Can you rank antidepressants from strongest to weakest? (5 main classes) 

In this blog post, we are going to answer the question, “Can you rank antidepressants from strongest to weakest?”. The use of antidepressants has increased drastically as more and more people get diagnosed with depression. 

an illness that wasn’t even considered a disease is not the world’s most commonly reported health concern. This blog will generally discuss antidepressants and we will talk about the strongest and the weakest antidepressants. 

Can you rank antidepressants from strongest to weakest?

Yes, you can rank antidepressants from strongest to weakest, but the ranking based solely on the strength of the antidepressant might not be practically applicable. This is because the strongest antidepressant may not be tolerated well by people and it may not be used as the first line of therapy.

If we look at the strength, Tricyclic antidepressants (TCAs) are considered the strongest antidepressants and they are among the oldest antidepressants. However, TCAs are the least tolerated antidepressants in today’s world and they are not used as the first line of therapy. 

This is why we are not just going to talk about strength here, but we will also talk about tolerability. So, let’s take a look at the ranking based on the strength and tolerability:

• Selective serotonin reuptake inhibitors (SSRIs) 
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) 
• Atypical antidepressants 
• Tricyclic antidepressants (TCAs) 
• Dopamine and norepinephrine reuptake inhibitors (DNRI) 
• Monoaminoxidase inhibitors (MAOIs) 

Selective serotonin reuptake inhibitors (SSRIs) 

SSRIs are the strongest and the most frequently prescribed antidepressants in the entire world. These drugs are very well tolerated and can significantly help restore your mental health. 

Even in the case of major depressive disorder, some doctors prescribe two SSRIs in combination, mostly Sertraline and Escitalopram, to help relieve the disturbing symptoms associated with persistent depression. 

SSRIs basically inhibit the reuptake of serotonin by blocking serotonin transporters (SERT). This way, more active serotonin is available to bind to its respective receptors. Serotonin is one of the main neurotransmitters that are closely related to depression. 

It is this chemical whose deficiency triggers depression in the first place. This is why SSRIs work in the best possible way to counteract such depression symptoms. However, SSRIs may not work in the best possible way for every individual. 

Some people may not tolerate this class of antidepressants at all, but there is nothing to worry about as there are plenty of other antidepressants available to replace SSRIs. Most commonly prescribed antidepressants include:

• Sertraline (Zoloft) 
• Fluoxetine (Prozac) 
• Escitalopram (Lexapro) 
• Paroxetine (Paxil) 
• Citalopram (Celexa) 

The above-mentioned SSRIs are in the exact order of their popularity. Sertraline is the most commonly prescribed SSRI. It shows a very good response in the majority of the population taking this med, but again, not everyone is lucky enough to achieve the best possible therapeutic outcome. 

Some people can not tolerate these antidepressants which may lead to the discontinuation of treatment with SSRIs. However, SSRIs are and will always remain the most commonly prescribed antidepressants. 

It has changed lives and helped people come out of the nerve-racking symptoms of depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and some other mental health-related problems. Some common side effects associated with the use of SSRIs include

• Nausea 
• Vomiting 
• Diarrhoea or Constipation 
• Acid reflux or heartburn 
• Abdominal pain 
• Loss of appetite 
• Weight gain or loss 
• Excessive sweating or night sweating (nocturnal/night hyperhidrosis) 
• Frequent urination 
• Polydipsia or excessive thirst
• Tremors 
• Muscle twitching and pain
• Drowsiness 
• Dizziness 
• Excessive tiredness or fatigue 
• Insomnia or inability to fall asleep 
• Xerostomia or dry mouth 
• Dysmenorrhea or heavy periods
• Flu-like symptoms including irritation in eyes and runny nose
• Sexual side effects 

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors are also quite frequently prescribed and they can be used either alone or in conjunction with other antidepressants. These meds hold great importance in the management and treatment of a variety of mental health conditions. 

Some of the SNRIs can also be used for the prophylaxis of migraine, like Venlafaxine. SNRIs are not so different from SSRIs in terms of mechanism of action, but they are different in some aspects. 

SNRIs work by inhibiting the reuptake of two excitatory monoamine neurotransmitters; serotonin and norepinephrine. They do so by blocking serotonin and norepinephrine transporters, SERT and NET respectively. 

This makes more active serotonin and norepinephrine available to bind to their receptors. This way, SNRIs help elevate your mood and other psychological functions. Some common SNRIs include:

• Venlafaxine (Effexor) 
• Duloxetine (Cymbalta) 
• Desvenlafaxine (Pristiq) 
• Milnacipran (Ixel) 
• Levomilnacipran (Fetzima) 

They are considered good and effective antidepressants, but they also possess some risks. Some of the common side effects associated with the use of SNRIs include:

• Drowsiness
• Fatigue
• Sleepiness or hypersomnia
• Decreased salivation leading to dry mouth 
• Vertigo 
• Loss of appetite 
• Excessive sweating
• Constipation or diarrhoea 
• Weight gain or loss
• Abdominal pain
• Bloating 
• Flatulence 
• Headache 
• Muscular pain

Atypical antidepressants 

Atypical antidepressants are also considered quite effective. They are so-called because of their distinct mechanism of action. Unlike other antidepressants, they do inhibit the reuptake of any excitatory neurotransmitter. 

Instead, atypical antidepressants have a dual mode of action. They can activate 5-HT1 receptors, which are one of the serotonin receptors. 

They also enhance the stimulatory action of the noradrenergic system which increases the secretion of serotonin, while preventing the inhibitory action of the noradrenergic system which hinders the release of serotonin. 

This means that instead of inhibiting the reuptake of serotonin from the synaptic cleft, atypical antidepressants work to increase the secretion of the said excitatory neurotransmitter. 

