A compiled Power point presentation on "Antipsychotic drugs" suitable for Undergraduate level medical students and also PG students in the subject of Pharmacology.
A compiled Power point presentation on "Antipsychotic drugs" suitable for Undergraduate level medical students and also PG students in the subject of Pharmacology.
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Typical antipsychotics and dopamine in psychosis Ann Sparks
Overview of TYPICAL/Second Generation Antipsychotics (Neuroleptics, Classic, Conventional, D2 Receptor Antagonists). Includes an historical context, Dopaminergic (Reward) Pathways, Symptoms of Psychosis, Side Effedts of Typical Antipsychotics, and animations (if they "translate!").
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Typical antipsychotics and dopamine in psychosis Ann Sparks
Overview of TYPICAL/Second Generation Antipsychotics (Neuroleptics, Classic, Conventional, D2 Receptor Antagonists). Includes an historical context, Dopaminergic (Reward) Pathways, Symptoms of Psychosis, Side Effedts of Typical Antipsychotics, and animations (if they "translate!").
Parkinson’s disease is a progressive disorder of the nervous system that, in the early stages, is characterized by mild signs that are often missed. These signs can be remembered by the mnemonic “SMART”
S = Shuffling-Gait
M = Mask-like Face
A = Akinesia
R = Rigidity
T = Tremor
antipsychotics history, managment of psychosis,side effect of antipsychotics, mechanism of antipsychotics, atypical antipsychotics,2nd generation antipsychotics.
A disorder of the central nervous system that affects movement, often including tremors.
Nerve cell damage in the brain causes dopamine levels to drop, leading to the symptoms of Parkinson's.
Parkinson's often starts with a tremor in one hand. Other symptoms are slow movement, stiffness and loss of balance.
Treatment consists of medications to increase dopamine.
Bioavailability and Bioequivalence StudiesPranav Sopory
BA and BE studies.
Seminar presented in All India Institute of Medical Sciences (AIIMS - New Delhi).
Focus in Pharmacokinetic parameters (Cmax, AUC)
Single dose PK study, Steady state PK study, Modified drug release PK study, In vivo mechanisms, invitro mechanisms, Pharmacodynamic Study, Comparatice Clinical Trials. Biowavers and Biosimilimars.
Reference: CDSCO guideline, USFDA guideline, ICH guidelines
Therapeutic prospects in Cancer Immunotherapy.
Interleukins for Renal Cell Carcinoma.
BCG for Bladder Cancer.
Vaccination Strategies: Oncolytic virus for melanoma, Dendritic Cell therapy for CA Prostate.
Immune Checkpoint inhibitors. PD1 and PD L1 inhibitors.
Adoptive Cell Therpay. CAR T Cell Therapy
Clinical efficacy. Costs.
JNC 8 guideline to Management of HypertensionPranav Sopory
JNC - 8 guidelines to management of Hypertension.
Rencent developments in CKD (Chronic Kidney Disease) and DM (Daibetes Mellitus) management.
Drugs discussed along with doses and side effects.
Compelling indiactions.
2017 AHA/ACC criteria for Hypertension management in brief.
>> Contains animation. Download and view.
Therapeutic Club on Tauopathy. Its pathophysiology and therapeutic targets. Interactive session held at All India Institute of Medical Sciences, New Delhi - 110029 on 28th October 2017.
Metronomic Chemotherapy Vs Best Supportive Care in Progressive Pediatric Tumors.Pranav Sopory
Journaal Club discussing the Randomised Clinical Trial (RCT) of metronomic chemotherapy in extra cranial, non-hematopoietic solid malignancies in paediatric population (aged 5-18 years). Courtesy Dr Atul Batra, Asst. Prof. Medical Oncology, IRCH, AIIMS.
Genetic and epigenetic biomarkers for therapeutic monitoring in neurological ...Pranav Sopory
Seminar held on Genetic and epigenetic biomarkers for therapeutic monitoring in neurological disorders.
Multiple Sclerosis, Alzheimer's Disease and Parkinson's Disease.
