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Psychotic Disorders II April 23, 2014 PSYC 2340: Abnormal Psychology Brett Deacon, Ph.D.

Psychotic Disorders II April 23, 2014 PSYC 2340: Abnormal Psychology Brett Deacon, Ph.D. Announcements. Please complete online course evaluations! Remaining schedule. In the News.

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Psychotic Disorders II April 23, 2014 PSYC 2340: Abnormal Psychology Brett Deacon, Ph.D.

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  1. Psychotic Disorders IIApril 23, 2014PSYC 2340: Abnormal PsychologyBrett Deacon, Ph.D.

  2. Announcements • Please complete online course evaluations! • Remaining schedule

  3. In the News • New study in Pediatrics: “Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay” http://pediatrics.aappublications.org/content/early/2014/04/09/peds.2013-3406 • Featured in blog: http://www.madinamerica.com/2014/04/antidepressants-pregnancy-autism-really-time-worry/

  4. From Last Class • Schizophrenia • Diagnostic criteria and cardinal features • Subtypes

  5. Diagnosing Schizophrenia • Disorganized speech (examples) • Circumstantial • Tangential • Loose associations/derailment/word salad

  6. Subtypes of Schizophrenia • DSM-IV rules for choosing the right subtype • 1. Easy if only one subtype is present • 2. If symptoms of multiple subtypes are present… • Catatonic subtype always assigned when prominent catatonic symptoms are present • Disorganized subtype assigned when disorganized symptoms are present (and no catatonic symptoms) • Paranoid subtype assigned when paranoid symptoms are present (and no catatonic or disorganized symptoms) • Undifferentiated subtype when symptoms don’t meet criteria for any subtype

  7. Guess what? No more Schizophrenia Subtypes in DSM-5 • Rationale for getting rid of subtypes: • “Although these subtypes were recognized as having poor reliability, low stability over time, and negligible prognostic value during the DSM-IV process, it was decided to retain these subtypes “because of the substantial clinical tradition”…Since [the DSM-IV] subtypes have little clinical utility and except for the paranoid and undifferentiated subtypes, the other subtypes are rarely utilized in most mental healthcare systems, this change should have little effect on routine clinical practice.”

  8. Other Psychotic Disorders • Delusional Disorder • Delusions without other positive or negative symptoms • Types of delusions include • Erotomanic • Grandiose • Jealous • Persecutory • Somatic • Rare and less disruptive

  9. Schizophrenia: Facts and Statistics • Worldwide lifetime prevalence = about 1% • Equivalent for men and women • Usually develops in early adulthood • Variable course but generally chronic

  10. Natural History of Schizophrenia

  11. Genetic Causes of Schizophrenia • Family Studies • Inherit a tendency for schizophrenia in general, not a particular subtype • Risk increases with genetic relatedness • No specific genes identified

  12. Familial Risk for Schizophrenia % Risk

  13. Genetics of Schizophrenia • “In a mocking jab at critics such as R. D. Laing and Thomas Szasz, psychiatric investigator Seymour Kety, the lead researcher of the influential yet severely flawed Danish schizophrenia adoption studies, famously wrote in 1974: “If schizophrenia is a myth, it is a myth with a strong genetic component!” Schizophrenia molecular genetic research was relatively new in those days, but now the results of decades of molecular genetic research are in: There appear to be no genes for schizophrenia. We could therefore revise Kety’s position to bring it in line with current scientific results: “If schizophrenia is a genetic disorder, it is a genetic disorder without any genes.” Jay Joseph, Psy.D., http://www.madinamerica.com/2013/02/five-decades-of-gene-finding-failures-in-psychiatry/

  14. Neurotransmitter Influences • The Dopamine Hypothesis • Drugs that increase dopamine (agonists) may cause schizophrenic-like behavior • Drugs that decrease dopamine (antagonists) may reduce schizophrenic-like behavior • Examples – Neuroleptics/Antipsychotics, L-Dopa for Parkinson’s disease

  15. Neurotransmitter Influences • Problems with the dopamine hypothesis • Many schizophrenics do not respond to neuroleptics • Symptoms subside several weeks after reuptake of dopamine is blocked • These drugs help little with negative symptoms • Some helpful drugs are weak dopamine antagonists • Inferring the cause of a disorder from responsiveness to drugs is a bad idea • Dopamine hypothesis is problematic and overly simplistic • Current theories – Emphasize many neurotransmitters

  16. Neurobiological Influences • Structural and functional abnormalities in the brain • Enlarged ventricles and reduced tissue volume • Hypofrontality – less active frontal lobes • A major dopamine pathway

  17. Neurobiological Influences • American Psychiatric Association’s response to MindFreedom hunger strike and associated demands: • “…Research has shown that serious neurobiological disorders such as schizophrenia reveal reproducible abnormalities of brain structure...”

