Current and Future Anxiolytics
PED3008 Lecture 5
Anxiolytics: Allay anxiety
Anxiogenic: Anxiety inducing
Current Anxiolytics:
SSRIs are first line of treatment.
Anxiety disorders are often comorbid with depression/affective disorders.
There is evidence that anxiety symptoms decrease in patients treated with anti-depressants which
target the 5-HT system (only thought to be part of anxiety)
Types of anxiolytics:
SSRIs- selective serotonin reuptake inhibitors. E.g., Escitalopram and fluoxetine.
Used to treat most anxiety disorders, generally well tolerated and used if anxiety is co-morbid with
depression.
SNRIs- selective noradrenaline reuptake inhibitors. E.g., venlafaxine.
Used to treat general anxiety disorder.
Tricyclic antidepressants, E.g., Imipramine.
Used to treat panic disorder and general anxiety disorder.
Monoamine oxidase inhibitors. E.g., phenelzine
Used to treat panic disorder, agoraphobia and social phobia.
5-HT1A Receptor agonist. E.g., Buspirone
Only used to treat general anxiety disorder.
Use depends on efficacy vs side effects
All have delayed onset of action.
Pharmacodynamics:
SSRIs, SNRIs and TCAs block 5-HT transporter, meaning there should be more 5-HT in synaptic cleft.
MAOIs inhibits 5-HT breakdown, leading to more in synaptic cleft
Buspirone inhibits further release of 5-HT
All increase 5-HT transmission (except buspirone)
, 5-HT Pharmacology:
SSRIs/TCAs cause an initial increase in anxiety- therapeutic effect is delayed by weeks.
5-HT1A receptor agonist buspirone does not cause initial increase in anxiety but therapeutic action is
also delayed.
Benzodiazepines start working straight away but sudden withdrawal leads to a sudden increase in
anxiety.
A decrease in 5-HT1A receptor expression/function=anxiety.
5-HT2C receptors:
Involved in anxiogenesis.
Receptors are excitatory- activation linked to increase in anxiety.
-Receptor agonists (MK-212) cause increase in anxiety-like behaviour.
-Receptor knock out (Heisler et al., 2007) decreases anxiety-like behaviour.
5-HT neurotransmission via 5-HT2C receptors is anxiogenic explaining the increase in anxiety.
Chronic antidepressant treatment decreases 5-HT 2C receptor facilitated neurotransmission in
basolateral amygdala.
PED3008 Lecture 5
Anxiolytics: Allay anxiety
Anxiogenic: Anxiety inducing
Current Anxiolytics:
SSRIs are first line of treatment.
Anxiety disorders are often comorbid with depression/affective disorders.
There is evidence that anxiety symptoms decrease in patients treated with anti-depressants which
target the 5-HT system (only thought to be part of anxiety)
Types of anxiolytics:
SSRIs- selective serotonin reuptake inhibitors. E.g., Escitalopram and fluoxetine.
Used to treat most anxiety disorders, generally well tolerated and used if anxiety is co-morbid with
depression.
SNRIs- selective noradrenaline reuptake inhibitors. E.g., venlafaxine.
Used to treat general anxiety disorder.
Tricyclic antidepressants, E.g., Imipramine.
Used to treat panic disorder and general anxiety disorder.
Monoamine oxidase inhibitors. E.g., phenelzine
Used to treat panic disorder, agoraphobia and social phobia.
5-HT1A Receptor agonist. E.g., Buspirone
Only used to treat general anxiety disorder.
Use depends on efficacy vs side effects
All have delayed onset of action.
Pharmacodynamics:
SSRIs, SNRIs and TCAs block 5-HT transporter, meaning there should be more 5-HT in synaptic cleft.
MAOIs inhibits 5-HT breakdown, leading to more in synaptic cleft
Buspirone inhibits further release of 5-HT
All increase 5-HT transmission (except buspirone)
, 5-HT Pharmacology:
SSRIs/TCAs cause an initial increase in anxiety- therapeutic effect is delayed by weeks.
5-HT1A receptor agonist buspirone does not cause initial increase in anxiety but therapeutic action is
also delayed.
Benzodiazepines start working straight away but sudden withdrawal leads to a sudden increase in
anxiety.
A decrease in 5-HT1A receptor expression/function=anxiety.
5-HT2C receptors:
Involved in anxiogenesis.
Receptors are excitatory- activation linked to increase in anxiety.
-Receptor agonists (MK-212) cause increase in anxiety-like behaviour.
-Receptor knock out (Heisler et al., 2007) decreases anxiety-like behaviour.
5-HT neurotransmission via 5-HT2C receptors is anxiogenic explaining the increase in anxiety.
Chronic antidepressant treatment decreases 5-HT 2C receptor facilitated neurotransmission in
basolateral amygdala.
