Mohammed T. Abou-Saleh

456 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYstringency, done mostly on younger patients, lithium was shownto substantially reduce the long-term morbidity of both unipolarand bipolar disorder 14,29 . Prospective controlled studies showedthat lithium was superior to placebo and tricyclics in theprophylaxis of bipolar illness. The majority of studies evaluatingits prophylactic efficacy in unipolar illness found it superior toplacebo, as effective as imipramine or amitriptyline, and moreeffective than mianserin and maprotiline. This may be related tothe greater heterogeneity of unipolar illness.Treatment of Bipolar DisorderElderly patients with late presentation or late-onset maniarespond well to standard antimanic treatment with neuroleptics,lithium and anticonvulsants 30,31 . Neuroleptic treatment is bestavoided in the elderly because of its known extrapyramidal sideeffects, except for floridly psychotic, agitated and behaviourallydisturbed patients, who need rapid control of symptoms. Lithiumremains the treatment of choice, followed by valproic acid 30 . Theevidence for the efficacy of lithium in late-life mania is based onretrospective and uncontrolled studies, and there have been nocontrolled studies of the efficacy of anticonvulsants in late-lifemania. It has been suggested that valproate is a safer alternativetreatment to lithium than carbamazepine, whether used as singleor adjunct treatment in elderly manic patients 30,31 . There are noguidelines regarding the optimal plasma concentration ofvalproate in relation to efficacy 30 .A recent evidence-based review of the treatment of mania,mixed state and rapid-cycling illness in younger populations 32concluded that lithium and divalproex sodium are effective inmania, whereas divalproex sodium and carbamazepine are moreeffective in mixed states. Divalproex sodium is the drug of choicefor rapid-cycling disorder. With bipolar depression, lithium isrecommended as a first-line treatment and the addition of asecond mood stabilizer or a TCA would be an appropriate nextstep 33 .The guidelines for the continuation and prophylactic treatmentof bipolar illness in late life are similar to those advocated foryounger patients, except for the notion of high recurrence ratesnecessitating prophylactic treatment even after a first onset manicepisode. Three sets of guidelines for the treatment of patients withbipolar disorder were reviewed 35 : the American PsychiatricAssociation Practice Guideline 15 , the Expert Consensus GuidelineSeries (1996) and the Clinical Practice Guidelines for BipolarDisorder from the Department of Veterans Affairs 36 . Lithiumremains the medication of choice for prophylaxis. A comparativeaudit of the prevalence of lithium therapy and the quality ofmonitoring in over-65s in Cambridge and Southampton showed awide variation and indicated that a dedicated monitoring serviceleads to a better quality of treatment supervision 37 .Who Responds to Prophylactic Lithium?Response to lithium varies between complete, with no furtherepisodes of illness, to partial, with the frequency and severity ofepisodes reduced, to failure to respond, when morbidity continuesunabated. Overall, 50–70% of patients with bipolar and severeunipolar illness show favourable responses to lithium, with a smallminority who are total non-responders. The latter are oftenpatients with rapid-cycling bipolar illness (those who suffer fourepisodes of illness per annum or more). The main reasons forfailure of prophylaxis are poor compliance and side effects such asweight gain, increased thirst, difficulties with memory, poorconcentration and loss of enthusiasm.A recent study examined the clinical and psychologicalcharacteristics of elderly patients receiving prophylactic lithiumin relation to long-term outcome of treatment (Abou-Saleh,unpublished). Elderly patients with bipolar illness had betteroutcome than those with unipolar illness. In their personalitycharacteristics, those who had an excellent response showedhigher scores on extraversion and energy output than those whoresponded less well. The most powerful predictor of long-termresponse, however, was their response during the first 6 months oftherapy, confirming the results obtained in younger patients 34 .Treatment ComplianceCompliance with treatment is a major problem in the elderly. Astudy by Johnson 38 showed that the dropout rate from a group ofdepressed patients treated in general practice increased from 16% atthe end of the first week to 68% at the end of 1 month. This wasrelated to doubts about the benefits and less related to the occurrenceof side effects. Of particular importance are the cognitive and sensoryimpairments of the elderly, low motivation, and poor communicationby doctors of the benefits and risks to patients and theirrelatives. In the background lurks a nihilistic attitude and doubtsabout the effectiveness of treatment in both patients and doctors.Prophylactic Lithium in the ElderlyHimmelhoch 39 , in an open study of the efficacy of lithium inelderly patients, reported a favourable response rate in two-thirdsof these patients. The majority of poor responders, however, hadneurological conditions, which probably impaired the efficacy oflithium. The present author reported the results of a series of openand controlled studies of the efficacy of lithium in conventionaland lower doses in the prophylactic management of affectivedisorders in old age 40 . In the Lithium Clinic at the MedicalResearch Council Neuropsychiatry Laboratory in Epsom, UK, 44male and 104 female patients with affective disorders werefollowed up for a period of 1–14.5 years (mean 4.9 years). Theyall received a slow-release lithium preparation at bedtime. Plasmalithium concentrations were maintained at 0.8–1.2 mmol/l 12 hafter dosing. Prophylactic lithium was started in 47 of thesepatients after 60 years of age. There was no significant differencein the Affective Morbidity Index (a composite index of severityand duration of affective episodes) between the younger and theseelderly patients, as shown in Table 80.1. Side effects in the oldergroup were similar to these in younger patients. In a furtherstudy 34 , 22 elderly patients over 60 years of age who startedlithium in late life received 25–50% reduction in lithium dosage ina double-blind situation. The elderly group of patients fared aswell on lower doses of lithium as younger patients and had asignificant reduction in subjective side effects, such as tremor andthirst (Table 80.2). However, results for the whole group, with amajority of younger patients, showed that a reduction of 50% indaily dosage was safe: patients who had the reduced dose oflithium and plasma lithium levels of 0.45–0.59 mmol/l showedreduced morbidity during the year of follow-up, compared withthe year preceding the trial, and showed fewer subjective sideeffects and adverse effects on thyroid and renal function.Side EffectsSubjective Side EffectsThe occurrence of subjective side effects during lithium therapy iswell documented 41 . Side effects in the early stage (within 6 weeks