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What is the lifetime prevalence of anxiety disorders?
What is the lifetime prevalence of anxiety disorders?
What is the main limitation of the monoamine hypothesis?
What is the main limitation of the monoamine hypothesis?
Which of the following antidepressants is indicated for agoraphobia, generalized anxiety disorder, and panic disorder?
Which of the following antidepressants is indicated for agoraphobia, generalized anxiety disorder, and panic disorder?
What is the target dose of Imipramine for anxiety disorders?
What is the target dose of Imipramine for anxiety disorders?
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Which of the following antidepressants is considered a second-line agent for anxiety and depression?
Which of the following antidepressants is considered a second-line agent for anxiety and depression?
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What is the initial dose of Escitalopram for anxiety disorders?
What is the initial dose of Escitalopram for anxiety disorders?
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What is the mechanism of action of Tricyclic Antidepressants (TCAs)?
What is the mechanism of action of Tricyclic Antidepressants (TCAs)?
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What is the main difference between SSRIs and SNRIs?
What is the main difference between SSRIs and SNRIs?
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What is the main characteristic of Serotonin Syndrome?
What is the main characteristic of Serotonin Syndrome?
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What is a common symptom of serotonin syndrome?
What is a common symptom of serotonin syndrome?
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Which of the following is a characteristic of benzodiazepines with high lipid solubility?
Which of the following is a characteristic of benzodiazepines with high lipid solubility?
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What is the main difference between BZ1 and BZ2 receptors?
What is the main difference between BZ1 and BZ2 receptors?
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What is the primary indication for benzodiazepines?
What is the primary indication for benzodiazepines?
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What is the half-life of clonazepam?
What is the half-life of clonazepam?
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Which of the following is a characteristic of antidepressant discontinuation syndrome?
Which of the following is a characteristic of antidepressant discontinuation syndrome?
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What is the primary mechanism of action of benzodiazepines?
What is the primary mechanism of action of benzodiazepines?
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What is the main difference between moderate and severe cases of serotonin syndrome?
What is the main difference between moderate and severe cases of serotonin syndrome?
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What is the recommended tapering schedule for antidepressant discontinuation syndrome?
What is the recommended tapering schedule for antidepressant discontinuation syndrome?
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What is the primary indication for clonazepam?
What is the primary indication for clonazepam?
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What is the primary mechanism of neurotransmission facilitated by benzodiazepines?
What is the primary mechanism of neurotransmission facilitated by benzodiazepines?
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Which of the following symptoms is NOT typically associated with mild cases of serotonin syndrome?
Which of the following symptoms is NOT typically associated with mild cases of serotonin syndrome?
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What is the primary difference between BZ1 and BZ2 receptors?
What is the primary difference between BZ1 and BZ2 receptors?
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Which of the following is a characteristic of clonazepam?
Which of the following is a characteristic of clonazepam?
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What is the primary treatment for antidepressant discontinuation syndrome?
What is the primary treatment for antidepressant discontinuation syndrome?
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Which of the following symptoms is commonly associated with antidepressant discontinuation syndrome?
Which of the following symptoms is commonly associated with antidepressant discontinuation syndrome?
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What is the primary difference between moderate and severe cases of serotonin syndrome?
What is the primary difference between moderate and severe cases of serotonin syndrome?
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Which of the following benzodiazepines is indicated for agoraphobia, panic disorder, and social anxiety disorder?
Which of the following benzodiazepines is indicated for agoraphobia, panic disorder, and social anxiety disorder?
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What is the primary characteristic of serotonin syndrome?
What is the primary characteristic of serotonin syndrome?
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What is the primary benefit of gradual tapering of antidepressants?
What is the primary benefit of gradual tapering of antidepressants?
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What is the primary mechanism by which tricyclic antidepressants (TCAs) work?
What is the primary mechanism by which tricyclic antidepressants (TCAs) work?
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What is a common adverse effect of tricyclic antidepressants (TCAs)?
