Psychiatry · Year 3 · from Psychiatry
Case 3: Mood Stabilizer Pharmacology - Lithium
Patient Demographics
- Age: 45 years old
- Sex: Male
- Occupation: Sales manager
Chief Complaint
"I think I'm stable now, but I want to make sure I understand my medication."
History of Present Illness
The patient is a 45-year-old man with a 15-year history of Bipolar I Disorder, currently stable on lithium 900 mg daily (lithium level 0.8 mEq/L). He is here for routine follow-up and medication education. He has had 4 manic episodes and 6 depressive episodes over the years, with his last episode (depression) 18 months ago.
He has been on lithium for 10 years with good response - his manic episodes have been completely prevented, and depressive episodes have been less frequent and less severe. He has tried valproate and lamotrigine in the past with less efficacy.
He is interested in better understanding his medication, particularly why he needs regular blood tests and what symptoms to watch for.
Current Medications
- Lithium 900 mg at bedtime (level 0.8 mEq/L)
- No other psychiatric medications
Medical History
- Hypothyroidism (developed on lithium, on levothyroxine)
- Mild chronic kidney disease (eGFR 62, attributed to long-term lithium)
Teaching Points: Lithium Pharmacology
Mechanism of Action (Incompletely Understood):
- Modulates intracellular signaling cascades
- Inhibits glycogen synthase kinase-3 beta (GSK-3β)
- Inhibits inositol monophosphatase
- Neuroprotective effects (increases BDNF, gray matter volume)
- Unique anti-suicidal effect (unrelated to mood stabilization)
Pharmacokinetics:
Absorption:
- Well absorbed orally
- Peak levels in 1-2 hours (immediate release)
- Extended release: Peak 4-5 hours
Distribution:
- Not protein bound
- Distributes in total body water
- Volume of distribution: 0.7-1.0 L/kg
Metabolism:
- NOT metabolized
- No hepatic involvement (unique among psych meds)
- Eliminated unchanged by kidneys
Elimination:
- Half-life: 18-24 hours
- Steady state: 5-7 days
- 95% renal excretion
- Reabsorbed in proximal tubule (competes with sodium)
Therapeutic Range:
- Acute mania: 0.8-1.2 mEq/L
- Maintenance: 0.6-1.0 mEq/L
- Toxicity begins: >1.5 mEq/L
- NARROW THERAPEUTIC INDEX
Monitoring Requirements
Lithium Levels:
- Trough level (12 hours post-dose, before morning dose)
- At initiation: Every 5-7 days until stable
- Stable patient: Every 3-6 months
- After dose change: 5-7 days post-change
- If any symptoms of toxicity
- After illness, dehydration, medication changes
Renal Function:
- Baseline BUN, creatinine, eGFR
- Every 6-12 months thereafter
- Lithium can cause interstitial nephritis, reduced GFR over time
- This patient: eGFR 62 - mild CKD, continue monitoring closely
Thyroid Function:
- Baseline TSH
- Every 6-12 months
- Lithium inhibits thyroid hormone release
- 25-30% develop hypothyroidism (treat with levothyroxine, can continue lithium)
- This patient: On levothyroxine for lithium-induced hypothyroidism
Other Monitoring:
- Calcium (lithium can cause hyperparathyroidism)
- ECG if cardiac history (can affect sinus node)
- Weight (some weight gain common)
Drug Interactions
Medications that INCREASE lithium levels (toxicity risk):
- NSAIDs (ibuprofen, naproxen) - reduce renal clearance
- ACE inhibitors, ARBs - reduce renal clearance
- Thiazide diuretics - reduce sodium, increase lithium reabsorption
- Dehydration/volume depletion - concentrates lithium
Medications that DECREASE lithium levels:
- Caffeine (mild)
- Theophylline
- Sodium loading
- Osmotic diuretics
Patient Instructions:
- Stay well-hydrated (especially in heat, with exercise)
- Avoid NSAIDs - use acetaminophen instead
- Inform all providers you take lithium before starting new medications
- Maintain consistent sodium intake
Lithium Toxicity
Signs of Toxicity (level >1.5 mEq/L):
Mild (1.5-2.0 mEq/L):
- Coarse tremor (vs. fine tremor at therapeutic levels)
- Nausea, vomiting, diarrhea
- Confusion, lethargy
Moderate (2.0-2.5 mEq/L):
- Ataxia
- Dysarthria
- Myoclonus
- Increased confusion
Severe (>2.5 mEq/L):
- Seizures
- Cardiac arrhythmias
- Coma
- Death
When to Seek Emergency Care:
- Severe diarrhea or vomiting (dehydration risk)
- Febrile illness with reduced fluid intake
- Confusion, ataxia, severe tremor
- Starting new medication that interacts
- Any concern for toxicity
Treatment of Toxicity:
- Hold lithium
- IV fluids for hydration
- Hemodialysis for severe toxicity
This Patient's Plan
Current Status:
- Stable on lithium 900 mg, level 0.8 mEq/L
- Hypothyroidism managed
- Mild CKD - monitor closely
Ongoing Monitoring:
- Lithium level every 3 months (given CKD)
- eGFR every 6 months
- TSH every 6 months
- Annual calcium
Patient Education Provided:
- Signs of toxicity
- Drug interactions (especially NSAIDs, ACE inhibitors)
- Importance of hydration
- When to seek emergency care
Follow-up: 3 months
Image Attribution
Image: Diagram showing mechanisms of action of major psychotropic drug classes at the synaptic level, including serotonin reuptake inhibition, dopamine receptor interactions, and GABA modulation. Source: Wikimedia Commons. Used for educational purposes under Creative Commons license.