Multidisciplinary Approach to Treatment of Patients with First- Episode Psychosis S. Charles Schulz, MD Professor Emeritus Psychiatrist, PrairieCare
Disclosure Information May 16, 2016 S. Charles Schulz, MD Disclosure of Relevant Financial Relationships I have the following financial relationships to disclose: • Grant/research support from: NIMH, Myriad/RBM, Otsuka • Consultant for: FORUM, Lundbeck, Merck Manual Disclosure of Off-Label and/or Investigative Uses I will be discussing off label use and/or investigational use in my presentation and identify those issues.
Introduction • In the last two decades there has been significant literature about First Episode Schizophrenia and the significance of Duration of Untreated Psychosis (DUP). • Recent work at NIMH has led to greater recognition of the needs of first episode patients and reducing the DUP – a federal government allocation has been made to states. • Recent assessment in this area reported the average length of time to first treatment at 78 weeks.
First Episode Psychosis An Integrated Care Model Identify & Treat Prodrome Day Treatment & Reduce DUP Neurocognitive Remediation Care Coordinator Medical Cognitive Evaluation of Behavioral Director 1 st Episode Treatment (CBT) Medication Family Treatment Psychoeduca- (In- and Out- tion & Support Patient
Sikich L, Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders. J Clin Psychiatry , 2008; 69[suppl 4]:21-25.
Initial Medial Work-up of First Episode Psychosis Freudenreich, et al., Early Intervention in Psychiatry 3:10-8; 2009 • The phrase “First Episode Psychosis” leads to the need for a careful initial evaluation to lead to an accurate assessment in the psychosis domain. • Family input to the initial assessment is crucial for the patient and begins support of families – also don’t forget siblings. • Leading university programs have work up strategies to make sure the illness is not caused by a medical issue – e.g. Wilson’s disease. • Some programs encourage neuropsychological assessment to assist in approving functional outcomes and identifying specific cognitive issues.
Normal Control vs Child High Risk HVLT-R t-score Group Mean Comparison 56 54 52 50 NC CHR 48 46 44 42 Baseline Exit a. Baseline Independent Samples t-test (2-tailed)*: p=0.095, t=-1.75, df=25 b. Exit Independent Samples t-test (2-tailed): p=0.155, t=-1.48, df=20 *Baseline Independent Samples t-test H o ≠ H a p<0.05 (sig.1-tailed), t=-1.75, df=25 Overgard S. et al., ICOSR, March 2015
Long-chain Omega-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-controlled Trial • Introduction : The authors note the usefulness of omega-3 fatty acids for psychiatric illness and lack of side-effects. They aimed to assess the compound in sub-threshold psychosis. • Methods : RCT in 81 subjects at ultra-high risk of psychotic disorder – 81 subjects were enrolled in this 12 month study. • Results : 76/81 subjects completed the trial. In the omega-3 group, 2/41 converted to psychosis while 11/40 converted in the control group. Of note is that symptoms were reduced. • Conclusions : The authors note a reduction of conversion to a psychotic disorder and note omega-3 was safe. Amminger et al., Arch Gen Psychiatry, 2010;67(2): 146-54.
The Neurapro-E Study: A Multicenter RCT of Omega-3 Fatty Acids and Cognitive-Behavioural Case Management for Patients at Ultra High Risk of Schizophrenia and Other Psychotic Disorders • Background : The authors note previous studies have examined strategies to prevent psychosis in prodromal subjects. They conducted a large study of omega-3 polyunsaturated fatty acids. • Methods : The design was a double-blind and placebo-controlled study of 6 months duration. They included case management. • Results : Impressively, the study included 304 subjects and 78% stayed in the trial for 6 months. At the ICOSR meeting, the authors note no difference between omega-3 and placebo, but many were prevented from progressing in the overall intervention. McGorry P et al., The Neurapro- E Study….Abstracts for the 15 th International Congress on Schizophrenia Research (ICOSR), March 2015 Colorado Springs, CO, USA
Discussion Points • Can the Prodrome be accurately identified using symptoms, biomarkers, family history (or genes)? • Are there ways to specify the direction of Prodromal symptoms in order to apply specific treatments? • Is there adequate data to recommend treatment approaches to the Prodrome? • In other branches of medicine, there are concerns of over diagnosis of early stages of illness. How can such concerns be dealt with in the Prodrome?
