Practical accomplishment of treatment
To avoid side effects patients should be monitored closely at the start of treatment, during an increase of intensity and during maintenance treatment (tab 1).
Table 1
Laboratory tests
| Test |
Start of treatment |
During the initial treatment phase |
During the maintenance phase |
| Lithium level in serum |
|
Every week for a month Every month the first 6 months At every dose change the lithium level is measured after 7 days |
Every 3 - 6 months At every dose change |
| TSH/T4 |
All |
After 6 months |
Every 6 months |
| Anti-TPO |
All |
|
|
| Calcium |
All |
After 6 months |
Annually |
| S-Creatinine |
All |
After 6 months |
Every 6 months |
| Electrolytes |
All |
After 6 months |
Annually |
| Pregnancy test |
Women |
|
|
| ECG |
More than 40 years of age or known risk factors for cardiac disease |
|
|
The serum concentration should be measured regularly. The association between serum concentration and effect is well documented (4). The therapeutic index is narrow and there is a short distance between lack of effect and intoxication. In Norway, the reference range for the serum concentration is 0.5 - 1.0 mmol/L measured at steady state in serum and 12 hours after the last intake of lithium. A somewhat lower serum concentration is adequate for some patients when lithium is used in combination treatment of depression. At levels above 1.2 mmol/L, the risk of side effects will increase and levels above 1.5 mmol/L will have toxic effects in most patients. Levels above 2.0 mmol/L are considered to be serious- potentially lethal - poisonings. Serum concentrations should be measured frequently at the start of treatment- weekly the first month and thereafter monthly for half a year. Afterwards lithium should be measured every three to six months, depending on the patient’s condition. For every dose change, the lithium level should be measured at steady state, after five to seven days.
The lithium level should be monitored closely in conditions that affect the fluid and electrolyte balance; e.g. diarrhoea, increased sweating and low fluid intake. Reuptake of lithium in the kidneys and thereby serum concentrations will increase with dehydration and hyponatremia. A high lithium level may lead to dehydration, because the drug blocks the effect of antidiuretic hormone on the renal tubules. In serious cases the patient may risk intoxication with normal doses.
A number of drugs may affect the lithium concentration in serum when used concomitantly. ACE inhibitors will increase the serum concentration of lithium secondary to excretion of sodium. Tiazide diuretics will also lead to an increased concentration of lithium because of reduced renal excretion. The same applies to non-steroid anti-inflammatory drugs. With concomitant use of lithium and these drugs, the lithium concentration should be monitored closely, especially in periods when dosing is changed.
According to the manufacturer, lithium is contraindicated in the first trimester of pregnancy and should only be used on a strict indication in the second and third trimesters. Bipolar disorder during pregnancy is associated with a risk to both mother and child and in some situations pharmacological treatment is appropriate. Lithium in therapeutic concentrations gives a small but measurable increase in the prevalence of congenital abnormalities (5). Some congenital abnormalities in the heart have been observed, but these are very rare - and the risk must be balanced against serious psychological disease in the mother (6). Thyroid abnormalities in children whose mothers have taken lithium in pregnancy, have also been described. When lithium treatment is considered necessary, the lowest dose should be given, preferably as monotherapy. The kidneys’ ability to excrete lithium may be affected during pregnancy and frequent serum monitoring is necessary.
Breast-feeding has been discouraged with lithium use. This is in contrast with more recent studies (7,8) that show low levels and good tolerance of lithium in children who are breastfed. Lithium treatment should not be interrupted during breastfeeding, but the child should be closely observed with measurements of serum concentrations, renal function and the relationship between thyroid stimulating hormone (TSH) and thyroxine (T4); TSH/T4. Small children can easily become dehydrated with conditions such as diarrhoea and the common cold, thus endangering lithium intoxication. Children with such conditions should be followed especially close.