PSYCH Flashcards
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is the economic cost of depression?
Describe the epidemiology and economic cost of depression
Years lost to disability
Carers, neglect risk
Loss of income
Social Services
Benefits
Sick Leave
Tax
A and E attednance, police time
Inpatient admissions
Appointments, and DNA
Treatment: pharma and non pharm
Suicide
Approx 12% of sick leave.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is the epidemiology of depression?
Describe the epidemiology and economic cost of depression
Depression is one of the most prevalent mental health disorders, affecting around 1 in 6 adults in the UK
Leading cause of disability world wide.
322 m people
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
Using the biopsychosocial model, what is depresion?
Evaluate various approaches to the question “What is depression?” in terms of the biopsychosocial model
bio: genetic, physical health, metabolic disorders, immune, stress, comorbidity, neurochemistry, age, sex
psycho: beliefs, behaviours, self-esteem, coping strategy, emotions, social skills, physical health
social: peer relationships, family circumstances, cultrue, social support, education, povity, life events, relationships
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
How is depression diagnosed?
Understand how depression is diagnosed on the basis of symptoms and be able to grade the severity of depression according to ICD-10 criteria
- persistent sadness or low mood;and/or
- loss of interests or pleasure
- fatigue or low energy
- at least one of these, most days, most of the time for at least 2 weeks
if any of above present, ask about associated symptoms:
* disturbed sleep
* poor concentration or indecisiveness
* low self-confidence
* poor or increased appetite
* suicidal thoughts or acts
* agitation or slowing of movements
* guilt or self-blame
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
Grade severity of depression using ICD10
Understand how depression is diagnosed on the basis of symptoms and be able to grade the severity of depression according to ICD-10 criteria
not depressed (fewer than four symptoms)
mild depression (four symptoms)
moderate depression (five to six symptoms)
severe depression (seven or more symptoms, with or without psychotic symptoms)
symptoms should be present for a month or more and every symptom should be present for most of every day
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
Pyschotic depression symptoms
Describe the types of psychotic symptoms which are seen in psychotic depression
An episode of depression as described in F32.2, but with the presence of hallucinations, delusions, psychomotor retardation, or stupor so severe that ordinary social activities are impossible; there may be danger to life from suicide, dehydration, or starvation. The hallucinations and delusions may or may not be mood-congruent.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What are cognitive symptoms of depression?
Describe the range of symptoms that can lead to a diagnosis of depression, including cognitive and somatic and how these are described in the Mental State Examination
Reduced attention
Impaired memory
Executive dysfunction
Lower processing speed
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
How are symptoms described in the mental state exam?
Describe the range of symptoms that can lead to a diagnosis of depression, including cognitive and somatic and how these are described in the Mental State Examination
Affective Symptoms:
Depressed mood: Feelings of sadness or hopelessness.
Irritability: Easily agitated or annoyed.
Cognitive Symptoms:
Negative thinking: Pessimism or self-criticism.
Poor concentration: Difficulty focusing or making decisions.
Somatic Symptoms:
Changes in appetite or weight.
Fatigue: Feeling tired or lacking energy.
Sleep disturbances: Trouble sleeping or early awakening.
Psychomotor changes: Restlessness or slowed movements.
Vegetative Symptoms:
Loss of interest or pleasure.
Social withdrawal: Isolation from others.
Suicidal Thoughts or Behaviors:
Suicidal ideation: Thoughts of death or self-harm.
Self-harm: Engaging in behaviors like cutting or burning.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What are somatic symptoms of depression?
Describe the range of symptoms that can lead to a diagnosis of depression, including cognitive and somatic and how these are described in the Mental State Examination
changes in appetite
lack of energy
sleep disturbance
and general aches and pains.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is the mental state exam?
Describe the range of symptoms that can lead to a diagnosis of depression, including cognitive and somatic and how these are described in the Mental State Examination
- mental state examination (MSE) is the observation of a patient’s present mental state and forms one part of a working diagnosis.
- The MSE allows you to assess patients’ risk of harm to themselves or others or both.
- When conducting an MSE, it is important to write down patients’ words and the order in which they are being expressed verbatim, to avoid them being misinterpreted.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is predisposing, precipitating and maintaining?
Use the frameworks of predisposing, precipitating and maintaining with the biopsychosocial model to be able to formulate the causes of depression in a patient
Predisposing (What is their “set up?” What were they working with initially?)
Precipitating (What acute event happened and how did it affect them?)
Perpetuating (What chronic things are going on?)
Protective (What is protecting them and keeping them well?)
