Substance Withdrawal

Introduction to Substance Withdrawal for MCCQE1

Substance withdrawal is a physiological and psychological response to the abrupt cessation or reduction of a substance after a period of heavy or prolonged use. For MCCQE1 preparation, understanding withdrawal syndromes is critical because they often present as medical emergencies in emergency departments and family practice settings across Canada.

As a future Canadian physician, you must demonstrate competency in the Medical Expert and Health Advocate CanMEDS roles by recognizing these syndromes early, managing them safely, and linking patients to long-term addiction care (e.g., RAAM clinics).

Neurobiology of Withdrawal

The underlying mechanism generally involves neuroadaptation. The brain attempts to maintain homeostasis in the presence of the substance.

• Depressants (Alcohol/Benzos): Enhance GABA (inhibitory) and inhibit NMDA/Glutamate (excitatory). Withdrawal results in decreased GABA and increased Glutamate $\rightarrow$ Autonomic Hyperactivity & Seizures.
• Stimulants (Cocaine/Meth): Increase dopamine/norepinephrine. Withdrawal results in catecholamine depletion $\rightarrow$ Depression, Fatigue, Anhedonia.

Alcohol Withdrawal Syndrome (AWS)

Alcohol withdrawal is high-yield for the MCCQE1. It is the most common life-threatening withdrawal syndrome seen in Canadian hospitals.

Clinical Timeline

Assessment: CIWA-Ar

The Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) is the gold standard in Canada for assessing severity.

• Score < 8: Mild withdrawal (supportive care).
• Score 8–15: Moderate withdrawal (medication likely needed).
• Score > 15: Severe withdrawal (high risk of complications).

Management of Alcohol Withdrawal

Pharmacotherapy

1. Benzodiazepines (First-line): Mimic alcohol’s effect on GABA receptors.
   • Diazepam (Valium): Long half-life, smoother taper. Avoid in severe liver failure.
   • Lorazepam (Ativan): Shorter half-life, no active metabolites. Preferred in liver failure or elderly.
2. Dosing Strategies:
   • Symptom-Triggered: Dose given only when CIWA-Ar > 8. Preferred in Canada (reduces total benzo dose and duration).
   • Fixed-Schedule: Fixed doses tapered over days. Used if strict monitoring is unavailable.

Opioid Withdrawal

While rarely fatal, opioid withdrawal causes significant suffering and drives the cycle of addiction.

Clinical Presentation

Think of a “severe flu” combined with sympathetic overdrive.

• Subjective: Intense craving, dysphoria, nausea, muscle aches.
• Objective:
  • Early: Yawning, lacrimation, rhinorrhea, diaphoresis.
  • Late: Mydriasis (dilated pupils), piloerection (“cold turkey”), vomiting, diarrhea, tachycardia.

Assessment: COWS

The Clinical Opiate Withdrawal Scale (COWS) is used to stage severity and determine induction timing for agonist therapy.

Management

Benzodiazepine Withdrawal

Similar mechanism to alcohol withdrawal but the timeline depends on the half-life of the specific benzodiazepine used.

• Short-acting (e.g., Alprazolam): Onset 1-2 days.
• Long-acting (e.g., Diazepam): Onset 2-7 days.
• Symptoms: Anxiety, insomnia, tremors, perceptual disturbances, seizures, psychosis.

Management:

• Stabilize on a long-acting benzodiazepine (e.g., Diazepam).
• Slow taper: Reduce dose by ~10% every 1-2 weeks (The Ashton Manual protocol).
• Carbamazepine/Gabapentin: May be used as adjuncts.

Stimulant Withdrawal (Cocaine/Methamphetamine)

• Pathophysiology: Dopamine depletion.
• Symptoms (“The Crash”):
  • Hypersomnia (excessive sleep).
  • Hyperphagia (excessive hunger).
  • Psychomotor retardation.
  • Severe depression and suicidality.
  • Vivid, unpleasant dreams.
• Management:
  • No FDA/Health Canada approved medications.
  • Supportive care (sleep, nutrition).
  • Suicide risk assessment is mandatory.

Comparison of Withdrawal Syndromes

Canadian Guidelines & Public Health

For MCCQE1, be familiar with the Canadian context of addiction medicine.

1. RAAM Clinics (Rapid Access Addiction Medicine):

   • A low-barrier care model widely adopted across Canada (e.g., Ontario, BC, Alberta).
   • Allows walk-in access for pharmacotherapy (OAT, anti-craving meds) and counseling.

