep, dysphoria, may start to
  use other substances or pursue supplies
• Late Hypersomnia and increased appetite lasts
  3 to 4 days
• Phase two Withdrawal
• Honeymoon 12 hours to 4 days reduced craving,
  improved mood and sleep pattern

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Stimulant Withdrawal

• Phase two Withdrawal
• Dysphoria depression, lethargy, anhedonia,
  reemergence of craving lasts 6 to 18 weeks
• Phase three Extinction
• Gradual improvement of mood, ability to
  experience pleasure, interest in environment
  lasts months

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Management of Cocaine Withdrawal

• Phase I bromocryptine ????
• Phase III desipramine ????

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• BREAK