What is the best antidepressant to take with Mirtazapine? (3+ possible interactions) 

In this blog post, we are going to answer the question, “What is the best antidepressant to take with Mirtazapine?”. Mirtazapine is an antidepressant which is used to treat a variety of mental health conditions. 

In some practices, Mirtazapine is combined with another antidepressant to achieve a better therapeutic response for the treatment and management of treatment-resistant depression. 

This blog will cover the best possible combinations of antidepressants with mirtazapine and we will also talk about the safety and efficacy of such combinations. 

What is the best antidepressant to take with Mirtazapine?

The best antidepressants to take with Mirtazapine are selective serotonin reuptake inhibitors (SSRIs) and Venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor (SNRI). 

The rest of the classes of antidepressants do not pair well with Mirtazapine because of the side effects that are associated with them. However, these combinations may also affect some people negatively, especially when the doses are high. 

This is why it is highly recommended to start the combination treatment with the lowest effective dose and not deviate from your prescription. 

How is Mirtazapine different from SSRIs and SNRIs?

Mirtazapine is considered an atypical antidepressant because its mechanism of action is entirely different from the most common classes of antidepressants; SSRIs and SNRIs. 

If we specifically talk about SSRIs, they inhibit the reuptake of serotonin by blocking serotonin transporters (SERT), which are usually responsible to take the leftover serotonin back to the presynaptic neuron. 

When the SERT is blocked, more serotonin remains available in the synaptic cleft for a longer period of time and it binds to its respective receptors and helps counteract the symptoms associated with depression, anxiety, and several other mental health-related problems. 

SNRIs have the same mechanism of action, but they also block norepinephrine transporters (NET). This way, SNRIs increase the amount of both serotonin and norepinephrine to counteract the symptoms associated with mental health conditions. 

Mirtazapine, on the other hand, does no such thing. Its exact mechanism of action is still a topic of debate. However, many experts have indicated that Mirtazapine has a dual mode of action. It can activate 5-HT1 receptors, which are one of the serotonin receptors. 

It also enhances 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. 

One thing that is the same with all of these antidepressants is the ability of these meds to increase the number of excitatory neurotransmitters in your brain. Serotonin and norepinephrine both are responsible for a huge number of functions.

Serotonin has receptors in almost every single part of your body, including your gastrointestinal tract. This neurotransmitter can affect your mood, cognition, reward, learning, memory, hunger, intestinal motility, and several other functions. 

Norepinephrine, on the other hand, is also associated with a lot of functions like contraction of skeletal and cardiac muscles etc. When it comes to the efficacy of the combination treatment, several research studies have suggested that Mirtazapine works well when it is combined with an SSRI or Venlafaxine. 

Patients respond well to this combination as compared to when Mirtazapine is used alone. The combination has great clinical importance in the management and treatment of major depressive disorder (MDD), generalised anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). 

What are the possible interactions between Mirtazapine, SSRIs and SNRIs? 

When Mirtazapine, which is an antidepressant itself, is combined with another antidepressant, it does possess the risk of some possible interactions. However, the dose at which you’re taking these meds can make a huge difference. 

When two antidepressants are taken together, the doses of both of the meds are adjusted and are usually far lower than the dose at which each of these meds is used individually. 

This is why overdosing on these meds can become life-threatening for some people because of the physiological side effects they cause. Some of the interactions include:

• Risk of serotonin syndrome 
• Increased sedation 
• Cardiovascular side effects 
• Gastrointestinal side effects 

Risk of serotonin syndrome

The risk of serotonin syndrome is the biggest concern when it comes to combining two or more antidepressants together. This is because all of these meds increase the number of excitatory neurotransmitters in your brain. 

If the doses are not properly adjusted or people don’t follow their doctor’s advice and take more than what is prescribed, the risk of serotonin syndrome increases. 

This is because too much serotonin, an excitatory chemical in your brain, can make your entire body start malfunctioning. It excessively binds to a huge number of its receptors throughout the body and causes disturbing symptoms. Some of which include:

• Nervousness 
• Convulsions 
• Confusion 
• Erratic behaviour 
• Fever with chills
• Muscle Shivering 
• The rapid change in blood pressure 
• Uncontrollable heartbeat
• Vision problems 
• Auditory and visual hallucinations 

These symptoms can vary from person to person. Some people can start getting these symptoms soon after taking the excessive dose of this combination. This is why you should always stick to your doctor’s recommended dose and never take more than the prescribed dose. 

Increased sedation 

Increased sedation or excessive drowsiness is one of the most common side effects associated with the use of Mirtazapine. The drug is considered one of those antidepressants which can significantly make you drowsy. 

SSRIs and SNRIs are also associated with drowsiness as a side effect. However, it may not affect everyone as SSRIs like Sertraline and Fluoxetine are also known for causing insomnia. 

There is no way to be certain what kind of sleep-related side effects you will get while being treated with SSRIs or SNRIs. 

Some case studies have indicated that the combination of Mirtazapine and these antidepressants can make some people extremely drowsy and can significantly affect their daytime activities. 

This can result in therapeutic failure because you can’t bear this continuous sedation. This is why you should always monitor your side effects and should immediately report to your healthcare provider if you experience anything unusual or severe. 

