Mood stabilisers and ECT

Maintenance Mood Stabilisers: Lithium & Sodium Valproate

Lithium: The Gold Standard

Lithium is an effective maintenance option for suitable bipolar patients. Evidence suggests possible suicide-risk benefit, but effect estimates vary; do not promise a fixed reduction to an individual. Renal, thyroid, interaction and reproductive risks require ongoing review.

• Therapeutic Drug Monitoring (TDM): Narrow therapeutic index! Serum levels must be drawn precisely 12 hours post-evening dose (standard 12-hour trough level):
  • Maintenance therapy: 0.6 to 0.8 mmol/L.
  • Acute mania: 0.8 to 1.0 mmol/L.
  • Frail elderly: 0.4 to 0.6 mmol/L.
  • Monitoring Frequency: Weekly during initiation until stable; then every 3 to 6 months indefinitely.
• Pre-Treatment Baseline & Ongoing Screening:
  • Renal function: Serum creatinine and eGFR (lithium causes nephrogenic diabetes insipidus and chronic tubulointerstitial nephropathy).
  • Thyroid function: TSH and Free T4 (lithium inhibits thyroid hormone release, causing hypothyroidism and goitre in up to 20% of patients; managed with thyroxine co-prescription without stopping lithium).
  • Serum calcium and PTH: Risk of lithium-induced hyperparathyroidism and hypercalcaemia.
  • 12-Lead ECG: Risk of sinus node dysfunction, T-wave flattening, and conduction blocks.
  • Beta-hCG: Rule out pregnancy (teratogenic risk of Ebstein anomaly: tricuspid valve downward displacement into the right ventricle; absolute risk is approximately 1 in 1,000–2,000 live births).
• Lithium Toxicity:
  • Precipitating Causes: Dehydration, febrile illness, salt restriction, acute kidney injury, or drug interactions.
  • Signs of Toxicity:
    • Mild ($1.5\text{ to }2.0\text{ mmol/L}$): Coarse tremor (distinct from benign fine postural tremor at therapeutic levels), nausea, vomiting, watery diarrhoea, muscle weakness, and ataxia.
    • Moderate ($2.0\text{ to }2.5\text{ mmol/L}$): Hyperreflexia, muscle fasciculations, nystagmus, dysarthria, marked confusion, and somnolence.
    • Severe ($> 2.5\text{ mmol/L}$): Delirium, generalized tonic-clonic seizures, stupor, coma, oliguria, acute renal failure, cardiovascular collapse, and death.
• Lithium toxicity: Stop lithium, assess renal function, electrolytes, ECG and neurological status, and give isotonic fluid according to volume status. Seek poison-centre/nephrology advice. EXTRIP recommends dialysis with impaired kidney function and lithium above 4 mmol/L, or decreased consciousness, seizures or life-threatening dysrhythmias irrespective of level; it suggests consideration above 5, with significant confusion or prolonged predicted clearance. Chronic toxicity can be serious at lower levels.
• Interpret serial lithium levels with whether poisoning is acute, acute-on-chronic or chronic, renal function and clinical findings. A fixed 2.0 or 4.0 cut-off without those conditions is inadequate.
• Dangerous Drug Interactions (elevate serum lithium levels):
  • NSAIDs (e.g., ibuprofen, indomethacin, celecoxib): Inhibit renal prostaglandin synthesis, reducing renal blood flow and GFR by up to 30%.
  • ACE Inhibitors / ARBs (e.g., ramipril, perindopril, candesartan): Reduce glomerular filtration pressure and alter proximal tubule sodium handling.
  • Thiazide Diuretics (e.g., hydrochlorothiazide, indapamide): Induce sodium loss in the distal convoluted tubule, triggering compensatory proximal tubular reabsorption of sodium and lithium.

Sodium Valproate (Epilim)

• Efficacy: Highly effective in acute mania, mixed affective states, and rapid-cycling bipolar disorder.
• Valproate reproductive safety: Australian warnings advise avoiding valproate for non-seizure indications in women of childbearing potential; it is contraindicated for bipolar treatment during pregnancy. If no suitable alternative exists, specialist review, documented risk education and effective contraception are essential. Do not import a named mandatory overseas pregnancy-prevention program or a universal dual-method rule into Australian law.
• Other Adverse Effects: Hepatotoxicity (elevated transaminases; rare fulminant hepatic necrosis), acute pancreatitis, marked weight gain, alopecia, hyperammonaemia, and polycystic ovary syndrome (PCOS).

Electroconvulsive Therapy (ECT)

Electroconvulsive therapy is one of the most effective and rapid interventions in acute psychiatry, delivering an electrical stimulus to the brain under general anaesthesia and muscle relaxation to induce a therapeutic generalized tonic-clonic seizure lasting at least 20 to 50 seconds.

• Clinical Indications:
  • Severe melancholic or psychotic depression refractory to pharmacotherapy.
  • Life-threatening depression with profound food/fluid refusal leading to severe dehydration and inanition.
  • High or imminent suicide risk requiring immediate life-saving response.
  • Severe catatonia.
  • Acute, refractory, severe mania with exhaustion ("manic delirium").
• Safety & Contraindications: ECT has no absolute medical contraindications. It is safe in pregnancy (fetal heart rate monitoring) and in the frail elderly. Relative contraindications requiring pre-treatment optimization include raised intracranial pressure, recent myocardial infarction ($< 3\text{ months}$), unstable cerebral aneurysms, and severe pulmonary disease.
• ECT consent: Discuss headache, short-term confusion and memory effects, including possible persistent retrograde memory loss. Individual anaesthetic, cardiac and pregnancy assessment is required; neither guaranteed rapid memory recovery nor blanket safety for every patient should be promised.

Lithium safety example

A patient stable on lithium develops diarrhoea and starts an NSAID. Review hydration, renal function, levels and neurological symptoms promptly; a previous therapeutic level is not current reassurance. Coarse tremor, ataxia or confusion requires urgent assessment and withholding further doses while seeking advice. Once the acute risk is addressed, agree an ongoing monitoring and sick-day plan with the treating team rather than abandoning effective long-term care. Explain interactions to the patient and pharmacist, including over-the-counter anti-inflammatory products.

Primary references (checked 7 October 2026): EXTRIP lithium recommendations.