CLINICAL HANDBOOK OF SCHIZOPHRENIA

392 VI. SPECIAL POPULATIONS AND PROBLEMSTREATMENT OPTIONSSince the inception of chlorpromazine in the 1950s, antipsychotic medications have been acentral component of schizophrenia treatment. The last several decades have witnessed abroadening array of antipsychotic medications, including the development of secondgeneration(atypical) antipsychotics. Atypical antipsychotics (clozapine, risperidone, olanzapine,quetiapine, ziprasidone, and aripiprazole) are classified as such primarily becausethey have a lower propensity than first-generation (typical) medications to cause movementdisorders, such as parkinsonism (tremor, rigidity, and/or slowed movements) and tardivedyskinesia (TD). This is particularly relevant in older populations because increased age is acardinal risk factor for developing both antipsychotic-induced parkinsonism and TD. Olderadults taking antipsychotics are up to five times more likely than similar younger patients toexperience these movement-related side effects. However, with the possible exception ofclozapine, none of these new medications has proved to be as significant a milestone in treatmentefficacy as the original discovery of antipsychotics in general. Despite its consistentlydemonstrated superior efficacy compared to other antipsychotics, clozapine is particularlydifficult to use in older adults because of its side effect profile (e.g., agranulocytosis,anticholinergic effects, sedation, seizures, and orthostasis).Although it is generally accepted that antipsychotic medication is indicated for olderadults with schizophrenia, debate remains as to how best to choose a specific antipsychoticmedication. Over the last several years, atypical antipsychotics (other than clozapine)have generally been considered first-line therapy for schizophrenia in all age groups (includingolder adults), with no distinction as to any single, preferred atypical agent. Thisstatus as first-line therapy has been due to well-established lower risks of movement disorderswith atypical drugs, as described earlier, as well as less proven but sometimestouted better overall tolerability and efficacy for negative symptoms compared to typicalagents. Regrettably, most pharmacotherapy trials for schizophrenia include a paucity ofolder adults. The largest randomized controlled trial specifically for older adults withschizophrenia, conducted with olanzapine and risperidone, demonstrated comparable efficacybetween the two medications.Yet recent comparisons of typical and atypical agents in general adult populationshave called into question appreciable differences between these medication classes inoverall treatment effectiveness. Additionally, serious risks of atypical antipsychotics inolder adults treated for dementia-related psychosis and agitation have emerged, namely, a1.6–1.7 times increased risk of death in patients with dementia taking these drugs comparedto those receiving a placebo, as well as increased rates of cerebrovascular adverseevents (e.g., stroke or transient ischemic attack). Whether these risks are specific to olderadults with dementia, and whether they also apply to first-generation antipsychotics, remainsto be determined. Certainly these risks should be thoroughly explored in futurestudies of older adults with schizophrenia. Although the lower risk of potentially irreversiblemovement disorders with atypical versus typical agents makes atypical medicationsan appealing choice for older adults (who are at elevated risk for such movement disorders),several atypical agents may be more problematic than older medications in causingmetabolic disturbances, such as weight gain, diabetes mellitus, and hyperlipidemia. Suchmetabolic disorders are already common problems in older adults and are important riskfactors for some of the top causes of morbidity and mortality among older adults (e.g.,heart disease and stroke).Considering all these various factors, there is not one clear and convincing first-lineantipsychotic medication for older adults with schizophrenia. So how, then, does one decideon antipsychotic therapy for the older adult with schizophrenia? There is no simple