What is the best antidepressant to take with mirtazapine? (3 choices)

In this article, we will discuss the best antidepressants to take with mirtazapine. We will also discuss some research studies and the potential risks of such combinations. 

What is the best antidepressant to take with mirtazapine?

The best antidepressants to take with mirtazapine include:

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

Selective serotonin reuptake inhibitors (SSRIs)

Mirtazapine can be combined with SSRIs, which typically include: (1)

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

SSRIs are commonly prescribed antidepressants and are often used as a first line of treatment for depression and anxiety. However, SSRIs monotherapy might not be sufficient for some individuals, or mirtazapine monotherapy might not yield satisfactory results. 

In such cases, it is common for doctors to consider a suitable combination of antidepressants. The combined use of mirtazapine with a suitable SSRI can offer potential health benefits. 

However, the decision to prescribe this combination depends on several patient-specific factors, and such combinations might not provide added therapeutic benefits compared to monotherapy with either of these medications. 

Therefore, it is important to rely on your doctor’s expertise and refrain from making any changes to your treatment plan.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

SNRIs can also be prescribed with mirtazapine. Venlafaxine, in particular, could be considered a drug of choice to combine with mirtazapine for the management of treatment-resistant depression (2). Other SNRIs might also be used after properly weighing the risk-benefit ratio. 

SNRIs typically include: (3)

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

However, such combinations should be closely monitored for side effects, as what works for one person may not work for another. Some individuals might not respond well or might have additional underlying factors that could make this combination unsuitable for them.

Bupropion (Wellbutrin)

Bupropion can also be prescribed with mirtazapine. It might not be considered an ideal choice, considering how both of these medications have different effects on your energy levels – bupropion is activating, and mirtazapine is a sedative antidepressant (4,5). 

However, this combination may provide more therapeutic benefits compared to monotherapy. It is also important to note that patient-specific factors are crucial in determining whether this is a suitable combination for them.

What does research suggest?

Several research studies have discussed the combined use of mirtazapine with other antidepressants. It is a known fact that antidepressants take 2-6 weeks to generate a response, and some individuals may take even longer (6). 

If an antidepressant does not begin to work, it typically means that either the choice of drug is not suitable to manage the symptoms of a specific individual or antidepressant monotherapy is not sufficient (6). 

This is where research suggests that combining mirtazapine with another antidepressant could be a good treatment approach in some cases.

The combination of mirtazapine and venlafaxine, according to research, is a safe and well-tolerated option to manage depression that does not respond to monotherapy (2). No serious adverse events were reported during the trials, and the response rate is also good enough to consider this combination as effective (2). 

Some research studies have also indicated that combining mirtazapine with an SSRI or an SNRI might not offer clinically significant results (7). These combinations might not provide any additional antidepressant effects when used together, making them less reliable treatment approaches. 

However, some studies do suggest that mirtazapine, when combined with SSRIs, can safely and effectively manage treatment-resistant depression and PTSD (8,9). Some studies have also shown that mirtazapine and bupropion can be more effective than an SSRI, such as fluoxetine monotherapy (10).

What are the potential risks of combining mirtazapine with other antidepressants?

The potential risks of combining mirtazapine with other antidepressants include:

Antidepressant CombinationsCommon Side EffectsRare Side Effects
Mirtazapine + SSRIsIncreased sedation, early anxiety, nausea, vomiting, diarrhoea, tiredness, and low energy levels.Serotonin syndrome, severe drowsiness, confusion.
Mirtazapine + SNRIsEnhanced sedative effects, nausea, vomiting, diarrhoea, tiredness, and low energy levels.Serotonin syndrome, increased blood pressure.
Mirtazapine + BupropionDry mouth, nausea, vomiting, constipation, lethargy, mood swings, etc. Increased risk of seizures and agitation.

These side effects can vary from person to person and some may require immediate medical attention. 

The overall efficacy of mirtazapine combination treatments 

As a pharmacist, I do suggest using mirtazapine in combination with a suitable antidepressant if monotherapy is not enough to manage your symptoms. I have come across many patients struggling with depression and related symptoms even while taking an antidepressant. 

Some of these patients do feel a lot better when their antidepressant is combined with psychotherapy. However, major depressive disorder may require psychotherapy along with a combination of antidepressants. 

If your depression is comorbid with insomnia, taking mirtazapine with a suitable antidepressant could be a good treatment approach. However, it is important to note that what works for someone else might not work for you. 

I have patients coming up to me all the time saying why a certain medication does not work for them but does help someone they know. It’s worth noting that we all have unique body physiology, and we can respond differently to medications. 

Just trust your doctor’s expertise, keep following the directions properly, and attend follow-up appointments to monitor your progress.


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  2. Hannan N, Hamzah Z, Akinpeloye HO, Meagher D. Venlafaxine-mirtazapine combination in the treatment of persistent depressive illness. J Psychopharmacol. 2007 Mar;21(2):161-4. doi: 10.1177/0269881107065738. Erratum in: J Psychopharmacol. 2008 Aug;22(6):698. PMID: 17329295. https://pubmed.ncbi.nlm.nih.gov/17329295/ 
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