3.5 Substance-Related and Addictive Disorders

Substance-Related and Addictive Disorders

Exam Tip: Understand the mechanisms and prescribing requirements for MAT. Methadone can only be dispensed for opioid addiction through specialized clinics, whereas Buprenorphine can be prescribed in office-based settings.

1. Substance Use Disorder (SUD) Framework

The DSM-5-TR integrates substance abuse and substance dependence into a single overarching diagnosis of Substance Use Disorder (SUD). The disorder is defined by a cluster of cognitive, behavioral, and physiological symptoms indicating the individual continues using the substance despite significant substance-related problems. An additional addiction specifier encompasses behavioral addictions such as Gambling Disorder.

Criteria (11 items):

1. Taking the substance in larger amounts or over a longer period than intended.
2. Persistent desire or unsuccessful efforts to cut down.
3. Much time spent obtaining, using, or recovering.
4. Craving (a strong desire or urge to use).
5. Recurrent use resulting in failure to fulfill major role obligations.
6. Continued use despite social/interpersonal problems.
7. Giving up important social, occupational, or recreational activities.
8. Recurrent use in physically hazardous situations.
9. Continued use despite knowledge of having a physical or psychological problem caused by it.
10. Tolerance (need for increased amounts to achieve effect).
11. Withdrawal (characteristic syndrome or taking substance to relieve withdrawal).

Severity Specifiers:

• Mild: 2-3 symptoms
• Moderate: 4-5 symptoms
• Severe: 6 or more symptoms

Remission Specifiers: Early remission is 3-12 months without criteria (except craving); sustained remission is ≥12 months. Additional specifiers include "on maintenance therapy" (e.g., buprenorphine, methadone) and "in a controlled environment" (e.g., prison, locked residential rehab).

2. Alcohol Use Disorder

Intoxication and Withdrawal

• Intoxication: Slurred speech, incoordination, unsteady gait, nystagmus, impairment in attention or memory. Pathology may include disinhibition and aggressive behavior at lower BAC, progressing to somnolence and coma at high BAC (>0.30-0.40%).
• Withdrawal: A medical emergency. Onset within 4-12 hours of last drink. Symptoms include autonomic hyperactivity (sweating, tachycardia >120 bpm, hypertension), hand tremor, insomnia, nausea, transient hallucinations (auditory or visual), anxiety, and generalized tonic-clonic seizures (typically 12-48 hours after last drink).
• Delirium Tremens (DTs): A severe form of withdrawal occurring 48-72 hours after cessation, characterized by delirium, vivid hallucinations, severe autonomic instability (tachycardia, fever), and a mortality rate of 5-15% if untreated.

CIWA-Ar Monitoring: The Clinical Institute Withdrawal Assessment-Alcohol Revised scale scores 10 items (nausea, tremor, paroxysmal sweats, anxiety, agitation, tactile/auditory/visual disturbances, headache, orientation) on 0-7 scales. Score <8 = minimal withdrawal; 8-15 = moderate (consider pharmacotherapy); ≥15 = severe withdrawal (initiate benzodiazepine treatment).

Treatment of Acute Withdrawal:

• Symptom-triggered Benzodiazepines based on CIWA-Ar scores. Lorazepam (1-2 mg) is preferred in hepatic dysfunction because it undergoes glucuronidation only (no oxidative metabolism, no active metabolites). Chlordiazepoxide (25-100 mg) and Diazepam (5-10 mg) have longer half-lives and smoother weaning but require intact hepatic metabolism.
• Thiamine (Vitamin B1) 100 mg IV/IM for 3-5 days to prevent Wernicke-Korsakoff syndrome. CRITICAL: Always give thiamine BEFORE glucose to avoid precipitating Wernicke encephalopathy in thiamine-deficient patients.
• Folate supplementation and electrolyte correction (magnesium, potassium, phosphate).

Wernicke-Korsakoff Syndrome

• Wernicke Encephalopathy: Acute neurological triad of ataxia, ophthalmoplegia (nystagmus, lateral rectus palsy), and confusion. Reversible with prompt thiamine administration.
• Korsakoff Syndrome: Chronic, often irreversible anterograde and retrograde amnesia with confabulation (fabricated memories to fill memory gaps). Results from untreated or recurrent Wernicke encephalopathy; mammillary body degeneration on MRI.

