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1 2 - Psychosis is a break from reality involving delusions, perceptual disturbances, disordered thinking (FTD), and disorganized behavior. - Schizophrenia and substance-induced psychosis Are examples of commonly diagnosed psychotic disorders. 3 Schizophrenia Spectrum and Other Psychotic Disorders 1. 2. 3. 4. 5. 6. 7. Schizophrenia Brief Psychotic Disorder Schizophreniform Disorder Schizoaffective Disorder Delusional Disorder Schizotypal (Personality) Disorder Substance/Medication-Induced Psychotic Disorder 8. Psychotic Disorder Due to Another Medical Condition 4 Scenario 1 19 year old male is brought to the ER by his roommate after the patient stated the voices are telling me to kill my teacher. the patient has become withdrawn and isolated over the last year. 6 weeks ago the patient started talking to himself became paranoid and started to be verbally and physically agressive. Think schiz-paranoid features 5 Scenario 2 25 year old female is brought to the ER by her family because they have been unable to get her to eat or drink anything for the past 2 days. the patient though awake is completely unresponsive vocally and nonverbally. she actively resists any attempt to be moved. her family reports over the last 7 months she has become withdrawn, socially isolated and bizarre, often speaking to people nobody else could see. Think schiz-catatonic features 3 Schizophrenia is a psychiatric disorder characterized by a constellation of abnormalities in thinking, emotion, perception and behavior. There is no single symptom that is pathognomonic, and the disease can produce a wide spectrum of clinical pictures. It is usually chronic and debilitating. 4 In general, the symptoms of schizophrenia are divided up into two categories: Positive symptoms Hallucinations, 2. Delusions, 3. Disorganized or bizarre Behavior, 4. Formal Thought disorder 1. Negative symptoms: 1. Anhedonia (no interest) 2. Affect (flat) 3. Alogia (poverty of speech) 4. Avolition (apathy) 5. Attention (poor) 8 Typical Course of the disease Three Phases: Symptoms of schizophrenia usually present in three phases: 1. Prodromal—decline in functioning that precedes the first psychotic episode. The patient may become socially withdrawn and irritable. He or she may have physical complaints . bizarre ideas, development of an interest in complex philosophical or religious ideas, strange perceptual experiences and abnormal affect. 2. Psychotic—perceptual disturbances, delusions, and disordered thought process/content, behavior. 3. Residual—occurs between episodes of psychosis. It is marked by flat affect, social withdrawal, and odd thinking or behavior (negative symptoms). Patients can continue to have hallucinations even with treatment. 7 Note: To make the diagnosis of schizophrenia, a patient must have symptoms of the disease for at least 6 months. 10 Diagnosis of Schizophrenia DSM-V Criteria (2013) Two or more of the following must be present for at least 1 month: 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (such as flattened affect) 11 Must cause significant social or occupational functional deterioration Duration of illness for at least 6 months (including prodromal or residual periods in which above criteria may not be met) Symptoms not due to medical, or substanceinduced disorder 12 Specifiers of Schizophrenia 1. Paranoid features—highest functioning type, older age of onset. Must meet the following criteria: _ Preoccupation with one or more delusions or frequent auditory hallucinations _ No predominance of disorganized speech, disorganized or catatonic behavior, or inappropriate affect 13 2. Disorganized features—poor functioning , early onset. Must meet the following criteria: _ Disorganized speech _ Disorganized behavior _ Flat or inappropriate affect 14 3. Catatonic features—rare. Must meet at least two of the following criteria: _ Motor immobility _ Excessive purposeless motor activity _ Extreme negativism or mutism _ Peculiar voluntary movements or posturing _ Echolalia or echopraxia 15 4. Undifferentiated features—characteristic of more than one subtype or none of the subtypes 5. Residual features—prominent negative symptoms (such as flattened affect or social withdrawal) with only minimal evidence of positive symptoms. (such as hallucinations or delusions) 16 Important Psychopathological Phenomena Included in (ICD-10) • • • • • • Thought Echo Thought Insertion Or Withdrawal Thought Broadcasting Delusional Perception Influence Or Passivity Hallucinatory Voices Commenting Or Discussing The Patient In The Third Person 17 Psychiatric Exam of Schizophrenics The typical findings in schizophrenic patients on exam include: _ Disheveled appearance _ Flattened affect _ Disorganized thought process _ Auditory hallucinations _ Paranoid delusions _ Ideas of reference (feel references are being made to them by the television or newspaper, etc.) _ Concrete understanding of similarities/proverbs _ Lack insight into their disease 15 Psychosis secondary to general medical condition Substance-induced psychotic disorder Delirium/Dementia Bipolar disorder Major depression with psychotic features Brief psychotic disorder Schizophreniform disorder Schizoaffective disorder Delusional disorder 16 Medical causes of psychosis include: 1. CNS disease (cerebrovascular disease, multiple sclerosis, neoplasm, Parkinson's disease, temporal lobe epilepsy, encephalitis) 2. Endocrinopathies (Addison’s/Cushing’s disease, hyper/hypothyroidism ,hyper /hypocalcemia , hypopituitarism) 17 3. Nutritional/Vitamin deficiency states (B12, folate, niacin) 4. Other (connective tissue disease [systemic lupus erythematosus, porphyria) 19 Note: Always be sure to include the importance of ruling out medical, or substance-induced conditions. 20 Schizophrenia affects approximately 1% of people over their lifetime. Men and women are equally affected but have different presentations and outcomes: Men tend to present around 20 years of age. Women present closer to 30 years of age. The course of the disease is generally more severe in men, as men tend to have more negative symptoms and are less able to function in society. 21 Schizophrenia rarely presents before age 15 or after age 45. There is a strong genetic predisposition: 50% concordance rate among monozygotic twins 40% risk of inheritance if both parents have schizophrenia 12% risk if one first-degree relative is affected There is a strong association with substance use which may be a form of self medication and depression. Postpsychotic depression occurs in 50% of patients. 22 Note: People born in winter and early spring have a higher incidence of schizophrenia for unknown reasons. (One theory involves seasonal variation in viral infections of mothers during pregnancy.) Pathophysiology of schizophrenia 23 The Dopamine Hypothesis - Though the exact cause of schizophrenia is not known, it appears to be partly related to increased dopamine activity in certain neuronal tracts - Evidence to support this hypothesis is that most antipsychotics that are successful in treating schizophrenia are dopamine receptor antagonists. In addition, cocaine and amphetamines increase dopamine activity and can lead to schizophrenic-like symptoms. 24 Note: It is often impossible (clinically) to differentiate an acute psychotic episode related to schizophrenia from one related to cocaine or amphetamine abuse, as these drugs excite dopaminergic pathways. 25 Theorized Dopamine Pathways Affected in Schizophrenia Prefrontal cortical—responsible for negative symptoms Mesolimbic —responsible for positive symptoms 26 Other Important Dopamine Pathways Affected by Neuroleptics Tuberoinfundibular—blocked by neuroleptics, causing hyperprolactinemia Nigrostriatal—blocked by neuroleptics, causing extrapyramidal side effects 27 Other Neurotransmiter Abnormalities Implicated in Schizophrenia Elevated serotonin some of the atypical antipsychotics (such as risperidone and clozapine) antagonize serotonin (in addition to their effects on dopamine). Elevated norepinephrine long-term use of antipsychotics has been shown to decrease activity of noradrenergic neurons. 28 Decreased gamma-aminobutyric acid (GABA)— recent data support the hypothesis that schizophrenic patients have a loss of GABAergic neurons in the hippocampus; this loss might indirectly activate dopaminergic and noradrenergic pathways. 29 Glutamate and N-methyl-d-Aspartate Glutamate is a major brain excitatory amino acid neurotransmitter and is critically involved in learning, memory and brain development. Interest in glutamate and the NMDA receptor In schizophrenia arose because of the similarity between phencyclidine (PCP) psychosis and the psychosis of schizophrenia. PCP is a noncompetitive antagonist of the NMDA receptor and produces a psychotic state that includes auditory hallucinations, delusions and negative symptoms. 29 Note: CT scans of patients with schizophrenia often show enlargement of the ventricles and diffuse cortical atrophy which are non-specific. 30 PROGNOSTIC FACTORS Schizophrenia is usually chronic and debilitating. 