What Is the Best Antidepressant for Anxiety and Depression?
No single drug is best for everyone. Most people start on an SSRI such as sertraline or escitalopram, and side effects, age and other medicines decide between them.
By withClaro Editorial · Medically reviewed by Dr. Jason Tan , Consultant Psychiatrist · 2026-11-09 · 11 min read
Key takeaways No antidepressant is best for everyone with anxiety and depression. SSRIs such as sertraline and escitalopram are common first choices because they treat both and are among the better tolerated. In 10 pooled trials, people with depression and high anxiety did slightly better on an SSRI than on bupropion. Their depression responded in 65.4% and 59.4%. Depression with strong anxiety tends to respond more slowly, and anxiety can rise after starting an antidepressant or changing the dose. In 99 Reddit threads, 151 people said what happened to their anxiety on an antidepressant. For 94 of them, it was clearly better. Most antidepressants work about equally well, so side effects often decide: weight, sleepiness, interactions and how hard a drug is to stop. On this page
What is the best antidepressant for both anxiety and depression? Did the psychiatrists rank antidepressants right? Did anxiety get better on an antidepressant, according to people on Reddit? Why can anxiety get worse before it gets better? Which antidepressants are least likely to cause weight gain? Where do buspirone and benzos fit? How does a prescriber choose, and what should you tell them? The best antidepressant for anxiety and depression is the one that suits you, and no single drug wins for everyone. Most people start on an SSRI such as sertraline or escitalopram, which treat both conditions and are among the better tolerated. Side effects, age and your other medicines decide between them.
Two psychiatrists, Greg Malzberg and his co-host Dr. Fu, ranked antidepressants in a May 2026 episode of the Psychofarm Podcast. The episode is aimed at clinicians and is mostly about major depression, with anxiety as a frequent companion. We checked what they said against trials and FDA labels, and counted what people on Reddit say about their own anxiety.
What is the best antidepressant for both anxiety and depression?
A 2018 Lancet review of 522 trials found all 21 antidepressants better than placebo for depression, with modest gaps between them. Sertraline and escitalopram were among the better tolerated. A 2009 review of 117 trials called sertraline a good choice for starting treatment of moderate to severe depression.
Both drugs also treat anxiety. Escitalopram is FDA approved for generalized anxiety disorder. Sertraline is approved for panic disorder, PTSD, social anxiety disorder and OCD.
Medication In depression trials In anxiety Sertraline (Zoloft), SSRI Better than placebo, among the better tolerated Approved for panic, PTSD and social anxiety. Worked for generalized anxiety in small samples Escitalopram (Lexapro), SSRI Better than placebo, among the better tolerated Approved for generalized anxiety Paroxetine (Paxil), SSRI Better than placebo Worked for generalized anxiety but was harder to tolerate Venlafaxine (Effexor XR), SNRI Better than placebo, with more dropouts than many Among the most effective for generalized anxiety Duloxetine (Cymbalta), SNRI Better than placebo, with more dropouts than many Among the most effective for generalized anxiety Bupropion (Wellbutrin) Better than placebo Can raise anxiety and agitation Mirtazapine (Remeron) Better than placebo, and very sedating Worked for generalized anxiety in small samples
A 2019 Lancet review of 89 trials in generalized anxiety ranked duloxetine, venlafaxine and escitalopram among the effective, fairly well tolerated options. Sertraline and mirtazapine also worked, but the samples were small. So the evidence does not crown one drug for both conditions.
When anxiety is strong, an SSRI has a small edge over bupropion. A 2008 analysis pooled 10 trials of 2,122 people with depression on bupropion or an SSRI. The SSRIs were sertraline, paroxetine, fluoxetine and escitalopram. Among those with high anxiety, depression responded in 65.4% on an SSRI and 59.4% on bupropion. With low anxiety, there was no difference.