Biomarkers and epigenetic explained. New epigenetic drug targets.
Explanation of Preclinical (Animal) Models of Seizure and Epilepsy.
General overview of Seizure and Epilepsy and its current Management. Need to develop newer drugs and Newer models. Current models for Acute Seizure. Kindling explained. PPT contains overview and Protocol.
Antibody drug conjugates current status and future perspectivesPranav Sopory
ADC are an emerging class of new anti-cancer agents.
They are the future of oncological management.
Discussed here are their past, present and probable future.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The POPPY STUDY (Preconception to post-partum cardiovascular function in prim...
Schizophrenia and Psychosis: Antipsychotics
1. Pharmacotherapy of
Psychosis
Dr Pranav Sopory
All India Institute of Medical Sciences
New Delhi
Mob: +91 9999491690
Email: pranav.sopory@gmail.com
LinkedIn: www.linkedin.com/drsopory
Self-portrait of a patient with Schizophrenia
2. Contents
• Introduction to Psychosis
• Major Dopaminergic Pathways
• Typical Antipsychotics (FGA) & Adverse Effects
• Atypical Antipsychotics (SGA) & Adverse Effects
• Adherence to Antipsychotics
• Phases of Treatment
• Newer Agents
3. What is psychosis?
• Psychosis is a symptom of an underlying mental disorder.
• Components:
1. Delusions (false beliefs)
2. Hallucinations (seeing or hearing things that others do not see or hear)
3. Incoherent speech and behavior that is inappropriate for the situation.
• Characteristic: Loss of insight
• Psychotic disorders are associated with:
1. Sleep problems
2. Social withdrawal
3. Lack of motivation
4. Difficulties carrying out daily activities.
https://www.nhs.uk/conditions/psychosis/
4. Psychotic disorders (DSM-V)
1. Mood disorders (major depression or mania) with psychotic features
2. Substance-induced psychosis
3. Dementia with psychotic features
4. Delirium with psychotic features
5. Delusional disorder
6. Schizophrenia (Prevalence in India : 2-3/1000)
5. Major Dopaminergic Projections
Goodman & Gilman’s The Pharmacological Basis of Therapeutics; 13th Edition,
Figure 13-11
1. Mesolimbic
2. Mesocortical
3. Nigrostriatal
4. Tuberoinfundibular
6. Case I
• A person quarrels and hits his neighbour. The next day he starts
feeling that he is being followed by the police who may arrest him.
He also feels that his neighbour is controlling him through radio
waves. He later suspects that his neighbour has transformed into a
demon. There are continuous voices commenting his each and
every action.
7. Mesolimbic Pathway
• MLP: VTA → NA
• Reward/ Addiction Pathway
• ↑ ↑ DA: Overactive MLP
Positive Symptoms:
1. Hallucinations & delusions
2. Disorganized thought & speech
3. Bizarre behaviors
Ventral Tegmental Area (VTA)
Nucleus Accumbens (NA)
9. 1. Typical Antipsychotics (FGA)
• 1933, France: Promethazine (anti-histaminic)
• Sedative side-effects noted & used as a pre-op ‘calming agent’
• 1950: Chlorpromazine developed and marketed as anti-anxiety pill.
• 1952, USA: 38 psychotic patients administered chlorpromazine.
• Results: ↓ delusional and hallucination episodes
• 1955: Chlorpromazine approved in USA for treatment of psychosis
Ban TA. Fifty years chlorpromazine: a historical
perspective. Neuropsychiatr Dis Treat. 2007
12. Adverse EffectsSpasm of
muscles of
tongue, face,
neck and back
Subjective and
objective restlessness.
