Benzodiazepine withdrawal

Background

• Very similar to alcohol withdrawal
• Occurs due to chronic use of benzodiazepines, leading to physiologic tolerance

Clinical Features

• Onset usually several days to up to 3 weeks
• More likely in patients with high doses or prolonged use
• Autonomic hyperactivity (e.g., diaphoresis, HR>100, hyperthermia)
• Nausea/vomiting
• Tremulousness, psychomotor agitation
• Anxiety, insomnia, irritability, agitation
• Psychosis (more common than in ETOH withdrawal)
• Seizure

Differential Diagnosis

Sedative/hypnotic withdrawal

• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Methanol
  • Isopropyl alcohol
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Gamma hydroxybutyrate (GHB)
• Baclofen
• Barbiturates
• Opioids
• Chloral hydrate

Seizure

• Epileptic seizure
  • First-time seizure
  • Seizure with known seizure disorder
  • Status epilepticus
  • Temporal lobe epilepsy
  • Non-compliance with anti-epileptic medications
  • Hyponatremia
  • INH toxicity
• Non-epileptic seizure
  • Meningitis
  • Encephalitis
  • Brain abscess
  • Intracranial hemorrhage
  • Alcohol withdrawal
  • Benzodiazepine withdrawal
  • Barbiturate withdrawal
  • Baclofen withdrawal
  • Metabolic abnormalities: hyponatremia, hypernatremia, hypocalcemia, hypomagnesemia, hypoglycemia, hyperglycemia, hepatic failure, uremia
  • Eclampsia
  • Neurocysticercosis
  • Posterior reversible encephalopathy syndrome
  • Impact seizure (head trauma)
  • Acute hydrocephalus
  • Arteriovenous malformation
  • Seizure with VP shunt
  • Toxic ingestion (amphetamines, anticholinergics, cocaine, INH, organophosphates, TCA, salicylates, lithium, phenothiazines, bupropion, camphor, clozapine, cyclosporine, fluoroquinolones, imipenem, lead, lidocaine, metronidazole, synthetic cannabinoids, theophylline, Starfruit)
  • Psychogenic nonepileptic seizure (pseudoseizure)
• Intracranial mass
• Syncope
• Hyperventilation syndrome
• Migraine headache
• Movement disorders
• Narcolepsy/cataplexy
• Post-hypoxic myoclonus (Status myoclonicus)

Altered mental status

Diffuse brain dysfunction

• Hypoxic encephalopathy
• Acute toxic-metabolic encephalopathy (Delirium)
  • Hypoglycemia
  • Hyperosmolar state (e.g., hyperglycemia)
  • Electrolyte Abnormalities (hypernatremia or hyponatremia, hypercalcemia)
  • Organ system failure
  • Hepatic Encephalopathy
  • Uremia/Renal Failure
  • Endocrine (Addison's disease, Cushing syndrome, hypothyroidism, myxedema coma, thyroid storm)
  • Hypoxia
  • CO2 narcosis
• Hypertensive Encephalopathy
• Toxins
• TTP / Thrombotic thrombocytopenic purpura
• Alcohol withdrawal
• Drug reactions (NMS, Serotonin Syndrome)
• Environmental causes
  • Hypothermia
  • Hyperthermia
• Deficiency state
  • Wernicke encephalopathy
  • Subacute Combined Degeneration of Spinal Cord (B12 deficiency)
  • Vitamin D Deficiency
  • Zinc Deficiency
• Sepsis
• Osmotic demyelination syndrome (central pontine myelinolysis)
• Limbic encephalitis

Primary CNS disease or trauma

• Direct CNS trauma
  • Diffuse axonal injury
  • Subdural/epidural hematoma
• Vascular disease
  • Intraparenchymal hemorrhage
• SAH
• Stroke
  • Hemispheric, brainstem
• CNS infections
  • Encephalitis
  • Anti-NMDA receptor encephalitis
  • Meningitis
• Neoplasms
  • Paraneoplastic Limbic encephalitis
  • Malignant Meningitis
  • Pancreatic Insulinoma
• Seizures
  • Nonconvulsive status epilepticus
  • Postictal state
• Dementia
  • Alzheimer's
  • Lewy Body Dementia
  • Frontotemporal Dementia

Psychiatric

• Acute psychosis
• Catatonia
• Excited delirium
• Malingering
• Steroid induced psychosis

Evaluation

• Evaluate for other causes of and complications of symptoms (see evaluation of seizure, altered mental status, hypertension, hyperthermia

Management

• Ensure patient and staff safety, airway protection if acutely agitated or seizing
• Benzodiazepines
  • Mild, can tolerate PO: Long-acting benzodiazepine (e.g., chlordiazepoxide)
  • Moderate/severe: IV diazepam
    • Consider substituting shorter half-life drugs with equivalent dose of diazepam
    • Equivalent diazepam dose = triazolam dose x 20 = alprazolam dose x 10 = lorazepam dose x 5
• After acute symptoms controlled, can prescribe gradual benzodiazepine taper
  • One taper strategy: decrease dose by 25% for first week, 25% second week, then by 12.5% for subsequent weeks
• Consider neurology consult if patient was using benzos for seizure control (may need further antiepileptic management)

Disposition

• Admit if:
  • Multiple seizures
  • Uncontrolled autonomic hyperstimulation
  • Decreased level of consciousness

See Also

• Benzodiazepines
• Alcohol withdrawal