L17-18 Antipsychotic Drugs & Mood Stabilizers Flashcards
Who are usually prescribed with antipsychotics?
Antipsychotics are mostly prescribed to adults but not children due to their Mechanism of Action (MoA).
They are prescribed for:
* Schizophrenia (30%)
* Bipolar Disorder / Manic States
* Reducing Agitation in Dementai Patients (Palliative Care)
* Others
e.g. Psychosis during a Depressive Episode, Tourette’s
Palliative Care
: care for patients and their families who are facing a serious, life-limiting illness
Schizophrenia
4 Domains of Schizophrenia Symptoms
Positive Symptoms
= addition of psychotic symptoms
e.g. hallucinations (mostly auditory), delusions, disorganized speech and behavior
Negative Symptoms
= decrease in emotional range, poverty of speech, and loss of interests and drive
e.g. social aversion, mood-related issues
Cognitive Symptoms
= Neurocognitive Deficits
e.g. deficits in working memory, attention, and executive functions; difficulty in understanding nuances and subtleties of interpersonal cues and relationships
Mood Symptoms
* patients often feel cheerful/sad; often are depressed
Schizophrenia
Target Audience of Schizophrenia
Schizophrenia affects ~1% of the population.
* onset in early adulthood (18-25 y.o.) - earlier for men than women
* possible late onset for women at post-menopause
Schizophrenia
Burden of Schizophrenia
Schizophrenia is one of the world’s top 15 leading causes of disability.
Individuals with Schizophrenia have an increased risk o premature mortality.
* Co-occuring medical conditions (e.g. heart and liver disease, diabetes) contribute to the higher premature mortality rate.
∵ under-detection and under-treatment of medical condition
* 4.9% of people with Schizophrenia die by suicide, with highest risk during early stages of the illness.
50% of individuals with Schizophrenia have co-occuring mental and/or behavioral health disorders.
High ‘Direct’ and ‘Indirect’ Costs
* ‘Direct’ Financial Costs of Healthcare
* ‘Indirect” Costs of Lost Productivity, Criminal Justice Involvement, Social Service Needs, Homelessness, etc.
4 Domains of Schizophrenia
Description of Positive Symptoms
Positive Symptoms
: psychotic behaviors not seen in healthy people
- Auditory and/or Visual Hallucinations
- Delusions
- Paranoia (Paraniod Delusion)
- Thought Disorder = unusual way of thinking
- Illogical Disturbances in the Flow, Order, and Content of Thought
- Disorganized Speech
- Absence of Clear, Goal-Directed Behavior
These symptoms respond well to antipsychotics.
Delusions
: false beliefs that involve a misinterpretation of experiences
Paranoia
= when someone distrusts others for no perceived reasons at all
Hallucinations
: false/distorted sensory experiences that seem real
4 Domains of Schizophrenia
Description of Negative Symptoms
Negative Symptoms
: psychotic behaviors characterized by a lessening or absence of normal behaviors and functions
* Avolition = decreased motivation / initation of goal-directed behavior
* Anhedonia = decreased ability to experience pleasure or identify activities as being pleasurable
* Flattened Affect = lack of emotional expression / reactivity
* Poverty of Speech
* Social Withdrawal
These symptoms are generally NOT improved by antipsychotics and may possibly be worsen.
4 Domains of Schizophrenia
Description of Cognitive Symptoms
Cognitive Symptoms
* Intellectual (IQ) Deterioration
* Working Memory Impairments
* Cognitive Inflexibility
* Processing Speed
* Attention
* Encoding Memory
esp. verbal information
* Decoding Prosodic (Tonal) Information from Speech
These symptoms are NOT improved and are sometimes worsened by antipsychotics.
Schizophrenia
What causes Schizophrenia?
The cause to Schizophrenia is a combination of genetics, environment, and biology (brain chemistry).
Schizophrenia Brain Chemistry
Dopamine Theory
= overactive dopamine transmission may lead to more positive symptoms
= underactive dopamine transmission may lead to more negative symptoms
* very novel
* Antipsychotic drugs treat Schizophrenia by blocking Dopamine.
Dopamine is a type of neurotransmitter, which are natural chemicals in the brain that help cells called neurons send and receive signals to each oter.
Schizophrenia
Early Evidence of Dopamine Theory
Twin Studies
Cardno and Gottesman from Cardiff, UK conducted a meta-analysis of 5 twin studies of Schizophrenia in 2000 that shows that monozygotic (MZ) (= identical) twins have a 50% chance of developing Schizophrenia.
→ Genetic factors play a major role in the etiology of Schizophrenia.
Genome Wide Association Studies (GWAS)
Genome-wide association studies (GWAS) help scientists identify genes associated with a particular disease (or another trait).
* by searching for Single Nucleotide Polymorphisms (SNPs) within the genome
Twin, adoption, and family studies have estabilished that Schizophrenia is a genetic disorder with high heritability.
* No single gene is involved.
Popular Theory
Multiple genes with common and rare mutations, including large deletions and insertions, combine to produce a very variegated clinical presentation and course.
Single Nucleotide Polymorphisms (SNPs) = small variations
Genome = entire set of DNA
Biological Insights from 108 Schizophrenia-Associated Genetic Loci
Schizophrenia is a highly heritable disorder influenced by many genetic factors. A large-scale genome-wide association study (GWAS) involving 36,989 cases and 113,075 controls identified 128 independent associations across 108 loci, with 83 being newly discovered. These associations are particularly enriched in genes expressed in the brain, supporting their biological relevance to schizophrenia. Some associations, such as those involving the DRD2 gene and glutamatergic neurotransmission, align with existing theories about schizophrenia’s pathology and potential treatments. Additionally, the findings suggest a possible link between the immune system and schizophrenia due to gene expression in immune-related tissues.
Article - Biological Insights from 108 Schizophrenia-Associated Genetic
Main Gene Loci Associated with Schizophrenia
Gene Loci associated with
* Glutamatergic Neurotransmission
* Voltage-Gated Calcium Channel Signalling
* Neurodevelopment
* Synaptic Plasticity
* Ion Channels
* miRNA
* Drug Target Receptors
Chlorpromazine
Chlorpromazine
* one of the first drugs found to be useful to reduce psychotic symptoms in Schizophrenia
* a neuroleptic agent - produces catalepsy in rodents and EPS in humans
* Its antipsychotic action’s relation to dopamine (D/DA)-receptor blockade led to the identification of other compounds as antipsychotics during 1950-1970s.
Extrapyrimidal Symptoms (EPS) = drug-induced movements
Discovery of Antipsychotics