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is the monoamine hypothesis?
Describe theories of the biological basis of depression, including the monoamine hypothesis, HPA axis abnormalities, and genetic factors
predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in the central nervous system.
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
What is the HPA axis abnormalities
Describe theories of the biological basis of depression, including the monoamine hypothesis, HPA axis abnormalities, and genetic factors
PSYCH Depression: Epidemiology & Biological Basis by Dr Rahmanian
How do genetics involve in depression?
Describe theories of the biological basis of depression, including the monoamine hypothesis, HPA axis abnormalities, and genetic factors
- Evidence that mood disorders are genetically transmitted, but how is still unclear
- Concordance rates are not 100%
- Twins also share similar psycho-social environments, which could account for the high concordance rate
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
What is the Monoamine Theory (Schildkraut, 1965)
Explain the existing theories describing the biological basis of depression
WHAT
MAO breaks down NA and serotonin and dopamine
Depression – functional deficit of monoamine
Mania – functional excess of monoamine
Overall reduced activity of central noradrenergic and / or serotonergic systems
EVIDENCE FOR
Reserpine depletes brain of NA and 5-HT and induces depression
Main antidepressant drugs increase amines in brain
AGAINST
Cocaine blocks amine uptake but has no antidepressant effect
Some antidepressants weak / no effect on amine uptake
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
What is the Neuroendocrine Theory
Explain the existing theories describing the biological basis of depression
WHAT
NAergic & 5-HT neurons input to hypothalamus
Hypothalamus releases corticotropin-releasing hormone (CRH)
CRH acts on pituitary – release of adrenocorticotrophic hormone (ACTH)
Cortisol release from adrenal cortex in response to ACTH in blood
Increased cortisol – behavioural effects mimic some depression symptoms
EVIDENCE FOR
Evidence of hyperactivity of HPA in depressed patients
incre [cortisol]plama in depressed patients
incre [CRH] in the cerebrospinal fluid
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Other theories of depression
Explain the existing theories describing the biological basis of depression
Neuroplasticity & Neurogenesis Evidence of neuronal loss and reduced neuronal activity in hippocampus and prefrontal cortex (decision making centres)
Antidepressants and electroconvulsive therapy (ECT) promote neurogenesis in these regions
5-HT promotes neurogenesis during development
**Monoamine main theory of depression but needs to be extended
**
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Pathophysiology of depression
Explain the existing theories describing the biological basis of depression
- Monoamine Hypothesis: Links depression to deficiencies in serotonin, norepinephrine, and dopamine.
- Glutamate/GABA Imbalance and disruptions in excitatory and inhibitory neurotransmitters may affect mood.
- HPA Axis Dysregulation: Chronic stress can lead to elevated cortisol levels, influencing mood.
- Abnormal thyroid function is associated with depressive symptoms.
- Structural Changes: Imaging studies reveal alterations in areas like the hippocampus and prefrontal cortex.
- Reduced generation of new neurons, especially in the hippocampus, is linked to depression.
- Certain genetic variations contribute to susceptibility to depression.
- Increased pro-inflammatory cytokines may impact neurotransmitter function.
- Changes in the sensitivity or function of neurotransmitter receptors play a role in depression.
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
What treatment is available?
Describe the pharmacotherapy available for the treatment of depression
CBT
Monoamine Oxidase Inhibitors (MAOIs)
Tricyclic Antidepressant Drugs (TCAs)
Selective Serotonin Re-uptake Inhibitors (SSRIs)
Other mixed 5HT/NA reuptake inhibitors (SNRIs)
NA reuptake inhibitors
Monoamine receptor antagonists (a2, 5HT2c, 5HT3)
Downregulation a2, 5HT1A, b1, b2, 5HT2A, 5HT3
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
MAOI
Discuss the pharmacological action (mechanism of action) of common antidepressants
Mechanism of Action:
MAOIs work by inhibiting the activity of monoamine oxidase, an enzyme that breaks down neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain.
By inhibiting MAO, these drugs increase the availability of these neurotransmitters in the synaptic cleft, potentially alleviating depressive symptoms.
Side Effects and Underlying Mechanisms:
Hypertensive Crisis: One significant side effect is the risk of a hypertensive crisis when consuming foods or drinks containing tyramine (e.g., aged cheese, certain wines), due to the inhibition of MAO in the gut.
Serotonin Syndrome: Concurrent use with other serotonergic medications can lead to serotonin syndrome, characterized by symptoms like agitation, confusion, rapid heart rate, and elevated body temperature.