That gap is about 6 people in 100, so bupropion can still be the right drug for some. If strong anxiety is part of your picture, say so at the appointment. If you are choosing between the two most common SSRIs, see how Lexapro and Zoloft compare .
Did the psychiatrists rank antidepressants right?
Mostly yes. The two psychiatrists rank antidepressants for major depression, and their top picks match what large trials show. A few details in their reasoning don't match the FDA labels, and two of their figures have no source we could find. Here is how each claim holds up against trials and labels.
What the hosts said What the research found Does it hold up? Sertraline is the go-to for a typical major depressive episode A 2009 review called it a good starting choice. A 2018 review put it among the better tolerated, alongside escitalopram Reasonable, but escitalopram is close Sertraline barely affects the heart's QTc interval, and stomach side effects fade within about a week At twice the top dose, QTc rose about 10 ms in a label study of 54 healthy people. Nausea and diarrhea are among its most common side effects QTc: yes, with caution. We found no source for the one-week figure The label caps escitalopram at 10 mg in older adults because of QTc risk The label recommends 10 mg a day for older adults. Its reason is higher drug levels, with exposure and half-life about 50% higher Partly: right dose, different reason Citalopram tops out at 40 mg, or 20 mg for people over 60 and poor CYP2C19 metabolizers Yes, because of QT risk. The label adds liver problems and drugs that block CYP2C19, such as cimetidine Yes Of the SSRIs, only paroxetine directly causes weight gain, though others occasionally add weight Paroxetine caused more gain than sertraline or fluoxetine in a 2000 trial. A UK study linked all antidepressants to more weight gain, but the link may not be caused by the drugs Fits: paroxetine stands out, and the wider link may not be direct Venlafaxine has the worst withdrawal of any antidepressant A 2024 review put it among several drugs with frequent and severe symptoms Partly: among the worst, not alone Don't combine an SSRI with an SNRI The Effexor XR label warns that other serotonin drugs, SSRIs included, raise the risk of serotonin syndrome. It asks for monitoring, not a ban Fits the label as caution. Don't stop either drug on your own Bupropion can make anxiety worse at first in very anxious people At 400 mg a day, the highest dose studied, agitation affected 9% against 2% on placebo. SSRIs did slightly better in anxious depression Yes Mirtazapine is very sedating and suits people who need to gain weight The label warns of sleepiness and of more appetite and weight gain Yes Benzodiazepines rank lowest, though a one-week prescription can help through a crisis The label carries a boxed warning on misuse, dependence and withdrawal. In generalized anxiety they worked but were harder to tolerate Short use only, under the label's warning. No source sets one week Buspirone helps anxiety, trauma and irritability in depression It worked for generalized anxiety in small samples. As an add-on to citalopram, it did about as well as bupropion Partly: modest data, and we found no source on trauma or irritability
On sertraline, one host was direct:
I think for run-of-the-mill, meets criteria, major depressive episode, you gotta go with Sertraline.
Trials back sertraline as a strong first choice, not a clear winner. On escitalopram in older adults, one of them said:
The FDA label kind of handcuffs you in the elderly population saying you can't go above 10 milligrams because you're being ultra careful about QTC prolongation.
The label gives a different reason, higher drug levels at older ages. If you are over 60, ask your prescriber whether your dose takes your age into account.
Did anxiety get better on an antidepressant, according to people on Reddit?
Most who said what happened to their anxiety said it got better
We read 99 recent threads on r/Anxiety, r/antidepressants, r/SSRIs and similar subreddits, comments included. Between the posts and the replies, 306 people wrote about their own time on an antidepressant. This count is about anxiety on any antidepressant, not split by drug. Of the 151 who said what happened to their anxiety, most said it improved at least partly.
What happened to their anxiety People Clearly better 94 Somewhat better, still struggling 23 Worse at first, then better 5 Too early to tell 4 Gave it time, and it didn't help 17 Got worse and stayed worse 8
Each person counts in one row. People often post when something goes wrong, so threads like these can lean toward the hard cases.
