Mood Stabilisers in Treatment of Bipolar Disorders

Types of Mood Stabilisers

1. Lithium

2. Sodium valproate

3. Carbamazepine

4. Lamotrigine

Lithium

Mechanism of action – unknown
     (possibly increase 5-HT function in the brain)

Pharmacokinetics

- onset: 5-7 days
- absorbed and excreted by kidney

- narrow therapeutic index (TI)

Caution!

1. conditions which raise lithium concentration

   - dehydration

   - sodium depletion, diarrhoea

   - thiazide therapy
2. conditions which is absolute/relatively contraindicated

   - CVS disease

   - acute infection

   - fever

   - pregnancy (teratogenicity)

Dosage

Acute mania: 0.8-1.5mmol/L

Prophylaxis/maintenance: 0.5-1.0mmol/L (or 1.2mmol/L)

Side Effects

Early
1. polyuria – dehydration (and risk of intoxication)

2. fine tremor (rx propranolol)

3. dry mouth

4. metallic taste

5. weakness and fatigue

Late

6. fine tremor

7. polydipsia (compensatory from polyuria)

8. hair loss

9. thyroid enlargement

10. hypothyroidism, cold intolerance

11. impaired concentration

12. weight gain

13. GI distress

14. sedation

15. acne

16. impaired memory

17. ECG changes (flattened T wave, widening of QRS)

Long Term

18. kidney failure – impaired concentrating ability

19. nephrogenic diabetes insipidus (interferes with ADH)

20. teratogenic (crosses placenta) – Ebsein’s anormaly

Toxicity Effect (>1.5mmol/L)

1. nausea, vomiting

2. diarrhea

3. coarse tremor

4. ataxia, dysarthria

5. muscle twitching, hyperreflexia

6. confusion, coma

7. convulsion

8. renal failure

9. cardiovascular collapse

Emergency Treatment of Lithium Toxicity

1. stop lithium immediately

2. high fluid intake

3. IV normal saline or hyperosmotic saline to stimulate osmotic diuresis

4. renal dialysis if necessary

Monitoring of Lithium Administration

1. baseline physical and laboratory assessment

2. hx and pe on CNS, GIT, metabolic, thyroid, renal

3. pregnancy test

4. ECG in patients >40yo

5. RP for BUN, serum creatinine, electrolyte, biannually

6. TFT – TSH biannually
7. serum lithium level measured after 4-7 days of administration

8. repeat weekly for x3/52

9. then repeat once every x3/12
10. repeat serum lithium when inefficacy or adverse effect

* timing of measurement must be 12 hours after last dose (at steady state level)

Drug Interactions

1. Increases lithium concentration in:

   - haloperidol

   - thiazide diuretics

   - muscle relaxants

   - antibiotics (metronidazole, spectinomycin)

   - anti-HT (ACEi, methyldopa)

2. Interactions with antipsychotics

   - potentiates extrapyramidal side effects

   - confusion, delirium

3. Interactions with SSRI or ECT

   - serotonin syndrome

Withdrawal Symptoms

1. irritability

2. emotional lability

3. relapse to mania

Indications

1. acute mania, classic features (rapid cycling ↓ efficacy)

2. bipolar maintenance

3. other mood disorder use

Sodium valproate

Mechanism of Action – increase GABA in CNS

Pharmacokinetics

- onset: 2-5 days

- metabolized in liver, excreted in kidney

Dosage

Starting: 250-500mg titrated upward by 250-500mg/day

Maintenance: 750-1250mg/day

Side Effects

1. sedation

2. tiredness, fatigue

3. tremor

4. GI disturbance

5. reversible hair loss (alopecia)

6. thrombocytopenia

7. weight gain

8. haemorrhagic pancreatitis

9. hepatotoxicity

10. teratogenic – neural tube defect
* monitor FBC and LFT for baseline and changes

Drug Interactions

1. Displacement of protein-bound drugs (antiepileptics)

   - increases plasma level

2. Inhibits metabolism of lamotrigine (give only 50% dose if combined treatment)

Indications

1. bipolar disorder, manic episode, rapid cycling

Lamotrigine

- effective in bipolar depression without inducing mania

- prevents depressive relapse in bipolar

Mechanism of Action – blocks sodium channel

Pharmacokinetics

- metabolized in liver, excreted in urine (65%), faeces (2%)

Dosage

Initial: 25mg/day for 2 weeks
Later: 50mg/day for next 2 weeks
Maximum dose: 100-300mg/day

Side Effects

1. skin reactions – rashes, SJ S, toxic epidermal necrolysis

2. nausea

3. headache, aseptic meningitis

4. tremor

5. dizziness

6. teratogenic (cleft palate)

Drug Interactions

1. Increases lamotrigine concentration in:

   - valproate

2. Combined lamotrigine-carbamazepine – Neurotoxicity

Carbamazepine

- fastest onset mood stabilizer (? citation needed)