Drug-Drug Interactions:
MAOIs can interact dangerously with a variety of medications, including other antidepressants, sympathomimetics, and certain cold and allergy medications. Combining these drugs can lead to a potentially life-threatening hypertensive crisis.
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Tricyclic Antidepressants (TCAs):
Discuss the pharmacological action (mechanism of action) of common antidepressants
Mechanism of Action:
TCAs block the reuptake of serotonin and norepinephrine in the synaptic cleft, leading to increased concentrations of these neurotransmitters in the brain.
Some TCAs also have antihistaminic and anticholinergic effects.
Side Effects and Underlying Mechanisms:
Anticholinergic Effects: Dry mouth, blurred vision, constipation, and urinary retention are common due to the blockade of acetylcholine receptors.
Orthostatic Hypotension: Blockade of alpha-adrenergic receptors can lead to a sudden drop in blood pressure upon standing.
Cardiotoxicity: TCAs can prolong the QT interval, increasing the risk of arrhythmias.
Drug-Drug Interactions:
TCAs can interact with a range of medications, including monoamine oxidase inhibitors, antihypertensives, and other drugs that affect neurotransmitter levels. Combining these medications may increase the risk of side effects.
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Selective Serotonin Reuptake Inhibitors (SSRIs):
Discuss the pharmacological action (mechanism of action) of common antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs):
Mechanism of Action:
SSRIs selectively inhibit the reuptake of serotonin, leading to increased serotonin levels in the synaptic cleft.
They are more specific to the serotonin transporter, which may contribute to a more favorable side effect profile compared to older antidepressants.
Side Effects and Underlying Mechanisms:
Sexual Dysfunction: Increased serotonin levels can lead to sexual side effects, such as decreased libido and delayed ejaculation.
Serotonin Syndrome: Although rare, combining SSRIs with other serotonergic medications can increase the risk of serotonin syndrome.
Drug-Drug Interactions:
SSRIs can interact with other medications that affect serotonin levels, such as MAOIs, leading to serotonin syndrome. They can also interact with drugs that affect bleeding risk, such as nonsteroidal anti-inflammatory drugs (NSAIDs).
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Other Tx for depression
Discuss the pharmacological action (mechanism of action) of common antidepressants
Buproprion
-inhibits NA, DA uptake but not 5HT uptake
-Also used to treat nicotine dependence
Mianserin
- a2, 5HT2A, a1 antagonist
- can cause bone marrow depression
Oestrogen
- for treatment of postpartum depression
- has actions on monoamine system, GABAergic, glutamatergic
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
Compare side effects
Compare and contrast side effects of common antidepressants
Monoamine Oxidase Inhibitors (MAOIs):
- Hypertensive Crisis: Risk with tyramine-rich foods.
- Serotonin Syndrome: Possible with serotonergic meds.
-
Tricyclic Antidepressants (TCAs):
- Anticholinergic Effects: Dry mouth, blurred vision.
- Orthostatic Hypotension: Sudden drop in BP.
- Cardiotoxicity: QT interval prolongation.
-
Selective Serotonin Reuptake Inhibitors (SSRIs):
- Sexual Dysfunction: Libido decrease, delayed ejaculation.
- Serotonin Syndrome: Rare but possible.
-
Other Antidepressants (e.g., SSRIs, SNRIs, Atypical):
- Common Side Effects: Nausea, insomnia, weight changes.
- Headache: Reported with several antidepressants.
Contrasts:
- MAOIs vs. SSRIs/TCAs: Unique risks, dietary restrictions.
- TCAs vs. SSRIs: More anticholinergic, higher orthostatic risk.
- SSRIs vs. Others: Favorable side effect profile.
PSYCH Antidepressant Drugs and the Psychopharmacology of Depression
New options
Discuss future treatment for the management of depression
Glutamatergic Agents:
Ketamine and Esketamine: These drugs target the glutamatergic system and have shown rapid-acting antidepressant effects. They are used in treatment-resistant depression.
Endocannabinoid System Modulators:
Cannabidiol (CBD): Some studies suggest potential antidepressant effects by modulating the endocannabinoid system, but more research is needed.
Genetic Testing:
Tailoring treatment based on an individual’s genetic profile to identify potential responders to specific antidepressants.
Biomarkers:
Identifying biological markers that predict treatment response and guide personalized interventions.
Psychedelic-Assisted Therapy:
Psilocybin and MDMA: Research is exploring the therapeutic potential of psychedelics in combination with psychotherapy for treating depression and PTSD.