40 to 50% of patients remain significantly impaired after their diagnosis, while only 20 to 30% function fairly well in society with medication. Several factors are associated with a better or worse prognosis 31 *Associated with Better Prognosis Later onset Good social support Positive symptoms Mood symptoms Acute onset Female sex Few relapses Good premorbid functioning 32 *Associated with Worse Prognosis Early onset Poor social support Negative symptoms Family history Gradual onset Male sex Many relapses Poor premorbid functioning (social isolation, etc.) TREATMENT Hospitalization Pharmacotherapy Acute Stabilization and maintenance Psychosocial therapy Others 33 34 A multimodality approach is the most effective, and therapy must be tailored to the needs of the specific patient. Delay in Rx -- worse prognosis 35 Hospitalization Establish an effective association bet pt and support systems in community Short stay (4-6 ws) is as effective as long stay Active behavioral approach is better Selfcare QOL (quality of life) Employment Social relationship 36 Pt linked to social agencies Day care centres Home visits 37 pharmacotherapy Pharmacologic treatment consists primarily of antipsychotic medications Antipsychotics are the mainstay treatment (biological) Other psychosocial th augment improvement Both should be integrated, -- best resuls 38 TREATMENT pharmacotherapy Chlorpromazine 1952 Dec syx and relapse rate 70 % remission rate 39 Typical Antipsychotics (neuroleptics), DRA 1st generaion Chlorpromazine, trifluoperazine , haloperidol. These are dopamine (mostly D2) antagonists. They classically treat positive symptoms They have important side effects and sequelae such as extra pyramidal symptoms. 40 Risperidone,, olanzapine, quetiapine, aripiprazole,, Illiperidone (Invega). clozapine These antagonize serotonin receptors (5-HT2) as well as dopamine receptors. Atypical neuroleptics are classically better at treating negative symptoms than traditional neuroleptics. They have a much lower incidence of extrapyramidal side effects, but have other SE (metabolic syndrome) 41 _ Medications should be taken for at least 4 weeks before efficacy is determined. If the medication fails, it is appropriate to switch to another medication in a different class. 41 phases of Rx: Acute phase: 4-8 Ws +ve psych syx + excitement Ddx Akathesia (anticholinergic) IM Aps +/- Benzo Haloperidol (EPS). Olanzapine im/po (rapidly dissolving) Chlorpromazine (hypotension) 42 Im Lorazepam 2mg (best absorption), short Less amount of AP needed so less AP SE 43 Continuaton/maintenance phase on Rx 20% relapse in a year without Rx 60 % relapse in a year In general 80% relapse within 5 yrs For how long continue Rx? 1st episode -- > 1yr (1-2y) , no consensus multi episodes (>2 in 5yrs) – at least 5 yrs 44 if Haldpl 50 mg /4w Flufenazine 25 mg /2-3w Fluanxol 20 mg 2-4w Risperidone consta 25mg/2w but check reasons for non-compliance * poor compliance use long acting AP psychoeducation is mandatory Use minimum effective dose 45 60 % initially responds (complete, mild sys) ensure adequate trial (4-6 w) with adequate dose Even if mild improvement continue for 3-6 months (mostly will continue improvement) Check compliance: ? plasma monitoring if low levels: non or poor compliance Rapid Poor metabolizers* absorption 46 so increase the dose -? SE -Shift to another class DRA - SDA - clozapine, esp if severe syxs, clear evidence -- Management of SE: -Usually start before improvement DRA: - low-potency sedation, Hypotention, anticholinergic - high-potency EPS 48 Behavioral therapy (social skills training) Attempts to improve patients’ ability to function in society. Patients are helped through a variety of methods to improve their social skills, become self-sufficient, and act appropriately in public. Poor eye contact, delay in response, odd behavior, asociability, Token economy (ward) 49 Family therapy Family oriented therapy Psychoeducation Stress is vital reducing and coping strategies Gradual integration into society Decrease high expressed emotions (imp) group therapy Effective in reducing social isolation Supportive –oriented is most helpful 50 Vocational therapy Regain old skills or develop new ones Through workshops and job assignment Cognitive therapy Some reports of ameliorating delusions and hallucinations in some patents Improve cognitive distortions and poor judgment 51 ECT Supplementary to AP For catatonic pts. For pregnant pts. Severe non –drug responder if drugs contraindication Psychosurgery Limited for severe, intractable cases 52 Note: Significant improvement is noted in 70% of schizophrenic patients who take antipsychotic medication 53 An 18 - year-old woman diagnosed with schizophrenia presents to the psychiatric emergency department after a suicide attempt by carbon monoxide poisoning. Medical evaluation was noncontributory and a urine toxicology screen was negative. The patient's mother reports that she has been refusing to take haloperidol (Haldol) for the past 3 weeks. The lifetime risk of death by suicide in patients with schizophrenia is closest to which of the following? (A) 1% (B) 5% (C) 10% (D) 30% (E) 50%