For many in the first row, the change was plain once it came. One person on r/SSRIs wrote:
I am on sertraline and it stopped rumination/ocd for me. I used to ruminate for hours and hours everyday and had really bad ocd. I am on 150 mg and after a few months I noticed that I am not anxious anymore.
Of the 94 whose anxiety clearly improved, 17 said how long they had been on the drug. Half of those 17 had been on it for 9 weeks or more.
Not everyone got there, even after a long time on one drug. One person on r/Anxiety wrote:
I've been on 40mg of Prozac for 2 years and have seen little to no difference in my anxiety, obsessive thoughts, or depression.
A rough start did not always mean a bad result. Of those who said their anxiety improved, a few described a hard first stretch. One person on r/Anxiety wrote:
I did have some increased anxiety and OCD for about two weeks
The same person had been happy on Lexapro for almost two years when they wrote.
Few people said what worried them before starting, just 11 of the 306. Fear of withdrawal later came up for 5, and weight for 3. One person on r/Anxiety wrote:
I too was worried about starting based on stuff I read here and elsewhere. Been almost 4 months. Best thing I could’ve done.
If you are starting, rate your anxiety and your mood separately each day. They often move at different speeds, and your prescriber will want to know which one changed.
Why can anxiety get worse before it gets better?
Anxiety can rise when you start an antidepressant or change the dose. The Zoloft label asks people to report new or worse anxiety or panic attacks right away. It flags the start and any dose change. Antidepressants start acting with the first dose, but you may feel the benefit only after a few weeks.
The bupropion label also lists agitation and anxiety among its side effects. One of the hosts warned other clinicians:
Beware of using it in patients who have a lot of baseline anxiety.
The host added that bupropion may help anxiety in the long run, but the early rise can be too much for some.
Depression with strong anxiety is also common and tends to respond more slowly. In a 2008 report from STAR*D, a large US study, 53.2% of 2,876 people starting citalopram had anxious depression. Compared with others, they were less likely to reach remission, took longer to get there and had more side effects.
The Zoloft label also says not to stop the drug without first talking to your prescriber. If anxiety spikes, call them and note when it started. If bupropion is the drug you were offered, see what bupropion can do to anxiety .
Which antidepressants are least likely to cause weight gain?
Among SSRIs, sertraline and fluoxetine are less linked to weight gain than paroxetine. A 2000 trial followed 284 people with depression for 26 to 32 weeks on fluoxetine, sertraline or paroxetine. Only paroxetine led to significant weight gain, and more people on it gained over 7% of their body weight.
One of the hosts sees paroxetine as the only SSRI that directly causes weight gain. The same host has seen the others add weight occasionally. Larger data paint a broader picture. A 2018 UK study of nearly 295,000 people found weight gain about 21% more common in people taking any antidepressant. The link may not be caused by the drugs themselves.
The mirtazapine (Remeron) label warns about increased appetite and weight gain. Mirtazapine is also very sedating: in US trials, 54% on it reported sleepiness against 18% on placebo.
How hard a drug is to stop also shapes the choice. A 2024 Lancet Psychiatry review of 79 studies found withdrawal symptoms in 31% after stopping an antidepressant and 17% after stopping placebo. Severe symptoms affected 2.8%. On venlafaxine, one host said:
Famously, the worst withdrawal syndrome out of all the antidepressants.
The review puts venlafaxine among the drugs with frequent and more severe symptoms, next to paroxetine and imipramine. Tell your prescriber which side effect would bother you most: appetite changes, sleepiness, sexual side effects or stopping later.
Where do buspirone and benzos fit?
Neither is a first choice for depression, but both come up when anxiety is strong. Buspirone treats generalized anxiety and is sometimes added to an antidepressant. Benzodiazepines (benzos) such as alprazolam (Xanax) are kept short because of dependence.
