Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N=1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent (\u27use as directed\u27 or \u27use with caution\u27 test categories) or incongruent (\u27use with increased caution and with more frequent monitoring\u27 test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response ( \u3e /=50% decrease in HAM-D17) and remission (HAM-D17 \u3c /=7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p=0.107); however, improvements in response (26.0% versus 19.9%, p=0.013) and remission (15.3% versus 10.1%, p=0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p=0.002), response (28.5% versus 16.7%, p=0.036), and remission (21.5% versus 8.5%, p=0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939)

Severity of depression and hypothalamic-pituitary-adrenal axis dysregulation: identification of contributing factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65507/1/j.1600-0447.1990.tb05465.x.pd

Plasma measures of B-endorphin-like immunoreactivity in depressives and other psychiatric subjects

We report the utilization of a very sensitive radioimmunoassay for plasma B-END, which has enabled us to examine the suppressibility of B-END-like material, under dexamethasone challenge, on a population of depressed patients. We have found that B-END-like material in plasma is suppressed by dexamethasone in a psychiatric control population, whereas suppression is less likely in endogenously depressed patients. There also appears to be a dissociation between cortisol and B-END measures (tested at 4:00 PM) in the endogenously depressed group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23836/1/0000075.pd

Self-reported diurnal mood changes, early morning awakening and the dexamethasone suppression test in endogenous depression

Several authors have suggested that Dexamethasone Suppression Test (DST) non-suppression is related to circadian alternations of hypothalmic-pituitary-adrenal function. Two clinical manifestations of altered circadian rhythms in depressed patients are early morning awakening and diurnal variation in mood. To observe whether these clinical symptom patterns were associated with an increased frequency of abnormal DSTs, we examined post-DST plasma cortisol concentrations and matched clinical ratings of early morning awakening and diurnal variation in mood in 49 patients with major depressive disorder, endogenous subtype. We found no significant association between these clinical and laboratory variables.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25785/1/0000346.pd

Serial dexamethasone suppression tests in simultaneous panic and depressive disorders

Recent work suggests that the simultaneous occurrence of major depressive disorder (MDD) and panic disorder (PD) may be of relevance for clinical findings, therapeutic outcome, and prognosis. It is of interest to know whether or not this relevance extends to biological findings. We addressed this question through comparison of serial Dexamethasone Suppression Test (DST) results in patients who had either MDD alone or simultaneous MDD and PD. We were unable to describe differences between the groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26790/1/0000346.pd

Plasma postdexamethasone cortisol levels in schizoaffective disorder

The degree of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in depressed patients with schizoaffective disorder was compared to that seen in patients with major depressive disorder with and without delusional features. The frequency of nonsuppression to dexamethasone was similar for all three diagnostic groups. Maximum postdexamethasone plasma cortisol was greater for delusional depressives, but did not differ between patients with major depressive and schizoaffective disorders. Modest correlations were found between postdexamethasone plasma cortisol levels, severity of illness, age, and recent weight loss, for patients with both major depressive disorder and delusional depression. For schizoaffective patients, associations between postdexamethasone plasma cortisol levels and various measures of severity of illness, but not age and recent weight loss, were found. Although HPA axis dysregulation occurs more frequently in all three of the studied diagnostic groups than in normal individuals, factors contributing to this dysregulation may be qualitatively different for schizoaffective patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27102/1/0000094.pd

Electroconvulsive therapy in delusional and non-delusional depressive disorder

Major depressive disorder (MDD) patients (n=66) treated with electroconvulsive therapy were stratified by the presence (n=30) or absence (n=36) of delusional symptoms (by Research Diagnostic Criteria) to compare their response to treatment. At discharge from hospital 83% of the MDD with psychosis group and 58% of the MDD without psychosis group were good responders (P=0.03). The implications of this are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28498/1/0000295.pd

Depression and panic in patients with borderline personality disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25659/1/0000211.pd

Sleep-onset REM period in paranoid schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25638/1/0000188.pd

Dexamethasone suppression test status and severity of depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27129/1/0000122.pd