No anxiety or agitation
Acute Dystonia
1-5 days
Akathisia
5-60 days
Bradykinesia, rigidity,
variable tremor, mask
facies, shuffling gait
Parkinsonism
5-30 days
Elderly at risk
Perioral tremor
(? Late variant
of
parkinsonism)
Rabbit syndrome
Months to years
Extreme rigidity, fever,
unstable blood pressure,
myoglobinemia
Neuroleptic
Malignant Syndrome
Weeks to months
13. Tuberoinfundibular Pathway
Pituitary Gland
• TIP: Hypothalamus → Anterior Pituitary
• Inhibition of Prolactin release
• ↓ ↓ DA: by FGA > SGA
Hyperprolactinemia
1. Galactorrhea & amenorrhea (F)
2. Sexual dysfunction or infertility (M+F)
Hypothalamus
M/c cause of non-adherence in young males
SCZ onset: M/c in adolescent males
14. Management of Side effects
• zc
REACTION Rx
Acute Dystonia Antiparkinsonian agents
(Diphenhydramine 25-50 mg IM or Benztropine 1-2mg IM
Akathisia Reduce dose or change drug.
Clonazepam.
Propranolol (low dose: 20-80 mg/d) more effective than
antiparkinsonian agents
Parkinsonism Dose reduction.
Change medication.
Antiparkinsonian agents.
Neuroleptic Malignant Syndrome Stop antipsychotic immediately.
Supportive Care.
Dantrolene & Bromocriptine.
Rabbit Syndrome Antiparkinsonian agents often helps
Hyperprolactinemia Rapid reversal on stopping antipsychotic.
Reduce dose or change drug. Goodman & Gilman’s The Pharmacological Basis of
Therapeutics; 13th Edition, Table 16-5
15. Case II
• A 24-year-old football player has been discharged after treatment of
a psychotic episode. While his hallucinations, delusions, and
paranoia have subsided, he is demonstrating marked cognitive
impairment. He has difficulty reading the newspaper, hardly speaks
to his family members, stays locked-up in his room for days and
doesn’t enjoy playing football anymore.
? Treat with Typical Antipsychotics
17. SGA: 5-HT2A>>D2 (Precise mechanism remains unclear!)
Mauri MC, Paletta S, Maffini M, et al. Clinical pharmacology of
atypical antipsychotics: an update. EXCLI J. 2014
Receptor Action Proposed Effect Clinical Effect
5-HT2A Strong Antagonist ↑ Neocortical DA ↓ Negative Symptoms
5-HT1A Partial Agonism ? ↓ Negative Symptoms
↓ Anxiety
5-HT2C Strong Antagonist ? ~same~
D2 Weak antagonist Same as Atypical ↓ Positive Symptoms
D2
5-HT2A
HIGH LOWFGA SGA
BLOCKADE
18. SGA: Differential D2 action
1. Fast-off-D2 Effect
• SGA: Lower affinity than DA
Seeman P. Clozapine, a fast-off-D2 antipsychotic.
ACS Chem Neurosci. 2014
Beaulieu JM et al., The Akt-GSK-3 signaling cascade in the
actions of dopamine. Trends Pharmacol Sci. 2007
G-protein-mediated signaling
β-Arrestin-2-mediated signaling
(Akt-GSK3)
FGA: Inhibit both pathways with similar efficacy
SGA: Inhibit cAMP-independent mainly
Explains ↓ EPS associated with SGA
2. cAMP-independent mechanisms
19. Classification of SGA
Classfn Receptor Affinity Drugs
SDA:
Serotonin-Dopamine Antagonists
(5-HT2A and D2) Risperidone and
Paliperidone (metabolite)
Ziprasidone
Iloperisone
Lurasidone
MARTA:
Multi-Acting Receptor Targeted
Antipsychotics
(SDA + M1, H1, 5-HT1A, 5-HT1C) Clozapine
Olanzapine
Quetiapine
Asenapine
D2/D3 receptor antagonists D2 and D3 Amisulpride
Partial D2 Agonism (3rd GEN.*) D2 Aripiprazole
General PD property: D2 BLOCKADE essential for antipsychotic effect !
