Note: Davidson's Principles and Practice of Medicine is not available in the textbook library. This algorithm is sourced entirely from Harrison's Principles of Internal Medicine, 22nd Edition (2025) — the closest available comprehensive internal medicine reference — Chapter 436: Seizures and Epilepsy.
Treatment Algorithm for Seizures
Harrison's Principles of Internal Medicine, 22e — Chapter 436
STEP 1 — IDENTIFY THE SEIZURE TYPE
Seizure Occurs
│
├──► PROVOKED (acute symptomatic)?
│ ├── Metabolic (electrolytes, glucose, Na⁺)
│ ├── Drug-induced (bupropion, cocaine, etc.)
│ └── Structural lesion (tumor, abscess, vascular malformation)
│
└──► UNPROVOKED / EPILEPTIC?
├── Focal (with/without impaired awareness)
├── Generalized-onset tonic-clonic (GOTC)
├── Typical absence
└── Atypical absence / Myoclonic / Atonic
STEP 2 — TREAT UNDERLYING CAUSE FIRST
| Cause | Treatment |
|---|
| Metabolic disturbance (↓Na⁺, ↓glucose, etc.) | Correct the metabolic abnormality; ASD usually not needed unless rapidly uncorrectable |
| Drug-induced (bupropion, cocaine) | Avoidance of offending agent; ASD usually not needed unless recurrence occurs off drug |
| Structural CNS lesion (tumor, AVM, abscess) | Treat the lesion; maintain ASD for 6–12 months post-treatment, then attempt withdrawal if seizure-free |
STEP 3 — WHEN TO START ANTISEIZURE DRUG (ASD)?
Single seizure ─────────────────────────────────────────────────────► Do NOT routinely treat
│
├─► PLUS any of the following risk factors? → TREAT
│ • Prior brain insult (stroke, trauma)
│ • EEG epileptiform abnormalities
│ • Significant brain imaging abnormality
│ • Nocturnal seizure
│ • Identified epileptogenic lesion (tumor, infection, trauma)
│
└─► Driving / employment considerations also weigh in favor of treatment
Recurrent seizures of unknown/irreversible cause → ALWAYS TREAT
STEP 4 — SELECT THE DRUG BY SEIZURE TYPE
Table 436-8 (Harrison's): Drug Selection
| Seizure Type | First-Line | Second-Line |
|---|
| Generalized-onset tonic-clonic | Lamotrigine, Valproic acid | Carbamazepine, Oxcarbazepine, Topiramate, Levetiracetam, Zonisamide |
| Focal (with/without impaired awareness) | Lamotrigine, Carbamazepine | Oxcarbazepine, Levetiracetam, Valproic acid, Topiramate, Zonisamide, Lacosamide, Gabapentin |
| Typical Absence | Valproic acid, Ethosuximide | Lamotrigine |
| Atypical absence / Myoclonic / Atonic | Valproic acid | Levetiracetam, Clonazepam, Lamotrigine, Topiramate, Zonisamide |
Worldwide, older drugs (phenytoin, valproic acid, carbamazepine, phenobarbital, ethosuximide) remain first-line because they are equally effective and significantly less expensive. Newer drugs are adjuncts or alternatives.
STEP 5 — TITRATION PRINCIPLES
Start at LOWEST dose → titrate slowly (allow ≥5 half-lives between dose changes)
│
├─► Serum drug levels: useful to establish dosing & check compliance
│ — NOT the primary target; clinical response + side effects take priority
│ — In low albumin (liver/renal disease): check FREE drug levels
│
└─► Minor side effects (sedation, dizziness, ataxia): usually resolve in days → continue
STEP 6 — INADEQUATE RESPONSE ON FIRST DRUG
Seizures persist at maximum tolerated dose?
