Olanzapine and risperidone

Palmer et al (1998) Health-care model based on Tran et al (1997) (USA) Olanzapine and risperidone... 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Examples of recent work carried out by the DSRU includes the examination of mortality rates and cardiac arrhythmias between sertindole and two other at)q)ical antipsychotics, olanzapine and risperidone. Tolterodine, an agent often used for urinary frequency and bladder instability, is the latest drug to be examined by the DSRU.135... 

Koro CE, Fedder DO, L ltaUen GJ, et al. Assessment of independent effect olanzapine and risperidone on risk of diabetes among patients with schizophrenia population based nested case-control study. BMJ 2003 326 283. 

Koro CE, Fedder IX), L ltalien GJ, et al. An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry 2002 59 1021-6. 

A variety of relatively uncommon dermatological side effects have been noted to be associated with antipsychotic agents. These include maculopapular rashes, urticaria, and erythema multiforme (Arana, 2000). Photosensitivity and skin pigmentation can also occur during treatment with these drugs. Although skin pigmentation has been most frequently reported with chlorpromazine, this can occur with thioridazine and trifluoperazine (Harth and Rapoport, 1996). In addition, treatment-induced alopecia has been reported for haloperidol, olanzapine, and risperidone (Mercke et ah, 2000). 

Of the atypical antipsychotics, clozapine, olanzapine, and risperidone have been studied the most. Clozapine was used to treat 10 treatment refractory acutely manic patients and 15 schizomanic patients. Using reduction in the YMRS score as the outcome measure, 72% improved (non-rapid cycling, bipolar patients). Comparison of olanzapine (5-20 mg) with placebo showed significant reduction of the YMRS in 49% vs. 24% of subjects by 3 weeks, with significant change evident by the first week. In a trial comparing risperidone at 6 mg with haloperidol at 10 mg and low-dose lithium (800-1200 mg/day) efficacy was similar over the 28 days of the trial. 

The receptor properties of quetiapine are similar to those for olanzapine and risperidone. This medication is rapidly absorbed, reaching peak plasma concentrations in 1.5 hours. It is metabolized by the liver. 

In a comparison of olanzapine and risperidone, 319 patients out of 19 153 who were given a prescription for olanzapine between lJanuary 1997 and 31 December 1999 developed diabetes, compared with 217 who were given a prescription for risperidone (n = 14 793) (779). Proportional hazards analysis showed a 20% increased risk of diabetes with olanzapine relative to risperidone (RR = 1.20 Cl = 1.00, 1.43). 

Ganguli R, Brar JS, Ayrton Z. Weight gain over 4 months in schizophrenia patients a comparison of olanzapine and risperidone. Schizophr Res 2001 49(3) 261-7. 

Roerig JL, Mitchell JE, de Zwaan M, Crosby RD, Gosnell BA, Steffen KJ, Wonderlich SA. A comparison of the effects of olanzapine and risperidone versus placebo on eating behaviors. J Clin Psychopharmacol 2005 25 413-8. 

In other studies, outcome variables have been discontinuation, relapse, and compliance (58) or quality of life (38). A re-analysis of data from two large double-blind comparisons of olanzapine with haloperidol (n = 1996) and of olanzapine with risperidone (n = 336) showed that in patients who had an initial response, there was no significant difference between olanzapine and haloperidol when outcome was measured using either 52-week relapse rates or the time to first non-compliance after 12 months, the estimated mean times to discontinuation were 271 days and 241 days respectively (58). There were no differences between olanzapine and risperidone. However, while the dose of olanzapine was well within the recommended range, the dose of haloperidol was too high (modal doses, 13 and 12 mg/day respectively). 

Biederman J, Mick E, Hammerness P, Harpold T, Aleardi M, Dougherty M, Wozniak J. Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children. Biol Psychiatry 2005 58 589-94. 

Note. None of these medications have FDA indication for the treatment of Alzheimer s disease. The literature and practice guidelines support the use of these medications for specific target symptoms. The FDA has issued a black box warning regarding the use of certain antipsychotic medications in the elderly, especially haloperidol, olanzapine, and risperidone. The warning notes that the use of these drugs is associated with an increase in death rates when used by the elderly patients with dementia. 

Olanzapine and risperidone versus haloperidol A prospective 6-month open study, promoted by Lilly, the market authorization holder of olanzapine, has been conducted, in which olanzapine n — 2128), risperidone (n = 417), and haloperidol (n = 112) were compared... 

The results of a similar study of ours, in which the study drugs were three atypical neuroleptics or antipsychotics, are given in Table 5-4. During the time of this study, clozapine, olanzapine, and risperidone were the only atypical neuroleptic or antipsychotic agents in general use at HCPC these three drugs were selectively used in accordance with the clinical criteria set by the Harris County Mental Health and Mental Retardation Authority. These criteria included documentation of at least two failures to respond clinically to treatment with different typical neuroleptic agents. 

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