In STAR*D, people still depressed on citalopram added buspirone or bupropion. Remission came for 30.1% with buspirone and 29.7% with bupropion. Side effects made 20.6% stop buspirone, against 12.5% for bupropion. The 2019 Lancet review found buspirone effective for generalized anxiety, though in small samples.
Benzodiazepines carry a boxed warning, the FDA's strongest, for misuse, dependence and withdrawal. The risk grows with dose and with length of use. The hosts put benzos in their lowest tier, as symptom relief that builds habit and tolerance. One of them still sees a place for about a week of use to get through a crisis. We found no source that sets that length.
If you are offered one, ask how long it is meant to last before you start it. If buspirone is the add-on, see how Buspar works for anxiety .
How does a prescriber choose, and what should you tell them?
No antidepressant is the strongest for everyone, and the right one is often found by trying.
In large comparisons most antidepressants work similarly on average, with only modest differences between them. They differ more in side effects, interactions and how hard they are to stop. Needing a second choice does not mean the first was a mistake.
Prescribers look at your main symptoms, other conditions, other medications and past response, yours or a close relative's. Some antidepressants are more activating and others more sedating, which can be matched to problems with sleep or energy.
If a medication has not helped enough after a fair trial, the options include:
adjusting the dose switching to another medication in the same class switching to a different class adding a second medication Medical review Medically reviewed by Dr. Jason Tan, Consultant Psychiatrist, on 27 October 2026, this section only. Next review: 27 October 2027.
When you have both anxiety and depression, it helps to tell your prescriber:
Which bothers you more right now, anxiety or low mood. How you sleep, and how much energy you have during the day. Which side effects worry you most: appetite, sleepiness, sexual side effects or withdrawal later. Every medicine and supplement you take, including any other antidepressant. Your age, and any liver or heart problems. Antidepressants you or a close relative took before, and how they went. Short daily notes show a pattern that memory tends to blur. The withClaro app lets you log mood, energy, sleep and appetite each day. It links side effects to your dose and turns the record into a report for your prescriber.
If you feel worse or more restless after starting, call your prescriber right away. If you're having thoughts of harming yourself, contact emergency services or a crisis line straight away. In the US, call or text 988. In the UK, call Samaritans on 116 123. Elsewhere, find a crisis line near you .
Download on the App Store Anxiety and mood can change at different speeds on a new antidepressant. The withClaro app lets you log mood, energy, sleep and appetite each day, track side effects against your dose and share a report with your doctor.
Frequently asked questions What is the most prescribed antidepressant for anxiety? We found no official US ranking for anxiety alone. SSRIs such as sertraline and escitalopram are common first choices, and escitalopram is FDA approved for generalized anxiety. Ask your prescriber which type of anxiety yours is, since approvals differ by type.
What are the top 10 medications for anxiety and depression? There is no agreed top 10. The usual options are SSRIs, SNRIs such as venlafaxine and duloxetine, bupropion and mirtazapine, with buspirone or a short benzodiazepine sometimes added. Bring your main symptoms and past medicines to your prescriber to narrow the list.
How to cope with SSRI side effects? On sertraline, nausea and diarrhea are among the most common side effects. Its label tells people to check with their prescriber before stopping. Write down what you notice and when, and call your prescriber if a side effect is hard to live with.
Is it normal to be scared of antidepressants? Yes, and the fear often comes from stories read online. One person on Reddit who was worried before starting later called it the best thing they could have done. Tell your prescriber what you read and which part worries you.
How to get over fear of taking new medication? It helps to make the fear specific: side effects, weight, withdrawal later or that the drug won't work. Write each one down. Ask your prescriber what to expect in the first weeks and which changes should make you call.
What is the best antidepressant for depression alone? In large reviews most antidepressants work about equally well on average for depression. Sertraline and escitalopram are among the better tolerated. Tell your prescriber which side effects you most want to avoid.
Related articles
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