What is a common adverse effect of tricyclic antidepressants (TCAs)?
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What is the primary advantage of selective serotonin reuptake inhibitors (SSRIs) over tricyclic antidepressants (TCAs)?
What is the primary advantage of selective serotonin reuptake inhibitors (SSRIs) over tricyclic antidepressants (TCAs)?
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What is the primary indication for venlafaxine?
What is the primary indication for venlafaxine?
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What is the primary concern when using imipramine in patients with cardiovascular disease?
What is the primary concern when using imipramine in patients with cardiovascular disease?
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What is the primary difference between escitalopram and venlafaxine?
What is the primary difference between escitalopram and venlafaxine?
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What is the primary risk of combining imipramine with other anticholinergic drugs?
What is the primary risk of combining imipramine with other anticholinergic drugs?
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What is the primary mechanism by which serotonin syndrome occurs?
What is the primary mechanism by which serotonin syndrome occurs?
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What is the primary recommendation for monitoring patients taking venlafaxine?
What is the primary recommendation for monitoring patients taking venlafaxine?
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What is the primary characteristic of antidepressant discontinuation syndrome?
What is the primary characteristic of antidepressant discontinuation syndrome?
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Study Notes
Antidepressants and Benzodiazepines
Overview of Anxiety Disorders
- Anxiety disorders are among the most common psychiatric illnesses with a lifetime prevalence of around 31%.
- They are frequently underdiagnosed and remain untreated in about 40% of diagnosed patients.
The Monoamine Hypothesis
- An incomplete theory attempting to describe the mechanisms of anxiety and depression and the mechanism by which antidepressants work.
- States that mood disorders result from abnormalities in serotonin, norepinephrine, and/or dopamine neurotransmission.
- Limitations:
- Antidepressants only work in about 50 – 70% of people.
- It takes several weeks before antidepressant effects are realized.
- Changes to neurotransmitter levels occur with the first dose.
Reuptake Inhibitors
- Types:
- Tricyclic antidepressants (TCA)
- Selective serotonin reuptake inhibitors (SSRI)
- Serotonin and Norepinephrine reuptake inhibitors (SNRI)
Tricyclic Antidepressants (TCA)
- Older class of reuptake inhibitors.
- Block neuronal reuptake of norepinephrine and serotonin.
- Increase the time neurotransmitters are present in the synapse and enhance neurotransmission.
- Limitations:
- Rather non-specific for the serotonergic and noradrenergic neurons they target.
- Affects more neuronal targets than necessary.
- Cross reacts with cardiac adrenoreceptors.
- Causes anticholinergic effects.
Imipramine (TCA)
- Indicated for:
- Agoraphobia
- Generalized anxiety disorder
- Panic disorder
- Adverse effects:
- CNS:
- Drowsiness
- Psychomotor impairment
- Agitation
- Headache
- Myoclonus
- Seizure
- Anticholinergic:
- Dry mouth
- Constipation
- Blurred vision
- Urinary retention
- Cognitive impairment
- Cardiovascular:
- Orthostatic hypotension
- Palpitations
- Dizziness
- Tachycardia
- Arrhythmias
- QTc interval prolongation
- CNS:
- Contraindications:
- Patients with suicidal ideation
- Use with caution in patients with existing cardiovascular disease, cognitive impairment, or history of seizure.
- Considered a second-line agent for anxiety and depression.
Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
- Considered first-line agents for anxiety and depression.