Classification: based on Receptor affinity
20. 18F PET-DOPA: D2 Occupancy and Behavioral Effects
D2 blockade:
• 65%: Anti-psychosis
• 72%: Hyperprolactinemia
• 80%: EPS
• 90%: NMS
Positron Emission Tomography in Schizophrenia: A New
Perspective, J Nucl Med April 2010 vol. 51 no. 4 511-520
Schizophrenia patient
Healthy volunteer
21. 3. Partial D2 receptor agonist: Third Generation
Dopamine
Dopamine +
Haloperidol
Aripiprazole
Dopamine +
Aripiprazole
Aripiprazole, Brexipiprazole, Cariprazine
}
• Antipsychotic activity requires:
80-95 % D2 occupancy.
25%
• Intrinsic D2 activity: 25%
• Sufficient postsynaptic signal to
remain below EPS threshold
• Better adherence than other drugs
22. Adherence to antipsychotics
• Highest rate of non-adherence among all chronic illnesses
• 75% over 2 year course*
Causes:
• Intolerable S/E
• Lack of insight
• Persistent residual disease
Leads to psychotic relapse
Management?
*Leucht S et al., Antipsychotic drugs versus placebo for relapse prevention in schizophrenia:
a systematic review and meta-analysis. Lancet. 2012 Jun 2;379(9831):2063-71.
Least tolerable: Haloperidol- Max. EPS
23. Depot preparations available in India
Grover S et al., Clinical Practice Guidelines for Management of Schizophrenia.
Indian J Psychiatry. 2017
Name of antipsychotic Dosage (mg) Timing (weeks)
Zuclopenthixol decanoate 200 4
Paliperidone palmitate 234 initially followed by
117 monthly
4
Fluphenazine decanoate 12.5-50 2
Haloperidol decanoate 50 4
Risperidone depot 25-50 2
Olanzapine pamoate 210-405 4
Diluent:
Decanoate: Oil-based (sesame/ coconut)
Water-based: palmitate, pamoate
24. Phases of treatment
I. ACUTE PHASE (F.E.P)
• Completely florid symptoms of psychosis
• High R/o harm to family members
• Parenteral adm. of antipsychotics with ↑ sedative action
• Lasts 4-6 weeks
II. CONTINUATION PHASE (Aim-based)
• Prevention of relapses
• Lasts 1 yr. (after F.E.P.), 5yrs (S.E.P.), Life-long (aggressive/suicidal)
III. MAINTENANCE/STABLE PHASE (Goal based)
• Improve functioning
• Improve QoL
D2 blockade achieved within hours
Clinically noticeable difference >2 weeks
PANS scoring possible
Mousavi SG et al., Onset of action of atypical and typical antipsychotics in the
treatment of acute psychosis. J Res Pharm Pract. 2013
25. Receptor Potency (Ki values)
FGA D2 5HT2A M1 A1A A1B H1
SGA
Goodman & Gilman’s The Pharmacological Basis of Therapeutics; 13th Edition,
Table 16-2
Ki: inhibitory constant
Smaller Ki: Greater binding affinity and smaller dose of drug needed for activity
27. Non-dopaminergic Side Effects
Receptor Side-Effect Comments
H1
Sedation & weight gain Highest risk
FGA: Chlorpromazine
SGA: Clozapine, Quetiapine
Useful: Agitated patients (acute psychosis)
M1
Blurred vision, constipation Highest risk: Clozapine
⍺1
Orthostatic hypotension Rx with fludrocortisone
Seen mostly in WEAK D2 blockers: FGA and SGA
28. Tolerance and Physical Dependence
• Loss of efficacy to antipsychotics doesn’t develop
• Antipsychotics are NOT addictive
• Tolerance to non-dopaminergic effects develop (H1, M1, ⍺1)
Chronic D2 blockade:
• Some patients develop postsynaptic supersensitivity: D2
High receptors
• On sudden withdrawal: Emergent Dyskinesia / Tardive Dyskinesia
Time: months to years
Risk proportional to D2 blockade
Rx: VMAT2 inhibitors
Valbenazine, Tetrabenazine
Orofacial dyskinesia
Widespread choreoathetosis
↑ activity in Nigrostriatal Pathway
Highest R/o Elderly: missed drug
29. Adverse Metabolic Effects (68%: MetS)
Insulin resistance:
Chlorpromazine: Initially used pre-surgery for insulinoma
Risk: Clozapine > Olanzapine ……… Ziprasidone (least)
↓ risk: Aripiprazole, Brexipiprazole, Cariprazine (GG-13E)
Elevated Triglycerides:
Clozapine > Olanzapine > Quetiapine
Weight independent: occurs within the first 6 weeks
As insulin resistance worsened: ↑ lipolysis: ↑
triglyceridemia
End result:
Type-2 DM & CAD (risk ↑ 50%)
Papanastasiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review.
