Schizophrenia

Schizophrenia overview

1. By M. JAGADEESH, PHARM.D, INTERN, CESCOP.

2. CONTENTS Definition Epidemiology Etiology Classification Pathophysiology Clinical Presentation Diagnosis Management Pharmacological therapy Non Pharmacological therapy

3. DEFINITION Schizophrenia is a complex, chronic mental health disorder characterized by an array of symptoms, including delusions, hallucinations , disorganized speech or behaviour, and impaired cognitive ability.

4. EPIDEMIOLOGY Schizophrenia affects more than 21 million people worldwide. One in two people living with schizophrenia does not receive care for the condition . More than 1.1 % of USA population is affected by the Schizophrenia. The prevalence of the disorder seems to be equal in males and females, although the onset of symptoms occurs at an earlier age in males than in females . Males tend to experience their first episode of schizophrenia in their early 20s, whereas women typically experience their first episode in their late 20s or early 30s.

5. ETIOLOGY Genetics: Genetic in origin: General population 1%. Monozygotic twins 47%. Dizygotic twins 12 %. One schizophrenic parent 12%. Two schizophrenic parents 40%. First-degree relative 12%. Second-degree relative 5-6% Viral hypothesis: Exposure to influenza in utero and excess winter births are interesting although indirect lines of evidence for a viral cause of schizophrenia . Immune dysfunctions: Anticardiolipin antibody and antinuclear antibody, two autoantibodies that are used as markers of autoimmune vulnerability, have been shown to be increased in patients with schizophrenia in some but not all studies of this illness. Two other markers relevant to autoimmune function , impaired T lymphocyte proliferative response to the mitogen phytohem agglutinin and impaired interleukin-2 production, have shown more consistent alterations in patients with schizophrenia than in control populations .

6. Birth complications: Hypoxia is one possible result of pregnancy and birth complications that has been shown to disrupt brain development. The hippocampus and some neocortical regions are particularly sensitive to shortfalls in oxygen . Thus , one proposed mechanism for a role of pregnancy and birth complications in the cause of schizophrenia involves hypoxia-mediated damage to these areas. Some studies suggest that the rate of obstetric complications are higher in early-onset schizophrenia, occur more often in males, in people with prominent negative symptoms, and no family history of schizophrenia.

7. CLASSIFICATION

8. PATHOPHYSIOLOGY

9. CLINICAL PRESENTATION Physical & Psychiatric Presenting Symptoms Hallucinations (mostly auditory) Delusions (mostly bizarre) Disorganized speech or behaviour Catatonic behaviour Negative symptoms Usually experience social &/or occupational dysfunction Physical exam usually unremarkable, but may find saccadic eye movements, hypervigilance , etc.

10. Positive Symptoms Hallucinations Delusions Disorganized thought Perception disturbances Negative Symptoms Blunted emotions Anhedonia Lack of feeling Cognition New Learning Memory Mood Symptoms Loss of motivation Social withdrawal

11. HALLUCINATIONS Hallucinations : A person sees, hears, smells, or feels that no one else can see, hear, smell, or feel. Auditory hallucinations: "Voices " are the most common type of hallucination in schizophrenia. The voices may talk to the person about his or her behavior, order the person to do things, or warn the person of danger. Sometimes the voices talk to each other. Visual Hallucinations: “ S eeing people " or " objects " that are not there . Others: S melling odors that no one else detects, and feeling things like invisible fingers touching their bodies when no one is near.

12. Auditory hallucinations Visual Hallucinations

13. DELUSIONS Delusions are " false beliefs . " The person believes delusions even after other people prove that the beliefs are not true or logical. People with schizophrenia can have delusions that seem bizarre, such as believing that neighbors can control their behavior with magnetic waves. They may also believe that people on television are directing special messages to them. Sometimes they believe they are someone else, such as a famous historical figure. They may have paranoid delusions and believe that others are trying to harm them , such as by cheating, harassing, poisoning, spying on, or plotting against them or the people they care about. These beliefs are called "delusions of persecution."

14. DIAGNOSIS Brain Imaging Findings CT : Lateral and third ventricular enlargement, reduction in cortical volume MRI : Increased cerebral ventricles PET : Hypoactivity of the frontal lobes Psychological Tests IQ tests : intelligence Neuropsychological : Tests consistent with bilateral frontal & temporal lobe dysfunction (deficits in attention, retention time & problem-solving ability) Personality (Projective Tests ): Abnormal findings, such as bizarre ideations, etc.

