Psychopharmacology Overview — SAQ

Stem

A 30-year-old woman with a 12-year history of bipolar I disorder, stable for the last five years on lithium carbonate 1000 mg nocte (last 12-hour trough level 0.8 mmol/L), presents to the emergency department with a two-day history of profuse watery diarrhoea and vomiting. She has continued to take her lithium throughout. Her partner reports that over the last 12 hours she has become increasingly confused, has developed a coarse tremor of both hands, is unsteady on her feet, and her speech is slurred. On examination she is drowsy, GCS 13, temperature 37.1 degrees C, heart rate 110, blood pressure 95/60, with a coarse tremor, dysarthria, ataxia, generalized fasciculations and hyperreflexia. Sodium 152 mmol/L, potassium 3.0 mmol/L, urea 14 mmol/L, creatinine 180 micromol/L (baseline 80), eGFR 32 mL/min/1.73 m^2. A 12-hour lithium level is sent and returns 3.1 mmol/L. ^[1]

Questions

a) What is the diagnosis, and what has precipitated it? (2 marks)

The diagnosis is acute lithium toxicity (level 3.1 mmol/L, well above the toxicity threshold of 1.5), with significant neurological features — coarse tremor, ataxia, dysarthria, confusion, fasciculations, hyperreflexia — and acute kidney injury. The precipitant is dehydration from gastroenteritis (sodium 152, urea 14, AKI): lithium is handled almost exclusively by the kidney, and volume depletion and sodium depletion trigger increased proximal tubular reabsorption of lithium, dramatically raising plasma levels even at unchanged dose. The patient continued lithium throughout her illness rather than holding the dose and seeking review — the key counselling point for every patient on lithium. ^[1]

b) Outline the immediate management in the first hour. (3 marks)

1. ABCDE: secure airway, IV access, continuous cardiac monitoring (lithium toxicity can cause arrhythmia and QT prolongation), GCS monitoring, treat any seizures with IV lorazepam. ^[2]
2. Stop lithium immediately and do not re-challenge.
3. Aggressive isotonic saline (0.9 percent sodium chloride) to restore intravascular volume, correct the prerenal AKI, and enhance renal lithium clearance. Aim for euvoalemia and good urine output. Avoid loop diuretics, thiazides, NSAIDs, ACE inhibitors and ARBs — all increase lithium reabsorption.
4. Correct hypokalaemia (potassium 3.0) and any other electrolyte or acid-base disturbance.
5. Arrange urgent haemodialysis — she meets EXTRIP criteria: significantly decreased conscious level/confusion with impaired renal function (eGFR 32) and a level (3.1 mmol/L) approaching the over-4.0 impaired-kidney threshold. ICU admission.

c) What are the indications for haemodialysis in lithium toxicity, and why is post-dialysis monitoring essential? (2 marks)

Indications for haemodialysis (EXTRIP consensus): extracorporeal treatment is recommended if kidney function is impaired and the lithium level is over 4.0 mmol/L, or in the presence of decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of the level; it is suggested if the level is over 5.0 mmol/L, with significant confusion, or when the expected time to bring the level under 1.0 mmol/L exceeds 36 hours; continue until clinical improvement or a level under 1.0 mmol/L. Lithium is small, water-soluble, not protein-bound, and distributes in total body water, so dialysis removes it efficiently — but post-dialysis rebound is common because lithium shifts from intracellular compartments back into plasma. Obtain serial lithium levels over the 12 hours after each dialysis session — post-redistribution rebound is maximal at 6 to 12 hours (typically 0.5 to 1.0 mmol/L) — and re-dialyse as needed until the level is below 1.0 mmol/L with clinical improvement. Sustained low-efficiency dialysis (SLED) or continuous renal replacement therapy is an acceptable alternative to intermittent haemodialysis. ^[2]

d) Describe the lithium monitoring schedule that should have prevented this presentation, and the patient counselling that every lithium patient must receive. (3 marks)

Pre-prescribing baseline: U&E, eGFR, TFTs, calcium, pregnancy test, ECG (if cardiac risk), weight and BMI. ^[4]

Initiation: start 400 to 600 mg lithium carbonate nocte; check the 12-hour trough level (drawn 12 hours after the last dose) at 5 to 7 days; titrate the dose to a maintenance level of 0.6 to 0.8 mmol/L (acute mania may target 0.8 to 1.0 under specialist care). Recheck weekly until stable. ^[3]

Long-term monitoring: lithium level every 3 months for the first year, then 6-monthly; U&E, eGFR, TFTs and calcium every 6 months; weight and BP regularly; ECG periodically if cardiac risk. ^[3]

Patient counselling (the counselling that would have prevented this admission): ^[5]

1. Maintain normal fluid intake — especially in hot weather, during exercise, and during any illness with vomiting, diarrhoea or fever.
2. If you are unwell with vomiting, diarrhoea or fever, or cannot eat or drink normally, OMIT the next dose of lithium and contact your doctor or the emergency department the same day. This is the single most important message.
3. Avoid NSAIDs (ibuprofen, naproxen, diclofenac), diuretics, and ACE inhibitors/ARBs without consulting the prescribing doctor — these raise lithium levels. Paracetamol is safe.
4. Report immediately: coarse tremor (different from the normal fine postural tremor of lithium), unsteadiness, slurred speech, confusion, muscle twitching, severe nausea, or any symptoms of toxicity.
5. Use reliable contraception and inform the doctor before any planned pregnancy (lithium carries Ebstein anomaly risk).
6. Carry a lithium alert card and inform any clinician, dentist or pharmacist that you take lithium.
7. Do not stop lithium abruptly — relapse of bipolar disorder can occur within weeks and suicide risk rises sharply.

References5ShowHide

1. [1]Okusa MD, Crystal LJ Clinical manifestations and management of acute lithium intoxication Am J Med, 1994.PMID 7942943
2. [2]Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal treatment for lithium poisoning: systematic review and recommendations from the EXTRIP Workgroup Clin J Am Soc Nephrol, 2015.PMID 25583292
3. [3]Grandjean EM, Aubry JM Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring CNS Drugs, 2009.PMID 19374461
4. [4]Malhi GS, Gessler D, Outhred T The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines J Affect Disord, 2017.PMID 28437764
5. [5]Gitlin M Lithium side effects and toxicity: prevalence and management strategies Int J Bipolar Disord, 2016.PMID 27900734