Ther Adv Psychopharmacol. 2013;3(1):33-51.
Proposed mechanisms:
1. Alter HPA axis: Cushing’s Syndrome
(Meyer and Stahl, 2009)
2. Genetic predisposition: 23% MetS in Indian pop.
(Bajaj and Varma et al. 2013)
Risk factors:
Women, SGA, polypharmacy, age >40 years
30. Adverse Cardiac Effects: ↑QTc → TdP → SCD
Antipsychotics block IKr channel: ↑ QTc
Dose dependent effect
↑ R/o when given with CYP 2D6 & 3A4 inhibitors
↑ R/o: pts. with LQTS
US-FDA black box warning for use in Geriatric patients
Least R/o with Aripiprazole
Beach SR et al., QTc prolongation, torsades de pointes, and
psychotropic medications. Psychosomatics. 2013
Drugs with High R/o ↑ QTc at Therapeutic Doses
Drug Class Drug Name
FGA Thoiridazine (max.), Haloperidol, Chlorpromazine, Pimozide
SGA Ziprasidone, Iloperidone, Quetiapine
31. Other Adverse Effects
1. Seizures: Class label warning (USA)
• Dose dependant
• Clozapine (5%) > Loxapine….. Haloperidol (least)
2. Agranulocytosis: Clozapine
• Genotypes: HLA-B38/B39/B67 and HLA-DQB105
3. Photosensitivity: Chlorpromazine
• UV exposure: Changes structure of drug
• Body reacts to new antigen
• Allergic response of light-exposed skin
Wiciński M, Węclewicz MM. Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring.
Curr Opin Hematol. 2018
↓GABA
32. Antipsychotics: Pharmacokinetics
1. Highly lipophilic: Accumulate in Brain
2. Short t1/2 (min to max: check table)
3. Biological t1/2 persists 24 hours: permit
OD dosage
4. Oral: High Absorption
• Concurrent Anticholinergic: Negligible
effect
• Exception: Asenapine
FPM: >98%
ODT only, F: 35%
Goodman & Gilman’s The Pharmacological Basis of
Therapeutics; 13th Edition, Table 16-5
5. Highly protein bound (acid-glycopr)
• Don’t displace albumin-bound drugs
6. Metabolized mainly by CYP2D6 &
CYP3A4
• Carbamazepine & Phenytoin C/I in pts
with Psychosis + Epilepsy
7. Safe in patients with Renal disease
33. Real World Effectiveness Studies (2009)
1. CATIE: Clinical Antipsychotic Trials of Intervention Effectiveness
2. CUtLASS: Cost Utility of the Latest Antipsychotic drugs in SCZ Study
Between [FGA Vs. SGA] & [Among SGAs*]
• Non-significant difference in terms of
1. Efficacy
2. Adherence
3. Side-effect profile
4. Cost-effectiveness
5. Improvement in QoL
Naber D, Lambert M. The CATIE and CUtLASS studies in schizophrenia: results and
implications for clinicians. CNS Drugs. 2009*except Clozapine
SGA as first line:
• ↓ EPS
• ↑ weight gain, hyperglycaemia and
dyslipidaemia.
(Lieberman JA et al., 2003; Schooler N
et al., 2005; Emsley RA et al., 2006)
34. Choosing an Antipsychotic:
1. Most Imp.: Avoidance of adverse effects based on patient and drug characteristics
2. Family H/o treatment
3. FGA for positive symptoms, SGA for negative symptoms: NOT ABSOLUTE
4. Medical comorbidity
5. Special population: Pediatric, geriatric, pregnancy & lactation
Grover S et al., Clinical Practice Guidelines for Management of Schizophrenia.
