bipolar, lithium

Mania features

Marked functional impairment + psychotic features - difficulties in employment, family responsibilities

- Duration: at least one week

- Hospitalisation required

Hypomania features

NO marked functional impairment or psychotic features - no profound difficulties in employment, family responsibilities

Duration: at least four days

Hospitalisation not required, less severe, shorter duration

Features of bipolar 1

Mania ± hypomania ± depression

≥1 manic episodes, usually depression episodes

Marked impairment both:

- Depression for 2 weeks

- Mania for 7 days

Affects both genders equally

Onset: late teens

Diagnosis: late 20s

Ratio manic: depressive episodes 1:3

Features of bipolar 2

Hypomania + depression episodes

Marked impairment depression

No marked impairment hypomania

Hypomania for 4 consecutive days

Depression for 2 weeks

More common in females

Onset: 29

Mania treatment

GOOD EVIDENCE: lithium, valproate, antipsychotics, AP + lithium or valproate

SUGGESTIVE EVIDENCE: carbamazepine

SHORT TERM: BDZ for agitation and insomna

Institute: sleep hygiene, structure and routine, limit activity

Address: alcohol/ substance misuse, smoking, meds that elevate mood

Implement: safety, self-harm, impulsive decisions, psychosis, housing, supervision, consultation, outcomes, monitoring

+ adjunctive psychotherapy and low-stimulating environment

Depression treatment

GOOD EVIDENCE: quetiapine

SUGGESTIVE EVIDENCE: lithium, valproate, olanzapine + fluoxetine/ lamotrigine

evidence for anti-depressant efficacy is poor

NON-PHARM

- Institute: sleep hygiene, regular exercise, diet

- Address: alcohol/ substance misuse, smoking, meds that alter mood

- Implement: individual/ family/friends education, psychological interventions (CBT), housing/family/employment support, assess risk/outcomes/monitoring

+ adjunctive psychotherapy (CBT, family focused therapy

Maintenance - prevention of relapse overview

FIRST LINE: lithium monotherapy

SECOND LINE: olanzapine, aripiprazole, risperidone/ quetiapine with valproate/lithium

THIRD LINE: carbamazepine, lurasidone, lamotrigine, alternative AP that has been effective during an acute episode

+ adjunctive psychotherapy (CBT, cognitive remediation

Lithium efficacy

Reduces mania symptoms after 3-4 weeks

AS EFFECTIVE at improving the symptoms of mania as

- haloperidol after 3 weeks

- olanzapine after 4 weeks

- valproate after 3-6 weeks

- carbamazepine after 4 weeks

- lamotrigine after 4 weeks

- quetiapine after 3 weeks

LESS EFFECTIVE than risperidone at reducing the symptoms of mania after 4 weeks

MORE EFFECTIVE than topiramate at reducing the symptoms of mania after 3-12 weeks

Lithium AE

GI disturbances, fine tremor, renal impairment (esp impaired urinary conc and polyuria), polydipsia, leucocytosis, weight gain, oedema (may respond to dose ↓), hypothyroidism

Metallic taste, nausea, diarrhoea, epigastric discomfort, weight gain, fatigue, headache, vertigo, tremor, acne, psoriasis, leucocytosis, nephrotoxicity, hypothyroidism (usually asymptomatic), hypercalcaemia, hyperparathyroidism, benign T wave changes on ECG

Lithium toxicity (range, predisposing factors, sx, tx)

>1.5mmol/L (adult), >1.2mmol/L (elderly)

Predisposing factors - renal impairment/dysfunction, thyroid dysfunction, dehydration (heavy sweating vomiting), >50, some drugs, low Na diet

SX: blurred vision, diarrhoea, N&V, muscle weakness, drowsiness, apathy, ataxia, flu-like illness, myoclonic jerks, coarse tremor, hyperreflexia, dysarthria, ↑ muscle tone, disorientation, psychosis, seizures, coma

TREATMENT: IV fluid replacement to ensure diuresis

• Hemodialysis if GFR <60mL/min, Li> 2.5 mM, delirium, seizures, coma, persistent clinical effects despite fluids -> ↑ Li CL

Pharmacokinetics lithium

F >85% - dependent on dose form

Distribution = 0.8 L/kg - not bound to plasma protein

CLR indicates filtration AND reabsorption

Lithium CL = filtration - reabsorption

Elimination = 0.25 x CLcr - not metabolised, renally excreted, similar to Na

- CLR = 26 mL/min

- GFR = 120 mL/min

- Not secreted

- 80% of filtered Li (proximal tube) load is reabsorbed with Na (proximal, distal, loop of henle, collecting tubules)

Variability: t1/2 = 27h (8-35h) = 4-5 days to reach SS

When to monitor Lithium conc

- Starting (once SS achieved)

- Prophylaxis: Every 3-6 months

- Dose changes (re-test in 5-10 days), interacting medications started/ceased

- Clinical signs of toxicity or lack of efficacy

- Dehydration or changed salt intake

What to monitor in Lithium TDM

THERAPEUTIC RANGE: 0.8-1.2mmol/L (acute mania), 0.4-1mmol/l (prophylaxis)

First few days and every 3-6 months: Plasma Lithium conc

Baseline, every 3-6 months (at least annually)

- Renal Function: Urea and creatinine, electrolytes

- Thyroid Function: TSH conc (Li can lead to hypothyroidism) - + monitor for clinical signs; fatigue, weight gain, slow HR

- Parathyroid Function: Calcium conc

- Weight: waist circumference, BMI (weight gain is a SE)

Baseline, follow-up - ECG if there is significant cardiac disease

DDI lithium (decrease lithium clearance)

increase drug conc

Thiazide and loop diuretics - sodium depleting = ↑ reabsorption of Li to try to maintain overall Na balance = ↑ Li reabsorption in renal tubules = ↓ renal CL

NSAID - inhibits PG synthesis (PG have a role in renal blood flow and regulating GFR) = ↓ renal CL

ACE inhibitors and AT2 antagonists - cause blood vessels to dilate = decrease renal blood flow = more reabsorption = ↓ renal CL

Other: low sodium diet, pregnancy, renal failure, infection/fever

DDI lithium (increase lithium clearance and other interactions)

Decrease drug conc:

Sodium bicarbonate: Alkalinization of urine -> promotes renal elimination

Potassium citrate - Alkalinization of urine -> promotes renal elimination

Pharmacodymanic interactions (no change in lithium concentration)

- anticonvulsants, SSRIs, CCBs (increased risk of neurotoxicity)

- increased risk of serotonergic syndrome