Ask anything
Ask anything
✕
Anxiety and depression · Comparison guide
The quick answer
Antidepressants like Lexapro, Zoloft and Prozac (SSRIs) and Effexor and Cymbalta (SNRIs) are the standard first treatment for anxiety and depression. They work through raising serotonin in the brain.
Joyous treats anxiety and depression with low-dose (microdose) ketamine, taken daily at home. Ketamine works through a different system — glutamate — and supports the brain's ability to form new connections.[2,3]
Where the two differ most:
| Feature | Joyous (Real-World Evidence Study) | SSRIs / SNRIs (Clinical Trials & Studies) |
|---|---|---|
| Works on | Glutamate and neuroplasticity | Serotonin (± norepinephrine) |
| Treats | Root causes (Addresses synaptic connectivity and neuroplasticity) | Symptoms (Modulates monoamine neurotransmitters) |
| Time to response | ~16 days (to cut scores in half) | 4–8 weeks (8–10-week trial in anxiety)[1,42] |
| Anxiety response | 87% (GAD-7, 6 weeks) | ~60% (on a first-line drug)[43] |
| Anxiety remission range | 59% (GAD-7, 6 weeks) | 20–47% (anxiety trials)[44] |
| Depression response | 86% (PHQ-9, 6 weeks) | 47% (STAR*D step 1)[16] |
| Depression remission range | 54% (PHQ-9, 6 weeks) | 28% (HAM-D, step 1)[16] |
| Weight gain | Not reported | 21% (higher risk of gaining ≥5% of body weight)[7] |
| Libido | Not reported | 59% (report sexual dysfunction)[8] |
| Emotional blunting | Not reported | 46%[9] |
| What you feel | 78% (relaxed in the body);56% (open to exploring feelings) | 71% (flat or numb, in a survey)[23] |
| Stopping | No withdrawal effects documented | 15–56% (discontinuation symptoms)[11,12] |
| Take together? | Usually, with your clinician's direction | — |
| Cost | $129/mo (3-month subscription, or $159/mo) | ~$3–$15/mo (+ visits)[4] |
Different instruments, populations and settings. Joyous data: moderate-or-worse symptoms at the start, stayed in treatment, no control group.
Ketamine vs SSRIs comes down to which brain system each one acts on.
SSRIs block serotonin reuptake, so more serotonin stays between neurons. The effect builds over weeks.[3]
Ketamine works on glutamate. Chronic stress and depression have been shown to break down the brain's communication network, causing patients to feel stuck in negative thought loops and patterns. By boosting glutamate signaling, ketamine can promote neuroplasticity, the brain's ability to form new connections and adapt over time. It can also encourage the growth of new synapses to support more flexible and resilient thinking. One key result of this process is the increase of BDNF, a protein that supports the growth and repair of brain cells.[2,20,21]
In animal studies, new synapses formed in the prefrontal cortex within 12–24 hours.[20,21] Ketamine addresses root causes of depression and anxiety rather than masking symptoms. That describes how it works, not what you'll feel.
How SSRIs and ketamine act on the brain
SSRIs
Ketamine
Antidepressants take 4–8 weeks to work. For anxiety, a fair trial is 8–10 weeks per drug, with dose changes every 2–4 weeks. If the first drug isn't the right one, the next trial begins.[1,42,46]
In our real-world evidence study of over 43,000 patients with moderate-or-worse depression, depression scores were down 38% by the end of week one, and a typical patient's score was cut in half in about 16 days (median). By week six:
In antidepressant trials, 60% respond to a first-line SSRI, SNRI or CBT for anxiety, and 20–47% reach remission.[43,44] For depression, the first medication in the STAR*D trial brought response in 47% and remission in 28%.[16]
Speed and response
~16 days
(Joyous median time to cut depression scores in half)
cut their anxiety score in half or better:
Joyous: Real-World Evidence Study · GAD-7 · six weeks · n = 41,510 · Antidepressants: first-line drug[43]
reached the remission range for anxiety:
Joyous: Real-World Evidence Study · GAD-7 under 5 · six weeks · Antidepressants: range across anxiety trials[44]
cut their depression score in half or better:
Joyous: Real-World Evidence Study · PHQ-9 · six weeks · n = 43,563 · Antidepressants: STAR*D, first drug[16]
reached the remission range for depression:
Joyous: Real-World Evidence Study · PHQ-9 under 5 · six weeks · Antidepressants: STAR*D, first drug (HAM-D)[16]
Different instruments (PHQ-9 vs HAM-D) and different patients. Context, not a head-to-head trial.