│
├─► Confirm: documented compliance (check drug level)
│
├─► Switch to second drug:
│ • Add second ASD → optimize second drug → slowly taper first drug
│ • Goal: MONOTHERAPY whenever possible
│
└─► Still refractory? → POLYPHARMACY
• ~50% of patients fail first drug
• Patients with structural lesions or multiple seizure types
most likely to need combination therapy
STEP 7 — REFRACTORY EPILEPSY (drug-resistant)
Failed ≥2 appropriate drugs at adequate doses?
│
├─► Surgical evaluation:
│ • Resection of seizure focus (most effective for focal epilepsy)
│ • Prerequisites: localizable focus on EEG/MRI; resectable region
│
├─► Neuromodulation:
│ • Vagus nerve stimulation (VNS)
│ • Thalamic deep brain stimulation (DBS)
│ • Responsive neurostimulation (RNS)
│
└─► Dietary therapy:
• Ketogenic diet (especially in children)
STEP 8 — WHEN TO DISCONTINUE THERAPY?
All of the following criteria should be met:
- Complete seizure control for 1–5 years
- Single seizure type (generalized > focal prognosis)
- Normal neurologic exam including intelligence
- No family history of epilepsy
- Normal EEG
→ If all met: taper gradually over 2–3 months
→ Most recurrences occur within first 3 months after stopping
→ Warn patient: avoid driving/swimming during withdrawal period
SPECIAL SITUATIONS
| Situation | Key Points |
|---|
| Catamenial epilepsy | Consider ↑ ASD dose peri-menstrually; medroxyprogesterone may help |
| Pregnancy | Maintain ASD (uncontrolled seizures > teratogenic risk); use monotherapy at lowest effective dose; folate 1–4 mg/day; vitamin K 20 mg/day (last 2 weeks) for enzyme-inducing drugs; neonatal IM vitamin K 1 mg at birth |
| Elderly | Increased seizure risk; monitor for osteoporosis with long-term ASD use |
| Contraception | Enzyme-inducing drugs (carbamazepine, phenytoin, phenobarbital, topiramate) reduce OCP efficacy → prefer IUD or LARC |
STATUS EPILEPTICUS — EMERGENCY ALGORITHM
GCSE (Generalized Convulsive Status Epilepticus)
Definition: seizures > 5 minutes, or repetitive without recovery
┌─────────────────────────────────────────────┐
│ IMMEDIATE (0–5 min) │
│ • Airway / Breathing / Circulation │
│ • IV access + labs (glucose, electrolytes, │
│ drug levels, toxicology, CBC, LFTs) │
│ • Treat hypoglycemia if present │
│ • Treat hyperthermia │
└─────────────┬───────────────────────────────┘
│
▼
┌─────────────────────────────────────────────┐
│ PHASE 1 — Benzodiazepine (5–20 min) │
│ • Lorazepam IV (first choice) │
│ • Diazepam IV/PR │
│ • Midazolam IM (if no IV access) │
└─────────────┬───────────────────────────────┘
│ Seizure continues?
▼
┌─────────────────────────────────────────────┐
│ PHASE 2 — Second-line ASD (20–40 min) │
│ • Fosphenytoin / Phenytoin IV │
│ • Valproic acid IV │
│ • Levetiracetam IV │
│ • Phenobarbital IV │
└─────────────┬───────────────────────────────┘
│ Seizure continues?
▼
┌─────────────────────────────────────────────┐
│ PHASE 3 — Refractory SE (> 40–60 min) │
│ • Intubate + ICU admission │
│ • Anesthetic doses: │
│ – Propofol infusion │
│ – Midazolam infusion │
│ – Pentobarbital infusion │
│ – Ketamine infusion │
│ • Continuous EEG monitoring MANDATORY │
│ • Aim: burst suppression pattern on EEG │
└─────────────────────────────────────────────┘
NCSE: treat urgently using same approach as GCSE
(EEG confirmation required; less metabolic urgency but still causes neuronal injury)
Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025), Chapter 436 — Seizures and Epilepsy, Tables 436-8 & 436-9, and Fig. 436-5