Seeing the Truth About Childhood Schizophrenia

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1 Page 1 Seeing the Truth About Childhood Schizophrenia Elizabeth Montagnese, M.D. Adult, Child and Adolescent Psychiatrist Quittie Glen Center for Mental Health in Annville, Pennsylvania This program has been supported by an educational grant from Bristol-Myers Squibb Seeing the Truth About Childhood Schizophrenia Speaker: Dr. Montagnese is board certified in adult, child, and adolescent psychiatry by the American Board of Psychiatry and Neurology. Dr. Montagnese provides comprehensive psychiatric evaluation and treatment for individuals, couples and families. Her primary area of focus is working with children and adolescents but she also treats adults.dr. Montagnese received her medical degree at Wayne State University in Detroit, Michigan. She completed her general psychiatry and child psychiatry training at the Penn State University Milton S. Hershey Medical Center.Dr. Montagnese is the medical director at Family and Children Services of Central Pennsylvania. This is a United Way funded nonprofit agency that serves the greater Harrisburg, York and Lancaster areas. To contact her at this agency please call Speaker Disclosure: Dr. Montagnese has no actual or potential conflicts of interest in relation to this program This program has been supported by an educational grant from Bristol-Myers Squibb PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Seeing the Truth About Childhood Schizophrenia Accreditation: Pharmacists L01-P Pharmacy Technicians L01-T Target Audience: Pharmacists & Technicians CE Credits: 1.0 Credit hour or 0.1 CEU for pharmacists/technicians Expiration Date: 10/20/2011 Program Overview: This program is designed to assist pharmacists review the facets of childhood schizophrenia, as well as the benefits of managing this disorder with medications. Their knowledge of available treatment options for children with schizophrenia will be enhanced. The program includes information on pharmacologic treatments, drug interactions, patient counseling, and a question/ answer period. Objectives: To state the theories associated with the causes of childhood schizophrenia, as well as detrimental affects that this disorder may have on its victim s lives, incorporating information on the prevalence of this predicament. To list therapeutic agents used in the treatment of childhood schizophrenia, and be able to state an agent s dosage schedule, mechanism of action, and side effects. Review the pharmacist s role in counseling patients on drug treatment strategies and medication adherence to improve quality of life and long-term maintenance of childhood schizophrenia patients. Jani s at the mercy of her mind. LA Times story, June 29, 2009 Jani Schofield, 6 year old Severe symptoms since toddlerhood There is something wrong with her brain.

2 Page 2 Epidemiology of Childhood-Onset Schizophrenia (COS) RARE!!!!! 1 in 40,0000 Adult-onset schizophrenia (AOS): 1% general population M:F ratio: :1 Very rarely diagnosed before age 5 Usually diagnosed between 7-12 years old Schizophrenia Statistics Emil Kraeplin documented cases of COS in 1919 Typical age of onset: males: 18 years of age females: 25 years of age Top 10 causes of disability worldwide Cost of Schizophrenia: 1990-accounted for 2.5% of health care expenditures+ nondirect costs($45 billion) $62.7 billion for direct and nondirect costs Unemployment rate is 70-80% 10% of those permanently disabled What is Childhood Schizophrenia? Neurodevelopmental disorder Fundamental continuity between AOS and COS Differences in Childhood Schizophrenia More severe illness Worse prognosis More insidious onset Harder to treat Misdiagnosis is common

3 Page 3 Diagnostic Difficulties with COS Complex disorder with diverse presentation Diagnosing COS Psychosis and thought disorder are difficult to assess in children Children s concept of reality changes with time Disorganized behavior/speech can be common in nonpsychotic children Symptoms change, emerge, evolve over time Rare disorder: lack of clinical familiarity Devastating illness - Life sentence Clinicians don t want to get it wrong Large overlap with other disorders Mean onset of symptoms: 4.6 years Mean onset of psychosis: 6.9 years Mean onset of diagnosis: 9.5 years 5 year time lag DSM Criteria for Schizophrenia DSM Criteria for Schizophrenia Two or more of following for 1 month: (A Criterion) Delusions Hallucinations Disorganized speech Disorganized behavior Social/occupational dysfunction Disturbance for at least 6 months with at least 1 month with criterion A Not due to substance, medical condition, mood disorder or PDD Negative symptoms: flat affect, avolition, alogia Only 1 if delusions bizarre or voice keeping commentary or 2 voices conversing

4 Page 4 Schizophrenia Subtypes Catatonic Paranoid Disorganized What is psychosis? What is real vs. fantasy Think of A Beautiful Mind Undifferentiated Residual Positive Symptoms Negative Symptoms Affective blunting Symptoms associated with distorted reality Delusions Hallucinations Things present in those with schizophrenia as compared to those without. Poverty of speech Thought blocking Adequate grooming Lack of motivation-apathy Things absent from those with schizophrenia as compared to those without. Anhedonia Social withdrawal

