Mohammed T. Abou-Saleh

TREATMENT OF LATE-ONSET PSYCHOTIC DISORDERS 523Table 95.3deliriumMedications/substances associated withCorticosteroidsDigoxinPain medicationsOpioidsMuscle relaxantsH2 blockersAnticholinergicsBenzodiazepine withdrawalAlcohol withdrawalAlcohol intoxicationthat the atypical antipsychotics clozapine and olanzapine alsohave anticholinergic side effects.An additional side effect of concern with the use ofantipsychotics is photosensitivity in those patients who are onchlorpromazine. Patients may experience irreversible degenerativepigmentation retinopathy, caused by doses of thioridazine greaterthan 800 mg/day. Weight gain is of especial concern in thosepatients with an obesity problem or who are known to gain weighteasily on medications. Weight gain can be seen with the use ofboth conventional and atypical antipsychotics.often mistaken for worsening of the psychotic symptoms, leadingone to erroneously increase the neuroleptic dose, when actuallylowering the dose may address this troublesome side effect. Inaddition, akathisia can be treated with benzodiazepines and/orb-blockers.Tardive dyskinesia (TD) is a potentially irreversible abnormalinvoluntary choreiform movement disorder. In the elderly, the 3year cumulative incidence of severe TDs was found to be 2.5%after 1 year, 12.1% after 2 years and 22.9% after 3 years 20 .Another study reported the cumulative rates for TD to be 25%after 1 year, 35% after 2 years and 53% after 3 years 21 . Factorsthat were predictive of TD included higher daily dose at studyentry, greater cumulative amounts of prescribed neuroleptics,greater severity of worsening negative symptoms, and the presenceof early EPS 21,22 . Caution should be used when administeringconventional neuroleptics in the elderly and they should only beprescribed when necessary and at the minimal effective dose 20 .Neuroleptic malignant syndrome (NMS) is a serious side effectwith the potential to be lethal. NMS presents with symptoms ofmuscle rigidity, fever, autonomic instability, fluctuating levels ofconsciousness and elevations in CPK and white blood cell counts.NMS can be seen with the use of all neuroleptics, including theatypical 23 .The potential cardiovascular effects of these drugs includeorthostatic hypotension and QRS prolongation, leading to anincreased risk for torsade de pointe. Orthostasis is of especialconcern in the elderly who, due to physiological changes, arealready at increased risk. In addition, in those patients who arealready suffering from orthostasis or who are being prescribedmedications known to have pressure-lowering effects, low-potencyneuroleptics should be avoided. Orthostatic hypotension placesthe elderly at increased risk of falls, leading to increased morbidityand mortality.The anticholinergic effects of these drugs can have bothtroubling and undesired peripheral and central effects. Peripheralside effects include dry mouth and eyes, blurred vision, constipation,and urinary retention, which is of especial concern in maleswho have prostatic hypertrophy. Central effects include worseningof cognition, confusion and/or delirium 3,24 . One should be awareTable 95.4Recommended doses in the elderlyDrug Initial dose Maximum doseClozapine 6.25 mg/day 50–100 ng/dayRisperidone 0.25–0.50 mg/day 2 mg/dayOlanzapine 2.5 mg/day 5–10 mg/dayQuetiapine 25 mg/day 100–150 mg/dayZiprasidone 20 mg/day 80–160 mg/dayAtypical AntipsychoticsAtypical antipsychotics are so defined because they are effective attreating both the positive and the negative symptoms ofschizophrenia, while having a lower incidence of extrapyramidalsymptoms and tardive dyskinesia. FDA-approved atypical antipsychoticsare clozapine, risperidone, olanzapine, quetiapine andziprasidone.ClozapineClozapine was the first atypical antipsychotic approved for use inthe USA. Compared to typical neuroleptics, it has a higher affinityfor the dopamine D2 receptor, being more selective for themesolimbic and mesocortical pathways. Clozapine continues tohave a favorable neurological side-effect profile but is reported tohave the following untoward effects: drowsiness, sedation,hypersalivation, tachycardia, dizziness, constipation, nausea andvomiting, the most concerning being agranulocytosis and seizures.It is recommended that clozapine treatment should be initiatedonly after a patient has failed two trials with conventionalantipsychotics. In a double placebo-controlled study of sixpatients, clozapine was found to have similar efficacy as inyounger patients. Although it was felt to be fairly safe in theelderly, the most frequent side effects were sedation, confusionand agranulocytosis 25 .Concern exists that the elderly may be at greater risk foragranulocytosis. In an Australian elderly study, the occurrence ofagranulocytosis was found to be 4% compared to 0.25% inyounger patients 25 . Increased sedation, hypersalivation, bradycardia,postural hypotension and delirium are frequent side effectsreported in the elderly with the use of clozapine 26–28 . Anotherpotential side effect is weight gain. One author found that 75% ofthe patients prescribed clozapine had gained an average of7.5 kg 29 . The potential for agranulocytosis requires constantmonitoring of blood, which may be difficult and costly in theelderly. Clozapine was tolerated as well as chlorpromazine in onestudy. In one open label report in 300 older adults, thediscontinuation rate for clozapine was 43% and agranulocytosisoccurred in two non-fatal cases 30 .Clozapine should be considered once a patient has failed twotrials of conventional neuroleptics. When prescribing clozapine, itis prudent to initiate treatment with a dose of 6.25 mg/day,followed by weekly titration of 6.25 mg/day until a therapeuticeffect is achieved and/or side effects develop 13,31 . Daily doses mayrange from 6.25 to 400 mg 31 . Clozapine should be initiated slowlyand titrated slowly. Chengappa 26 has reported that the rapidtitration of this drug can lead to drug intolerance and poorresponse.