Antimanic Drugs
The use of antimanic drugs
The antimanic drugs considered in this chapter are lithium salts, carbamazepine, and semisodium valproate (containing valproic acid). Lithium carbonate and lithium citrate are particularly useful in the prophylaxis of bipolar mood disorder, as well as having a role in the treatment of mania itself. The antiepileptic drug carbamazepine may be used as an alternative to lithium salts in the prophylaxis of bipolar mood disorder in patients who do not respond to lithium salts, particularly in those who are rapid cyclers suffering at least 4 relapses (mania or depression) per year. Valproic acid (semisodium valproate) is an effective treatment for mania in many cases of bipolar disorder.
Two other groups of drugs may also be used in the treatment of mania, namely benzodiazepines and antipsychotic drugs.
Benzodiazepines, which are briefly discussed in Chapter 12, can be used in the short-term treatment of the initial symptoms of mania, but should not be used long-term as they are associated with a risk of dependency.
In general, antipsychotic drugs act more rapidly than lithium salts in the treatment of mania or hypomania. (One patient is reported to have drawn the analogy that acute mania was like being in an-out-of-control car, with antipsychotic drugs acting as if pressure were being applied to the brake pedal, whereas lithium therapy felt more like the effect of adjusting the accelerator pedal.) In mild to moderate mania it may be better to treat with lithium or another mood stabilizer (such as valproic acid) alone, owing to their specific antimanic action and also in order to reduce the level of side-effects.
The novel antipsychotic asenapine has recently become available for bipolar I disorder.
Treatment strategies for bipolar I disorder
Maron and Young (2011) have suggested the treatment strategies for bipolar I disorder shown in Table 6.1.
Table 6.1 Treatment strategies for bipolar I disorder. Reproduced from Maron and Young (2011). | |||
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Lithium salts
The lithium salts most commonly used in clinical psychiatric practice are:
Lithium carbonate (e.g. Camcolit®, Liskonum®, and Priadel®)
Lithium citrate (e.g. Li-Liquid® and Priadel® liquid).
StructureThe active ingredient of lithium salts is the lithium ion, Li+. Lithium is an element, in the same group in the periodic table as the metals sodium, potassium, and rubidium. It has the atomic number 3 and an atomic mass of 6.941.
Indications
Circumstances in which lithium salts are used include the:
prophylaxis of bipolar mood disorder
treatment of mania or hypomania
treatment of resistant depression
prophylaxis of recurrent depression
treatment of aggression
treatment of self-mutilation.
Contraindications and cautions
Lithium therapy should not be used in the following conditions:
Cardiac failure.
Renal impairment.
Other conditions associated with sodium ion imbalance, such as
primary hypoadrenalism (Addison’s disease)
congenital adrenal hyperplasia
corticosterone methyl oxidase deficiency types I and II
hyporeninaemic hypoaldosteronism
pseudohypoaldosteronism type I
Barrter’s syndrome
following renal transplantation
following relief of urinary tract obstruction
acute interstitial nephritis.
Pregnancy—if at all possible, lithium therapy should be avoided in pregnancy, as lithium is associated with a risk of teratogenicity.
Lithium should be stopped or the dose reduced (with careful monitoring of fluid balance and electrolytes) in the following conditions:
diarrhoea
vomiting
intercurrent infection—particularly if profuse sweating occurs.
Lithium should be used with caution in the following conditions:
lactation
myasthenia gravis.
It is not recommended that lithium be used in childhood, while a reduced dose should be used in the elderly. While lithium therapy may be continued during minor surgery, so long as fluid balance and electrolytes are monitored carefully, in general lithium should be stopped 24 hours before major surgery.
How to use lithium salts
Being an element, lithium (actually, Li+ cations) are not metabolized but are excreted mainly by the kidneys. Given that lithium has a narrow therapeutic index (see ‘Monitoring’, p.119), it is necessary to carry out tests of renal function before initiating treatment with lithium. In most patients this involves checking the plasma urea, electrolytes, and creatinine levels. If, however, there is an indication of poor renal function, then full renal function studies need to be carried out before starting lithium treatment.
