Mohammed T. Abou-Saleh

MANAGEMENT OF ACUTE MANIA 487adults is 20–80 h. Older patients require much lower doses forclinical efficacy because of delayed metabolism and therefore amuch longer half-life. A clinical response is usually seen in thedose range 2–6 mg in divided doses in such patients.Side EffectsThe most common side effects are ataxia, disinhibition, drowsinessand sedation. A paradoxical effect (excitation, agitation,irritability) has been observed, and is more likely to occur inpatients with underlying neurological illness. Clonazepam canpotentiate other sedating drugs, such as antihistamines andalcohol.Benzodiazepine use is always recommended as short-termtherapy only. Patients maintained on clonazepam may developtolerance and dependence after 6 months of consistent use. Theuse of benzodiazepines in the elderly is of special concern, due tothe potential to cause decrease in cognition, alertness or balance.Clonazepam should always be gradually tapered to avoid withdrawalsymptoms.LorazepamEfficacyLorazepam is a short-acting benzodiazepine that has provedeffective in the treatment of acute mania 72,73,97,99 . Lorazepam isfrequently used as an adjunctive medication for the control ofsymptoms of acute mania until the mood-stabilizer becomeseffective. Like clonazepam, the use of lorazepam has decreased theuse of neuroleptics for agitation during the acute manicepisode 74,75 . This medication is not indicated for maintenancetreatment. The use of lorazepam in the elderly bipolar patient isnot well studied.Dose and MetabolismLorazepam is available in both oral and intramuscular forms, andabsorbed rapidly with either route of administration. It is themost common benzodiazepine used in geriatric populations due toits short half-life (10–20 h), large therapeutic index, no metabolites,gluconoride conjugation and rapid onset of action. The doserange is generally 1–4 mg/day in divided doses for a geriatricpopulation, titrated by individual response side effects.Side EffectsLike all benzodiazepines, increased and persistent sedation mayincrease the risk of falling, especially in the elderly. Paradoxicalbehaviors and disinhibition can occur in a small percentage ofpatients, most commonly those with underlying neurologicalillness. Lorazepam also potentiates other sedating drugs; therefore,close monitoring is required when using lorazepam in theelderly.ANTIPSYCHOTIC MEDICATIONSAcute manic episodes of moderate to severe degree, or manicepisodes associated with symptoms such as hallucinations,delusions, paranoia or severe irritability or agitation, can betreated initially with antipsychotic medications. Most typicalantipsychotic medications effect clinical improvement by blockingdopamine pathways in the brain and provide sedation throughantihistamine effects. Atypical antipsychotic medications arethought to effect clinical change through a combination ofdopamine-blocking effects and serotoninergic activity. Clozapine,risperidone and olanzapine have been reported to be effective inthe treatment of acute mania, both as single agents and inadjunctive treatment 76–81 . These studies, however, have notinvolved elderly patients.High-potency typical antipsychotics tend to cause significantextrapyramidal symptoms, such as rigidity, bradykinesia, tremor,dystonia, akathisia and a Parkinson-like syndrome, but a lowincidence of hypotension, cardiovascular toxicity and sedation.Low-potency typical antipsychotics cause significant sedation,postural hypotension and peripheral anticholinergic effects. Thenewer atypical antipsychotics have less severe side effects, but stillmay cause sedation, orthostasis or extrapyramidal side effects.Given the high risk of such side effects in geriatric patients, lowpotencyneuroleptics should generally be avoided. The atypicalantipsychotics are increasingly being used, due to their preferredside-effect profile. The use of antipsychotic medications inconjunction with other medications appears to have limitedadverse interactions; however, a few studies have reported thedevelopment of neurotoxicity from the combined use of typicalantipsychotic medications and lithium 82–84 .Geriatric patients typically require lower doses than middleagedpatients. Lower doses also minimize important side effects,particularly the risk of tardive dyskinesia in the long-term use ofneuroleptics. Once acute symptoms improve, the antipsychoticdosage can be lowered or even discontinued while stabilizingpatients on antimanic medications.ELECTROCONVULSIVE THERAPY (ECT)Electroconvulsive therapy (ECT) has been shown to be a highlyeffective treatment for acute mania 85–87 . Several studies of bothgeriatric and general adult manic patients have shown animprovement in approximately 80% with ECT 88,89 . This isespecially significant, since ECT is frequently used for patientswho have been resistant to other treatments or who havesignificant medical co-morbidities.ContraindicationsEven though there are no absolute contraindications for ECT, therisk of morbidity and mortality is increased in certain conditions.These include space-occupying intracerebral lesions or otherconditions that may increase intracranial pressure, unstablevascular aneurysms or malformations, intracerebral hemorrhage,recent acute myocardial infarction or severe uncontrolledhypertension 90 . However, if ECT is required, risks can usuallybe minimized by pharmacologic treatment during ECT.Risks and Adverse EffectsUsually, elderly patients tolerate ECT very well. The mortalityrate for elderly patients is 0.01%, roughly the same as for theanesthesia induction itself 88,91,92 . Two-thirds of the deaths arefrom cardiac complications, such as ischemia, arrhythmias andtransient severe increases in blood pressure. Most incidents occurimmediately after the treatment or in the recovery period.Side effects commonly observed during ECT include confusionand short-term memory loss. The latter is generally temporary,but occasionally some patients complain of prolonged loss,although no organic or irreversible changes in the brain have