- Examples:
- Escitalopram (SSRI)
- Venlafaxine (SNRI)
Escitalopram (SSRI)
- Indicated for:
- Generalized anxiety disorder
- Major depressive disorder
- Agoraphobia
- Panic disorder
- Social anxiety disorder
- Adverse effects:
- CNS:
- Anxiety
- Agitation
- Insomnia
- Headache
- Extrapyramidal effects
- GI:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Increased risk of upper GI bleeding
- Other:
- Dry mouth
- Increased sweating
- Sexual dysfunction
- May prolong QTc interval
- CNS:
- Dosing:
- For anxiety disorders: 5-20 mg/day PO
- For major depressive disorder: 10-20 mg/day PO
Venlafaxine (SNRI)
- Indicated for:
- Generalized anxiety disorder
- Major depressive disorder
- Social anxiety disorder
- Adverse effects:
- Similar to Escitalopram
- Dosing:
- For anxiety disorders: 37.5-300 mg/day PO
- For major depressive disorder: 37.5-375 mg/day PO
Serotonin Syndrome
- Range from mild symptoms to life-threatening.
- Symptoms:
- Mild:
- Mild hypertension
- Tachycardia
- Mydriasis
- Diaphoresis
- Shivering
- Tremor
- Myoclonus
- Moderate:
- Hyperthermia
- Hyperactive bowel sounds
- Horizontal ocular clonus
- Mild agitation
- Hypervigilance
- Pressured speech
- Severe:
- More severe hyperthermia
- Dramatic swings in pulse rate and blood pressure
- Delirium
- Muscle rigidity
- Mild:
Antidepressant Discontinuation Syndrome
- Occurs with rapid discontinuation or dose reduction.
- Symptoms:
- Anxiety
- Crying
- Headache
- Increased dreaming
- Insomnia
- Irritability
- Myoclonus
- Nausea
- Electric shocks
- Tremor
- Flulike symptoms
- Imbalance
- Sensory disturbances
- Prevention:
- Gradual tapering by approximately 25% per week
- Slower tapering may be needed in some individuals
Benzodiazepines
- Act as positive allosteric modulators of GABA-A receptors.
- GABA-A receptors are found in high concentrations in the cortex and limbic system.
- GABA is inhibitory and reduces the excitability of neurons.
- Classification:
- By elimination half-life:
- Short acting: 1-12 hours
- Intermediate acting: 12-40 hours
- Long acting: 40-250 hours
- By potency:
- Lower potency options: fewer adverse effects
- Higher potency options: faster onset of action, increased risk of adverse effects
- By elimination half-life:
Clonazepam
- Indicated for:
- Generalized anxiety disorder
- Agoraphobia
- Panic disorder
- Social anxiety disorder
- Characteristics:
- High-potency long-acting benzodiazepine
- Half-life: 18-50 hours
- Onset of action: 20-60 minutes
- Peak concentration: 1-4 hours
- Duration: 6-8 hours
- Adverse effects:
- CNS:
- Drowsiness
- Psychomotor impairment
- Fatigue
- Muscle weakness
- Reduced concentration
- Confusion
- Dysarthria
- Ataxia
- CNS:
Introduction to Antidepressants and Benzodiazepines
- Anxiety disorders are among the most common psychiatric illnesses, with a lifetime prevalence of around 31%.
- Major depressive disorder has a lifetime prevalence of 10% and accounts for over 5% of population illness-related productivity loss.
The Monoamine Hypothesis
- The monoamine hypothesis is an incomplete theory attempting to describe the mechanisms of anxiety and depression and the mechanism by which antidepressants work.
- The hypothesis states that mood disorders result from abnormalities in serotonin, norepinephrine, and/or dopamine neurotransmission.
- Limitations of the hypothesis include:
- Antidepressants only work in about 50-70% of people.
- It takes several weeks before antidepressant effects are realized.
- Changes to neurotransmitter levels occur with the first dose.
Reuptake Inhibitors
- Tricyclic antidepressants (TCA) are an older class of reuptake inhibitors.
- Selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) are other classes of reuptake inhibitors.
Tricyclic Antidepressants
- TCAs block neuronal reuptake of norepinephrine and serotonin, increasing the time neurotransmitters are present in the synapse and enhancing neurotransmission.
- TCAs are rather non-specific for the serotonergic and noradrenergic neurons they target, affecting more neuronal targets than necessary.
- Adverse effects of TCAs include:
- Anticholinergic effects (dry mouth, constipation, blurred vision, urinary retention, cognitive impairment).
- Cardiovascular effects (orthostatic hypotension, palpitations, dizziness, tachycardia, arrhythmias, QTc interval prolongation).
Imipramine
- Imipramine is a TCA indicated for agoraphobia, generalized anxiety disorder, and panic disorder.
- Adverse effects of imipramine include:
- CNS effects (drowsiness, psychomotor impairment, agitation, headache, myoclonus, seizure).
- Anticholinergic effects (dry mouth, constipation, blurred vision, urinary retention, cognitive impairment).
- Cardiovascular effects (orthostatic hypotension, palpitations, dizziness, tachycardia, arrhythmias, QTc interval prolongation).
SSRIs and SNRIs
- SSRIs and SNRIs are considered first-line agents for anxiety and depression.
- Examples of SSRIs and SNRIs include:
- Escitalopram (SSRI)
- Venlafaxine (SNRI)
Escitalopram
- Escitalopram is a SSRI indicated for agoraphobia, panic disorder, social anxiety disorder, and major depressive disorder.
- Adverse effects of escitalopram include:
- CNS effects (anxiety, agitation, insomnia, headache, extrapyramidal effects).
- GI effects (nausea, vomiting, diarrhea, constipation, increased risk of upper GI bleeding).
- Other effects (dry mouth, increased sweating, sexual dysfunction, and may prolong QTc interval).
Venlafaxine
- Venlafaxine is a SNRI indicated for generalized anxiety disorder, social anxiety disorder, and major depressive disorder.
- Adverse effects of venlafaxine include:
- CNS effects (anxiety, agitation, insomnia, headache, extrapyramidal effects).
- GI effects (nausea, vomiting, diarrhea, constipation, increased risk of upper GI bleeding).
- Other effects (dry mouth, increased sweating, sexual dysfunction, and may prolong QTc interval).
Serotonin Syndrome
- Serotonin syndrome is a range of symptoms from mild to life-threatening, resulting from increased serotonin levels in the body.
- Symptoms of serotonin syndrome include:
- Mild cases: mild hypertension, tachycardia, mydriasis, diaphoresis, shivering, tremor, myoclonus, and hyperreflexia.
- Moderate cases: hyperthermia, hyperactive bowel sounds, horizontal ocular clonus, mild agitation, hypervigilance, and pressured speech.
- Severe cases: severe hyperthermia, dramatic swings in pulse rate and blood pressure, delirium, and muscle rigidity.
Antidepressant Discontinuation Syndrome
- Antidepressant discontinuation syndrome occurs with rapid discontinuation or dose reduction of antidepressants.
- Symptoms of antidepressant discontinuation syndrome include:
- Anxiety, crying, headache, increased dreaming, insomnia, irritability, myoclonus, nausea, electric shocks, tremor, flulike symptoms, imbalance, and sensory disturbances.
- The syndrome can be reversed by restarting the antidepressant and tapering more slowly.
Benzodiazepines
- Benzodiazepines act as positive allosteric modulators of GABA-A receptors, enhancing inhibitory neurotransmission.
- Benzodiazepines can be classified by:
- Elimination half-life: short-acting (1-12 hours), intermediate-acting (12-40 hours), and long-acting (40-250 hours).
- Potency: lower potency options have fewer adverse effects, while higher potency options have a faster onset of action but increase the risk of adverse effects.
Clonazepam
- Clonazepam is a high-potency long-acting benzodiazepine indicated for agoraphobia, panic disorder, and social anxiety disorder.
- Adverse effects of clonazepam include:
- CNS effects: drowsiness, psychomotor impairment, fatigue, muscle weakness, reduced concentration, confusion, dysarthria, and ataxia.
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Description
This lecture covers the mechanism of action, adverse effects, and potential syndromes associated with SSRIs, SNRIs, benzodiazepines, and antidepressants in the context of anxiety and depression.