5 Page 5 Hallucinations Hallucinations in COS Think of 5 senses: visual, auditory, olfactory, gustatory, tactile Usually frightening, morbid, macabre Can be friendly, company Most common presenting symptom Auditory hallucinations: 80% of COS Visual hallucinations: 30% of COS Tactile/olfactory hallucinations: rare Developmental considerations Hallucinations in isolation = schizophrenia Imaginary friends > 7yrs old: cause for concern Auditory Hallucinations Usually negative Command Conversing Commenting Persecutory May be friendly Visual Hallucinations Almost always accompanied by auditory hallucinations

6 Page 6 Delusions Difficult to assess in children A fixed false belief Bizarre-illogical 50-60% of COS Nonbizarre- can really occur Childhood themes: monsters, animals, family, fantasy figures Persecutory Less complicated in childhood Somatic Ideas of reference Grandiose Religious ideas Thought Disorder is disruption in flow of conscious verbal thought that is inferred from spoken or written language. Flight of ideas Derailment Thought blocking Pressured speech Tangentiality Perseveration Word salad Neologisms Echolalia Illogical Thought Disorder in COS Disturbance of Affect in COS % of COS Difficulty with assessment and definition in children 74% of COS Blunted Flat Inappropriate

7 Page 7 The Prodrome The Prodrome Onset of decline from baseline functioning Latent schizophrenia Don t meet full criteria Nonspecific symptoms Important: early detection is protective cognitive functioning overall functioning social isolation personal hygiene Difficulties with attention Change in emotions Flattening of affect The Prodrome Differential Diagnosis of COS Bizarre preoccupations Change in sleep/appetite Aggression, anxiety Neuromotor or sensory changes Abnormal eye tracking movements Brief, intermittent psychosis Pervasive developmental disorder Affective disorders PTSD Conduct Developmental language disorder Cognitive problems Conduct disorders Personality disorders Dissociative disorder Substance abuse

8 Page 8 Differential Diagnosis of COS Theories of Causation General medical causes: Delirium Seizures CNS lesions Neurodegenerative disorder Toxins No family history: 1% Genetic First degree relative: 10% Identical twin: 50% Gene markers: GAD1 affecting GABA and neureglin Infections Theories of Causation Structural Brain Abnormalities Infection Birth trauma Rh incompatibility Prenatal insults Abnormal protein and NT Synthesis Excessive glutamate release (excito-toxic damage) Hot area of research Lateral ventricular volume Total and regional gray matter volumes Basal ganglia volumes

9 Page 9 Structural Brain Abnormalities in COS Structural Brain Abnormalities in COS Gray matter loss in back to front pattern White matter loss in front to back pattern Exaggerated synaptic pruning Slower brain growth Lopsided brain growth Composite MRI scan data showing areas of gray matter loss over 5 years, comparing 12 normal teens (left) and 12 teens with childhood onset schizophrenia. Red and yellow denotes areas of greater loss. Front of brain is at left. Similar changes as AOS Differs from other neuropsychiatric disorders Not yet diagnostic May predict presymptomatic adolescents Comparison of the Patterns of Cortical Gray Matter (GM) Loss in Childhood-Onset Schizophrenia (COS) (Between Ages 12 and 16 Years) to That Seen in Normal Cortical Maturation (Between Ages 4 and 22 Years) Structural Brain Abnormalities in COS Unaffected family members: early loss of gray matter, normalizes by age 20 Help in finding genetic markers Help in identifying trajectory influences Gogtay, N. Schizophr Bull :sbm103v1-103; doi: /schbul/sbm103 Copyright restrictions may apply.

10 Page 10 Morbidity and Mortality People with schizophrenia that are in the public mental health system die 25 years earlier that the general population!! Schizophrenia can be lethal. Course of Disease 4 phases: prodrome, acute, recuperative, recovery/residual phase Chronic illness No cure Very treatable Without treatment-downhill course Diagnostic Work Up Treatment of COS Comprehensive diagnostic evaluation Labs: complete metabolic panel, thyroid, urinalysis, toxicology screen, HIV, chromosomal analysis, folate, B12, RPR Screen for infections, heavy metals (Wilson s) EEG MRI Cognitive testing Comprehensive, multi-modal Psychological needs Social needs Educational needs Cultural needs Family needs Physical needs

11 Page 11 Treatment of COS Now, let s get to the meds Psychopharmacology Psychotherapy: individual and family Case management Educational interventions Social skills training Inpatient/day treatment Neurological/medical services Residential treatment Rarely, ECT Antipsychotics revolutionized treatment Chlorpromazine (Thorazine) st of the Typical antipsychotics First used as an anesthetic How do antipsychotics work? Antipsychotic Use in Children Target dopaminergic neurons Increase dopamine=psychosis Dopamine blockers Atypicals also block serotonin Typical agents affect nigrostriatal tract and mesolimbic tract Nigrostriatal area also affects involuntary movements Most use in children is off label Lack adequate data in children Small sample sizes Need more controlled trials Younger patients are more sensitive to adverse effects of drugs as compared to adults Reason for EPS

12 Page 12 Antipsychotic Use in Children Start low and go slow! Continual monitoring Routine labs Baseline and serial weight, height and BMI Dietary education FDA Approval of Atypical Antipsychotics for COS Risperidone and Aripiprazole are approved for childhood schizophrenia for ages yrs. June, 2009: FDA advisory panel recommended approving Quetiapine and Olanzapine for treatment of childhood schizophrenia for ages yrs. Pre-med workups Atypical Agents Labs ECG Informed consent Newer Affect D2 and 5HT(2A) receptors Reason for increased efficacy Affects positive (D2) and negative (5HT) symptoms Don t effect nigrostriatal tract as much-less EPS Affect mesolimbic and mesocortical tracts

13 Page 13 Side Effects of Atypicals Side Effects of Atypicals Weight gain!!!!! Increased glucose, lipids, triglycerides: Metabolic Syndrome Sedation and anticholinergic symptoms Extra pyramidal symptoms: akathesia, dystonia, Parkinsonism Common reason for medication noncompliance Increased prolactin levels: gynecomastia, galactorhea Can also cause Neuroleptic Malignant Syndrome and Tardive Dyskinesia Thought to cause less EPS and less chance of Tardive Dyskinesia How do we choose an atypical? Side effect profile- make them work for patient Any absolute contraindications or medical risks Other meds: drug-drug interactions Cost!!!! Insurance Patient/family perceptions Doctor s own perceptions about meds Atypical Agents Generic Name Trade Name Daily Dosage (mg) Forms available Aripiprazole Abilify INJ, soln, tabs-d Clozapine Clozaril tabs-d Olanzapine Zyprexa 5-20 INJ, tabs-d Palipaeridone Invega 6-12 tabs Quetiapine Seroquel tabs Risperidone Risperdal 1-12 tabs-d, soln, INJ Ziprasidone Geodon tabs

14 Page 14 Risperidone (Risperdal) Olanzapine (Zyprexa) 1993 Only depot form of atypical-not used in children Depot form q 2 weeks Very sedating Excessive weight gain Metabolic syndrome Weight gain, sedation and high prolactin most common Above 6 mg daily- EPS Quetiapine (Seroquel) Aripiprazole (Abilify) Moderate for weight gain Slit lamp eye exam recommended-cataracts, not often done Very sedating Used in low doses for sleep-off label Not a full DA antagonist Dopamine stabilizer Agonist in areas of low activity More weight neutral Low incidence of metabolic syndrome

15 Page Weight gain Seizures Clozapine (Clozaril) Excessive salivation Agranulocytosis- serious, fatal Weekly biweekly WBC count Specific protocol-complex to manage Used in refractory cases: in children, only after failure of 2 other atypical antipsychotics Ziprasidone (Geodon) 2001 Short acting injectable available Can be used for acute agitation More weight neutral than other atypicals Lower incidence of metabolic syndrome Cardiac side effects In children: 1/3 those started on clozapine discontinue due to severe side effects Typical Antipsychotics Jani s at the mercy of her mind. Still use these Generally more second line in COS Recent debate that risks comparable to atypicals Much cheaper Haloperidol, chlorpromazine, perphenazine

16 Page 16 References Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision, American Psychiatric Association, 2000 Physicians Desk Reference, 2008 Schizophrenia, A Clinician s Guide, 1995, American Psychiatric Press Lieberman JA, Stroup TS, McEvoy JP, et al, Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia, N Engl J Med, 2005;353: NIMH, Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE), Wu EQ, Birnbaum HG, et al, The Economic Burden of Schizophrenia in the United States in 2002, JClinPsych, 2005, Sept;66(9): Practice Guidelines for the Treatment of Patients with Schizophrenia, Second Edition, 2002, American Psychiatric Association Practice Parameters for the Assessment and Treatment of Children and Adolescents With Schizophrenia, J.Am.Acad.ChildAdolesc.Psychiatry, 40:7 Supplement, July 2001 References Lieberman, J., Metabolic Changes Associated with Antipsychotic Use, PrimCare Companion J Clin Psychiatry 2004;6(suppl 2):8-13. Battaglia, J., Compliance with Treatment in Schizophrenia, Medscape CME. Narasimhan, M., Bailey, S.B., Schizophrenia, Metabolic Syndrome, and Antipsychotics Challenges, Controversies, and Clinical Management, Medscape CME. Childhood Schizophrenia, Child and Adolescent Psychiatry, 2nd Ed.,Lewis, M., 1996, M., White, T., Afshan, A., Schulz, C., The Schizophrenia Prodrome, Am.J.Psychiatry, 163(3): , March Shari Roan, Jani s at the mercy of her mind, Los Angeles Times, June 29, Russel, A., The Clinical Presentation of Childhood-Onset Schizophrenia, Schizophrenia Bulletin, 20(4): , References Notes Gogtay, N., Rapport, J., Childhood-Onset Schizophrenia: Insights From Neuroimaging Studies, J.Am.Acad.ChildAdolesc.Psychiatry, 47(10) , Oct Greenstein et al, Remission Status and Cortical Thickness in Childhood- Onset Schizophrenia, J.Am.Acad.ChildAdolesc.Psychiatry, 40 (10) , Oct Rapport et al, Autism Spectrum Disorder and Childhood-Onset Schizophrenia: Clinical and Biological Contribution to a Relation Revised, J. Am.Acad.ChildAdolesc.Psychiatry, 48 (1) 10-18, Jan.2009.