Tricyclic antidepressants

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Tricyclic antidepressants


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An 8-year-old is brought to the pediatrician by their parents for bedwetting, which occurs around 2-3 times per week. The patient has tried avoiding fluid intake three hours prior to bedtime, enuresis alarms, and desmopressin therapy; however, the symptoms have persisted. The patient has two older siblings, both of whom were toilet trained by the age of 4 years old. The patient has no other medical conditions and has been meeting all other developmental milestones. Temperature is 37.2°C (99.0°F), pulse is 60/min, and blood pressure is 104/65. Physical examination reveals a well-nourished child who is at the 75 percentile for height and weight. Examination of the penis and testes reveals no significant findings. Urinalysis is unremarkable. Which of the following would be the next best step in management?  

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Amitriptyline p. 599

migraine headaches p. 536

tension headaches p. 536


Tricyclic antidepressants, or TCAs, are mainly used to treat major depressive disorder.

This disorder causes a persistent feeling of sadness and loss of interest in everyday activities.

Even though the exact cause of depression is still unknown, there's some evidence that suggests it’s related to low levels of neurotransmitters like serotonin, norepinephrine, and dopamine.

Tricyclic antidepressants work by increasing the levels of serotonin and norepinephrine to alleviate the symptoms of depression.

Alright, now within the brain, there are many different types of neurons, but we’re just going to focus on two: serotonergic neurons which produce serotonin, and noradrenergic neurons which produces norepinephrine.

Each of these neurons synthesizes and stores their neurotransmitters in small vesicles.

So, when an action potential reaches the presynaptic membrane, these vesicles fuse with the membrane, releasing neurotransmitters into the synaptic cleft.

Once released, serotonin or 5-HT binds to 5-HT2 receptors on the postsynaptic membrane, thereby increasing neural stimulation and regulating mood, feeding, and reproductive behavior.

On the other hand, norepinephrine binds to norepinephrine receptors on the postsynaptic membrane, boosting alertness.

As long as there’s a high enough concentration of neurotransmitters in the synaptic cleft, the postsynaptic neurons will continue to fire.

Now, serotonergic neurons, on their presynaptic membrane, have serotonin transporters or SERT, while noradrenergic neurons have norepinephrine transporters or NET.


Tricyclic antidepressants (TCAs) are a class of medications used to treat depression, anxiety disorders, migraine, and chronic pain. They are named for their chemical structure, which includes three rings of atoms.

TCAs work by preventing serotonin and norepinephrine reuptake from the synaptic cleft, thus enhancing the effect of both neurotransmitters on postsynaptic neurons. Some common TCAs include amitriptyline, imipramine, and nortriptyline.

Common side effects include dry mouth, blurred vision, constipation, dizziness, and drowsiness. TCAs can also cause more serious side effects, such as heart rhythm disturbances, seizures, and an increased risk of suicide, particularly in younger individuals.


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