Atypical Antipsychotic

1. RISPERIDONE
DR. SARANG PANDIT
JUNIOR RESIDENT
LATA MANGESHKAR HOSPITAL
NAGPUR

3. HISTORY
• Developed by Janssen Clag, subsidy of
Johnson and Johnson 1988-1992
• First approved by FDA in 1994
• Present in WHO list of most important
medications needed in basic health system

4. Timeline of Major
Antipsychotic Therapies
Ziprasidone
1950 1960 1970 1980 1990 2001 2003 2007
ECT, etc.
Chlorpromazine
Fluphenazine
Thioridazine
Haloperidol Clozapine
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Consta
Paliperidone
Consta = Long-acting injectable risperidone

5. Antipsychotic drugs are not curative and do
not eliminate the fundamental thinking
disorder, but they often:
1.Decrease the intensity of hallucinations
and delusions.
2.Permit the psychotic patient to function in
a supportive environment.

6. Chemistry and Preparations
• It is Benzisoxizole derivative.
• C23-H27-FN4-O2.
• Trade names :- Risnia, Risdone, Sizodon.
Formulation Strength
Tablet (Including mouth
dissolving)
0.25/0.5/1/2/3/4
Solution 1mg/mL
Injection (Powder for
suspension, ER)
12.5/25/37.5/50

7. PHARMACOKINETICS
Absorption
o PO
• Absolute oral bioavailability is 70%.
• Tmax is 1 hr for Risperidone (parent compound), 3 h (9-
hydroxyrisperidone extensive metabolizers), or 17 h (9-
hydroxyrisperidone poor metabolizers).
• Steady state is approximately 1 day(extensive metabolizers) or
approximately 5 days (poor metabolizers).
• Food - DOES NOT affect absorption.
o IM
• Release of the drug-3rd wk after injection.
Maintained from 4-6 wk.
Subsides by 7th wk.
• Steady state is reached after 4 injections.

8. Distribution
• Rapidly distributed.
• Vd :– 1-2 L/kg.
• Protein binding is approximately 90% (parent compound)
and approximately 77% (9-hydrox yrisperidone).
Metabolism
• Extensively metabolized in liver - CYP2D6 to major active
metabolite 9-hydroxyrisperidone.
• 9-hydroxyrisperidone has similar activity to risperidone.

9. Elimination
• Eliminated in urine (70%) and feces (14%).
o PO
• The half-life is 20 h (overall mean half-life) for
combined risperidone and 9-hydroxyrisperidone.
o IM
• The half-life of risperidone plus 9-
hydroxyrisperidone is 3 to 6 days.

10. MECHANISM OF ACTION
Receptor (NT) Action
D1,D2,D3, D4, D5
(Dopamine)
Blocks mesolimbic pathway, prefrontal cortex, limbic pathway,
tubero-infudibular pathway
5HT2A, 5HT2C
(Serotonin)
2A – ↓ EPS, improvement of –ve symptoms as compared to
typical
2C – Weight gain
α1 High affinity. Orthostatic hypotension, sedation.
α2 Greater +ve, -ve, affective, cognitive symptom control.
H1 Sedation, ↓ in vigilance, drowsiness & weight gain.
•It blocks 65% of D2 receptors (lowest threshold for
antipsychotic efficacy)
•At 6mg/day - 80% of D2 receptors are blocked and EPS
can occur.

12. INDICATIONS AND DOSAGES
ACUTE PSYCHOSIS AND SCHIZOPHRENIA
o ADULTS
• INITIAL DOSE SHOULD NOT BE GREATER THAN 2
MG/DAY,
• DOSE INCREASE OF 1-2 MG/DAY ACCEPTABLE BUT
SHOULD BE SPACED 24 HRS APART
• TARGET DOSE IS 2-8 MG/DAY IN OD/DIVIDED
DOSAGE

13. INDICATIONS AND DOSAGES
o ADOLESCENTS (13 TO 17 Y OF AGE )
• PO INITIATE TREATMENT WITH 0.5 MG ONCE DAILY
AS A SINGLE DOSE IN THE MORNING OR EVENING. IF
INDICATED, DOSAGE ADJUSTMENTS SHOULD BE AT
INTERVALS OF NO LESS THAN 24 H, IN INCREMENTS
OF 0.5 TO 1 MG/DAY, AS TOLERATED, TO A
RECOMMENDED DOSAGE OF 3 MG/DAY (DOSE
RANGE, 1 TO 6 MG/DAY).
• PATIENTS EXPERIENCING PERSISTENT SOMNOLENCE
MAY BENEFIT FROM ADMINISTERING HALF THE DOSE
TWICE DAILY.

14. INDICATIONS AND DOSAGES
BIPOLAR MANIA
o ADULTS
• 2 TO 3 MG/DAY ONCE DAILY INITIALLY. ADJUST
DOSE AT INTERVALS OF NO LESS THAN 24 H, IN
INCREMENTS/DECREMENTS OF 1 MG/DAY (USUAL
DOSAGE, 1 TO 6 MG/DAY). NO DATA TO SUPPORT
SHORT-TERM TREATMENT BEYOND 3 W K.

15. INDICATIONS AND DOSAGES
o ADOLESCENTS (13 TO 17 Y OF AGE )
• START WITH 0.5 MG ONCE DAILY. IF INDICATED,
DOSAGE ADJUSTMENTS SHOULD OCCUR AT
INTERVALS OF NO LESS THAN 24 H AND IN
INCREMENTS OF 0.5 OR 1 MG/DAY, AS
TOLERATED, TO A RECOMMENDED DOSAGE OF
2.5 MG/DAY (DOSE RANGE, 0.5 TO 6 MG/DAY).