  18. Neurobiological Influences • Psychiatrist Nancy Andreasen’sresearch on antipsychotics and the brain • Her research previously found that progressive brain volume reductions in schizophrenic patients, and that this shrinkage was associated with a worsening of negative symptoms, functional impairment and cognitive decline • Medications didn’t stop this process • “The medications currently used cannot modify an injurious process occurring in the brain, which is the underlying basis of symptoms,” she said.

  19. Neurobiological Influences • Long-term Antipsychotic Treatment and Brain Volumes (Ho et al., 2011) http://archpsyc.ama-assn.org/cgi/content/short/68/2/128 • Study methods: Two hundred eleven patients with schizophreniawho underwent repeated neuroimaging beginning soon after illnessonset, yielding a total of 674 high-resolution magnetic resonancescans. On average, each patient had 3 scans (2 and as many as5) over 7.2 years (up to 14 years). • Results  During longitudinal follow-up, antipsychotic treatmentreflected national prescribing practices in 1991 through 2009.Longer follow-up correlated with smaller brain tissue volumesand larger cerebrospinal fluid volumes. Greater intensity ofantipsychotic treatment was associated with indicators of generalizedand specific brain tissue reduction after controlling for effectsof the other 3 predictors. More antipsychotic treatment wasassociated with smaller gray matter volumes. Progressive decrementin white matter volume was most evident among patients who receivedmore antipsychotic treatment. Illness severity had relativelymodest correlations with tissue volume reduction, and alcohol/illicitdrug misuse had no significant associations when effects ofthe other variables were adjusted. • in a 2008 interview with the New York Times, Andreasen confessed that the “more drugs you have been given, the more brain tissue you lose.”

  20. Neurobiological Influences • ”AndreasenDrops a Bombshell: Antipsychotics Shrink the Brain” • http://www.madinamerica.com/2011/02/%ef%bb%bfandreasen-drops-a-bombshell-antipsychotics-shrink-the-brain/ • “In this study, Andreasen took periodic MRI scans of 211 schizophrenia patients treated from seven years to 14 years. She found that long-term use of the old standard antipsychotics, the new atypical antipsycotics, and clozapine are all “associated with smaller brain tissue volumes.” • “The other reason this is such a bombshell is that antipsychotics are widely prescribed now to children, often to control their “behavior,” and to adults with bipolar diagnoses. They are being used to treat “non-psychotic” conditions. The risk-benefit analysis for those patients will be dramatically changed by the findings of this study.”

  21. Neurobiological Influences • Conclusions about neurobiology and schizophrenia • Schizophrenia – diffuse neurobiological dysregulation • Structural and functional brain abnormalities • Not unique to schizophrenia • Causation not yet established

  22. Psychosocial Influences • Family Interactions • The “schizophrenogenic” mother • Dominant, cold, rejecting, conflict-inducing • High expressed emotion (EE) and relapse • Criticism, hostility, and emotional overinvolvement • Patients with high EE families at 3.7 greater risk of relapse than those in low EE families

  23. Medical Treatment • Historical precursors • Lobotomy • Insulin coma therapy • Electroconvulsive therapy (ECT)

  24. Medications • Antipsychotic Medications (aka Major Tranquilizers, Neuroleptics) • Discovered by accident in the 1950s • Current on-patent drugs known as atypical antipsychotics

  25. Antipsychotic Medications • Antipsychotic medications have become the fifth highest revenue-generating class of medications in the United States, with total 2011 sales of $18.2 billion (IMS Health, 2012) • Given the 1% lifetime prevalence of schizophrenia, how is that possible?