Cardiovascular side effects

Mirtazapine, SSRIs, and Venlafaxine, all of these meds can cause arrhythmia, heart palpitations, and QT prolongation. However, they are not considered that common, but there is no way to predict who will get these side effects and who will not. 

SSRIs are usually considered safe to be used for the management and treatment of depression in cardiac patients. However, they may cause some complications when used in combination with meds like Mirtazapine which can also cause arrhythmia and heart palpitations. 

This is why you should never start using this combination without your doctor’s approval if you are a heart patient and should always stick to your doctor’s recommended prescription. 

Gastrointestinal side effects 

All of these antidepressants are associated with one common type of side effect; gastrointestinal. Mirtazapine can cause acid reflux and heartburn. It can also cause nausea, vomiting, and diarrhoea. The same is the case with SSRIs and Venlafaxine. 

Some SSRIs like Sertraline, Fluoxetine, and Paroxetine are more commonly associated with increased stomach acidity and it may upset you if you already have an ulcer. When such drugs are combined together, they may cause even more pronounced gastrointestinal side effects.

However, your doctor may advise you to follow a gut-friendly diet and take your medication in between meals to help prevent acid reflux. Again, the proper use of medicines is the only way to ensure a good therapeutic response. 

Antidepressants don’t work overnight and you can’t expect them to treat your depression overnight. This is why you should take your meds carefully and should never take more than the recommended dose. 

Conclusion 

In this blog post, we have discussed the best antidepressants to use in combination with Mirtazapine, which is an antidepressant itself. We have learned that according to research, the best antidepressants to take with Mirtazapine are SSRIs and Venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor (SNRI). 

The rest of the classes of antidepressants do not pair well with Mirtazapine because of the side effects that are associated with them. However, these combinations may also affect some people negatively, especially when the doses are high. 

This is why it is highly recommended to start the combination treatment with the lowest effective dose and not deviate from your prescription. 

FAQs: best antidepressant to take with Mirtazapine 

Can you take another antidepressant with mirtazapine?

Yes, you can take another antidepressant with Mirtazapine. The best antidepressants to take with Mirtazapine are selective serotonin reuptake inhibitors (SSRIs) and Venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor (SNRI). The rest of the classes of antidepressants do not pair well with Mirtazapine because of the side effects that are associated with them. However, these combinations may also affect some people negatively, especially when the doses are high.

What antidepressant can I take with mirtazapine?

With Mirtazapine, you can take SSRIs like Zoloft (Sertraline), Lexapro (Escitalopram), Celexa (Citalopram), Paxil (Paroxetine), and Prozac (Fluoxetine). Mirtazapine can also be paired with Venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor (SNRI). The rest of the classes of antidepressants do not pair well with Mirtazapine because of the side effects that are associated with them. However, these combinations may also affect some people negatively, especially when the doses are high. 

What works well with mirtazapine for anxiety?

Several studies suggest that Mirtazapine can be used with Paroxetine for the safe and effective treatment of generalised anxiety disorder (GAD) and social anxiety disorder (SAD). However, other SSRIs can also be combined with Mirtazapine for the treatment and management of symptoms associated with anxiety. Make sure you stick to your doctor’s directions for a safe and effective therapeutic outcome. 

Are mirtazapine and sertraline a good combination?

Mirtazapine and Sertraline can be a good combination for some people, but you should only take them if prescribed by your healthcare provider. This combination should be used at lower doses. The combination therapy of antidepressants at higher doses can be dangerous. 

This is because both of these meds are supposed to increase the number of excitatory neurotransmitters in your brain. Too much excitatory activity can cause drastic consequences and can increase the risk of a rare condition called serotonin syndrome. 

What antidepressant works well with mirtazapine?

Several studies have suggested that mirtazapine works well when it is used in combination with an SSRI or an SNRI. However, a combination of antidepressants can only be taken when prescribed by your healthcare provider. 

This is because when two meds for the same illness are used, the doses are adjusted. Individual therapy comes with higher doses, while combination therapy has to be adjusted on comfortable doses to help avoid the side effects. 

References 

• Norio Watanabe, Ichiro M Omori, and Toshi A Furukawa (2011) – Mirtazapine versus other antidepressive agents for depression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158430/#__ffn_sectitle
• Combined treatment with mirtazapine linked to better outcomes in patients with acute depression, review shows https://pharmaceutical-journal.com/article/news/combined-treatment-with-mirtazapine-linked-to-better-outcomes-in-patients-with-acute-depression-review-shows
• Debbie Tallon, Nicola Wiles, John Campbell, Carolyn Chew-Graham, Chris Dickens (2016) – Mirtazapine added to selective serotonin reuptake inhibitors for treatment-resistant depression in primary care (MIR trial): study protocol for a randomised controlled trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526304/
• Mirtazapine Tablet – Uses, Side Effects, and More https://www.webmd.com/drugs/2/drug-13706-4047/mirtazapine-oral/mirtazapine-oral/details#:~:text=Mirtazapine%20is%20used%20to%20treat,(neurotransmitters)%20in%20the%20brain.
• National Library of Medicine – Mirtazapine https://medlineplus.gov/druginfo/meds/a697009.html