If Lexapro isn't working anymore, or Zoloft or Prozac, the usual next moves are a higher dose, a different drug, or a second medication added to the first. Each takes weeks to judge.
Is your SSRI not working? STAR*D followed 2,876 adults who started on citalopram, and their odds of remission fell at every step: 28% on the first drug, 18–25% on the second, 12–20% on the third and 7–14% on the fourth.[16,17,29,30]
Antidepressants not working doesn't mean nothing will. The usual next step is a non SSRI antidepressant: bupropion, mirtazapine or venlafaxine. It's a fair choice, but these are still antidepressants, so you're still waiting weeks to learn whether they work.[17,29]
Beyond switching drugs, the main SSRI alternatives are psychotherapy, TMS, esketamine and ketamine. Ketamine and esketamine work on glutamate rather than serotonin.[6,15,31]
Ketamine for treatment-resistant depression has been studied in adults whose earlier medications didn't help.[15,31] Esketamine (Spravato), a related drug, is FDA-approved for it.[41] Joyous prescribes ketamine off-label. We've treated well over 100,000 patients with anxiety and depression, which makes us the largest ketamine therapy provider in the world.
SSRIs and SNRIs relieve symptoms for many. Their side effects are well documented, and they're a main reason many stop: across 73 trials, side effects drove 2.6 times as many dropouts as placebo.[10]
In our check-ins, 78% felt relaxed in their body, 56% felt an openness that helped them explore their feelings, and 63% described feeling "slightly different, but very subtle." 50% improved on positive emotions and 41% on relationships. You stay fully present and anchored to your surroundings while the medicine works.
Weight gain, sexual dysfunction and emotional blunting are NOT among ketamine effects.
Drowsiness during the session is the most common side effect: 1 in 4 felt it in week one, and fewer than 1 in 5 by week six. Some lightheadedness comes with it early on, and every side effect we measured became less common over those six weeks.
Common SSRI and SNRI side effects next to what Joyous patients report feeling
Common on SSRIs and SNRIs
Reported on Joyous
Stopping antidepressants can bring on antidepressant discontinuation syndrome, often called SSRI withdrawal. Antidepressant withdrawal symptoms include dizziness, brain zaps, nausea, irritability, flu-like feelings and rebound anxiety. Estimates run from 15% above placebo (a 2024 analysis of 79 studies, with 1 in 35 severe) to 56% (a survey review). Symptoms usually last days to weeks, and some report months.[11,12]
The advice has changed. Coming off antidepressants, also called weaning off meds, now means a slow taper over months, not the 2–4 weeks once recommended.[27] If you're asking how to get off antidepressants, do it with your prescriber, not alone. Short-half-life drugs, usually paroxetine and venlafaxine, tend to be the hardest.[11,27]
Stopping carries its own risk. In anxiety, 36% relapse within a year of stopping, against 16% of those who stay on.[48]
Ketamine is classified as a Schedule III controlled substance. However, at the low doses we use (microdoses), ketamine is not addictive. The dose is designed not to produce a high, and in our patient data the risk of developing a ketamine problem during treatment was judged low and has not been reported.
No withdrawal syndrome is described for low-dose ketamine.
Substance use disorder is a screening exclusion.