  26. Antipsychotics at UW • Case examples from student health

  27. The Medco Report • Review of prescription drug claims from 2001 to 2010 among over two million insured Americans http://www.medscape.com/viewarticle/753789 • Changes in antipsychotic prescriptions

  28. Use of Antipsychotic Medications

  29. Antipsychotics for Anxiety Disorders • Comer et al. (2011): trends in antipsychotic use among outpatients with anxiety disorders seen by psychiatrists

  30. Antipsychotics for Anxiety Disorders

  31. Antipsychotic Use in the Military • “Concern over antipsychotic drugs given to soldiers” -ABC News; http://www.abc.net.au/news/2013-04-24/concern-over-anti-psychotic-drug-given-to-soldiers/4649704 Professor Friedman recently described the American military as operating a "psychoactive drug canteen". “What I discovered was that the military is using antipsychotic drugs in our soldiers at rates that far exceed comparable rates in the civilian population," he said. "In other words from 2005 to 2011 the rate of use of antipsychotic drugs rose 1,100 per cent.“ "(They were) obviously using enormous amounts of antipsychotic drugs off-label, for purposes that they're really not intended, or for indications that are way outside their usual use and way outside what most psychiatrists and non-psychiatric physicians would ever use these drugs for."

  32. US Prescriptions of Antipsychotics for People Younger than 21: 1993 to 2002 Olfson, Blanco, Liu, Moreno, & Laje (2006)

  33. Antipsychotic Use in Children • From 1993 to 2002, the estimated number of outpatient physician visits among patients younger than 21 years of age that included a prescription antipsychotic changed from approximately 201,000 in 1993 to 1,224,000 in 2002 – an increase of over 600% (Olfson, Blanco, Liu, Moreno, & Laje, 2006)

  34. Antipsychotic Use in Children • Increase in antipsychotic prescriptions to kids aged 2 to 5 (Olfson et al., 2010) http://www.palmbeachpost.com/health/more-toddlers-young-children-given-antipsychotics-161867.html • 1999-2001: 1 in 1,300 kids on an antipsychotic • 2007: 1 in 630 • “Prescribing antipsychotics to children in the upper range of that age span -- ages 4 and 5 -- is justifiable only in rare, intractable situations in which all other treatments, including family and psychological therapy, have been tried and are not working, Olfson said.”

  35. Antipsychotics in the News • From the NY Times (2009): http://www.nytimes.com/2009/12/12/health/12medicaid.html?_r=1 • Children on Medicaid are prescribed antipsychotics at 4 times the rate of those with private insurance (4% vs. 1%) • Most common problems were ADHD, conduct disorder, and “childhood bipolar disorder”

  36. Antipsychotics in the News • From the St. Petersburg (FL) Times: http://www.tampabay.com/news/health/article987612.ece • In 2008, a new regulation was passed requiring doctors to get approval from an expert panel before prescribing an antipsychotic to a child younger than age 6 • Results: antipsychotic prescriptions decreased by almost 75% • Use among infants < 1 year old decreased from 23 to 0

  37. Antipsychotics in the News • Off-label marketing • Illegal but common practice • Example: Eli Lilly recently paid massive settlement to US government for illegal off-label marketing of Zyprexa, the best-selling antipsychotic • FDA approved for schizophrenia and bipolar • Illegally marketed for dementia, Alzheimer’s, agitation, aggression, hostility, depression, sleep problems

  38. Antipsychotics in the News • From the US Justice Dept.http://www.dodig.mil/IGInformation/IGInformationReleases/EliLillyPressRelease.pdf: • “Eli Lilly knew that significant weight gain and obesity were adverse side effects of Zyprexa and that weight gain and obesity were factors in causing hyperglycemia and diabetes.” • “Lilly instructed the sales force to recommend Zyprexa for all adult patients with behavioral symptoms like agitation, aggression, hostility, mood and sleep disturbances, and depression.” • “Eli Lilly's management created marketing materials promoting Zyprexa for off-label uses, trained its sales force to disregard the law, and directed its sales personnel to promote Zyprexa for off-label uses. Anticipating the possibility of resistance from primary care physicians to prescribing Zyprexa, defendant Eli Lilly specifically trained its sales representatives on how to respond to doctors' concerns about off-label uses of Zyprexa, and how to continue to promote Zyprexa for off-label conditions. Eli Lilly retained medical professionals to speak to doctors during peer-to-peer sessions about off-label uses of Zyprexa. When promoting Zyprexa to health care providers, Lilly emphasized that the weight gain side effect of the drug was a therapeutic benefit for patients who had trouble maintaining their weight.”

  39. Antipsychotics in the News • Cost of Lilly’s record settlement: $1.415 billion

  40. Antipsychotics in the News • 2008 Zyprexa sales: $4.696 billion • 2007 Zyprexa sales: $4.761 billion

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