- prevent recurrence of affective depression

- patients unresponsive to lithium

- rapidly recurring bipolar disorder

Mechanism of Action - blocks Na channels, inhibits AP

Pharmacokinetics

- onset: 5-7 days

- metabolized in liver

- excreted in urine (72%) and faeces (28%)

Dosage

Starting: 400mg/day, increased up to 800-1000mg/day

Side Effects

1. drowsiness

2. dizziness

3. nausea

4. diplopia (double vision)

5. skin rash

6. agranulocytosis, leukopenia, aplastic anaemia

7. hyponatraemia
8. elevated liver enzymes
9. teratogenic – neural tube defect

* monitor FBC, LFT for baseline and subsequent changes

Drug Interactions

1. increased metabolism of some drugs and OCP

Indications

1. bipolar disorder, mixed episode, rapid cycling

2. trigeminal neuralgia

The ABCs of Rapid Sequence Induction

Rapid Sequence Induction

Definition: a technique to safely secure the airway with an endotracheal tube. Used in patients who are at risk of regurgitation and aspiration of gastric contents on induction of anaesthesia.

Regurgitation: passive movement of gastric contents into the pharynx. This is normally prevented by the upper and lower oesophageal sphincters.

The lower oesophageal sphincter is formed by the lowest 2-4 cm of the oesophagus. The major component of the upper oesophageal sphincter is the cricopharyngeus muscle.
Protective laryngeal reflexes are also lost during GA.

Aspiration: regurgitation occurs and gastric contents then enter the trachea and lungs.

Indications 1. Full stomach or conditions considered as full stomach     eg: stress, delayed gastric emptying,       emergency cases 2. Obese 3. Pregnant 4. History of hiatal hernia 5. Intestinal obstruction

Checklist 1. Anaesthetic machine and breathing circuit 2. Routine patient monitoring applied 3. Airway equipment 4. Tipping trolley 5. Suction switched on and immediately to hand 6. Drugs – including emergency drugs 7. A trained assistant

Technique

1.     Preparation and echking of equipment, tilting trolley and suction

2.     Pre-oxygenation – delayed onset of muscle relaxant, avoid face mask ventilation

3.     Administration of intravenous pre-calculated dose of induction agent

4.     Administration of suxamethonium – depolarizing muscle relaxant onset faster 30s compared to non-depolarising muscle relaxant onset 2-3 minutes*

5.     Cricoid pressure (Sellick’s manoeuevre) – cricoid cartilage at level C6

6.     Intubate and confirm ETT placement

7.     Remove cricoid pressure

* bag mask technique during 2-3 minute period may insufflate the stomach and increase intra-gastric pressure and regurgitation

Pre-oxygenation

- high flow oxygen for 3 minutes of tidal breathing or four vital capacity breaths, target 85% O₂

- tight fitting face mask, ensure no leakage

Cricoid pressure

The cricoid cartilage is the only complete ring of cartilage in the larynx. Pressure on the cricoid cartilage compresses the oesophagus against the cervical vertebrae, thus preventing the passage of gastric and oesophageal contents, should passive regurgitation occur.

Light cricoid pressure (10 Newtons [N]) is applied before intravenous induction. The force is increased (30 N) after loss of consciousness. It is the responsibility of the anaesthetist to ensure that cricoid pressure has been applied. The direction of the force is posterior. A force of 30 N is approximately equal to a 3 kg weight.

Two-finger technique – the index finger and thumb are placed on each side of the cricoid arch, with force applied by both.

Three-finger technique – the thumb and middle finger are placed on each side of the cricoid arch with force applied by the index finger in the midline.

A two-handed technique is used if a cervical spine fracture is suspected. The second hand is placed behind the neck to prevent posterior displacement of the spine on applying cricoid pressure. Manual in-line stabilization of the neck must also be used.

Muscle relaxant (Suxamethonium)

- Fast onset of action providing paralysis in approximately 30-45 s

- Short duration of action of 5-8 min

- dosage: 1.5mg/kg

- post-administration, face mask remained applied with airway held open until fasciculations ceased and jaw relaxed.

Contraindications to Suxamethonium

1. anaphylaxis

2. malignant hyperthermia

3. major burns

Gastric Aspiration

Tilt the trolley head down, suction the oropharynx, intubate immediately and inflate the cuff. Pass a suction catheter down the endotracheal tube (ETT) to clear any aspirate before starting ventilation with 100 % oxygen (to prevent contamination of the distal airways).

A higher FiO2, Positive End-Expiratory Pressure (PEEP) or bronchodilators may be needed to maintain oxygenation.

If significant pulmonary aspiration has occurred the patient should be transferred to a high dependency area post-operatively.

Mendelson Syndrome

syndrome of pneumonitis following aspiration of gastric contents was originally described by Mendelson in obstetric patients. Features include hypoxia, bronchospasm and pulmonary oedema. Treatment is mainly supportive including oxygen, bronchodilators, physiotherapy and assisted ventilation if required.

sourced from: RCoA and AAGBI