Usually you can take them together, under your clinician's direction. Ketamine and SSRI co-use is standard in recent trials, and no serotonin-syndrome interaction is established.[38] Benzodiazepines like Xanax can blunt ketamine's effect[39] but are often okay to take alongside in lower doses with your clinician's review. Tell your clinician everything you take.
Replacing an antidepressant is a different question, and it's yours and your prescriber's to answer. About 1 in 4 new Joyous patients arrive with an active SSRI or SNRI prescription.
One in five Joyous patients come wanting to stop taking SSRIs. That's their goal, not our promise. Joyous does not offer a taper protocol or wean you off antidepressants, and any change is made as directed by your prescribing provider. However, half of the patients who come in with existing SSRI/SNRI prescriptions are no longer taking the drugs when they finish Joyous treatment.
While some patients report reducing their SSRI usage after starting ketamine, discontinuation should always be managed under a physician's direct supervision to avoid adverse withdrawal effects.
For
Against
For
Against
A note from our clinical team
Mental healthcare shouldn’t require you to put your life on pause. We built a daily, provider-directed protocol that is highly efficacious and fits into real routines — meeting you where you are, at home.
Treatment for real life. Be Joyous.
Get startedKetamine is FDA approved but prescribed off-label for anxiety and depression. Side effects can occur; your clinician will review risks with you. Joyous is not for emergencies.
Not as a rule, and Joyous doesn't claim it can. About 1 in 4 new Joyous patients (26%) arrive with an active SSRI or SNRI prescription, and about half of patients who arrive on an SSRI/SNRI are no longer filling it by the time they leave. Any change to an antidepressant is made as directed by your prescribing provider. 20% of those who join us say they came wanting to stop taking SSRIs, which is their goal, not our recommendation.
Ketamine isn't an SSRI. It's an FDA-approved anesthetic prescribed off-label for depression, anxiety and other mental health conditions, and it works on glutamate instead of serotonin, supporting neuroplasticity and addressing root causes. Esketamine (Spravato), a related drug, is FDA-approved for treatment-resistant depression.[37,41]
It's not a benzodiazepine — Xanax and Klonopin work on GABA; ketamine works on glutamate.
Usually, with your clinician's review. Ketamine and Lexapro, and ketamine and Zoloft, are generally continued together. Ketamine and Wellbutrin (bupropion), and ketamine and Xanax, are reviewed case by case. Benzodiazepines like Xanax can blunt ketamine's effect but are often okay at lower doses with your clinician's review. Lamotrigine and MAOIs also interact with ketamine, so tell your clinician everything you take.[39,40,41]
Antidepressants can: in a large cohort, the risk of gaining 5% or more of body weight was 21% higher. Weight gain is not a ketamine effect. If weight is your concern, bupropion is the usual choice among antidepressants that don't cause weight gain.[7]
Often, once a prescriber lowers the dose or switches the drug. 46% of those on antidepressants report emotional blunting. It is not a ketamine effect: on Joyous, 78% felt relaxed in their body and 56% felt open to exploring their feelings.[9]
SSRIs aren't addictive in the dependence sense, but stopping them can cause discontinuation symptoms. Ketamine has abuse potential at high recreational doses. At the Joyous dose, ketamine is not addictive: the dose is designed not to produce a high, and in our patient data the risk of developing a ketamine problem during treatment was judged low and has not been reported. Substance use disorder is a screening exclusion.[11,12,26]
There is no established PSSD treatment for post-SSRI sexual dysfunction, and ketamine isn't one. Prevalence is unknown.[49]
Joyous costs $129 a month on a three-month plan or $159 a month with no commitment, medication included and not billed to insurance. In our patient data, 86% of those who started with moderate-or-worse depression and 87% with moderate-or-worse anxiety had their scores cut in half or better within six weeks, among those who stayed in treatment. Whether that's worth it depends on what the last 4–8 weeks on an antidepressant did for you.
