Mohammed T. Abou-Saleh

LONG-TERM MANAGEMENT 457Table 80.1 General details of patients and relationship between age andmorbidity during lithium therapy (results expressed as mean+SEM)Age whenlithiumstarted(years)nof starting lithium) include nausea, loose stools, fatigue, muscleweakness, polydipsia, polyuria and hand tremor.During maintenance, weight gain, mild memory impairmentand hand tremor are common complaints and polydipsia andpolyuria may persist. The rate of occurrence of these side effectsand their severity is related to plasma lithium concentrations. Theelderly are particularly vulnerable to side effects. Smith andHelms 42 examined the incidence and severity of side effects inelderly patients receiving lithium in comparison with youngerpatients. Whilst there was no difference in the total incidence ofside effects, there was a trend for more serious side effects to occurmore frequently in the elderly: 33% of the elderly experienced‘‘confusion’’ vs. 12% of the younger group. Worthy of note is thatthe patients were maintained on relatively high plasma concentrationsfor this age group, 0.86–1.26 mmol/l. Patients withneurological conditions (parkinsonism and facial dyskinesia)develop neurotoxicity at relatively low plasma levels of less than0.65 mmol/l 39 . In a recent investigation, Coppen and Abou-Saleh 26reported that prevalence rates of subjective side effects in elderlypatients receiving low-dose lithium (plasma lithium levels of 0.52–0.6 mmol/l) were similar to those of younger patients maintainedon similar plasma levels.Thyroid EffectsEpisodes priorto lithiumYears onlithiumAMI b460 47 4.9+0.6 3.8 a +0.4 0.18+0.0340–60 79 4.2+0.3 5.5 +0.4 0.17+0.02540 22 4.4+0.6 5.3 +0.7 0.14+0.03a Significantly lower than (40–60 years) group p50.01 and (less than 40 years) groupp50.05.b Affective Morbidity Index.Table 80.2 Morbidity and plasma lithium level in 22 elderly patientsbefore and during trial period (results expressed as mean+SEM)AMIPlasma lithiumlevel (mmol/l) n Before trial During trial40.8 8 0.16+0.08 0.17+0.060.60–0.79 6 0.40+0.17 0.36+0.120.45–0.59 8 0.22+0.15 0.36+0.20Elderly patients on prophylactic lithium are more likely todevelop hypothyroidism than younger ones and women aremore susceptible than men. This may be related to the increaseddisposition of women to develop autoimmune thyroid disease inmiddle and old age. Indeed, pre-existing thyroid disease is themajor vulnerability factor for the development of hypothyroidismduring lithium therapy. Coppen and Abou-Saleh 26 studied thyroidfunction in 125 patients receiving low-dose plasma levels oflithium. Women had significantly higher levels of thyroidstimulating hormone (TSH) than men, and all four patientswith abnormally high TSH levels were unipolar women. Of the 11patients who received replacement thyroxine, 10 were unipolarpatients. Thyroid function has been related to increased affectivemorbidity during receipt of prophylactic lithium and has beenimplicated in the development of rapid-cycling bipolar disorder.Renal EffectsOverall, 5–10% of patients on prophylactic lithium developtubular kidney damage complicated with glomerular pathology.There is no evidence that these changes are conducive to renalinsufficiency, which rarely occurs in patients who have sufferedlithium intoxication or had pre-existing renal disease. Lithiumdose requirements show a decrease with age, which could beaccounted for by the age-dependent fall in glomerular filtrationrate and lithium clearance. With age, there is a decrease in musclemass, which limits the value of measuring serum creatinine levelsas an indicator of renal function. Age-related decrease in thevolume of distribution of lithium also contributes to higherplasma levels in the elderly. The daily dosage of lithium requiredto achieve a given plasma level may be half the dose required for ayounger patient. A number of studies have evaluated renalfunction in relation to the dosage regimen, comparing a once perday dosage regimen to a twice-daily regimen. Contrary to theconventional wisdom, of avoiding higher peak plasma levelsassociated with a single daily dosage regimen, this regimen wasfound to be safer for renal function than a divided daily dosageregimen: functional and structural abnormalities were morepronounced in the group of patients who received lithium individed doses than those who received it in the single daily dosageregimen, suggesting that it may be more important to have regularperiods with lower levels than it is to have lower peaks.Optimum Plasma LevelsIn an open trial of lithium in elderly patients with mania (age65–77 years), two-thirds of patients responded at levels of 0.52–0.8 mmol/l (mean 0.58 mmol/l). Two weeks after obtaining thatrange, two patients developed neurotoxicity and two patients onlyresponded when the levels were raised to 0.9 mmol/l 44 . Severalretrospective and prospective controlled trials have evaluated theefficacy and safety of variable lithium dosage levels in bipolar andunipolar disorder 45 . Some of these studies have included elderlypatients. Overall, the minimal effective lithium level of themajority of patients is 0.4–0.8 mmol/l. Bipolar patients mayrequire higher dosages/levels than unipolar patients 46 . It is evidentthat lower dosages/levels are associated with less severe subjectiveside effects and adverse effects on thyroid and renal function. Aprospective open study examined the ongoing morbidity of 128patients with unipolar, bipolar and schizoaffective disordersmaintained at low doses of lithium (mean level 0.56 mmol/l)over a period of 1 year 26 . Affective morbidity was measured forthree age brackets: 560 years; 66–70; and 470 years. Elderlypatients aged 70+ had remarkably less morbidity than the twoyounger groups, but similar side effects (Table 80.3).Shulman et al. 48 followed up 43 elderly patients (mean age 74years) maintained on 12-hourly lithium levels of 0.5 mmol/l for anaverage period of 2 years. The majority of patients responded wellto lithium, which was well tolerated, and compliance wasexcellent. The most common side effects were hand tremor inone-third of the patients and polyuria or polydipsia in onequarter.Lithium InteractionsSpecial consideration should be given to lithium interactions withdrugs commonly prescribed for the elderly. Lithium may interact