Bonnie L. Szarek

A Comparison of Adequately vs. Inadequately Treated Depressed Patients

The authors reviewed the records of 201 nonbipolar depressed inpatients to a) determine the level of somatic therapies prescribed and b) compare the characteristics and global outcomes of patients given “adequate” vs. “inadequate” treatment. A stepwise multiple regression analysis revealed that patients given higher levels of somatic therapy were significantly (p<.001) more likely to be older and have depression with psychotic features and less likely to have compulsive personality disorders. These patients also had significantly longer hospitalizations. A separate stepwise regression analysis showed that patients given higher levels of somatic therapy had superior outcomes (p<.001). The proportion of this sample given no antidepressant medication or electroconvulsive therapy (18.4%) and the proportion given “adequate” treatment (45.3% to 63.7%, depending on the criteria applied) were comparable to the findings of other published reports.

Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder.

AIM This study aimed to determine the effect of the CYP2D6 genotype on the length of hospitalization stay for patients treated for major depressive disorder. METHODS A total of 149 inpatients with a diagnosis of major depressive disorder at the Institute of Living, Hartford Hospital (CT, USA), were genotyped to detect altered alleles in the CYP2D6 gene. Prospectively defined drug metabolism indices (metabolic reserve, metabolic alteration and allele alteration) were determined quantitatively and assessed for their relationship to length of hospitalization stay. RESULTS Hospital stay was significantly longer in deficient CYP2D6 metabolizers (metabolic reserve <2) compared with functional or suprafunctional metabolizers (metabolic reserve ≥2; 7.8 vs 5.7 days, respectively; p = 0.002). CONCLUSION CYP2D6 enzymatic functional status significantly affected length of hospital stay, perhaps due to reduced efficacy or increased side effects of the medications metabolized by the CYP2D6 isoenzyme. Functional scoring of CYP2D6 alleles may have a substantial impact on the quality of care, patient satisfaction and the economics of psychiatric treatment.

Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes.

AIMS We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores. METHODS A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices. The data were used to create distributions and rankings of innate drug metabolism capacity to which individuals can be compared. Drug-specific indices are a combination of the drug metabolism indices with substrate-specific coefficients. RESULTS The combinatory drug metabolism indices proved useful in positioning individuals relative to a population with regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific indices generate pharmacogenetic guidance of immediate clinical relevance, and can be further modified to incorporate covariates in particular clinical cases. CONCLUSIONS We believe that this combinatory approach represents an improvement over the current gene-by-gene reporting by providing greater scope while still allowing for the resolution of a single-gene index when needed. This method will result in novel clinical and research applications, facilitating the translation from pharmacogenomics to personalized medicine, particularly in psychiatry where many drugs are metabolized or activated by multiple CYP450 isoenzymes.

Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients

AIMS To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis. METHODS CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices. RESULTS We found that a greater metabolic reserve index score is related to lower LDLc and higher HDLc, and that a greater metabolic alteration index score corresponds with higher LDLc and lower HLDc values. We also discovered that the sertraline drug-specific indices correlated with cholesterol and triglyceride values. CONCLUSIONS Overall, we demonstrated how a multigene approach to CYP450 genotype analysis yields more accurate and significant results than single-gene analyses. Ranking the individual with respect to the population represents a potential tool for assessing risk of dyslipidemia in major depressive disorder patients who are being treated with psychotropics. In addition, the drug-specific indices appear useful for modeling a variable of potential relevance to an individuals risk of drug-related dyslipidemia.

Increased carrier prevalence of deficient CYP2C9, CYP2C19 and CYP2D6 alleles in depressed patients referred to a tertiary psychiatric hospital

OBJECTIVE This study compared the types and carrier prevalences of clinically significant DNA polymorphisms in the cytochrome P450 (CYP450) genes CYP2C9, CYP2C19 and CYP2D6 in major depressive disorder patients with a control group of nonpsychiatrically ill, medical outpatients. METHOD We conducted a case-control study using 73 psychiatric outpatients diagnosed with depression and referred to a tertiary center, The Institute of Living (Hartford, CT, USA), for treatment resistance or intolerable side-effects to psychotropic drugs. The controls were 120 cardiovascular patients from Hartford Hospital being treated for dyslipidemia but otherwise healthy and not psychiatrically ill. DNA typing to detect polymorphisms in the genes CYP2C9, CYP2C19 and CYP2D6 was accomplished with the Tag-It™ mutation detection assay and the Luminex xMAP® system. RESULTS The percentage of individuals in psychiatric versus control groups with two wild-type alleles for CYP2C9, CYP2C19 and CYP2D6 genes, were 50 versus 74% (p < 0.001), 71 versus 73% (not statistically significant) and 36 versus 43% (trend, p < 0.2), respectively. Within the psychiatric population, 57% of individuals were carriers of non-wild-type alleles for 2-3 genes, compared with 36% in the control population (p < 0.0001). The balance, 43% in the psychiatric population and 64% in the control, were carriers of non-wild-type alleles for none or one gene. CONCLUSIONS These findings reveal that clinically relevant CYP2C9 polymorphisms occur more frequently in depressed psychiatric patients than in nonpsychiatric controls. The same trend was found for polymorphisms in the CYP2D6 gene. We found a significant cumulative metabolic deficiency in the psychiatric population for combinations of the CYP2C9, CYP2C19 and CYP2D6 genes. The significant enrichment of CYP2C9-deficient alleles in the psychiatric population validates a previously reported association of this gene with the risk for depression disorders. The high prevalence of carriers with deficient and null alleles suggests that CYP450 DNA typing may play a role in the management of psychiatric patients at tertiary care institutions.

Metabolic Abnormalities in Adult and Geriatric Major Depression With and Without Comorbid Dementia

J Clin Hypertens (Greenwich). 2010;12:456–461. ©2010 Wiley Periodicals, Inc.

Metabolic Syndrome in Psychiatric Inpatients Treated for Depression

That metabolic syndrome (MetS) is associated with schizophrenia is well established but recent findings suggest that the risk of MetS may be similar in patients with major depressive disorder (MDD). The investigators identified all admissions age 18–59 with a clinical diagnosis of MDD (n = 1,776) at an urban, not-for-profit hospital in the US to determine the prevalence of MetS and of each of its five ATP III criteria. Descriptive statistics were used to determine the prevalence of MetS and its component measures and χ2 analyses to compare these results with the most recent National Health and Nutrition Examination Survey Data (NHANES). Stepwise logistic regressions were used to identify associated demographic and clinical features. In the subset of patients for whom all metabolic measures were available (n = 1,028), 23.4% (n = 241) had MetS and 75.6% (n = 777) met at least one criterion for the syndrome. Compared with the NHANES sample, MDD patients were more likely to have elevated glucose (p

Survey of Osteoporosis in an Inpatient Geriatric Psychiatric Setting: A Pilot Study

Osteoporosis is a major public health issue. We examined geriatric psychiatric inpatients’ awareness of having osteopenia and/or osteoporosis. The much lower proportion of our patients reporting a history of osteoporosis suggests that it might be under-diagnosed in this psychiatric population. A high proportion of our sample were treated with psychotropics that may decrease bone mineral density, however, most were not receiving any treatment for osteoporosis and fewer than expected were aware of a history of osteoporosis. Education of patients about this silent disease should be a priority for psychiatric nurses and the treatment team in an inpatient psychiatric setting.