Medication-Assisted Treatment (MAT) for Alcohol

3. Opioid Use Disorder

Intoxication and Overdose

• Intoxication: Euphoria followed by apathy, pupillary constriction (miosis), drowsiness, slurred speech, impairment in attention.
• Overdose Triad: Pinpoint pupils, respiratory depression, coma. Fatal due to hypoxia and aspiration risk.
• Overdose Reversal: Naloxone (Narcan) - a short-acting mu-opioid antagonist. Initial dose 0.4-2 mg IM/IN; repeat as needed. Naloxone has a shorter half-life (1-2 hours) than most opioids, so patients must be observed for re-sedation and recurrent respiratory depression; fentanyl analogs may require repeated dosing.

Opioid Withdrawal

Intensely uncomfortable but generally not life-threatening (unlike alcohol/benzo withdrawal). Onset varies by opioid half-life: heroin 6-12 hours, methadone 24-48 hours. Symptoms: Dysphoric mood, nausea/vomiting, muscle aches, lacrimation, rhinorrhea, pupillary dilation (mydriasis), piloerection ("cold turkey"), sweating, diarrhea, yawning, insomnia, low-grade fever.

Clinical Assessment: Use the Clinical Opiate Withdrawal Scale (COWS). Score ≥5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, >36 = severe withdrawal.

MAT for Opioid Use Disorder

• Buprenorphine: Partial mu-opioid agonist. High receptor affinity but low intrinsic activity. Has a "ceiling effect" for respiratory depression, making it safer than full agonists. Often combined with Naloxone (Suboxone) to deter IV diversion (naloxone is inactive sublingually). Prescribers previously required a DEA X-waiver; the X-waiver training requirement was eliminated in 2023, but patient caps of 30 (then 100) still apply to non-X-waivered prescribers.
• Methadone: Full mu-opioid agonist. Long half-life (24-36 hours) prevents withdrawal and cravings. Can prolong QTc; baseline and periodic ECG recommended, especially at doses >100 mg/day or with other QT-prolonging drugs. Heavily regulated; for OUD, it must be administered at a certified Opioid Treatment Program (OTP) and observed daily.
• Naltrexone: Mu-opioid antagonist. Blocks the effects of illicit opioids. The patient must be completely opioid-free for 7-10 days before initiation to avoid precipitated withdrawal. Available as monthly IM injection (Vivitrol, 380 mg) — useful for adherence.

4. Other Substances

• Stimulants (Cocaine/Amphetamines): Intoxication presents with tachycardia, pupillary dilation, elevated BP, perspiration/chills, agitation, and potentially drug-induced psychosis (tactile hallucinations/"meth bugs"/formication). Withdrawal presents as a "crash" with severe dysphoria, fatigue, vivid unpleasant dreams, and hypersomnia/hyperphagia. No FDA-approved MAT for stimulant use disorder; treat with supportive care, CBT/contingency management, and antidepressants for depressive symptoms.
• Sedative, Hypnotic, or Anxiolytic (Benzodiazepines): Intoxication resembles alcohol. Withdrawal is similar to alcohol withdrawal and carries a high risk of life-threatening seizures. Requires a slow taper (10% dose reduction per week) using a long-acting benzodiazepine (diazepam) or phenobarbital. Severe withdrawal may require inpatient detox.
• Cannabis: Intoxication involves conjunctival injection (red eyes), increased appetite, dry mouth, and tachycardia. Withdrawal (often overlooked) begins within 1-3 days of cessation, peaks at 1 week, and includes irritability, anger, sleep difficulty, decreased appetite, and restlessness.
• Hallucinogens (PCP, LSD, Psilocybin): Intoxication features perceptual disturbances (illusions, hallucinations), synesthesia, derealization; PCP specifically causes nystagmus (horizontal, vertical, rotatory), hypertension, violent behavior, analgesia, and hyperthermia. PCP intoxication may require benzodiazepines for agitation and acidification of urine to enhance excretion; antipsychotics can be used cautiously for severe psychosis.

5. Clinical Vignette

A 42-year-old male with severe OUD (heroin, IV use) presents seeking help. He last used heroin 18 hours ago and has a COWS score of 22 (moderate withdrawal). He has hepatitis C with mildly elevated LFTs. Plan: Initiate buprenorphine/naloxone (Suboxone) 4 mg/1 mg sublingually once withdrawal is established (avoid precipitated withdrawal — confirm moderate withdrawal on COWS first). Provide naloxone rescue kit and overdose education. Counsel on hepatitis C treatment and HIV/HCV testing. Arrange behavioral counseling (CBT or contingency management). Avoid naltrexone until opioid-free for 7-10 days. Avoid methadone initiation unless referring to OTP.