What is the Difference Between SSRI and Tricyclic Antidepressants

The key difference between SSRI and tricyclic antidepressants is that SSRIs increase the serotonin levels in the brain by selectively inhibiting the reuptake of serotonin from the synaptic cleft and consider the first-line therapy for treating depression, while tricyclic antidepressants inhibit the reuptake of both serotonin and norepinephrine from the synaptic cleft and act as competitive antagonists of α-cholinergic, muscarinic, and histaminergic receptors in the post-synaptic neuron.

Depression is a mental health disorder associated with persistent sadness, loss of interest in pleasure activities, and recurring thoughts of death or suicide. Antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are crucial in alleviating depressive feelings and improving mental health. However, these two medications differ in their mechanism of action, selectivity, side effects, and indications. Therefore, understanding the difference between SSRI and tricyclic antidepressants is important for healthcare professionals and individuals seeking effective treatment options.

CONTENTS

1. Overview and Key Difference
2. What are SSRIs 
3. What are Tricyclic Antidepressants
4. Similarities – SSRI and Tricyclic Antidepressants
5.  SSRI vs Tricyclic Antidepressants in Tabular Form
6. Summary –  SSRI vs Tricyclic Antidepressants

What are SSRIs?

Selective serotonin reuptake inhibitors (SSRIs) are prescribed to treat persistent or severe depression. They are generally considered the first-choice medication due to their fewer side effects, efficacy, and tolerability. In addition to treating depression, these drugs are used to treat anxiety, obsessive-compulsive disorders, severe phobias, and premature ejaculation. The mechanism of action of SSRIs involves increasing the serotonin levels in the brain. Serotonin is a neurotransmitter that influences mood, emotion, and sleep. As the name suggests, SSRIs inhibit the serotonin transporters of the presynaptic neuron, allowing serotonin to remain in the synaptic cleft. Serotonin in the synaptic cleft allows binding with the post-synaptic neurons, resulting in the transmission continuing in the nearby nerve cells. Studies on the pharmacodynamics of SSRIs suggest that, unlike other antidepressants, SSRIs have a negligible effect on other neurotransmitters, such as dopamine or norepinephrine.

SSRIs are primarily taken orally as tablets, capsules, or suspensions as a once-daily medication and are not generally recommended for pregnant and breastfeeding women.   SRIs are metabolized in the liver by the cytochrome p450 system. The effect of SSRIs will take 2 to 6 weeks to display the effects of treatment. During treatment, anxiety, insomnia, and sexual dysfunction should be monitored.

What are Tricyclic Antidepressants?

Tricyclic antidepressants such as amitriptyline, amoxapine, and doxepin are other drugs used to treat major depressive disorder. In addition, they are used for treating migraine, obsessive-compulsive disorders, insomnia, and anxiety. Both tricyclic antidepressants and SSRIs show comparable effectiveness in treating depression. However, tricyclic antidepressants tend to have more adverse effects due to their anticholinergic activity and a lower threshold for overdose. Therefore, tricyclic antidepressants are not used as the first-line therapy for depression. However, these drugs are known for their longer half-life.

The chemical structure of tricyclic antidepressants includes a three-ringed structure attached to a secondary or tertiary amine. These antidepressants act on several neurotransmitters, including inhibiting serotonin and norepinephrine reuptake. The increased serotonin and norepinephrine levels contribute to the antidepressive functions of tricyclic antidepressants. In addition, they act as competitive antagonists on the post-synaptic neuron receptors such as α-cholinergic, muscarinic, and histaminergic receptors. Tricyclic antidepressants are also primarily administered orally as forms of tablets, capsules, and solutions. Unlike SSRIs, tricyclic antidepressants lead to undesired side effects such as constipation, dizziness, and xerostomia due to their varying receptor affinities.

What are the Similarities Between SSRI and Tricyclic Antidepressants?

• SSRIs and tricyclic antidepressants are effective in treating depression.
• They typically require several weeks of consistent use to achieve their full therapeutic effect.
• Both medications require dosage adjustments based on individual response and tolerability.
• They can potentially cause discontinuation syndrome if abruptly stopped.
• SSRIs and TCAs are often prescribed for an extended period to relieve symptoms and prevent relapse.

What is the Difference Between SSRI and Tricyclic Antidepressants?

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are commonly prescribed to alleviate depressive feelings and improve mental well-being. However, there is a difference between SSRIs and tricyclic antidepressants in terms of their mechanism of action, efficacy, and side effects. SSRIs selectively inhibit serotonin reuptake to increase the serotonin levels in the brain and, therefore, are considered the first-line therapy for depression. In contrast, tricyclic antidepressants inhibit the reuptake of both serotonin and norepinephrine. In addition, tricyclic antidepressants also act on the α-cholinergic, muscarinic, and histaminergic receptors owing to their undesirable side effects. Tricyclic antidepressants are associated with a high risk of overdose compared to SSRIs; therefore, routine blood monitoring is required during treatment.

Below is a summary of the difference between SSRIs and tricyclic antidepressants in tabular form for side-by-side comparison.

Summary – SSRI vs Tricyclic Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are two antidepressants used to treat depression and improve mental well-being. SSRIs are known for their selective inhibitory activity on serotonin reuptake, while tricyclic antidepressants inhibit serotonin and norepinephrine reuptake. SSRIs are better tolerated with milder side effects. In contrast, tricyclic antidepressants cause more severe side effects due to their affinity with receptors such as α-cholinergic, muscarinic, and histaminergic receptors. SSRIs are considered first-line therapy for depression, while tricyclic antidepressants are prescribed when SSRIs are ineffective. Tricyclic antidepressants are associated with a higher overdose risk than SSRIs; therefore, routine blood monitoring is required during treatment. Understanding this difference between SSRI and tricyclic antidepressants is crucial in selecting the most suitable antidepressant treatment for individuals.

Reference:

1. Raggi, Alberto, et al. “Clonazepam for the Management of Sleep Disorders.” Neurological Sciences, vol. 44, no. 1, 2022, pp. 115–128.
2. Moraczewski J, Aedma KK. “Tricyclic Antidepressants.” Treasure Island (FL): StatPearls Publishing.

Image Courtesy:

1. “Serotonin-2D-skeletal” By CYL – Own work (Public Domain) via Commons Wikimedia
2. “Amitriptyline2DACS”  By Fuse809 at English Wikipedia (CC BY-SA 3.0) via Commons Wikimedia