SCHIZOPHRENIA.pptx

Types, etiopathogenesis, management of Schizophrenia.

1. AMEENA KADAR K A SECOND SEM M PHARM DEPT. OF PHARMACY PRACTICE SANJO COLLEGE OF PHARMACEUTICAL STUDIES SCHIZOPHRENIA

2. INTRODUCTION Schizophrenia is one of the most complex and challenging psychiatric disorder. Schizophrenia represents a heterogeneous syndrome of disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning. It is a psychotic disorder marked by severely impaired thinking, emotions and behaviours. Schizophrenic patients are unable to filter sensory stimuli and may have enhanced perception of sounds, colours and other features of their environment. Most schizophrenics, if untreated can gradually withdraw themselves from the interactions with other people and lose their ability to take care of personnel needs. 2

3. EPIDEMIOLOGY 3 The lifetime prevalence of schizophrenia ranges from 0.3% to 0.7%. Schizophrenia most commonly has its onset in late adolescence or early adulthood and rarely occurs before adolescence or after the age of 40 years. Although the prevalence of schizophrenia is equal in males and females, the onset of illness tends to be earlier in males. Males most frequently have their first episode during their early 20s, whereas with females it is usually during their late 20s.

4. TYPES OF SCHIZOPHRENIA 4 Paranoid Schizophrenia: The most common type of schizophrenia. Patients are usually preoccupied with paranoid delusions or auditory hallucinations. Cognitive function is usually preserved; if thought disorder is present, it does not prevent description of delusions or hallucinations.

5. 5 Disorganized Schizophrenia: The patient tends to have disorganized speech and behavior with a flat affect. Hallucinations and delusions are not well formed and fragmented. The patient may also have bizarre mannerisms and grimacing. Catatonic Schizophrenia: Motor symptoms are most notable. The patient may either demonstrate rigid immobility or excessive purposeless movement. The patient may be silent and withdrawn or may become loud and shout. Bizarre voluntary movements such as posturing may also occur. The patient may fluctuate between the two extremes.

6. 6 Undifferentiated Schizophrenia: The patient meets the criteria for a diagnosis of schizophrenia but does not meet the criteria for a specific type, or the patient may meet the criteria for multiple types of schizophrenia. No one type appears to be dominant. Residual Schizophrenia: The patient does not have acute psychosis, but some symptoms of schizophrenia remain. Largely negative symptoms are seen, such as flat affect, social withdrawal, and loose associations. Prominent delusions or hallucinations are not present.

7. SYMPTOMS 7 POSITIVE SYMPTOMS DELUSION HALLUCINATIONS COMBATIVENESS INSOMNIA NEGATIVE SYMPTOMS AFFECTIVE FLATTENING ALOGIA ANHEDONIA AMOTIVATION APATHY ASOCIAL BEHAVIOUR DISORGANISED SYMPTOMS DISORGANISED SPEECH THOUGHT DISORDER DISORGANISED BEHAVIOUR POOR ATTENTION

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11. ETIOPATHOGENESIS 11 Although the cause of schizophrenia remains unknown, there are many theories and models. Vulnerability model This model postulates that the persistent characteristic of schizophrenia is not the schizophrenic episode itself but the vulnerability to the development of such episodes of the disorder. The episodes of the illness are time limited but the vulnerability remains, awaiting the trigger of some stress. Such vulnerability can depend on premorbid personality, the individual's social network or the environment. Manipulation and avoidance of stress can abort a potential schizophrenic episode.

12. 12 Developmental model The developmental model postulates that there are critical periods in the development of neuronal cells which, if adversely affected, may result in schizophrenia. Two such critical periods are postulated to occur when migrant neural cells do not reach their goal in fetal development and when supernumerary neural cells slough off at adolescence. This model is supported by neuroimaging studies which show structural brain abnormalities in patients with schizophrenia.

