Psychosis

Dolly Chauhan
M.Pharm

1. Psychosis Presented by: Dolly Chauhan M.pharm (Pharmacology) 1 st year MRSPTU , Bathinda Department of Pharmaceutical Sciences and Technology

2. Introduction True psychosis usually involves severe symptoms such as Delusions and paranoia. The common belief that anyone who goes crazy or is aggressive must be psychotic is not strictly correct in medical terminology. Psychotic disorders mainly focus on the symptoms where the person is detached from reality, and the main such symptoms are delusions and paranoia (extreme and irrational distrust of others) or hallucinations.

3. Definition P sychosis : It is a chronic neurological Behaviour and mental illness effect 1% of population and now a days mainly adolescence. Psychosis refers to an abnormal condition of mind described as involving a “ loss of contact with reality ”. People experiencing psychosis may exhibit some personality changes and thought disorder. Depending on the severity , this may be accompanied by unusual or bizarre (strange) Behaviour, as well as difficulity with social interaction and impairment in carrying out daily life activities. Schizophrenia : (Split mind ) Disorientation of thought is there Eugen Bleuler = Given the term Schizophrenia in 1908

4. Personalities Hypochondria – Excessive anxiety about Health Paranoid – Delusions of harass and injury Obsessional – Obsession about certain things Hysterical – To attract the attention

5. Important areas of brain involved in mental function Reticular Formation – Attention , Arousal anxiety ( ability to con. And control thoughts is impaired). Limbic System – control affect ( Emotions ) mainly prefrontal cortex and deep temporal cortex Basal ganglia : for control of voluntary movements , habit learning ,eye movements and emotions CTZ receptors – include dopamine , serotonin ,histamine ,substance P , opioid and acetylcholine receptors.

6. Psychiatric disorders - 1. Psychosis / Schizophrenia – the ability to recognize reality is lost In this , severe distortion of thinking process False belief –Delusions False Perception – Hallucination Neurodevelopment Disorder

7. Contii… 2. Neurosis – patients are aware about their problem. Eg Anxiety, phobia, obsession (obsessive compulsive disorder) and depression due to loss of money and property. 3.Affective disorde rs (Disorders of mood) Two phases, 1 st is manic phase (excited , violent and difficult to control ) and other is depressive phase (sad mood). If both are present then it is Bipolar Disorder and If 1 st phase is present (Unipolar Disorder).

8. H istory In 1950s , Reserpine an alkaloid from plant Rauwalfia serpentina is used to treat psychosis .In this Dopamine level is decreased and at higher dose side effects like extra pyramidal side effects. Decrease in serotonin and noradrenaline is also there. Side effects are hypotension , Sedation , diarrhea ,Depression and suicidal tendency. Promethazine – Increase in sleep time of barbiturates and for anesthetic practice. Chlorpromazine – 1952 1 st Safe effective anti psychotic agent.

9. Schizophrenia 1. Positive Symptoms –( Energetic ) Something added in personality Delusion – False belief The positive symptoms of schizophrenia are associated with " losing touch " with reality. These symptoms may include: Seeing, hearing, or even feeling things that no one else can Beliefs in something even after it's proven to be false Disorganized thinking, such as trouble organizing thoughts or connecting them logically Involuntary movements or the lack of movement altogether

10. Conti.. Negative symptoms Negative symptoms may mean a disruption in normal everyday emotions and behaviors. These symptoms can sometimes be mistaken for depression or other conditions and may include: Behavior where the person's face or voice does not move or show emotion A lack of feeling pleasure in everyday life An inability to take part in or to stick with planned activities Talking only a little, even when asked to talk

11. Contii… Associated symptoms These symptoms may be subtle compared to the positive symptoms mentioned above. They may include: Difficulty with memory or paying attention Difficulty understanding information to make decisions Smiling or laughing for no appropriate reason Depressed mood (loss of interest) Lack of interest in food (refusing to eat) Disturbed sleeping patterns

12. Selective thought Defects in selective attention and our brain adapt quickly too new environment and distinguish between significant and non- significant stimuli. But in schizophrenia it is not able to do that. Eg. more attention to tickling of clock attract more attention and assume.

