Bipolar Depression (Manic-Depression)

• Affects 1%(Example Location : New Zealanders) of the population (35,000 New Zealanders)
• Genetic predisposition:
  • No family history then risk is 1%
  • One parent then risk is 20%
• Symptoms: 
  • Manic Phase: elation, pleasure, energy, racing thoughts, invincible, grandiose (­self esteem), irritable, aggressive, lack of judgement (eg reckless driving, spending sprees, sexual indiscretion)
  • Depressive Phase: same symptoms as for major depressive episode
• History questions for mania:
  • How do you feel about yourself?
  • Do you feel that you are special?
  • Have you needed less sleep?
  • How much have you been spending lately
• Classifications of Bipolar Depression 
  • Mixed Episode: rapidly alternating mood – at least 1 week in which the criteria are met for a manic episode and a MDE nearly every day
  • Bipolar 1: one or more manic or mixed episodes, usually accompanied by MDEs
  • Bipolar 2: one or more MDEs accompanied by at least one hypomanic episode 
  • Cyclothymia: At least 2 years of numerous periods of hypomanic symptoms and depressive symptoms that don‟t meet criteria for mania or MDE (cf Dysthymia)
• Mood stabilising medication:
  • Lithium carbonate (requires regular blood tests.  Can they get to the lab?)
  • Carbamazepine (Tegretol)
  • Sodium Valproate (Epilim)
  • All have similar efficacy, Lithium most common 
  • Antipsychotic or tranquillising medication often added during early stages to reduce agitation and hyperactivity 
  • Antidepressant medication can be used during depressive phase (although therapeutic delay a problem), and withdrawn gradually when it resolves. If used in isolation without a mood stabiliser, may precipitate a manic phase as the depression lifts
• Can be very stressful on relationships for family members

 Lithium

• Indication: In bipolar, but also recurrent unipolar. Not good for acute mania – takes 2 – 4 weeks, full response may take 6 months
• Pharmacokinetics: 
  • Variable absorption. T½ is 18 hrs in young, 26 hours in elderly. Excreted unchanged. 80% reabsorbed in proximal tubule 
  • Renal clearance of Li reduced by diuretics, NSAIDs, theophylline, caffeine, dehydration, low sodium 
  • Clearance related to tubular sodium load. If ­Na excretion (eg loop and thiazide diuretics) then ¯Li excretion. 
  • ACE inhibitors ®­Li levels

• Monitoring:
  • Narrow therapeutic range for maintenance treatment: 0.4 – 0.8 mmol/l 
  • Therapeutic drug monitoring for Li is mandatory when: side effects, relapse of symptoms, serious illness (eg dehydration), dose adjustment
  • Check thyroid and renal function before starting
  • Monitoring every three months should include Li levels, electrolytes, thyroid function 
  • Monitor 12 hrs after immediate release, 5 hrs after slow release. Slow release preparations prevent peaks in plasma conc. (® nausea, headache)

• Side Effects:
  • Minor symptoms such as tremour and nausea do not predict serious toxicity:
    • Tremor (especially elderly), nausea, loose bowel motions (especially if levels > 0.8 mmol/L)
    • Polyuria (especially when starting)
    • Weight gain: approx 4 kg
    • Pretibial oedema
    • Metalic taste
  • Dose dependent adverse effects:
    • 1.5 – 3 mmol/l – ataxia, weakness, drowsiness, thirst, diarrhoea
    • 3 – 5 mmol/l – confusion, spasticity, convulsions, dehydration, coma, death 
  • Dose independent: hypothyroidism (reversible in early stages), nephrogenic diabetes insipidous, ECG changes & arrhythmias, acne, GI disturbance, weight gain, ¯bone calcium 
  • Long term Li does not change GFR or lead to renal failure