This document discusses psychotic disorders and schizophrenia. It defines schizophrenia as a serious mental illness characterized by illogical thoughts, bizarre behavior, and experiences like hallucinations. The diagnostic criteria for schizophrenia include symptoms like delusions and hallucinations. Positive and negative symptoms are assessed using scales. Treatment involves antipsychotic medications, including typical antipsychotics which block dopamine receptors, and atypical antipsychotics which are less likely to cause motor side effects but can increase risks like weight gain. Clozapine is reserved for treatment-resistant cases due to potential side effects. Patient counseling involves ensuring adherence to treatment and monitoring for side effects or relapse.

1. Psychotic Disorders
Muhammad Junaid Farrukh
Pharm D, M Clin Pharm
Hamdard Institute of Pharmaceutical Sciences
Islamabad Campus

2. Psychosis
• Psychosis is a loss of contact with reality, usually including
false beliefs about what is taking place or who one is
(delusions) and seeing or hearing things that aren't there
(hallucinations).
2

3. Psychosis is also part of a number of
psychiatric disorders, including:
• Bipolar disorder (manic or depressed)
• Delusional disorder
• Depression with psychotic features
• Personality disorders (schizotypal, shizoid,
paranoid, and sometimes borderline)
• Schizoaffective disorder
• Schizophrenia
3

4. Definition
Schizophrenia is a serious mental illness characterized by
illogical thoughts, bizarre behavior and speech, and
delusions or hallucinations, such as hearing voice
(American psychiatry association)

5. Pathophysiology

6. Diagnostic criteria for Schizophrenia
(DSM IV) diagnostic and statistical manual of mental
disorders
A. Characteristic symptoms
(1) delusions
(2) hallucinations
(3) disorganized speech (e.g., frequent derailment or
incoherence)
(4) grossly disorganized or catatonic behavior
(5) negative symptoms, i.e., affective flattening
B. Social/occupational dysfunction: Failure to achieve
expected level of interpersonal, academic, or occupational
achievement).
C. Duration: Continuous signs of the disturbance persist for
at least 6 months

7. Positive and negative symptoms scoring
To assess a patient using PANSS, an approximately 45-minute clinical interview is
conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the
interview as well as reports of family members or primary care hospital workers
Positive scale
7 Items, (minimum score = 7, maximum score = 49)
•Delusions
•Conceptual disorganization
•Hallucinations
•Hyperactivity
•Grandiosity
•Suspiciousness/persecution
•Hostility
Negative scale
7 Items, (minimum score = 7, maximum score = 49)
•Blunted affect
•Emotional withdrawal
•Poor rapport
•Passive/apathetic social withdrawal
•Difficulty in abstract thinking
•Lack of spontaneity and flow of conversation
•Stereotyped thinking

8. Positive and negative symptoms scoring
General Psychopathology scale
16 Items, (minimum score = 16, maximum score = 112)
•Somatic concern
•Anxiety
•Guilt feelings
•Tension
•Mannerisms and posturing
•Depression
•Motor retardation
•Uncooperativeness
•Unusual thought content
•Disorientation
•Poor attention
•Lack of judgment and insight
•Disturbance of volition
•Poor impulse control
•Preoccupation
•Active social avoidance
PANSS Total score minimum = 30, maximum = 210

9. Positive and negative symptoms scoring
CGI Severity of
Illness
Corresponding
PANSS score
Mildly ill 58
Moderately ill 75
Markedly ill 95
Severely ill 116

10. Treatment of schizophrenia
Typical
• Chlorpromazine
(Largactil®)
• Flupenthixol
(Fluanxol®)
• Haloperidol
(Serenace® Haldol®)
• Sulpiride (Dogmatil®)
• Thioridazine
(Melleril®)
• Trifluoperazine
(Stelazine®)
Atypical
• Amisulpiride (Solian®)
• Quetiapine (Seroquel®)
• Ziprasidone (Zeldox®)
• Risperidone
(Risperdal®)
• Olanzapine (Zyprexa®)
• Clozapine (Clozaril®)
• Aripiprazole (Abilify®)

11. Typical antipsychotics - MOA
 Blocks receptors for dopamine,
acetylcholine, histamine and
norepinephrine
 Current theory suggests dopamine2
(D2) receptors suppresses psychotic
symptoms
 All typical antipsychotics block D2
receptors

12. Typical antipsychotics Ex: Haloperidol

13. Typical antipsychotics - cont
• Properties
• Effective in reducing positive symptoms during acute
episodes and in preventing their recurrence
• Less effective in treating negative symptoms
• Some concern that they may exacerbate negative
symptoms
• Higher incidence of EPS

14. EPS
Early
reaction
Can be
managed with
drugs
Late reaction
Drug
treatment
unsatisfactory

15. Dystonias
• Develops within a few hours to 5 days after first dose
• Muscle spasm of tongue, face, neck and back
• Oculogyric crisis (involuntary upward deviation of eyeballs)
• Opisthotonus (tetanic spasm of back muscles, causing trunk
to arch forward, while head and lower limbs are thrust
backwards)
• Laryngeal dystonia can impair respiration
• Management
• Anticholinergics (Benztropine, diphenhydramine IM/IV)
• Add scheduled benztropine / diphenhydramine with
antipsychotic