13. Causes Genetics Trauma Psychiatric disorder Psychoactive drugs (alcohol) and substance abusers ( cocaine ) Sensory Impairment ( deafness > blindness) Social isolation Migration Widowhood

14. Etiology 1 ) Genes : only environment can not produce Psychosis. DISC 1 : Disrupted in schizophrenia . Gene is responsible for migration and receptor tethering Neurogeulin : Synaptic development, plasticity and proper development. Absence of gene cause clinical schizophrenia. Dyskindin : Tethering of NMDA receptor Maternal virus infection : Prenatal

15. Contii.. 2) Venternal tegmented area (VTA) or neuronal anatomical theory : VTA is responsible for emotion for love ,care, attention and emotion Two area are there : Mesocortical (prefundal cortex ) in this there is decrease in D1 and negative symptoms are seen. Mesolimbic :( Amygdela,hippocampus) in this there is increase in D2 and positive symptoms are seen.

16. Conti… 5) Theory of NMDA : NMDA hypofunction hypothesis , NMDA decrease social interaction NMDA hypofuction causes decrease activity which further decrease in DA and negative symptoms are seen. 5 HT2 increase : increase of DA directly proportional to schizophrenia.

17. Associated medical conditions Multiple Sclerosis Vitamin deficiency (B12 and nicotinic acid) Hepatitis Hypothyroidism Diabetes mellitus Dementia

18. Signs and symptoms Hallucination Delusions Thought Disorders Loss of contact with reality Depression Emotional Changes Personality Changes Behaviour Changes

19. Pathogenesis Brain imaging studies of psychosis, investigating both, changes in brain structure and brain function of people undergoing psychotic episodes , have showen mixed results. Investigating structural changes in brain shows that there was significant gray matter reduction in the cortex of people before and after psychosis. Functional brain scans have revealed that the areas of brain that react to sensory perceptions are active during psychosis . One clear finding is that persons with tendency to have psychotic experiences seem to show increased activation in right hemisphere of the brain.

20. Conti…. Pathogenesis of psychosis can be explained on the basis of Neurotransmitter Abnormalities : 1. Dopamine hypothesis : It states that psychosis results from an overactivity of dopamine function in the brain, particularly in mesolimbic pathway . The major sources of evidence given to support this theory are: Amphetamine produces excess of dopamine Antipsychotic drugs decrease the con. of dopamine in blood Homovanallic acid con. In plasma is increased in psychosis which indicates abnormal turnover of dopamine 2. 5 HT hypothesis: serotonin level increases in patients with psychosis.

21. Types of Psychotic Disorders Schizophrenia Bipolar Disorder Psychotic Depression Schizoaffective Disorder Drug induced Psychosis

22. Clinical types Somatic type Persecutory type Grandiose type Jealous type Erotomatic type

23. Somatic type Also called Monosymptomatic hypochondriacal psychosis. Delusions related to body. Eg. – patient might feel that foul smell emanates from them. That some of their body parts are misshapen ( eg . Nose) or non functioning ( eg . Intestine). That lice or other parasites have infested their body.

24. Persecutory type Most common type Patient believes that he is conspired and harassed or bodily injured ,or followed or poisoned by others.

25. Grandiose type Exalted (extreme happiness) ideas about oneself, of birth , possessions and achievement. In a religious context may believe that they are the chosen prophets of GOD and have mysterious powers to head the masses.

26. Jealous type More common in males Othello syndrome - a psychiatric disorder in which a person holds a strong delusional belief (false belief) that their spouse is being unfaith Held firmly on inadequate grounds and are unchanged even in the face of evidence that they are false.

27. Conti….. Other secondary delusions may be present like he is drugged or poisoned to put to sleep. Elaborate steps are taken to catch paramour ‘red handed’ and private detectives may be engaged to watch the movement of his spouse. They are very resistant to treatment Continues till divorce or separation or death of spouse.

28. Erotomanic type More prevalent in females. Also known as ‘ Clermbault s Syndrome. Patient believes that another person, usually of higher status or endowed with greater qualities, is loving her. Persue their objects of delusion physically or through letters and presents. Very often the affected woman is not attractive ,hails from a poor socio – economic strata and works at a lower level job. If males affected – may be violent or aggressive with the objects of love.

29. Management Hospitalization if severe impairment or suicidal / homicidal threats / patient non- cooperative for treatment. Antipsychotic + antidepressants Antipsychotics control agitation and treat the psychotic features. Drug of choice – Pimozide 68% full remission , 22% partial remission.

