Extension of a Pilot Study: Impact From the Cytochrome P450 2D6 Polymorphism on Outcome and Costs Associated With Severe Mental Illness

Abstract

The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review. Information on total hospitalization days and total costs were gathered for a 1-year period. Forty-five percent of the patients received medications that were primarily dependent on the CYP2D6 enzyme for their elimination. When the analysis was restricted to just those patients in each group receiving medication heavily dependent on the CYP2D6 enzyme, the following were observed: (1) a trend toward greater numbers of ADEs from medications as one moved from the group with ultrarapid CYP2D6 activity (UM) to the group with absent CYP2D6 activity (PM); (2) the cost of treating patients with extremes in CYP2D6 activity (UM and PM) was on average $4,000 to $6,000 per year greater than the cost of treating patients in the efficient metabolizer (EM) and intermediate metabolizer (IM) groups; and (3) total duration of hospital stay was more pronounced for those in CYP2D6 PM group. Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.

Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications

“…Multiple prescription and over-the-counter drug use is particularly common in the U.S., a country in which genotype incidence rates are not intuitively obvious and in which a high rate of serious and fatal adverse drug reactions occurs [70]. Furthermore, a study conducted in a psychiatric setting in the U.S. has shown that CYP2D6 polymorphisms can have a marked effect on the cost of treating a patient; UM and PM patients were found to cost between $4,000 and $6,000 per year more to treat than EM or IM individuals [71]. Thus, genotyping for individuals receiving single or multiple drugs that are metabolized by CYP2D6 may help clinicians to avoid adverse drug-drug interactions and to individualize treatment with medications better.…”

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

“…In a study of 100 consecutive psychiatric inpatients genotyped for CYP2D6 on admission, the number of adverse effects in patients treated with CYP2D6 substrates were highest in PMs and higher in IMs than in EMs or UMs. 46 The costs of treating patients of the UM or PM phenotype were found to be 4000-6000 USD higher per year than those of the IM or EM phenotype and the duration of treatment was longer among PMs. 46 With respect to treatment of schizophrenia with perphenazine, thioridazine or haloperidol, significant oversedation has been found to be linked to the CYP2D6 genotype in three different studies.…”

What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

“…After Affymetrix marketed the first GeneChip for HIV genotyping, it developed one for CYP2D6 and CYP2C19 testing, which appeared to be costeffective in a 1996 pilot study when first-generation psychiatric drugs were used. [16] Roche Diagnostics (Indianapolis, IN, USA) took over the marketing. [14] Some small companies developed other parallel systems of genetic testing and US labs started offering CYP2D6 and CYP2C19 testing.…”