2. Harm Reduction:

   • A core pillar of the Canadian Drugs and Substances Strategy.
   • Examples: Supervised consumption sites, Naloxone kit distribution, needle exchange programs.
   • Goal: Reduce adverse health, social, and economic consequences of drug use without necessarily requiring abstinence.

3. Indigenous Health:

   • Recognize the impact of intergenerational trauma and colonization on substance use rates.
   • Practice Cultural Safety and Trauma-Informed Care.

4. Choosing Wisely Canada:

   • “Don’t prescribe opioids for acute pain in workers who are ready to return to work… without a plan for tapering.”
   • “Don’t initiate opioids for chronic non-cancer pain without a trial of non-opioid modalities.”

Key Points to Remember for MCCQE1

• Delirium Tremens is a medical emergency with high mortality; distinguish it from alcoholic hallucinosis by the presence of autonomic instability and global confusion.
• Lorazepam is the benzodiazepine of choice for alcohol withdrawal in patients with liver disease (remember the mnemonic LOT: Lorazepam, Oxazepam, Temazepam are metabolized by glucuronidation, bypassing P450).
• Buprenorphine/Naloxone (Suboxone) is generally preferred over Methadone for first-line OAT due to a better safety profile (less risk of overdose).
• Pupil Size:
  • Opioid Intoxication $\rightarrow$ Constricted (Pinpoint).
  • Opioid Withdrawal $\rightarrow$ Dilated (Mydriasis).
• Always assess for polysubstance use. A patient withdrawing from opioids may also be withdrawing from alcohol.

Sample Question

Case Presentation

A 54-year-old male is admitted to the surgical ward following an emergency appendectomy. Two days post-operatively, the nursing staff calls you because the patient has become increasingly agitated and confused. He is trying to pull out his IV lines and claims there are spiders crawling on his bed sheets.

Vital Signs:

• Temp: 38.5°C
• HR: 118 bpm
• BP: 165/95 mmHg
• RR: 22/min
• O2 Sat: 96% on room air

History: His chart reveals no known past medical history, but his wife mentions he has been “drinking heavily” since losing his job last year.

Question: Which one of the following is the most appropriate initial pharmacologic intervention?

Options

• A. Haloperidol
• B. Propofol
• C. Lorazepam
• D. Thiamine
• E. Carbamazepine

Explanation

The correct answer is:

• C. Lorazepam

Detailed Explanation: This patient is presenting with signs of Delirium Tremens (DTs), the most severe form of alcohol withdrawal. The clinical picture includes:

1. Timeline: 48 hours (2 days) after cessation of alcohol (hospitalization often forces cessation).
2. Symptoms: Global confusion, agitation, and tactile hallucinations (formication).
3. Autonomic Instability: Fever, tachycardia, and hypertension.

Lorazepam (Benzodiazepine) is the correct choice. Benzodiazepines are the mainstay of treatment for alcohol withdrawal and DTs. They cross-react with GABA receptors to reduce autonomic hyperactivity and prevent seizures. Lorazepam is often preferred in hospital settings, especially if liver function is unknown or compromised, as it has no active metabolites.

• A. Haloperidol: Antipsychotics lower the seizure threshold and should not be used as monotherapy for alcohol withdrawal. They may be used cautiously as an adjunct for severe agitation after adequate benzodiazepine dosing, but are not the initial intervention.
• B. Propofol: Used for refractory DTs in an ICU setting when high-dose benzodiazepines fail. It requires intubation and mechanical ventilation. It is not the initial step on a surgical ward.
• D. Thiamine: While essential to prevent Wernicke’s Encephalopathy, it does not treat the acute autonomic instability or agitation of DTs. It should be given, but Benzodiazepines are the priority to stabilize the life-threatening withdrawal state.
• E. Carbamazepine: Sometimes used for mild-to-moderate outpatient withdrawal management, but not appropriate for the acute management of Delirium Tremens with autonomic instability.

References

1. Medical Council of Canada. (n.d.). MCCQE Part I Clinical Decision-Making and Multiple-Choice Question Guidelines.
2. Bruneau, J., et al. (2018). Management of opioid use disorders: a national clinical practice guideline. CMAJ, 190(9), E247-E257.
3. Choosing Wisely Canada. (n.d.). Opioid Use Disorder. Retrieved from choosingwiselycanada.org .
4. Centre for Addiction and Mental Health (CAMH). (2020). Alcohol Withdrawal Management Guidelines. Toronto, Canada.
5. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
6. British Columbia Centre on Substance Use (BCCSU). (2019). Provincial Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder.