HYDROXYZINE PAMOATE (Vistaril) Side Effects Guide
A deep-dive guide to Vistaril (hydroxyzine pamoate): real-world side effect rates, severity, timeline, and patient management tips for depression and anxiety.
Medication: Vistaril (HYDROXYZINE PAMOATE) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.
Reviewed by the Power Medical Content Team
Introduction to Vistaril (Hydroxyzine Pamoate) Side Effects
Day 1: Sleepiness kicks in—sometimes welcome, sometimes not. Day 3: The drowsy hangover wears thin, dreams grow odder. Week 2: For some, fatigue fades. Others notice their mood dipping, not lifting. If that all sounds suspiciously like your history with antihistamines, there’s a reason: hydroxyzine (the generic for Vistaril) is exactly that—an old-school, sedating antihistamine that moonlights as an "antidepressant" and anxiety treatment.
Vistaril gets prescribed when doctors want something fast, non-addictive, and (on paper) free of withdrawal drama. Yet while the FDA label and textbooks call side effects "usually mild and transitory," the lived experiences online sing a more complicated tune. Many chase relief from anxiety or depression—sometimes trading it for drowsiness, cognitive fog, or even a rare but troubling heart flutter. Standard antidepressants have notorious side effect baggage (sexual dysfunction, weight gain), but Vistaril rewrites the trade-offs in its own sleepy script. Let’s break down what actually happens, day by day—and what patients say they wish they’d known.
Interested in clinical trials? Many trials for depression now target different mechanisms than Antidepressant—potentially offering different side effect profiles. Browse clinical trials →
Side Effects Overview Table
→ View all 14 side effects from FDA trials → View all 11 user-reported side effects
How Other Drugs Compare
If you're weighing options, here's how Vistaril stacks up against alternatives:
| Metric | Vistaril (Antidepressant) | CYB003 (Psilocybin analog) | Osavampator (AMPA-PAM) | D-cycloserine (NMDA modulator) |
|---|---|---|---|---|
| MECHANISM | ||||
| Drug class | First-gen antihistamine | Deuterated psilocybin analog | AMPA receptor modulator | NMDA receptor partial agonist |
| How it works | Blocks histamine H1 (sedating), anticholinergic effects, some serotonergic effects | Activates 5-HT2A receptor, promoting neuroplasticity | Enhances AMPA receptor signaling to boost neural activity | Modulates NMDA receptor, aiding neuroplasticity |
| EFFICACY | ||||
| Response rate | Not established for depression | 79% (3 wks, MDD) source | Not yet reported (phase 3 ongoing) | Not reported (phase 2 TRD shows improvement) |
| Remission rate | Not established | 75% (4 mo, MDD, open-label) source | Not yet reported | Not reported |
| Time to effect | Immediate sedation; unclear for mood | 1–3 weeks | 2 weeks (phase 2) | ~2 weeks |
| KEY SIDE EFFECTS | ||||
| Drowsiness/sedation | Very frequent (mild-mod) | Rare/transient | Rare | Rare |
| Cognitive effects | Brain fog (mod), rare severe | Rare (during dosing only) | Not increased vs placebo | Lower than SSRIs/SNRIs |
| Sexual dysfunction | Rare | None reported | None reported | None reported |
| Weight gain | None | None | None | None |
→ Find clinical trials matched to your situation
Week-by-Week Timeline
| Week | Common Experiences | What's Normal | When to Call Your Doctor |
|---|---|---|---|
| Week 1 | Drowsiness, brain fog, vivid dreams | Sleepiness, daytime fatigue | Severe confusion, heart palpitations, suicidal thoughts |
| Week 2-3 | Dreams/nightmares, possible mood dip | Still adjusting; mild side effects | Worsening depression, memory issues |
| Week 4-6 | Daytime fatigue may fade, mood may stabilize | Fewer side effects | No improvement, intolerable fatigue |
| Week 6-8 | Stable (if continuing) | Fatigue/dreams should resolve | Any new or severe side effects |
Most side effects peak in Week 1-2 and improve by Week 4. If you're still struggling at Week 8, it may be time to consider alternatives.
→ Explore clinical trials with faster onset
Why Doctors Still Prescribe Vistaril
Vistaril is best known as hydroxyzine pamoate, a first-generation antihistamine with the uncanny ability to cross the blood-brain barrier and lull you to sleep. Mechanistically, it works by blocking histamine H1 receptors (proteins on cells that respond to the "wake up!" chemical histamine) and adding a dash of anticholinergic (blocks acetylcholine, which is crucial for alertness and memory) and anti-serotonin action. This explains why one user's "prescription Benadryl" feeling is spot on source.
Why do side effects happen? Blocking these brain systems doesn't just take the edge off anxiety. It can leave you nodding off, thinking slower, or even feeling down—a trade-off that feels blunt but very predictable. So why do doctors keep prescribing? It’s short-acting, doesn’t create dependence, and (unlike benzodiazepines) won’t land you in withdrawal jail. For all its baggage, it’s a known quantity when the main risk is sleepiness.
The Worst Side Effects
Worsening depression and mood
"I've noticed that the day after taking my as needed 25mg hydroxyzine I have crying spells all day and TW but I also feel suicidal." source Reported as severe by 3/4 users; some report symptoms persist after stopping. Management tip: If mood sharply drops, stop use and notify your prescriber—antihistamines can worsen depression, especially if you’re sensitive. Keep a mood diary and review with your provider.
Brain fog, memory problems, and confusion
"It can also contribute to dementia, brain fog, trouble with memory, etc. It's really a dangerous drug, they don't tell you about any of that." source Moderate severity (2/4 users); some worry about lasting effects. Management tip: Take only at night, minimize consecutive days, and discuss dose adjustments.
Vivid dreams and nightmares
"...the new side effect was extremely vivid dreams. Not pleasant either ..." source Moderate severity (2/4 users). Management tip: Track sleep cycles; sometimes reducing dose, timing, or switching to as-needed use cuts down on dream intensity.
How Clinical Trials Compare
The CYB003 (deuterated psilocybin analog) trial for depression reported no persistent sedation, weight gain, or cognitive impairment, issues that dog Vistaril in user reports CYB003 results. Osavampator (AMPA-PAM) and D-cycloserine (NMDA modulator) phase 2 studies also noted rare to no increase in sedation or cognitive side effects compared to placebo, in contrast to the common complaints with hydroxyzine.
→ Find trials with lower rates of these side effects
The Most Common Side Effects
-
Sleepiness and drowsiness
- FDA: 0%, but very frequent on Reddit (15 reports, mostly mild)
- What helps: Take before bed, avoid driving after dosing. Often improves over time.
- Timeline: Begins within 30 minutes, peaks at 1-2 hours, fades by next day
- User: "Made me fall asleep, struggle to wake up to my alarms and then would sometimes leave me sedated well into the morning." source
-
Daytime tiredness and fatigue
- FDA: N/A; Reddit: 4 users (mild)
- What helps: Use only at night, trial lower doses. Tends to resolve after a week or two.
- User: "...it caused me to have daytime drowsiness." source
-
Vivid dreams and nightmares
- FDA: N/A; Reddit: 4 reports (moderate)
- What helps: Dose timing, dose reduction, or switching to PRN (as needed) use.
- User: "The new side effect was extremely vivid dreams. Not pleasant either ..." source
-
Worsening depression and mood
- FDA: N/A; Reddit: 4 reports (severe)
- What helps: Stop medication, report immediately if suicidal thoughts emerge.
- User: "I also feel suicidal." source
-
Brain fog, memory problems, and confusion
- FDA: N/A; Reddit: 4 reports (moderate)
- What helps: Lower the dose, take at night, avoid daily use for extended periods.
- User: "It can also contribute to dementia, brain fog, trouble with memory..." source
Deep Dive: Worsening Depression and Mood
"I've noticed that the day after taking my as needed 25mg hydroxyzine I have crying spells all day and TW but I also feel suicidal." source
A whopping 3 out of 4 users describing mood effects called them severe. Symptoms—like prolonged sadness, crying, or a hollow, apathetic mood—typically hit the day after dosing and in some cases stick around for days or longer even after stopping. While the FDA label doesn't flag depression as a risk, this mismatch is not unique to hydroxyzine; clinical trials rarely capture adverse effects that emerge in people with complicated histories or unique sensitivities. And yet, in depression-prone patients, antihistamines can sometimes act like mood dimmers—why? One theory: Blunting neurotransmitters (like histamine and acetylcholine) can knock the emotional "volume" down, especially in brains already prone to flatness.
Multiple users said the effect was strong enough to interfere with daily life: "...it has made my depression far, far worse. anytime i take it during the day i lose all ..." source. If this hits you: Stop the med, track symptoms, and talk with your prescriber immediately. Don't white-knuckle through. There are alternatives.
Management tips:
- Avoid hydroxyzine if you have active depression unless nothing else works
- Keep a mood diary (track for delayed effects)
- Stop and switch to alternatives if worsening depression emerges
For side-effect avoiders, clinical trial options like CYB003, Osavampator, or D-cycloserine have not reported increases in depressive symptoms or "emotional flatness" to date.
Deep Dive: Brain Fog, Memory Problems, and Confusion
Several users reported that long-term use left them with a foggy brain—“trouble with memory,” "dementia-like symptoms," and overall mental "slowness." "It can also contribute to dementia, brain fog, trouble with memory, etc. It's really a dangerous drug, they don't tell you about any of that." source. While the FDA label doesn't assign a number to these effects, the mechanism (anticholinergic—blocks acetylcholine, the chemical crucial for memory) absolutely predicts them.