16. INDICATIONS AND DOSAGES
IRRITABILITY ASSOCIATED WITH
AUTISTIC DISORDER
• CAN BE ADMINISTERED ONCE DAILY OR HALF THE TOTAL
DAILY DOSE TWICE DAILY. USE CAUTION WITH DOSAGE
FOR CHILDREN WEIGHING LESS THAN 15 KG. FOR
PATIENTS LESS THAN 20 KG, THE INITIAL DOSAGE IS 0.25
MG/DAY. AFTER A MINIMUM OF 4 DAYS, THE DOSAGE
MAY BE INCREASED TO 0.5 MG/DAY. MAINTAIN THIS DOSE
FOR A MINIMUM OF 14 DAYS. I F SUFFICIENT CLINICAL
RESPONSE IS NOT OBTAINED, THE DOSAGE MAY BE
INCREASED IN INCREMENTS OF 0.25MG/DAY AT
INTERVALS OF NO LESS THAN 14 DAYS.

17. • FOR PATIENTS 20 KG OR MORE, THE INITIAL DOSAGE
IS 0.5 MG/DAY. AFTER A MINIMUM OF 4 DAYS, THE
DOSAGE MAY BE INCREASED TO 1 MG/DAY.
MAINTAIN THIS DOSE FOR A MINIMUM OF 14 DAYS.
I F SUFFICIENT CLINICAL RESPONSE IS NOT
OBTAINED, THE DOSAGE MAY BE INCREASED IN
INCREMENTS OF 0.5 MG/DAY AT INTERVALS OF NO
LESS THAN 14 DAYS.

18. INDICATIONS AND DOSAGES
OTHER OFF LABEL USES
– TOURETTE SYNDROME
– PTSD
– PSYCHOSIS RELATED TO ALZHEIMERS
– BEHAVIOUR DISTURBANCES RELATED TO MENTAL
RETARDATION
– TREATMENT RESISTANT OCD
– BIPOLAR DEPRESSION

19. Adverse effects
CNS :- EPS (Including Parkinsonism, dystonia,
tremors, akathasia & dyskinesia); tardive
dyskinesia; automatism (m/c in Paeds.);
drowsiness
CVS :- Tachycardia, palpitations, postural
hypotension (d/t α-blockade), QTc prolongation
(mild), AV bundle branch blockade (rare)
RS :- Dyspnea, cough, rhinitis and URTI (Paeds.)
GIT :- Abdominal pain & hypersalivation (m/c),
dyspepsia, dry mouth, nausea and diarrhea.

20. Haematological :- Anemia, epistaxis (rare)
Genito-Urinary :- Ejaculatory disorder,
priapism, sexual dysfunction (men), non
purpural lactation and menstrual irregularities
(women) [d/t hyperprolactinemia]
Dermatological :- Rash, giant urticaria &
angioedema

21. Black Box warning
• Increased Mortality in Elderly Patients with Dementia-Related
Psychosis :- Elderly patients with dementia-related psychosis
treated with antipsychotic drugs are at an increased risk of
death.
• Cerebrovascular Adverse Reactions, Including Stroke, in
Elderly Patients with Dementia-Related Psychosis :-
Cerebrovascular adverse reactions (e.g., stroke, transient
ischemic attack), including fatalities were reported in patients
(mean age 85 years; range 73-97) in trials of risperidone in
elderly patients with dementia-related psychosis. Risperidone
is not approved for the treatment of patients with dementia-
related psychosis.

22. • Neuroleptic Malignant Syndrome
• Clinical manifestations
1. Hyperpyrexia, muscle
rigidity, altered mental
status, and autonomic
instability (irregular pulse or blood
pressure, tachycardia, diaphoresis, and
cardiac dysrhythmia).
2. Additional signs may
include elevated creatine
phosphokinase (CPK),
myoglobinuria,
rhabdomyolysis, and acute
renal failure.
• Management
1. Immediate discontinuation
of antipsychotic drugs
2. Intensive symptomatic
treatment and medical
monitoring
3. Treatment of any
concomitant serious
medical problems for which
specific treatments are
available.

23. Tardive Dyskinesia
• A syndrome of potentially irreversible,
involuntary, hyperkinetic movements.It causes
facial movements like constant chewing,tongue
protrusion&facial grimacing.
• Caused D/t chronic blokage of nigrostriatal
pathway.
• T/t- non-specific pharmachotherapy, but
discontinuation of drug may help

24. • Hypercholesterolemia,Hyperglycemia &
Diabeties Mellitus :- less risk than other anti
psychotics.
• Orthostatic Hypotension & Syncope :- due to α-
receptor antagonist properties
• Hyperprolactinemia :-
– ↑ prolactin levels [mean of 15.4 ng/dL].
– ↓ reproductive functioning - galactorrhea, amenorrhea,
anorgasmia. If left untreated, leads to decreased bone
mineral density in both sexes, with hypogonadism.
– F/H/O Breast cancer s/b enquired before T/t.

25. Special population
• Pregnancy :- Category C drug.
• Lactation :- Excreted in breast milk.
Milk : plasma conc. < 0.5
• Geriatric :- Use cautiously as prone for
orthostatic hypotension. Concomitant
administration with Furosemide increases risk
of mortality in elderly patients.

26. Overdosage
• No mortality reported even upto 360 mg of
Risperidone.

27. DRUG INTERACTIONS
• Inhibition of CYP2D6 by drugs such as
paroxetine & Fluoxetine blocks formation of
active metabolite.
• Combined use of risperidone with SSRI can
result in significant hyperprolactnemia.

28. THANK YOU
THANK YOU