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
Define normal and pathological anxiety
*LOB: Explain the distinction between normal and pathological anxiety
Anxiety is a feeling of worry, unease, or nervousness that varies from mild to severe.
However, pathological anxiety occurs when a person experiences intense anxiety, far beyond expected levels for the situation
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B00 Generalized Anxiety Disorder
*LOB: Describe the classification of anxiety disorders
characterised by marked symptoms of anxiety that persist for at least several months, for more days than not, manifested by either general apprehension (i.e. ‘free-floating anxiety’) or excessive worry focused on multiple everyday events,
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B01 Panic Disorder
*LOB: Describe the classification of anxiety disorders
recurrent unexpected panic attacks that are not restricted to particular stimuli or situations. Panic attacks are discrete episodes of intense fear or apprehension accompanied by the rapid and concurrent onset of several characteristic symptoms (e.g. palpitations or increased heart rate, sweating, trembling, shortness of breath, chest pain, dizziness or lightheadedness, chills, hot flushes, fear of imminent death).
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B02 Agoraphobia
*LOB: Describe the classification of anxiety disorders
marked and excessive fear or anxiety that occurs in response to multiple situations where escape might be difficult or help might not be available, such as using public transportation, being in crowds, being outside the home alone
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B03 Specific Phobia
*LOB: Describe the classification of anxiety disorders
marked and excessive fear or anxiety that consistently occurs upon exposure or anticipation of exposure to one or more specific objects or situations
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B04 Social Anxiety Disorder
*LOB: Describe the classification of anxiety disorders
Marked and excessive fear or anxiety that occurs consistently in one or more social situations such as social interactions (e.g., having a conversation), doing something while feeling observed (e.g., eating or drinking in the presence of others), or performing in front of others (e.g., giving a speech).
The individual is concerned that he or she will act in a way, or show anxiety symptoms, that will be negatively evaluated by others (i.e., be humiliating, embarrassing, lead to rejection, or be offensive).
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B05 Separation Anxiety Disorder
*LOB: Describe the classification of anxiety disorders
Separation anxiety disorder is characterised by marked and excessive fear or anxiety about separation from specific attachment figures. In children and adolescents, separation anxiety typically focuses on caregivers, parents or other family members and the fear or anxiety is beyond what would be considered developmentally normative.
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
What is 6B06 Selective Mutism
*LOB: Describe the classification of anxiety disorders
Selective mutism is characterised by consistent selectivity in speaking, such that a child demonstrates adequate language competence in specific social situations, typically at home, but consistently fails to speak in others, typically at school. The disturbance lasts for at least one month, is not limited to the first month of school, and is of sufficient severity to interfere with educational achievement or with social communication.
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
How is anxiety diagnosed?
*LOB: Understand how a diagnosis of anxiety disorder is reached
the symptoms be considered excessive and unreasonable, and that they cause significant distress or impairment in daily functioning.
Mental state exam
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
Possible advantage of phobic disorder
Describe the possible biological advantages of phobic and obsessive-compulsive disorders
For example, people can be more predisposed to fearing things (such as heights or snakes) that have historically presented a mortal threat to humans.
Biological preparedness is the idea that organisms are biologically predisposed to quickly learning associations between stimuli, responses, and reinforcers (Seligman, 1971).
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
Possible advantages of obsessive-compulsive disorders.
*LOB: Describe the possible biological advantages of phobic and obsessive-compulsive disorders
the ability of some organisms to learn to avoid common dangers without the need to experience them in real life would have conferred a clear advantage on the individuals who possessed this trait over those who did not.
For example, ritualised behaviour is quite common in children at around 30 months of age, appears to decline at the age of three and tends to disappear at around four when the child becomes thoroughly familiar with his or her surroundings
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
Features and management of phobic disorder
Outline the clinical features and approaches to management of phobic and obsessive-compulsive disorders
Assessments are based on self-reports, clinical interviews, and behavioural observations.
Cognitive behavioural therapy, especially exposure therapy, is considered the first-line treatment for patients with frequent symptoms.
Therapy can also be delivered through self-help, internet-assisted, and/or therapist-assisted modalities.
Patient motivation and available resources are important to consider when reviewing treatment options.
Exposure therapy.
PSYCH Anxiety and Related Disorders by Dr Mohammed Al-Rawi
Features and management of obsessive-compulsive disorder.
Outline the clinical features and approaches to management of phobic and obsessive-compulsive disorders
Patients tend to seek treatment from 3 to 4 doctors and spend on average around 9 years in treatment before a correct diagnosis is made. The average amount of time that lapses between onset of symptoms and appropriate treatment is 17 years.
