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)

Annual meeting theme for 1992: Developmental neurobiology and clinical course

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29029/1/0000061.pd

Abnormal phosphoinositide turnover in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29487/1/0000573.pd

Depression in Children with Autism/Pervasive Developmental Disorders: A Case-Control Family History Study

Limited information is available about the occurrence of depression in children with autism and other pervasive developmental disorders (PDD). Although depression has been described in autistic children, questions about its validity have often been raised. One approach to address this issue is to investigate family histories of those autistic children diagnosed with clinical depression. Based on data available in nonautistic children, autistic children with depression would be expected to show an increased family history of depression. Since studies of this nature have not been attempted in autistic children, we compared the family history of 13 autistic/PDD children with depression (11 male; 2 female; M full-scale IQ 86.2, SD 24.2; M age 10.4 years, SD 2.2) with 10 autistic/PDD children without a history of current or previous depression (9 male; 1 female; M full-scale IQ 67, SD 12.9; M age 10.5 years, SD 1.6). Diagnosis of depression was based on the DSM-III-R criteria and confirmed independently by two psychiatrists. Ten (77%) of the depressed children had a positive family history of depression compared to 3 (30%) of the nondepressed group, t (21) = −2.4; p = .02. These findings lend support to the validity of depression as a distinct condition in some children with autism/PDD and suggest that, as in the normal population, autistic children who suffer from depression are more likely to have a family history of depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44616/1/10803_2004_Article_425080.pd

Negative symptoms of schizophrenia: The need for conceptual clarity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29173/1/0000219.pd

Extended antidepressant maintenance and discontinuation syndromes

Unipolar and bipolar depression are episodic, recurrent illnesses for the majority of patients. Because each episode engenders considerable costs for patients, families, and society, prevention of recurrences has high priority. Numerous studies demonstrate that maintenance antidepressants or mood stabilizing medications are efficacious in preventing recurrences. A review of maintenance studies supports the view that all antidepressants perform significantly better than placebo in preventing recurrences of depression—with the stipulation that full antidepressant doses be employed. Earliest studies, conducted two decades ago, evaluated tricyclics (TCAs), heterocyclics, and lithium, while recent studies have focused on selective serotonin reuptake inhibitors (SSRIs). Compliance is essential. Strategies for enhancing compliance include selection of medications with reported safety and few side effects, education of patients and families, referral to patient advocacy groups, and use of new technological compliance aids. Preliminary data suggest that SSRIs are better tolerated than TCAs; fewer patients discontinue these agents due to side effects. Selection criteria for maintenance treatment have not been well determined, but three or more prior episodes is recognized as a relatively strong indicator. Other clinical or genetic criteria have also been suggested. For various reasons, patients may discontinue medications, and when this happens withdrawal phenomena may occur. Withdrawal effects are well documented for all antidepressants and can be profound with TCAs. After stopping some SSRIs, a few withdrawal symptoms may have similarities with those following discontinuation of TCAs, but unique “CNS-like” effects are frequently described, including brief recurrent episodes of dizziness, lightheadedness, vertigo, electric shock-like sensations, and gait instability. These appear to be half-life dependent, with agents with shorter half-lives having more discontinuation symptoms. If antidepressant medications must be discontinued, a gradual taper is preferable, perhaps extending three to six months or longer to prevent discontinuation effects, enable adaptation at the receptor level and allow earlier recognition and treatment of recurrent depressive symptoms. Depression and Anxiety, Volume 8, Supplement 1:43–53, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35217/1/7_ftp.pd

Perceptions of treatment value, therapeutic orientation, and actual experience of psychiatric residents

Although a fairly extensive literature exists on how psychiatrists develop professionally,1-9 three important areas remain inadequately documented. First, doubts remain about the ideologic orientation of residents toward psychiatry. Second, how psychiatry residents perceive the value of various treatment modalities used in psychiatry is essentially undetermined. Third, the actual experience that residents accumulate in using various treatment modalities requires considerable elaboration. These deficiences of information are striking since a psychiatrist's professional identity is clearly related to what he believes valuable and what experiences he incorporates in his practice.10 The investigators that have evaluated these three topics have concentrated on the attitudes toward treatment approaches mainly of practicing psychiatrists,11-15 although the work by Stone and his colleagues is a major exception.16In this era of concern about the question "what is a psychiatrist?" (as shown by the existence of an American Psychiatric Association Committee to study this subject), renewed attention must be given to the possible danger of premature theoretic closure among psychiatry residents. If ideologic closure occurs early in residency, the acquisition of new knowledge will clearly be impaired.The present study evolved from our observations that residents in several residency programs in the Washington, D.C./Baltimore, Md. vicinity seemed to share the same opinions about the worth of various therapies regardless of level of training and orientation of their programs. Most residents also seemed to be firmly set in their opinions at an early stage. To provide some data for these subjective impressions, we decided to survey a relatively large population of psychiatry residents. Several main questions were formulated: How do residents from different training programs rate the value of various psychiatric treatments when applied to three hypothetic psychiatric conditions? Do residents in different levels of training rate treatment modalities differently? What is the self-reported treatment orientation among the population of psychiatry residents? Does premature ideologic closure appear to be present?Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22608/1/0000158.pd

Chronic fatigue syndrome: The need for an integrative approach

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29088/1/0000123.pd