What is the best antidepressant to take with Xanax? (5 options)

In this article, we will discuss the best antidepressants to take with Xanax (alprazolam), a benzodiazepine. We will also discuss some research studies and how one can ensure the safe and effective use of this combination.

What is the best antidepressant to take with Xanax?

The best antidepressants to take with Xanax are selective serotonin reuptake inhibitors (SSRIs), including: (1)

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

SSRIs are one of the most commonly prescribed antidepressants to be used as the first line of drugs for depression and anxiety. Xanax is a benzodiazepine, which is a sleep-inducing anti-anxiety medication. (2)

Xanax has a much faster onset of action compared to SSRIs, which may take 4-6 weeks to kick in (1,2). However, there are some limitations to the use of Xanax for the long-term management of anxiety. 

This is because Xanax is a Schedule IV controlled substance with a high risk of addiction and abuse, compared to SSRIs, which are not considered drugs of abuse by the Drug Enforcement Administration (DEA) (2). So, SSRIs are considered the choice of drugs for long-term management of anxiety.

However, SSRIs can sometimes increase anxiety or cause insomnia during the early course of treatment, and these meds can take more than a month in some cases to kick in. 

In such cases, Xanax can be taken to manage early anxiety and insomnia. Such combinations are considered safe for short-term use. However, both Xanax and SSRIs are prescription medications and should never be taken without your doctor’s approval.

What does research suggest?

Several research studies have discussed the combined use of Xanax and SSRIs, including the clinical safety and efficacy of such treatment plans. One research study indicated that alprazolam (the active ingredient in Xanax) can be used in cases of depression comorbid with clinical anxiety (3). 

Although SSRIs are approved by the FDA to treat both of these conditions, due to their delayed onset of action, these antidepressants might not be the best solution in severe cases (3). 

This is where the combined use of Xanax with a suitable SSRI can manage anxiety and insomnia much faster than SSRI monotherapy, and the patient feels more calm and relaxed during the early course of their SSRI treatment (3). 

The duration of Xanax can vary in such cases, as some doctors start tapering it off when the SSRI kicks in, whereas some providers recommend their patients take it for a longer duration.

Another research study focused on the antidepressant effects of alprazolam and indicated that this benzodiazepine is as effective in managing depression as a low-dose tricyclic antidepressant (4). 

This makes alprazolam a good option to combine with antidepressants in the case of Major Depressive Disorder (MDD) to manage various symptoms of depression, anxiety, and insomnia effectively. 

Some research studies have also indicated that Xanax can help reduce nervousness/jitteriness associated with some SSRIs, including fluoxetine (5).

What are the potential risks of taking Xanax with antidepressants?

The potential risks of taking Xanax with antidepressants include: (1,2)

Increased risk of additive side effects

Taking Xanax with antidepressants can increase the risk of additive side effects or side effects that are common with both of these drugs. These may include:

  • Increased sedation
  • Tiredness
  • Dizziness
  • Lightheadedness
  • Dry mouth
  • Nausea
  • Constipation
  • Changes in appetite or weight
  • Joint or muscle pain
  • Irritability
  • Headaches

Severe side effects

The combined use of Xanax and antidepressants can cause some serious side effects, such as blackouts, risk of falling/injuries, seizures, cognitive impairment, dementia, etc. These side effects are not that common and can be influenced by various patient-specific factors. 

However, some of these side effects require immediate medical attention and should be swiftly reported.

How to ensure the safe use of Xanax with SSRIs?

The following steps are important to ensure the safe use of Xanax with SSRIs:

  • Stick to the recommended doses of Xanax and the antidepressant. Your doctor carefully calculated the right amount for you. Taking more won’t speed things up; it might lead to problems instead. The typical Xanax dosage recommendations include: (2)
ConditionInitial DoseMaximum Daily Dose
Generalised Anxiety Disorder (GAD)0.25 mg to 0.5 mg three times daily4 mg per day (divided doses)
Panic Disorder0.5 mg three times daily10 mg per day (divided doses)
  • Take Xanax at the same time each day. This helps maintain a steady level in your system for consistent relief. If you forget, don’t double up on the next dose. Stick to your regular schedule.
  • Understand how long you’re supposed to take Xanax. Do not take it for longer than recommended.
  • Skip alcoholic drinks while taking Xanax and antidepressants concomitantly. Alcohol can amplify the sedative effects, making you drowsy or dizzy.
  • Pay attention to changes in how you feel and report anything that concerns you to your provider. 

Understanding the benefits and risks of Xanax and antidepressants

As a pharmacist, I know many patients who take an SSRI, such as sertraline or fluoxetine in the morning, and Xanax at night. This combination helps them sleep well as the antidepressant manages depression and related symptoms. 

However, I always advise such patients to ensure the safe and effective use of these medications together. You should always stick to the recommended doses, as dose adjustment is the key to making this combination safe for you.

I have also come across cases where patients took more than the recommended dose of Xanax without consulting their prescribing physician first. 

It’s quite easy to become addicted to Xanax and trust me, I know how difficult it becomes for people to keep this addiction at bay. So, following the prescribed dosage is the most important thing here to remember. Some people may be scared to take Xanax first because of its addiction potential. 

However, the safe use of any medication can prevent it from harming you. You should monitor your side effects if you’re new to the combination of Xanax and antidepressants and report anything that concerns you to your provider.


  1. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32119293. https://www.ncbi.nlm.nih.gov/books/NBK554406 
  1. George TT, Tripp J. Alprazolam. 2023 Apr 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30844192. https://www.ncbi.nlm.nih.gov/books/NBK538165 
  1. Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Prim Care Companion J Clin Psychiatry. 2008;10(3):222-8. doi: 10.4088/pcc.v10n0307. PMID: 18615162; PMCID: PMC2446479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446479/ 
  1. Warner MD, Peabody CA, Whiteford HA, Hollister LE. Alprazolam as an antidepressant. J Clin Psychiatry. 1988 Apr;49(4):148-50. PMID: 3281931. https://pubmed.ncbi.nlm.nih.gov/3281931/ 
  1. Amsterdam JD, Hornig-Rohan M, Maislin G. Efficacy of alprazolam in reducing fluoxetine-induced jitteriness in patients with major depression. J Clin Psychiatry. 1994 Sep;55(9):394-400. PMID: 7929020. https://pubmed.ncbi.nlm.nih.gov/7929020/ 

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