They are also serotonin-specific and may or may not affect other neurotransmitters. The exact mechanism of action is still a topic for research. Some common atypical antidepressants include:

• Mirtazapine (Remeron) 
• Vortioxetine (Trintellix) 
• Trazodone (Desyrel) 
• Nefazodone (Serzone) 

Like every other class of antidepressants, atypical antidepressants are also associated with some side effects. However, there is one thing that makes these antidepressants stand out for the early treatment of the major depressive disorder (MDD); their faster onset of action.

SSRIs and SNRIs are believed to start working in about 4 to 6 weeks. It can actually take much longer than that for some people. However, atypical antidepressants like Mirtazapine can start to work in 2 to 3 weeks. 

This is why experts believe that these meds can start working on your symptoms much quicker than SSRIs and they can be used in combination for persistent depression. Some of the common side effects associated with the use of atypical antidepressants include:

• Sleepiness or drowsiness 
• Excessive tiredness or fatigue 
• Dizziness or lightheadedness 
• Xerostomia or dry mouth 
• Anxiety 
• Agitation 
• Confusion 
• Gain of appetite
• Weight gain 
• Gastrointestinal side effects including nausea, vomiting and diarrhoea/Constipation 

Tricyclic antidepressants (TCAs) 

Tricyclic antidepressants, although they’re considered the strongest when it comes to the strength, lie on number fourth because of their tolerability issues. These meds work by inhibiting the reuptake of serotonin and norepinephrine, but they do bind to a number of other receptors which is the main cause of the side effects. Some of the TCAs include

• Elavil (Amitriptyline) 
• Pamelor (Nortriptyline) 
• Tofranil (Imipramine) 

Some of the side effects associated with the use of TCAs include:

• Painful urination 
• Dry mouth or xerostomia
• Gastrointestinal side effects, including nausea and vomiting 
• Weight gain
• Vertigo 
• Drowsiness or extreme fatigue 
• Constipation 
• Abdominal pain
• Enlarged breasts
• Heartburn
• Excessive sweating 

Monoaminoxidase inhibitors (MAOIs) 

Monoaminoxidase inhibitors (MAOIs) are those antidepressants which are always used alone. They can not be paired with other antidepressants because of their mechanism of action. 

They work by inhibiting the enzyme monoaminoxidase which is responsible for the breakdown and metabolism of serotonin and norepinephrine. 

If they are paired with any other antidepressant, the drastic effects that are caused by the combination can give rise to a number of complications. Common MAOIs include

• Nardil (Phenelzine) 
• Marplan (Isocarboxazid) 
• Emsam (Selegiline) 
• Parnate (Tranylcypromine) 

Conclusion 

In this blog post, we have discussed the strongest and weakest antidepressants, but we learned that the ranking based solely on the strength of the antidepressant might not be practically applicable. 

This is because the strongest antidepressant may not be tolerated well by people and it may not be used as the first line of therapy, solely because of the side effects it might cause. This is why we ranked antidepressants on the basis of their strength and tolerability, instead of just strength. 

Make sure you always talk to your healthcare provider before starting any antidepressant. These meds should always be taken carefully and proper use is the key to safe and effective therapeutic outcomes. 

FAQs: Antidepressants strongest to weakest 

What are the stronger antidepressants?

SSRIs are the strongest and the most frequently prescribed antidepressants in the entire world. These drugs are very well tolerated and can significantly help restore your mental health. Even in case of major depressive disorder, some doctors prescribe two SSRIs in combination, mostly Sertraline and Escitalopram, to help relieve the disturbing symptoms associated with persistent depression. SSRIs basically inhibit the reuptake of serotonin by blocking serotonin transporters (SERT).

What is the number 1 prescribed antidepressant?

Zoloft is the most commonly prescribed antidepressant, almost in the entire world. It is a selective serotonin reuptake inhibitor (SSRI). It works by inhibiting the reuptake of serotonin by blocking serotonin transporters (SERT). Zoloft is generally well tolerated and it has changed many lives, but it may cause serious side effects in some individuals. Make sure you ask your healthcare provider before using Zoloft. 

What are the top 3 antidepressants?

The top three classes of antidepressants are:

• Selective serotonin reuptake inhibitors (SSRIs) 
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) 
• Atypical antidepressants 

What is the best antidepressant for energy and motivation?

The best antidepressants for energy and motivation include:

• Wellbutrin (Bupropion) 
• Prozac (Fluoxetine) 
• Effexor (Venlafaxine) 

Wellbutrin is considered one of the strongest antidepressants to elevate your mood and energy levels. The distinct mechanism of action of this antidepressant is the reason why it stands out from the other antidepressants when it comes to increasing your energy levels. Wellbutrin is a dopamine and norepinephrine reuptake inhibitor. 

What type of antidepressant gives you energy?

The type of antidepressant that treats your depression-induced lethargy can help boost your energy levels. The most common examples include Wellbutrin and Prozac. The kind of antidepressant you should take depends on the type of symptoms you have. If you suffer from depression-induced insomnia. There’s no point in taking a medication like Wellbutrin as it’ll make you even more restless. For such a person, taking an antidepressant that can help you fall asleep is a better choice. 

References 

• The most effective antidepressants for adults revealed in major review  https://evidence.nihr.ac.uk/alert/the-most-effective-antidepressants-for-adults-revealed-in-major-review/
• Selective Serotonin Reuptake Inhibitors https://www.ncbi.nlm.nih.gov/books/NBK554406/
• SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants https://pubmed.ncbi.nlm.nih.gov/16142213/
• Tricyclic antidepressants https://www.ncbi.nlm.nih.gov/books/NBK557791/ 
• Monoaminoxidase inhibitors https://www.ncbi.nlm.nih.gov/books/NBK539848/