16. Parkinsonism
• Occurs within first month of therapy
• Management
• Centrally acting anticholinergics (scheduled benztropine /
diphenhydramine / benzhexol with antipsychotics) and
amantadine
• Avoid levodopa as it may counteract antipsychotic effects
• Switch to atypical antipsychotics

17. Akathisia
• Develop within first 2 months of therapy
• Compulsive, restless movement
• Symptoms of anxiety, agitation
• Management
• Benzodiazepines (e.g. lorazepam)
• Anticholinergics (e.g. benztropine, benzhexol)
• Reduce antipsychotic dosage or switch to low potency
agent

18. Tardive dyskinesia (TD)
• Develops months to years after therapy
• Involuntary movements of tongue and face
• Can interfere with chewing, swallowing and
speaking
• Symptoms are usually irreversible
• Management:
• Mild: Use milder atypical
• Severe: Clozapine
• Gradual drug withdrawal

19. Atypical antipsychotics
Ex: Risperidone

20. Atypical antipsychotics
• Properties
• Available evidence to show advantage for some
(clozapine, risperidone, olanzapine) but not all atypicals
when compared with typicals
• At least as effective as typicals for positive symptoms
• May be more efficacious for negative symptoms (still
under debate)

21. Atypical antipsychotics
• Properties – cont
• Less frequently associated with EPS
• More risk of weight gain, new onset
diabetes, hyperlipidemia
• Novel agents, more expensive

22. Atypical antipsychotics
• All atypical antipsychotics are equally
effective at therapeutic doses
• Except clozapine
• Most effective antipsychotic
• For resistant schizophrenia
• 2nd line due to life-threatening side effect

23. Atypical antipsychotics
Drug Advantages Disadvantages
Clozapine For treatment-resistant
cases, little EPS
Risk of fatal agranulocytosis
Risperidone Broad efficacy, little or no
EPS at low doses
EPS and hypotension at high
doses
Olanzapine Effective with positive and
negative symptoms, little
or no EPS
Weight gain
Quetiapine Similar to risperidone,
maybe less weight gain
Dose adjustment with
associated hypotension, BD
dosing
Ziprasidone Perhaps less weight gain
than clozapine, Inj A/V
QT prolongation
Aripiprazole Less weight gain, novel
mechanism potential
Uncertain

24. Atypical antipsychotics
• 1st line atypical antipsychotics
• All atypicals except clozapine
• NICE recommendations
• Atypical antipsychotics considered when choosing 1st
line treatment of newly diagnosed schizophrenia
• Treatment option of choice for managing acute
schizophrenic episode
• Considered when suffering unacceptable Adverse
effects from a conventional antipsychotic
• Changing to an atypical not necessary if typical
controls symptoms adequately and no unacceptable
Adverse effects

25. Atypical antipsychotics
• 2nd line atypical antipsychotic
• Clozapine
• Most effective antipsychotic for reducing symptoms
and preventing relapse
• Use of clozapine effectively reduce suicide risk
• 1% risk of potentially fatal agranulocytosis
• Acute pronounced leukopenia with great reduction
in number of neutrophil
• NICE recommendations
• Clozapine should be introduced if schizophrenia is
inadequately controlled despite sequential use of 2 or
more antipsychotic (one of which should be an
atypical) each for at least 6-8 weeks)

26. Depot antipsychotics
• Depot APs
• Fluphenazine decanoate
• Flupenthixol decanoate
• Risperidone
• Depot APs may confer an advantage over conventional oral APs by
improving adherence to drug treatment.
• Depot preparations could ensure continuous drug delivery, overcome
bioavailability problems and avoid the risk of overdose with oral
medications.
• However, depot preparations do not allow flexibility in administration and
dose adjustment.
• Patients may also complain of side effects at site of injection e.g. pain,
oedema, pruritus and sometimes a palpable mass.

29. Common side effects of atypical antipsychotics

30. Patient counselling and Family education
Patient should be counseled to follow the prescribed medications.
Family member are advised
 to monitor patients routine
 To check if he is taking medicine in time or any family member take
self responsibility to administer medicine
 To ensure monthly administration of i/m depot to minimize risk of
relapse
 If patient shows any signs or symptoms of relapse or ineffective
treatment report the doctor immediately

31. References
 https://ww1.cpa-
apc.org/Publications/Clinical_Guidelines/schizophrenia/november2005/Pharmacotherapy.asp
 http://www.ncbi.nlm.nih.gov/pubmed/16086618
 http://bjp.rcpsych.org/content/195/52/S13.full.pdf
 http://www.ingentaconnect.com/content/apl/pcp/2001/00000005/00000003/art00005
 Conley RR, Mahmoud R. Am J Psychiatry 2001; 158: 765-774.
 Zhong KX et al. Poster presented at the 16th European College of
Neuropsychopharmacology Congress, Prague, Czech Republic, 2003
 http://www.ncbi.nlm.nih.gov/pubmed/15231461