13. 13 Ecological model The ecological model postulates that external factors involving social, cultural and physical forces in the environment, such as population density, individual space, socio-economic status and racial status, influence the development of the disorder. The evidence in support of such a model remains weak. 4. Neurodevelopmental Theory Schizophrenia occurs as a result of an in uterodisturbance during pregnancy. Potential causes of this disturbance include upper respiratory infection, obstetric complication and neonatal hypoxia.

14. 14 5. Genetic Theory A strong genetic link exists for the development of schizophrenia. Risk of developing schizophrenia further increases to 40% when both parents have a history of schizophrenia. Monozygotic twins have demonstrated a 48% risk of developing schizophrenia if one twin has the disease. Studies are going to locate specific genes to the development of schizophrenia.

15. 15 6. Dopamine Theory The dopamine hyperactivity in the brain is responsible for psychotic symptoms present in schizophrenia. While dopamine hyperactivity is present in mesolimbic pathway, other areas of the brain such as the prefrontal, frontal and temporal cortices have decrease activity during acute psychosis. Other neurotransmitters thought to be involved in schizophrenia include 5-HT, glutamate. The role of glutamate is also being evaluated because one of its major functions is to regulate dopamine activity. Glutamate deficiency has been found to cause similar effects to that of dopamine hyperactivity.

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18. 18 7. Psychosocial Theories These theories propose that situation such as stress, poor interpersonal skills, conflicting family, communication and various socio-economic influences are linked to development of schizophrenia. 8. Neurotransmitter Abnormalities Abnormalities in the dopaminergic system Hypo dopaminergic activity in the meso -cortical system, leading to negative symptoms. Hyper dopaminergic activity in the mesolimbic system, leading to positive symptoms.

19. 19 PARTS OF THE BRAIN ASSOCIATED WITH SPECIFIC FUNCTIONS

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21. DIAGNOSIS 21 The Diagnostic and Statistical Manual of the American Psychiatric Association , text revision ( DSM-IV-TR ), is the latest edition of the guide for diagnosing and classifying schizophrenia and other psychiatric disorders. Compared with previous DSM editions, the DSM-IV-TR places a greater emphasis on negative symptoms and the social and occupational dysfunction associated with schizophrenia . Psychosis has many causes, and all must be excluded before the diagnosis of schizophrenia is made. In addition, a diagnosis can be made only if the DSM-IV-TR criteria are met.

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23. 23 ICD 10 and DSM-IV diagnostic criteria for schizophrenia.

24. 24 Schizophrenic patients appear to have small brains with large ventricular volumes, indicating a relative deficit of neurons. Structural and functional brain imaging studies have strongly suggested that regions of the medial temporal lobe (e.g., hippocampus) have diminished numbers of neurons and also have demonstrated the inability of individuals with schizophrenia to activate the frontal cortex and successfully execute tasks that require frontal cortical function . Ventricular enlargement and cortical atrophy, as seen on CT scan , have been correlated with chronic course, severe cognitive impairment, and non responsiveness to neuroleptic medications. Decreased frontal lobe activity seen on PET scan has been associated with negative symptoms.

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26. 26 Differential Diagnosis for Schizophrenia (DSM-IV-TR) Drug-induced psychosis is an important differential diagnosis when evaluating patients with schizophrenia-like symptoms.

27. TREATMENT 27 There is currently no known cure for schizophrenia. Treatment options include psychotherapy as well as pharmacotherapy. The goals and objectives of treatment are as follows: Minimize symptoms of schizophrenia Improve quality of life and social/occupational functioning Prevent relapse and hospitalization Minimize adverse effects of medications Prevent suicide attempts or self-harm .

28. NON PHARMACOLOGICAL MANAGEMENT 28 Psychosocial rehabilitation programs include: Case Management Psycho-education Targeted Cognitive Therapy Basic Living Skills Social Skills Training Basic Education Work Programs Supported Housing Financial Support.

29. PHARMACOLOGICAL MANAGEMENT 29 ANTIPSYCHOTICS First-generation ( typical antipsychotics ) and second-generation ( atypical antipsychotics ). Current American Psychiatric Association (APA) guidelines recommend using an atypical antipsychotic first , owing to less risk for extrapyramidal symptoms (EPS). Patients who prefer or have a history of response to typical antipsychotics may first use typical antipsychotics. Response to medications is not immediate, and maximal treatment response may take 6 months or longer to be seen .