Cognitive behavioural therapy in the form of exposure and response prevention, alone or in combination with a selective serotonin-reuptake inhibitor (SSRI) or clomipramine, is a first-line therapy.
While controlled trials with SSRIs have demonstrated a selective efficacy in OCD, up to 40% to 60% of patients do not have a satisfactory outcome.
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What is an anxiolytic?
*LOB: Describe the difference between an anxiolytic and a hypnotic
Anxiolytics are a class of drugs used to treat anxiety disorders.
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What is a hypnotic?
*LOB: Describe the difference between an anxiolytic and a hypnotic
Hypnotics are a class of drugs used to treat insomnia.
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Appreciate the uses and therapeutic window and anxiolytics and hypnotics.
*LOB: Describe the difference between an anxiolytic and a hypnotic
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Anxiolytic and hypnotic drug classes include (but are not limited to):
*LOB: Describe the difference between an anxiolytic and a hypnotic
- Benzodiazepines and Z-drugs (GABA receptor modulators)
- 5-HT1A receptor agonists
- 𝛽-noradrenergic receptor antagonists
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What is the role of GABA
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
GABA is the major inhibitory neurotransmitter in the central nervous system (CNS).
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What does GABA do?
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
Activate ligand-gated ion channel (GABAA) and G-protein coupled (GABAB) receptors
Pentameric structure so multiple binding sites.
Multiple binding sites:
- Agonists/antagonists e.g. GABA
- Benzodiazepine binding site
- Channel blockers e.g. picrotoxin
- Channel modulators e.g. GA
- Allosteric modulators e.g. barbiturates
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What are barbituates?
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
are a class of GABAA receptor positive allosteric modulators that are no longer recommended as anxiolytics and hypnotics.
increases GABA affinity for its binding site and produces a general enhancement of its neuroinhibitory actions
Benzodiazepines are therefore classed as positive allosteric modulators
increase the activity of GABAA receptors
Responsible for severe depressant effect on CNS
USE: epilepsy and GA
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Benzodiazepine duration of action
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
M for Midazolam M for Mini (shortest)
Diazepam D for Day 24 hours +
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Benzodiazepine side effects
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
Barbiturates and benzodiazepines can be associated with unwanted side-effects (e.g. amnesia) and can induce tolerance and withdrawal symptoms.
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What are Z drugs?
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
Z-drugs (e.g. zolpidem, zopiclone) are a class of GABAA receptor positive allosteric modulators that are used as hypnotics.
Z-drugs bind to the benzodiazepine binding site on the GABAA receptor
Z-drugs are ultrashort/short-acting
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Where on GABA do drugs bind?
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
GABA binds at Alpha
Benzos at Gamma
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
5HT1A receptor agonists
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
Serotonin has important roles in sleep and wakefulness, in addition to mood and emotional behaviours
5-HT1A receptor agonists (e.g. buspirone) are a class of drugs primarily used to treat generalised anxiety disorder (GAD).
Buspirone activates 5-HT1A auto-receptors – this inhibits 5-HT release
Buspirone also inhibits the activation of noradrenergic neurons – decreases arousal reactions
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
5HT1A receptor agonists vs SSRI
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
5HT1A receptor agonists
Activates 5-HT1A auto-receptors – decrease 5-HT release
SSRI
Block serotonin re-uptake transporter (SERT) - more 5-HT available
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
Why is Buspirone (5-HT1A) used for Generalised Anxiety rather than SSRI?
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
- 5-HT1A receptors are auto-inhibitory
- buspirone can induce desensitisation of auto-inhibitory 5-HT1A receptors - this can lead to downregulation of 5-HT1A receptors
- desensitisation and downregulation of 5-HT1A receptors ultimately results in heightened excitation of serotonergic neurons and enhanced 5-HT release
PSYCH Anxiolytic Drugs and Hypnotics by Dr Dean Semmens
What are 𝛽-noradrenergic receptor antagonists
*LOB: Discuss the mechanism of action of clinically important anxiolytic and hypnotic drugs.
Noradrenaline is the major neurotransmitter of the sympathetic nervous system (e.g. cardiovascular tone)
Noradrenaline also has roles in attention, arousal and sleep and wakefulness
A drug target for peripheral manifestations of anxiety (e.g. 𝝱-noradrenergic receptor antagonists)
𝛽-noradrenergic antagonists reduce some of the peripheral manifestations of anxiety
Include tachycardia, sweating, gastrointestinal problems and tremor
Effectiveness dependent on blocking peripheral sympathetic responses (“fight or flight”) rather than central effects
