Table 31.25-2 Side Effects of Antipsychotic Agents Item Conventional AntipsychoticsClozapineRisperidoneOlanzapineQuetiapineZiprasidoneAripiprazole 0a 0 +++ +++ + 0 to + + + 0 0 to + +++ +++ 0 0 +++ 0 to + ?

0 to +b (+) 0 +c + + 0 to + 0 to + 0 0 + to + + 0 ++ 0 to + + 0 to + ? + + + +c 0 0 to + + 0 0b 0 +++ 0 to + 0 to + 0a ? 0 +c ? 0c 0 to + 0 to + 0 0 0c 0 ++ 0 to + ? 0a ? 0 +c + 0 +++ 0 to + 0 0 0d 0 0 0 ? 0 ? ? +e + ? 0 0 0 0 0 ? 0 to + 0 ? Central nervous system Extrapyramidal symptoms (EPS)0 to + +a,b Tardive dyskinesia +++ Seizures 0 to + Sedation, somnolence + to + + + Other Neuroleptic malignant syndrome + Orthostatic hypotension + to + + + QTc 0 to + + + Liver transaminase increase 0 to + + Anticholinergic side effects 0 to + + + Agranulocytosis 0 Prolactin increase + + to + + + Decreased ejaculatory volume 0 to + Weight gain 0 to + + Nasal congestion 0 to + Sexual dysfunction + to + +

0, none or not significantly different from placebo; +, mild; + +, moderate; + + +, marked;?, insufficient data. a Not significantly different from placebo-treated group, which may have received conventional antipsychotic before entering the study and could have extrapyramidal side effects carried forward into the initial weeks of the investigation. b Dosage-related extrapyramidal side effects above 6 mg/day. c Transient. d Dosage-related increases within the normal range. e Dose-related, not significantly different from placebo with 15 mg or 20 mg. Adapted from Casey DE: Side effect profiles of new antipsychotic agents. J Clin Psychiatry. 1996;57(Suppl):40.

Table 31.25-3 Comparison of Usual Dosing for the Currently Available Serotonin-Dopamine Antagonists in Schizophrenia Antipsychotic Clozapine (tablets) Typical Starting Dosage 12.5 mg once or twice a day Maintenance Therapy Dose Range Titration 150-300 mg/day in divided doses, or 200 mg as a single dose in the evening 28 mg once a day Maximum Recommended Dosage

Risperidone (tablets 1 mg once a day and oral solution)

Risperidone IM long 25-50 mg every 2 acting wks Olanzapine (tablets 5-10 mg/day and orally disintegrating tablets) Quetiapine (tablets) 25 mg twice a day

Start with oral risperidone for 3 wks 10-20 mg/day

The dosage should be increased to 25-50 mg on the second day. 900 mg/day Further increases may be made in daily increments of 25-50 mg to a target dose of 300-450 mg/day. Subsequent dosage increases should be made no more than once or twice weekly in increments of no more than 100 mg. Increases to 2 mg once a day on the second day and 4 mg once a 16 mg/day day on the third day. In some patients, a slower titration may be appropriate. When dosage adjustments are necessary, further dosage increments of 12 mg/day at intervals of not less than 1 wk are recommended. Starting dose: 25 mg every 2 wks. 50 mg for 2 wks Dosage increments of 5 mg once a day are recommended when 20 mg/day required, at intervals of not less than 1 wk. 800 mg/day

Lowest dose needed to Increase in increments of 25-50 mg 2 or 3 times a day on the maintain remission second and third day, as tolerated, to a target dosage of 500 mg daily by the fourth day (given in 2 or 3 doses/day). Further dosage adjustments, if required, should be of 25-50 mg twice a day and occur at intervals of not fewer than 2 days. Ziprasidone 20 mg twice a day 20-80 mg twice a day Dosage adjustments based on individual clinical status may be (capsules) with food made at intervals of not fewer than 2 days. Ziprasidone For acute agitation: Not applicable For acute agitation: Dosages of 10 mg may be administered (intramuscular) 10-20 mg, as every 2 hrs, and dosages of 20 mg may be administered every 4 required, up to a hours up to a maximum of 40 mg/day. maximum of 40 mg/day. Aripiprazole (tablets) 10-15 mg once a day 10-30 mg/day Dosage increases should not be made before 2 wks. Note: Information taken from U.S. Prescribing Information for individual agents. a Dosage adjustments may be required in special populations.

80 mg twice a day For acute agitation: 40 mg/day, for not more than 3 consecutive days

30 mg/day