30. 30 After a treatment response is seen, patients should be maintained on the current therapy for a minimum of 6 months. Most patients will require chronic therapy, because 80% of first-episode patients who do not receive antipsychotic treatment will relapse within 5 years.

31. TYPICAL ANTIPSYCHOTICS 31 Mechanism of action. The antipsychotic effect of these medications is primarily mediated through the blockade of dopamine type 2 (D2) receptors . Agents within this medication class vary in their activity at histamine, muscarinic, and receptors , although these receptors are not responsible for desired therapeutic activity. Eg: Chlorpromazine Trifluperazine Thioridazine Perphanazine Fluphenazine

32. 32 Haloperidol Loxapine . Potency. Typical antipsychotic agents are classified by their potency for the dopamine receptor into high, moderate, and low-potency antipsychotics. High-potency agents have a higher affinity for the dopamine receptor and are associated with higher risk for the development of EPS. Low-potency agents have less affinity for dopamine receptors; and although they have less risk for causing EPS, they are associated with more adverse effects from their activity at histamine, muscarinic, and receptors. Efficacy . When dosed in equivalent doses, the various typical antipsychotics have similar efficacy .

33. 33 Typical antipsychotics are thought to be as effective as atypical antipsychotics for positive symptoms but are less effective for negative symptoms.

34. 34 Adverse effects . Typical antipsychotics are associated with several adverse effects. The activity of the various typical antipsychotics at the dopamine , muscarinic, and histamine receptors is responsible for many of the adverse effects of these medications.

35. 35 Extrapyramidal side effects can occur with all the typical antipsychotics, especially with high potency typical antipsychotics. Four types of extrapyramidal side effects have been described: Acute dystonia Akathisia Pseudoparkinsonism Tardive dyskinesia. Acute dystonia describes sudden muscle spasms that primarily occur in the eye, neck, face, and throat muscles. An acute dystonic reaction can be a medical emergency; therefore , use of an intravenous or intramuscular treatment may be warranted for quick symptom resolution.

36. 36 Management includes the use of anticholinergic agents like benztropine and diphenhydramine ; if ineffective, benzodiazepines can also be used. Prevention of future reactions may be achieved by decreasing the dose of antipsychotic, using oral anticholinergic, or changing therapy to an atypical antipsychotic . Akathisia is described as inner restlessness associated with feelings of having to move. (a) Patients with akathisia may pace or be unable to sit still. This may occur within days to a few months after the initiation of therapy or increase in dose. ( b) Treatment of akathisia includes dose reduction of the antipsychotic, lipophilic-blockers or benzodiazepines. Therapy may also be changed to an atypical antipsychotic. Anticholinergic agents may not be useful in the treatment of akathisia.

37. 37 Pseudo-parkinsonism clinically appears similar to idiopathic Parkinson disease and includes symptoms like shuffling gait, masklike face, cogwheel rigidity, and resting or pill-rolling tremor . This can occur within 1 to 3 months after starting therapy or increasing the dose of the antipsychotic agent. This is treated by changing to an atypical antipsychotic, decreasing the dose, and/or adding an anticholinergic agent . Tardive dyskinesia (TD) usually does not occur until the patient has been taking antipsychotics for a year or more. It is a movement disorder that can occur in various locations of the body, including the face, tongue, hips, and extremities . Movements can be dystonic ( fixed ) or choreoathetoid (rhythmic).

38. 38 Common movement disorders include tongue chewing, lip smacking, and rhythmic movements of the trunk . TD may be irreversible, so patients taking antipsychotics should be monitored closely for the appearance of any movement disorders. A tool such as the Abnormal Involuntary Movement Scale (AIMS) is available to assist in monitoring TD. Vigilant monitoring for signs of TD is the best way to prevent it from occurring. Stopping the causative agent (if possible) and switching to an atypical antipsychotic may be the best treatment for preventing irreversible TD. Multiple treatments have been used to attempt to treat TD, although none have been definitively proven to be effective . These include vitamin E, benzodiazepines, baclofen, and reserpine.