First Episode Psychosis An Integrated Care Model Identify & Treat Prodrome Day Treatment & Reduce DUP Neurocognitive Remediation Care Coordinator Medical Cognitive Evaluation of Behavioral Director 1 st Episode Treatment (CBT) Medication Family Treatment Psychoeduca- (In- and Out- tion & Support Patient
Cognitive Deficits in Recent-Onset and Chronic Schizophrenia Sponheim S.R., Jung R.E., Seidman L.J., Mesholam-Gately R., Manoach D.S., O’Leary D.S., Ho B.C., Andreasen N.C., Lauriello J., Schulz S.C. Cognitive Deficits in Recent-Onset and Chronic Schizophrenia. Journal of Psychiatric Research 2010;(44)7:421-428
Relationship between Duration of Untreated Psychosis and Outcome in First Episode Schizophrenia: A Critical Review and Meta-analysis Perkins DO et al., Am J Psychiatry 2005;162:1785-1804
First Episode Psychosis An Integrated Care Model Identify & Treat Prodrome Day Treatment & Reduce DUP Neurocognitive Remediation Care Coordinator Medical Cognitive Evaluation of Behavioral Director 1 st Episode Treatment (CBT) Medication Family Treatment Psychoeduca- (In- and Out- tion & Support Patient
An MRI Study of Adolescent Patients with Either Schizophrenia or Bipolar Disorder as Compared to Healthy Control Subjects Friedman L. et al., Biological Psychiatry , 1999
Alterations in Patterns of Gyrification in Children and Adolescents with Schizophrenia White et al., (2003) Biological Psychiatry
Cortical Folding Defects as Markers of Poor Treatment Response in First Episode Psychosis • Importance : Authors noted no reliable predictors to distinguish first episode psychosis patient’s treatment response. They assessed gyrification. • Participants : Total subjects = 126 First Episode = 80 Controls = 46 Patients received 12 weeks of treatment. • Results : o Patients had hypogyria compared to controls. o Nonresponders had hypogyria on both insula areas, left frontal and right temporal regions. o Seen in both affective and non-affective psychosis. • Conclusions : Gyrification may be a useful predictor. Early neurodevelopmental issues may predict unfavorable prognosis. Palaniyappan L et al., JAMA Psychiatry online Aug 14, 2013.
Cortical Folding Defects as Markers of Poor Treatment Response in First Episode Psychosis Clusters Showing Differences in Gyrification Among Responders, Nonresponders, and Controls. No clusters showed significant results in the opposite directions to the contrasts shown in the Figure. All clusters are displayed on a reconstructed average white matter surface (fsaverage in FreeSurfer software) and survived multiple testing using Monte- Carlo simulation with a cluster inclusion criterion of P = .05. The left hemisphere is on the left side of the image, and the right hemisphere is on the right side. The exact values of clusterwise probability for the clusters are presented in Table 2. JAMA Psychiatry. 2013;70(10):1031-1040.
Changes in Resting State Connectivity Following Treatment in First Episode Schizophrenia • Background : Resting state fMRI used to describe disrupted connectivity of brain functional networks. Further there are changes alterations pre and post treatment in schizophrenia. • Methods : Twelve subjects with schizophrenia who had suffered first episode and did not have previous medication treatment had an image on a 3T MRI scanner. The subjects received antipsychotic medication and then a second scan. They received PANSS interviews at the time of both scans. They received second generation antipsychotic treatment. • Results : The data was prepared with the relation of symptom measures and network organization. Treatment was 10 weeks. There was a statistical correlation of positive symptoms and change in diversity of connectivity. • Discussion : This technique can assist in pathophysiology of treatment. It can help in assessing individual treatment. Schulz SC et al., SIRS Poster, 2012.
Association of Changes in Network Organization with Change in Clinical Symptoms in First Episode Schizophrenia Patients Following 10 Weeks of Treatment Changes in Resting State Connectivity Following Treatment in First Episode Schizophrenia S.Charles Schulz, Shauna M Overgaard, Chen DaChun, Xue-Dong Yang, Thomas R Kosten, Xiang Yang Zhang, Kelvin O Lim, SIRS, 2012
Neuropsychologic Test Results of Adolescents
First Episode Psychosis An Integrated Care Model Identify & Treat Prodrome Day Treatment & Reduce DUP Neurocognitive Remediation Care Coordinator Medical Cognitive Evaluation of Behavioral Director 1 st Episode Treatment (CBT) Medication Family Treatment Psychoeduca- (In- and Out- tion & Support Patient
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