Psychosis refers to abnormal mental state involving loss of contact with reality. Common symptoms include delusions and hallucinations. It is caused by several factors like genetics, trauma, substance abuse etc. Important brain areas involved are limbic system and basal ganglia. Various types of psychotic disorders exist including schizophrenia, bipolar disorder, and drug-induced psychosis. Treatment involves hospitalization, antipsychotic drugs to control symptoms, and psychotherapy. First and second generation antipsychotics are used but come with adverse effects like extrapyramidal symptoms, weight gain, and metabolic issues.

1. Psychosis
Presented by: Dolly Chauhan
M.pharm (Pharmacology) 1st year
MRSPTU , Bathinda

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
 Psychosis : 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 disorders (Disorders of mood)
 Two phases, 1st 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 1st phase is present
(Unipolar Disorder).

8. History
 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 1st 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
Dopamine 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 ,α2 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