15. MANAGEMENT

16. PHARMACOLOGICAL THERAPY

17. SIDE EFFECTS ALGORITHM

18. COEXISTING SYMPTOMS ALGORITHMS

19. FIRST GENERATION ANTIPSYCHOTIC (FGA) DOSAGE GUIDELINES DRUG STARTING DOSE DOSE RANGE USUAL MAX. DOSE CHLORPROMAZINE 50–100 mg/day 300–1000 mg/day 1000 mg/day FLUPHENAZINE 5 mg/day 5–20 mg/day 20 mg/day FLUPHENAZINE D 12.5–25 mg IM/2–3 weeks 6.25–50 mg IM/2–4 weeks 100 mg IM/4 weeks HALOPERIDOL 2–5 mg/day 2–20 mg/day 20 mg/day HALOPERIDOL D 25–50mg IM/2 weeks 50–200 mg/2–4 weeks 300 mg/3–4 weeks LOXAPINE 20 mg/day 50–150 mg/day 150 mg/day MOLINDONE 20 mg/day 50–150 mg/day 150 mg/day PERPHENAZINE 4–8 mg/day 16–64 mg/day 64 mg/day THIOTHIXENE 5–10 mg/day 15–50 mg/day 50 mg/day TRIFLUOPERAZINE 2 mg BID 5–40 mg/day 40 mg/day

20. SGA STARTING DOSE TITRATION RANGE MAX. DOSE SCHEDULE CLOZAPINE 12.5 mg/day (half a 25 mg tab)   Starting day 3, dose increased every 3 days Day 2 : 25 mg HS Day 3 : 25 mg BID Day 6 : 25 mg AM, 50 mg HS Day 9 : 50 mg BID Day 12 : 75 mg BID Day 15 : 100 mg BID Day 18 : 125 mg BID Day 21 : 150 mg BID Day 24 : 100 mg AM, 200 mg HS 300–900 mg/day     (serum level for doses > 600 mg/day) 900 mg/day BID   Eventual maintenance dose schedule is: BID (1/3 in AM, 2/3 in PM) OLANZAPINE 5–10 mg/day 5 mg/week 10–20 mg/day 40 mg/day a HS QUETIAPINE 25 mg BID 50 mg/day 300–800 mg/day 800 mg/day BID RISPERIDONE 1–2 mg/day 1 mg/2–3 days 2–6 mg/day 16 mg/day b HS or AM ZIPRASIDONE 40–80 mg/day 20–40 mg/2–3 days 80–60 mg/day 160 mg/day BID   The presence of food can increase ziprasidone’s absorption up to twofold SECOND GENERATION ANTIPSYCHOTIC (SGA) DOSAGE GUIDELINES

21. COMPARISON OF ANTIPSYCHOTIC ADVERSE EFFECTS   Drug   EPS   TD Orthostatic hypotension   Prolactin   Sedation Weight gain Anti- cholinergic Clozapine + / – – + + + + / – + + + + + + + + + + + + Risperidone + / + + + + + + + + + + + Olanzapine + + + + / – + + + + + + + Quetiapine + / – + / – + + + / – + + + + + Ziprasidone + + + + + + / – – Haloperidol + + + + + + + + + + + + + + + Chlorpromazine + + + + + + + + + + + + + + + + + + + + + – none + mild +/– mild to none ++ moderate +++ moderately severe ++++ severe

22. NON PHARMACOLOGICAL THERAPY Psychosocial Rehabilitation Individual Psychotherapy Group Psychotherapy Psychoeducational Treatment Social Skills Training Cognitive Remediation Cognitive Adaptation Training Family Therapy

23. FAMOUS PEOPLE WITH SCHIZOPHRENIA Dr . John Forbes Nash Jr.  is a Nobel Prize-winning mathematician known for his genius as well as his paranoid schizophrenia.  British guitarist  Peter Green  became famous for his signature sound and as a founding member of  Fleetwood Mac , making nearly every list of the world’s best guitarists.

24. Legendary football coach Vince Lombardi rarely started rookies, but he took a chance with  Lionel Aldridge in 1963. Eduard Einstein – 1910-1965 Son of Albert Einstein Age of Diagnosis: 20

25. REFERENCES Jerald kay et al, Essentials of Psychiatry, 2006 John Wiley. Nabeel Kouka , Psychiatry for medical students and residents, 2009. http://www.online-psychology-degrees.org/20-famous-people-with-schizophrenia / https:// www.nimh.nih.gov/health/statistics/prevalence/schizophrenia.shtml http:// www.healthline.com/health-lideshow/faces-of-schizophrenia#1