39. 39 5. Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal adverse effect of antipsychotics. Signs and symptoms include fever, severe rigidity, altered mental status, unstable blood pressure, tachycardia, incontinence, elevated creatine kinase, and increased white blood count. NMS has a sudden onset, and should prompt immediate discontinuation of all antipsychotics . Antipsychotics are recommended not to be restarted for at least 2 weeks following the resolution of NMS. It is also recommended to restart antipsychotic therapy with a different medication. Treatment includes supportive care and the use of bromocriptine and/or dantrolene .

40. ATYPICAL ANTIPSYCHOTICS 40 Eg: Clozapine, risperidone , olanzapine, quetiapine , ziprasidone , aripiprazole, paliperidone , asenapine , iloperidone and lurasidone The mechanism of action for atypical antipsychotics is different from that of the typical antipsychotics . With the exception of aripiprazole, the atypical antipsychotics are dopamine antagonists but also potently block 5-H T 2A-receptors . They block 5-HT to a greater extent than dopamine. Aripiprazole is a partial dopamine and 5-HT1A -agonist and a 5-H T 2A-antagonist. Asenapine has a high affinity for 5-HT, dopamine, alpha, and histaminergic receptors with low affinity for muscarinic receptors.

41. 41 Iloperidone acts at numerous 5-HT and dopamine receptors and has high affinity for alpha-1 receptors. Lurasidone is a partial agonist 5-HT 1A-receptor with no affinity for muscarinic or histaminergic receptors. Receptor affinity differs for the various atypical antipsychotics. All atypical antipsychotics have activity at the 5-HT 2A-receptor and dopamine receptor. Atypical antipsychotics may have increased efficacy for negative symptoms compared to typical antipsychotics.

42. 42 GENERAL ADVERSE EFFECTS OF ANTIPSYCHOTICS

43. 43 Neuroleptics/antipsychotics and their commonly associated attributes and problems

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45. 45 Unique formulations of atypical antipsychotics are available for patients. Orally disintegrating tablets. Risperidone , olanzapine, aripiprazole, and asenapine are avail0ffable as orally disintegrating tablets. Asenapine must be given sublingually to increase its absorption . If the tablet is swallowed, its bioavailability significantly decreases from 35% to less than 2%. b . Intramuscular formulations. Ziprasidone , olanzapine, and aripiprazole are available in intramuscular formulations for use in acutely agitated patients with schizophrenia. Ziprasidone may be given as 10 or 20 mg. The 10 mg dose may be repeated in 2 hrs , and the 20 mg dose may be repeated in 4 hrs. The maximum daily dose is 40 mg.

46. 46 Olanzapine may be given as 10 mg. The 10 mg dose may be repeated every 2 hrs up to a maximum of 30 mg daily . ( 3) Aripiprazole may be given as 9.75 mg. The 9.75 mg dose may be repeated every 2 hrs up to a maximum of 30 mg daily.

47. 47 TREATMENT ALGORITHM

48. REFERENCES 48 https :// www.researchgate.net/publication/267099264 Pathology and Therapeutics for Pharmacists, A basis for clinical pharmacy practice Third Edition Russell J Greene, Norman D Harris. Page No : 408-423. Clinical Pharmacy and Therapeutics, Roger Walker, Cate Whittlesea , Fifth Edition. Page No : 479-486. Applied Therapeutics: The Clinical Use Of Drugs Ninth Edition, Mary Anne Koda -Kimble, et.al., Page No : 78.1 – 78.25. Pharmacotherapy: A Pathophysiological approach, Tenth Edition, Joseph T Dipiro et.al., Page No : 2948-2955. Comprehensive Pharmacy Review for NAPLEX Eighth Edition, Leon Shargel , Alan H. Mutnick , Paul F. Souney , Larry N. Swanson, Page No : 793-799.

49. 49 HAVE A GOOD DAY!!