30. Conti…. Antidepressants of SSRI (selective serotonin reuptake inhibitors ) groups such as Fluoxetine is preferred. Many may be refractory to treatment. Electroconvulsive treatment (shock) may be needed for secondary repression. Psychotherapy

31. Antipsychotic drugs (neuroleptics) Classification 1. Phenothiazines : Aliphatic side chain : Chloropromazine , triflupromazine Piperidine side chain: Thioridazine Piperazine side chain: Trifluoperazine, Fluphenazine 2 . Butyrophenones: Haloperidol, Trifluperidol,penfluridol 3.Thioxanthenes: Flupenthixol 4.Other heterocyclic: Pimozide, Loxapine 5.Atypical antipsychotics: Clozapine, Risperidine,Olanzapine,Aripiprazole

32. Pharmacotherapy of mental illness Pathophysiology if mental illness in not clear , it maybe dopaminergic overactivity in limbic system (schizophrenia and mania), deficit in monoamines (NA, 5HT) (depression). Treatment is empirical, symptoms oriented and not disease specific. Depending on the Primary use ,the psychotropic drugs may be grouped into: Anti- psychotic Anti manic Anti depressants Anti anxiety Psychomimetic

33. Pharmacotherapy of mental illness First Generation anti psychotics drugs : The first generation anti psychotics drugs ( typical) are competitive inhibitors at a variety of receptors , but their antipsychotic effects reflect competitive blocking of D2 D opamine receptors. First generation are more likely to be associated with movement disorders, particularly for drugs that bind tightly to dopaminergic neuroreceptors, such as haloperidol.

34. Contii… Second Generation anti psychotic drugs ; The second generation anti psychotic drugs (Atypical) have fewer extrapyramidal symptoms (EPS) than the first generation agents, but are associated with higher risk of metabolic side effects, such as diabetes, hypercholesterolemia, and weight gain. The second generation drugs appear to owe their unique activity to blockade both serotonin and dopamine receptors.

35. Pharmacology of chlorpromazine (CPZ) Dopamine receptor Blocking activity in the brain : All of the first generation and most of second generation antipsychotic drugs block dopamine receptors in the brain and periphery (except Clonazapine –like atypical ). The clinical efficacy of typical antipsychotic drugs correlates closely with their relative ability to block D2 receptors in the mesolimbic system of the brain. Uses : Management of Psychotic disorders Management of the manic phase in bipolar disorder Anti emetic management of severe nausea and vomiting Management of severe Behaviour disturbance in children

36. Second generation anti psychotic agents Second Generation anti psychotic drugs : They have weak D2 blocking but potent 5HT2 antagonistic activity. Extrapyramidal side effects are minimal , and they may improve the impaired cognitive function in psychotics.

37. Clozapine First atypical antipsychotic agent, weak D2 blocking actions; few or no extrapyramidal effects Both + ve and –ve symptoms of schizophrenia are improved, used as reserve drug in resistant schizophrenia. The differing pharmacological profile may be due to its relative selectivity for D4 receptors (which are sparse in basal ganglia) and additional 5 HT as well as a blockade.

38. Risperidone Combination of D2 + 5 HT2 receptor blockade . In addition it has high affinity for α1 , α 2 and H1 receptors; blockade of these may contribute to efficacy as well as side effects like postural hypotension.(Light headedness or dizziness when you stand up after sitting or lying down ). Risperidone is more potent D2 blocker than clozapine , extrapyramidal side effects are less only at low doses Caution : increased risk of stroke in the elderly .

39. Drugs used during pregnancy The commonly used antipsychotic medications during  pregnancy are olanzapine, risperidone, and quetiapine; there is no specific evidence that they cause fetal malformations

40. Adverse Effects 1. CNS : Drowsiness, lethargy, mental confusion more with low potency typical anti- psychotics. 2. CVS : Postural hypotension palpitation ,inhibition of ejaculation (especially with thioridazine ) are due to α adrenergic blockade. 3. Anticholinergics : Dry mouth and constipation ( by olanzapine) ,blurring of vision. 4. Endocrine : Hyperprolactinemia (due to D2 blockade) is common with typical neuroleptics and resperidine .This can lower Gn levels, but amenorrhoea, infertility , galactorrhoea and gynaecomastia occur infrequently after prolonged treatment. 5. Metabolic effects : Elevation of blood sugar and triglycerides levels.

41. Contii… 5 . Extrapyramidal disturbances : Mainly with high potency drugs like fluphenazine ,haloperidol ,pimozide , etc. A ) Parkinsonism :with typical manifestations –rigidity ,tremor ,hypokinesia . B) Acute muscular dystonia :Bizarre muscle spasms ,mostly linguo -facial muscles-tongue thrusting and locked jaw. Akathisia : Restlessness,feeling of discomfort.

42. Contii…. Malignant neuroleptic syndrome : due to high dose of potent drugs, rigidity immobility , tremor and hyperthermia . Intravenous dantrolene may benefit .Bromocriptine in large dose has been found useful. Tardive dyskinesia : in this purposeless involuntary facial and limb movements like constant chewing. Miscellaneous: Weight gain