Lithium salts are administered orally at a dose that leads to a serum lithium ion concentration of between 0.4-1mmol/L 12 hours after the last dose, 4-7 days after the initiation of treatment.
Different lithium preparations vary in the bioavailability, and therefore it is recommended that if the preparation is to be changed, then the serum lithium ion concentration precautions should be taken again.
After dosage stabilization, the lithium salt may be given once daily rather than in divided doses, although there are no hard and fast rules. Those who administer it once daily often prefer to give the daily dose at night, in order to reduce the impact of side-effects.
For patients in whom compliance is problematic, and for those suffering from dysphagia, an oral solution and a liquid preparation of lithium citrate are available as alternatives to tablets of lithium carbonate or lithium citrate. Note that 200mg lithium carbonate is the bioequivalent of 509mg lithium citrate, in respect of lithium.
The manufacturers’ dosage recommendations are as follows.
Camcolit®
Serum monitoring should be carried out (see ‘Monitoring’, p.119).
For treatment, initially start with 1-1.5g daily.
For prophylaxis, initially start with 300-400mg daily.
It is not recommended for use in children.
Liskonum®
Serum monitoring should be carried out (see ‘Monitoring’, p.119).
For treatment, initially start with 450-675mg twice daily; 225mg twice daily in the elderly.
For prophylaxis, initially start with 450mg twice daily; 225mg twice daily in the elderly.
It is not recommended for use in children.
Priadel® tablets
Serum monitoring should be carried out (see ‘Monitoring’, p.119).
For treatment, initially start with 0.4-1.2g daily as a single dose or in 2 divided doses; 400mg daily in the elderly and in patients weighing less than 50kg.
For prophylaxis, initially start with 0.4-1.2g daily as a single dose or in 2 divided doses; 400mg daily in the elderly and in patients weighing less than 50kg.
It is not recommended for use in children.
Priadel® liquid
Plasma monitoring should be carried out (see ‘Monitoring’, p.119).
For treatment, initially start with 1.04-3.12g daily in 2 divided doses; 520mg twice daily in the elderly and in patients weighing less than 50kg.
For prophylaxis, initially start with 1.04-3.12g daily in 2 divided doses; 520mg twice daily in the elderly and in patients weighing less than 50kg.
It is not recommended for use in children.
Li-Liquid® (oral solution)
Plasma monitoring should be carried out (see ‘Monitoring’, p.119).
For treatment, initially start with 1.018-3.054 g daily in 2 divided doses; 509mg twice daily in the elderly and in patients weighing less than 50kg.
For prophylaxis, initially start with 1.018-3.054 g daily in 2 divided doses; 509mg twice daily in the elderly and in patients weighing less than 50kg.
It is not recommended for use in children.
Side-effectsThe side-effects of lithium include:
gastrointestinal disturbances
renal impairment:
polyuria
impaired urinary concentration
polydipsia
dry mouth
metallic taste
weight gain
oedema
fatigue
fine tremor.
Note that oedema should not be treated with diuretics, since thiazide and loop diuretics reduce lithium excretion and so may cause lithium intoxication; oedema may respond to a reduction in the daily lithium dose.
Lithium intoxication
Signs of lithium intoxication are:
blurred vision
increasing gastrointestinal disturbances:
anorexia
vomiting
diarrhoea
muscle weakness
mild drowsiness and sluggishness progressing to giddiness with ataxia
lack of coordination
tinnitus
dysarthria
nystagmus
renal impairment
coarse tremor.
Lithium treatment should be stopped immediately under these circumstances. The serum lithium ion concentration should be re-checked and appropriate steps taken to reverse the toxicity.
Severe overdosage
At serum lithium ion concentrations of greater than 2mmol/L, the following effects occur:
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