What are the strongest antidepressants for severe depression? 

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In this blog post, we are going to answer the question, “What are the strongest antidepressants for severe depression?”. Antidepressants are one of the most commonly prescribed medications nowadays, because of the widespread depression and other mental health conditions. 

However, not every antidepressant is effective when it comes to the management and treatment of the major depressive disorder (MDD). Here we are going to talk about some good options which may help you recover from this nerve-racking mental illness. 

What are the strongest antidepressants for severe depression

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The strongest antidepressants for severe depression include:

  • Selective serotonin reuptake inhibitors (SSRIs) – Monotherapy or combination therapy of two SSRIs 
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) – Monotherapy or combination therapy 
  • Atypical antidepressants – Monotherapy or combination therapy with SSRIs
  • Dopamine-norepinephrine reuptake inhibitors (DNRIs) – Monotherapy or combination therapy with SSRIs

Selective serotonin reuptake inhibitors (SSRIs) – Monotherapy or combination therapy of two SSRIs

SSRIs are one of the most commonly prescribed antidepressants. These drugs are very well tolerated and can significantly help restore your mental health. 

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

A combination of these antidepressants is preferred over monotherapy for MDD because this type of depression is more severe and persistent in nature. It does not usually respond to monotherapy and a stronger treatment regimen is required. 

SSRIs can be paired with other antidepressants for the management and treatment of MDD and we will discuss such combinations shortly. 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. Most commonly prescribed antidepressants include:

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

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) – Monotherapy or combination therapy 

SNRIs can also be used for the management and treatment of severe kinds of depression. High doses of SNRIs can also be used in some patients, but only in those who can tolerate the drug well. 

For those who can not bear the effects caused by the higher doses, two antidepressants are paired together. For the treatment of MDD, SNRIs can be paired with SSRIs, another SNRI, Bupropion, or Mirtazapine. 

Some of these combinations hold great importance and can successfully manage the most severe kinds of depression. Studies suggest that several case studies showed good responses to the combination treatment of Bupropion and SNRIs. 

However, the combination of Venlafaxine and Bupropion stands out from the rest of them. Research shows that these two together can be used for the treatment and management of persistent depression. 

The combination is also quite effective when it comes to the treatment of post-traumatic stress disorder (PTSD). Bupropion is considered a good antidepressant for eating disorders. 

These two can help people who suffer from depression comorbid with an eating disorder. Bupropion can also be paired with Duloxetine.

The combination of these two antidepressants at low doses can help quite significantly to counteract your symptoms associated with major depressive disorder (MDD), anxiety, and other mental health conditions. 

However, one important thing to bear in mind is that not everyone can tolerate the combination of antidepressants, and those who can tolerate them should always stick to the adjusted doses.

Mirtazapine and Venlafaxine also hold great clinical importance in treating and managing treatment-resistant depression. Some of the 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 – Monotherapy or combination therapy with SSRIs

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 activity 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. These meds can either be used alone or in combination with SSRIs or SNRIs. Some common atypical antidepressants include:

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

Several studies suggest that the combination of Mirtazapine with either an SSRI or an SNRI can be a lifesaver. This is because they both have different mechanisms of action. This way, the two drugs act in their own ways to counteract the symptoms associated with MDD. 

The drugs with the same mechanism of action may cause some common, additive, or synergistic side effects. However, the proper use of this combination is the key to achieving your desired therapeutic response. 

If you take more than the prescribed dose, you may be subjected to some terrible side effects. 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 

Dopamine-norepinephrine reuptake inhibitors (DNRIs) – Monotherapy or combination therapy with SSRIs

DNRIs are also considered strong antidepressants when it comes to the treatment and management of treatment-resistant depression. The most commonly used DNRI is Bupropion, which is known as Wellbutrin. This medication can either be used alone or paired with SSRIs or SNRIs. 

The combination of these meds is considered safer as compared to other combinations because of the distinct mechanism of action of Bupropion. It is a Dopamine-norepinephrine reuptake inhibitor. 

This means that the drug actively inhibits the reuptake of dopamine and norepinephrine, but does not affect the amount of serotonin. This can come in handy when you combine Bupropion with serotonin-specific antidepressant-like SSRIs. 

This way the risk of serotonin syndrome decreases, which can occur as a result of too much serotonergic activity in your brain. Some of the side effects associated with the use of Wellbutrin include:

  • Anxiousness 
  • Unexplainable excitement and happiness 
  • Insomnia or inability to fall asleep 
  • Xerostomia or dry mouth 
  • Dizziness 
  • Drowsiness 
  • Nausea with or without vomiting 
  • Abdominal pain 
  • Headache 
  • Tremors 
  • Weight loss 
  • Loss of appetite 
  • Tinnitus or ringing in the ears 
  • Excessive sweating 
  • Altered sense of taste and smell
  • Constipation 
  • Throat infection 
  • Increased frequency of urination

Conclusion

In this blog post, we have discussed the strongest antidepressants for the treatment and management of major depressive disorder (MDD). Antidepressants are one of the most commonly prescribed medications nowadays, because of the widespread depression and other mental health conditions. 

However, not every antidepressant is effective when it comes to the management and treatment of the major depressive disorder (MDD). Those which do work include SSRIs, SNRIs, atypical antidepressants, DNRIs, and tricyclic antidepressants. 

TCAs, however, are not commonly used because of the terrible side effects they produce. This is why you should always stick to your doctor’s recommended treatment regimen. 

FAQs: Strongest antidepressant for severe depression 

Which antidepressant is best for major depression?

The strongest antidepressants for major depressive disorder (MDD) include:

  • Selective serotonin reuptake inhibitors (SSRIs) – Monotherapy or combination therapy of two SSRIs 
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) – Monotherapy or combination therapy 
  • Atypical antidepressants – Monotherapy or combination therapy with SSRIs
  • Dopamine-norepinephrine reuptake inhibitors (DNRIs) – Monotherapy or combination therapy with SSRIs

What is the strongest medication for depression?

SSRIs are one of the most commonly prescribed antidepressants. These drugs are very well tolerated and can significantly help restore your mental health. In the case of major depressive disorder (MDD), some doctors prescribe two SSRIs in combination, mostly Sertraline and Escitalopram, to help relieve the disturbing symptoms associated with persistent depression. A combination of these antidepressants is preferred over monotherapy for MDD because this type of depression is more severe and persistent in nature.

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 is the first drug of choice for depression?

The first drug of choice for depression is selective serotonin reuptake inhibitors (SSRIs). These drugs are very well tolerated and can significantly help restore your mental health. In the case of major depressive disorder (MDD), some doctors prescribe two SSRIs in combination, mostly Sertraline and Escitalopram, to help relieve the disturbing symptoms associated with persistent depression.

Is there a medication that treats both depression and anxiety?

Yes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are approved by the Food and Drug Administration (FDA) for the management and treatment of both anxiety and depression. However, you need to take these meds for 4 weeks or more to see noticeable changes in your mental health condition. 

What is the best combination of antidepressants?

There are a huge number of possibilities when it comes to the combination of antidepressants. It’s hard to tell which one is considered the best, as all of the combinations act uniquely for different mental health conditions. However, research suggests that the combination of two SSRIs, mainly Sertraline and Escitalopram is considered a good, safe, and effective choice for the treatment and management of depression, anxiety, and several other mental health conditions. 

References 

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