106 HANDBOOK OF PSYCHIATRIC DRUGS LITHIUM
106 HANDBOOK OF PSYCHIATRIC DRUGS LITHIUM
For bipolar maintenance, lithium has the longest and largest database of clinical experience and by far the greatest number of patients studied in rigorous clinical trials. In randomized trials, the relapse rate in patients treated with lithium is about 37% compared with 79% with placebo. Predictors of poor response to lithium are listed in Table 3-9.
Most patients starting lithium maintenance are already taking lithium after an acute episode. A medical history should also have been obtained that included questions about: past medical and family history of renal, thyroid, cardiac, and central nervous system disorders; other drugs a patient may
be taking (including prescription, over-the-counter, and illicit); the use of such common substances as caffeine, nicotine, and alcohol; and special diets or diet supplements. They should also have had baseline medical tests, including assessment of thyroid function (thyroid panel plus thyroid-stimulating hormone) and renal function (blood urea nitrogen, creatinine, and routine urinalysis), a complete blood count, electrolyte determinations, an electrocardiogram, and a physical exami- nation (see Table 3-4).
If a patient who is to start lithium maintenance therapy is not already taking lithium, a slower titration than that used for acute mania can be utilized. A physically healthy, average- size adult may be started with 300 mg of lithium carbonate twice daily, or 600 mg at night if a slow release formulation is employed. An elderly, ill, or slightly built individual can begin with as little as 300 mg per day. Because it takes about five days
Predictors of Poor Response to Lithium Prophylaxis
Rapid or continuous cycling Mixed states or dysphoric mania Alcohol or drug abuse Non-compliance with treatment Cycle pattern of depression–mania–euthymia Personality disturbance History of poor interepisode functioning Poor social support system Three or more prior episodes
107 to achieve a steady state (longer in the elderly and those with
MOOD STABILIZERS
renal impairment), a 12 hour trough lithium level should be drawn at approximately that interval. Dose adjustments can
be made at intervals of five or more days, with repeat levels as needed to obtain a therapeutic level. Levels between 0.8 and
1.0 mEq/L afford threefold greater protection against recur- rent episodes than a range of 0.4 to 0.6 mEq/L. Furthermore, patients in the higher range are less likely to experience subsyn- dromal symptoms (hypomania or minor depression) and, if such symptoms do appear, are less likely to go on to a full episode. However, higher blood levels are associated with more side effects and the risk of non-compliance. Sometimes education and reassurance are sufficient to keep patients at higher levels. In addition, remedies are available to treat some of the more aggravating side effects (e.g., beta blockers for tremor). Side effects may diminish with a decrease in lithium level, but both psychiatrist and patient should be aware that this may decrease the level of protection against mood swings.
There have been no systematic studies of the lithium level– clinical response relationship in elderly patients, but because older people are more sensitive to side effects, it may be prudent to attempt to maintain elderly bipolar patients at lower plasma lithium concentrations. It should also be kept in mind that a given dose will frequently produce higher blood levels as a person ages (likely due to gradual reduction in renal func- tion), so dose reduction may be necessary over time.
Monitoring of patients on maintenance lithium treatment focuses on three elements: blood level, renal function, and thyroid function. The following is a reasonable regimen for monitoring over time: