Charles P. Samenow, MD, MPH Department of Psychiatry George Washington University

Transcription

1 Charles P. Samenow, MD, MPH Department of Psychiatry George Washington University

2 Objectives Identify the epidemiology, symptomatology, course, causality (including genetic risk) and treatment options for schizophrenia, schizophreniform, brief psychotic, schizoaffective and delusional disorders. Identify the diagnostic criteria for the psychotic disorders Define positive, negative, cognitive and affective symptoms in the context of psychotic disorders. Describe conditions associated with the treatment of psychotic disorders including tardive dyskinesia, akisthesia, dystonia and parkinsonism.

3 Disorders To Consider Schizophrenia Brief Psychosis Schizophreniform Disorder Delusional Disorder

4 Other Disorders to Consider Mood Disorder Psychosis Schizoaffective Bipolar Disorder Major Depression with Psychotic Features Psychosis Secondary to General Medical Condition Substance Induced Psychosis Schizoid and Schizotypal Personality Disorder

5 Symptoms in Psychosis NEGATIVE SYNDROME Attention deficits, Asociality, Anhedonia, Apathy, Avolition, Alogia POSITIVE SYNDROME Hallucinations, Delusions, Disorganized Speech and/or Behavior and/or Affect, Agitation and Aggression COGNITIVE SYMPTOMS Problems with: Working Memory, Attention, Executive Functioning, Learning, Planning,& Cognitive Flexibility MOOD & ANXIETY SYMPTOMS Depression, anxiety, suicidality Bobo & Richelson, in preparation

6 Positive Symptoms Usually occur during psychotic episodes Usually involve distinct abnormal behaviors Includes Delusions (e.g. grandeur, persecution, death) Bizarre vs. Non-Bizarre Hallucinations (e.g. auditory, visual, tactile, olfactory) Disorders of thought (e.g. ideas of reference, thought insertion, thought broadcasting, loosening of association, word salad, clang associations) Agitation/Aggression

7 Symptoms Clip SymptomMedia/SymMediaClips1.html

8 Negative Symptoms Usually occurs during non-psychotic periods. Generally involves a loss of normal behaviors Includes Reduced speech (poverty of thought and content) Low initiative (anergia, anhedonia, avolition) Social withdrawal Diminished affect (blunting) Thought blocking

9 Symptoms Clip SymptomMedia/SymMediaClips1.html index3.html#delusions

10 Cognitive Symptoms Working Memory Executive Function Attention Learning

11 Mood Symptoms Depression Anxiety Suicide

12 Dopamine Hypothesis of Schizophrenia Mesocortical pathway Hypoactivity: negative, cognitive, and mood symptoms Nigrostriatal pathway (part of EP system) Tuberoinfundibular pathway (inhibits prolactin release [D2]) Mesolimbic pathway Hyperactivity: positive symptoms (hallucinations, delusions)

13 Clinical profile: Dopamine (D2) blockade Mesolimbic D2 EFFICACY: (+) SSX Mesocortical D2 INEFFICACY: (-) SSX, cognition, mood Nigrostriatal D2 SIDE EFFECTS: EPS Tuberoinfundibular D2 SIDE EFFECTS: HPL

14 Schizophrenia DSM-IV-TR Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1- month period (or less if successfully treated): delusions hallucinations disorganized speech grossly disorganized or catatonic behavior negative symptoms

15 Schizophrenia (Cont) Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person's behavior or thoughts, or two or more voices conversing with each other.

16 Schizophrenia (Cont) Social/occupational dysfunction Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms

17 Schizophrenia Exclusions (1) No Major Depressive Episode, Manic Episode, or Mixed Episode have occurred concurrently with the active-phase symptoms (2) If mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods. (3) The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition.

18 Schizophrenia (Subtypes) Paranoid Type Preoccupation with one or more delusions or frequent auditory hallucinations

19 Schizophrenia (Subtypes) Catatonic Type motor immobility as evidenced by catalepsy (including waxy flexibility) or stupor excessive motor activity (that is apparently purposeless and not influenced by external stimuli) extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing echolalia or echopraxia

20 Schizophrenia (Subtypes) Disorganized Type disorganized speech disorganized behavior flat or inappropriate affect

21 Schizophrenia (Subtypes) Undifferentiated Type A type of Schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the Paranoid, Disorganized, or Catatonic Type

22 Schizophrenia (Subtypes) Residual Type Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for Schizophrenia, present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

23 Schizophrenia Clip flvvideofiles/psychiatricdisorders/ psychiatricdisorders.html

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25 Biological Variables Genetics Is probably caused by the combination of several genes Has been identified with genes of Chromosome 22 and Chromosome 6 Twin studies (monozygotic 40-50% > 1 st degree 10% > general population 1%) Brain Abnormalities Reduction of blood flow to the left Globus Pallidus Problems in the frontal lobes Medial temporal lobe is thinner Anterior Hypothalamus is smaller (especially left Side) Lateral and third ventricles are enlarged Sulci are also enlarged (especially in the temporal and frontal lobes Indicated reduced numbers of neurons

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27 Biological Variables Brain Damage Birth trauma (obstetrical issues) Viral infections that impair neural development during the second and third trimester. Nutritional issues

28 Psychological Variables Stress Diathesis Model Stress Vulnerability Protective factors model Risk Factors Family History Urban Areas Northern Hemisphere Winter Month Birth Pregnancy Complications Loss of Parent During Childhood Lower Socioeconomic Status

29 Social Variables Downward Drift vs. Social Causation

30 Course of Schizophrenia Prodromal Negative Symptoms Males: Females: Late Onset: > 40 yo (more common in women) Acute Positive Symptoms Recovery 30%: improvement or return to fx 30% intermittent hospitalization 30% institutionalized or incapacitated Note: 10% commit suicide

31 Prognostic Factors Good Later Age of Onset Sudden Onset Female Higher Level of functioning prior to onset Good Compliance Family History of Mood Disorders Paranoid Subtypes Worse Early Age of Onset Male More Negative Symptoms More Brain Abnormalities Lower level of function prior to onset Substance Abuse Disorganized Subtype

32 Schizophrenia (Treatment) HIGH MEDIUM LOW Fluphenazine (D) Trifluoperazine Thiothixine Haloperidol (D) Perphenazine Prochlorperazine Loxapine Acetophenazine Triflupromazine Chlorprothixine Mesoridazine Thioridazine Chlorpromazine EPS, HPL Anti-H1: Sedation, wt gain Anti-α-1: Orthostasis, reflex tachycardia Anti-M1: Blurry vision, dry mouth, constipation, urinary retention, tachycardia, memory problems or delirium in susceptible patients EPS, HPL Anti-H1 Anti-α-1 Anti-M1 Seizure, arrythmias, retinitis, skin discoloration, photosens

33 Extrapyramidal Side Effects (EPS) n Acute dystonia - Sudden, sustained, forceful (painful) - Torticollis, opisthotonos, oculygyric crisis, pharyngeal or lingual swelling, laryngeal dystonia n Akathisia - Motoric restlessness or discomfort, relieved by movement - Increased risk of suicide and hostility/aggression n Drug-induced Parkinsonism n Tardive dyskinesia

34 Name the EPS n Masked facies and a slow oscillating bilateral hand tremor develop in a man 6 weeks after initiation of HAL. Exam reveals diffuse hypertonia. VSS. n Pacing, restless, fidgety. Increase in HAL dose makes it worse. n Involuntary slow, writhing puckering movements of lips, with occasional tongue protrusion. H/O extensive past use of high potency typical neuroleptic (years). n Treatment includes anticholinergic medicines such as Benadryl or Cogentin

35 Tardive Dyskinesia v=r0ebgpyztca

36 NEUROLEPTIC MALIGNANT SYNDROME: DIAGNOSTIC FEATURES MENTAL STATUS CHANGE Acute, rapid onset Delirium, confusion AUTONOMIC INSTABILITY Fever/hyperpyrexia, Tachycardia, Severe HTN Diaphoresis NEUROMUSCULAR FINDINGS Lead pipe rigidity LAB ABNORMALITIES CPK elevation, myoglobinuria à oliguric renal failure Leukocytosis

37 Atypical Antipsychotics n Clozapine (Clozaril TM ) n Risperidone (Risperdal TM & Risperdal CONSTA TM ) n Olanzapine (Zyprexa TM ) n Quetiapine (Seroquel TM ) n Ziprasidone (Geodon TM ) n Aripiperazole (Abilify TM ) n Paliperidone (Invega TM & Invega Sustenna TM ) n Iloperidone (Fanapt TM )

38 5-HT/DA Hypothesis n D2 and 5-HT2A blockade in mesolimbic circuit à efficacy for positive syndrome n Preservation (enhancement?) of DA tone - Mesocortical à preserved/improved cognition à improved negative syndrome - Nigrostriatal à lower EPS propensity - Tuberoinfundibular à lower HPL propensity

39 A. B. 5HT DA DA release C. D. 5HT DA +/- DA release

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41 Atypical Antipsychotics Weight Gain Increased Blood Glucose Increased Triglycerides Possible Sedation Prolongation of QTc

42 Depot Antipsychotic Drugs Advantages/Disadvantages Advantages n Automatic compliance n Reduced short-term relapse Haldol Thorazine Risperdal Consta Disadvantages n Side effects not quickly extinguished n Risk of tardive dyskinesia* n Toxicity/hypersensitivity reactions to not quickly extinguish *Typicals only

43 Brief Psychotic Disorder Same criteria as schizophreni, but Lasting from 1 day to 1 month Eventual return to the premorbid level of functioning Women > Men Personality Disorders are a risk factor

44 Schizophreniform Disorder Similar criteria as Schizophrenia, but.. Lasts less than six months, and More than one month Equal in Men and Women

45 Delusional Disorder Non-bizarre delusions.025% prevalence Mean Age of Onset: 40 Women > Men Hallucinations may be present Disorganized Thought/Behavior not usually present Less responsive to antipsychotic meds

46 Types of Delusions Erotomanic Grandiose Jealous Persecutory Somatic Mixed

47 Schizoaffective Disorder features of both schizophrenia, including hallucinations, delusions, and distorted thinking, and a mood component, such as depression or mania diagnosis is made when the patient has features of both illnesses but does not strictly meet diagnostic criteria for either schizophrenia or a mood disorder alone 0.5% Prevalence Women > Men Slightly better prognosis than Shizophrenia

48 Schizoid/Shizotypal Schizoid: characterized by excessive detachment from social relationships and a restricted range of expression of emotions in interpersonal settings. Schizotypal: acute discomfort with, and reduced capacity for, close relationships as well as by cognitive or perceptual distortions and eccentricities of behavior Acute psychotic symptoms not present!