Indian J Psychiatry. 2017
35. Special population
1. Pediatric population
• Adolescent SCZ (13-17 yr): Aripiprazole, olanzapine, risperidone, quetiapine, lurasidone
• R/o Amenorrhea in girls & Gynaecomastia in boys (Amisulpride: Max. Hyperprolactinemia)
2. Geriatric population
• Highest risk: EPS & TD (25%)
• ↑ R/o CAD & SCD
• Amisulpride ( D2/D3# - Least action on α1, H1 or M1 ; Ki = 10,000): Safest
3. Pregnancy
• All drugs: lipophilic - cross the placenta
• R/o GDM, high birth weight & prematurity
36. Refractory Illness
a.k.a. Refractory Schizophrenia
Characteristic: Negative symptoms
• 30% pts. (after 4-5 weeks of Rx of Acute phase)
• 60% of these pts. respond with Clozapine
Newer Hypothesis:
• Resistant SCZ is another subset of SCZ.
Veerman SR et al., Memantine augmentation in clozapine-refractory schizophrenia: a
randomized, double-blind, placebo-controlled crossover study. Psychol Med. 2016
The Glutamate Hypothesis of
Schizophrenia:
NMDA Receptor mediated excitotoxicity at
Prefrontal cortex:
Neurodegeneration
Cognitive impairment and Negative symptom
39. Parkinson Disease Psychosis (PDP)
• Incidence: 60%
• Risk not established with levodopa use.
• Psychosis not linked to dopaminergic pathways
• Rx: SGA (Clozapine & Quetiapine)
Kianirad Y, Simuni T. Pimavanserin, a novel antipsychotic for management of Parkinson's disease psychosis.
Expert Rev Clin Pharmacol. 2017
• Neuroimaging study:
Elevated 5-HT2A receptor binding density
in temporal and occipital lobe in PD pts.
with auditory & visual hallucination.
40. 4. 5-HT2A inverse agonist: Pimavanserin
Pimavanserin:
• Specific inverse agonist of 5-HT2A receptors
• Devoid of D2 receptor activity (The only antipsychotic)
• USFDA approved (2016) for PDP
Kianirad Y, Simuni T. Pimavanserin, a novel antipsychotic for management of Parkinson's disease psychosis.
Expert Rev Clin Pharmacol. 2017
41. Summary: Pharmacotherapy of Psychosis
1. First Generation (Typical Antipsychotics)
2. Second Generation (Atypical Antipsychotics)
3. Third Generation (Partial D2 Agonist)
4. 5-HT2A inverse agonist
42. Conclusion
Only 2 certainties in management:
1. Clozapine for resistant schizophrenia
2. Pimavanserin for PDP
Typical: ↑EPS, Atypical: ↑Metabolic syndrome
No drug is exclusively D2 selective
D2 blockade: essential for anti-psychotic action (except Pimavanserin)
Management should be patient specific, not generalized
43. Thank you very much.
1972 1974
John F. Nash
(Mathematician)
Nobel Prize winner
‘The Scream’
by
Vincent Van Gogh
(Artist)
Syd Barrett
(Musician)
Pink Floyd
Parveen Babi
(Actor)
Editor's Notes
Loss of insight: Difficulty determining what is real and what is not (unaware of the disease)
Based on dopamine hypothesis
Check legend..
Conmtains superscript a b c d etc etc….
Tighter than Dopamine!
Most tolerable: Amisulpride- Min. EPS
Should medicine be stopped if its causing sedation? Tolerance will develop soon
Prevalence: 68% (double of normal population)
Clozapine: >10kg increase
Aripiprazole: 0.4 kg increase
Weight independent: occurs within the first 6 weeks (weight hasn’t increased yet)
MetS in India: same as in schizophrenicpeople
Don’t displace SSRI : polypharmacy OK
Tourette’s Syndrome: Aripiprazole (First Line) --- decreases DA in basal ganglia and decreases tics