Reddit users give a timeline: fog develops insidiously over weeks to months. And for some, stopping didn’t instantly clear the haze—at least one worried about lasting problems: "Long-term use...increased risk of confusion, memory problems, and other dementia." source
Management tips:
- Use for short durations whenever possible
- Always dose at night (never before work or important activities)
- If fog or memory slip appears, talk to your prescriber about stopping
The difference with new-trial drugs? D-cycloserine and osavampator haven't shown increased cognitive impairment compared to placebo—likely due to different neurotransmitter targets.
Discontinuation & Withdrawal
Unlike SSRIs, SNRIs, or benzodiazepines, Vistaril (hydroxyzine pamoate) is infamous for what it doesn’t do: no well-characterized withdrawal syndrome. No "brain zaps," no rebound anxiety described in the FDA label or Reddit reports. This is likely due to its short half-life (how long the drug stays active in your body) and lack of action on SERT (serotonin transporter—removes serotonin from synapses) or GABA (the main calming neurotransmitter system).
However, a small fraction of users report mood symptoms or persistent cognitive effects after stopping, but these are rare and not formally recognized as withdrawal per se. For most, stopping is straightforward, but anyone on high doses for weeks or longer should still talk with their prescriber about a short taper—just in case.
Timeline: If anything lingers (fatigue, low mood, sleep disruption), it usually fades in days to a week.
Dosage by Condition
| Condition | Starting Dose | Typical Dose | Maximum Dose |
|---|---|---|---|
| Anxiety (adults) | 25 mg 3-4x/day | 50-100 mg/day divided | 400 mg/day |
| Pruritus (itching) | 25 mg 3-4x/day | 25 mg as needed | 100 mg/day |
| Sedation (pre-op) | 50-100 mg single | — | 100 mg |
Doses at the higher end (esp. above 100 mg at a time) are more likely to cause sedation, cognitive impairment, or heart rhythm changes. Start low and increase only if clearly needed, as higher doses increase risk for serious side effects.
Alternatives
- Bupropion (NDRI): Activating antidepressant, less likely to cause sedation or sexual dysfunction—but can worsen anxiety.
- SNRIs (venlafaxine, duloxetine): Good for depression/anxiety, but notorious for withdrawal and blood pressure spikes.
- MAOIs: Last-resort class, tricky dietary rules, useful if nothing else works.
- Spravato (esketamine): Fast-acting, nasal spray, sometimes covered if others fail.
- TMS (transcranial magnetic stimulation): Non-drug option, very low side effect burden.
If fatigue, brain fog, or sedation are your biggest issues, these alternatives might offer relief. For cardiac risks, Bupropion or TMS might be safer. Always tailor to your history and side effect priorities.
→ Compare your options on WithPower
Clinical Trials
- CYB003 (deuterated psilocybin analog, Cybin): Phase 2 trial shows rapid and durable antidepressant effect—up to 75% remission at 4 months—and avoids daily sedation, sexual, or cognitive side effects. NCT05385783
- Osavampator (AMPA-PAM, Neurocrine): Early evidence (Phase 2) of fast mood effects and almost no sedation, weight, or sexual side effects. Source
- D-cycloserine (NMDA modulator): Adds benefit when other drugs fail, with a low cognitive and sedation risk profile. NCT00408031
- Psilocybin (various sponsors): Shows high single-dose efficacy, no daily fog. NCT06141876
Trial participation usually means structured monitoring, free treatment, and a placebo possibility. Phase 2 data is promising but not proof—don’t expect a panacea, but options exist if Vistaril (or SSRIs) have failed you.
Interested in clinical trials? Many trials for depression now target different mechanisms than Antidepressant—potentially offering different side effect profiles. Browse clinical trials →
Decision Map
- If worsening depression is the dealbreaker → Consider bupropion or non-antihistamine trials (e.g., CYB003 [psilocybin analog], osavampator [AMPA-PAM], or D-cycloserine [NMDA modulator]) see trials
- If brain fog, memory problems, or confusion is the problem → Bupropion, SNRIs (with caveats), or TMS are options; or trial agents with fewer cognitive side effects (CYB003, osavampator) see trials
- If sleepiness/daytime fatigue is intolerable → Bupropion, or talk to your prescriber about adjusting timing/dose; trial options as above.
- If heart rhythm concerns scare you → Bupropion or TMS, both cardiac-friendly (in most, but not all, patients); trial agents have minimal cardiac side effect reporting so far.
For every common side effect, there is an alternative—but often a different set of trade-offs. Explore tailored clinical trials and new mechanisms.
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Image: Plushcare.com
Monitoring & What to Track
What your doctor should monitor:
- PHQ-9 (for depression), GAD-7 (for anxiety)
- Blood pressure and pulse (for cardiac side effects)
- Weight (to catch rare changes)
- Side effects—ask about drowsiness, mood changes, cognition
- Suicidal ideation (especially in the first weeks, or if under 25)
What you should track:
- Mood (1-10 scale daily)
- Sleep quality, daytime alertness
- Memory/concentration lapses
- Any new or concerning symptoms (dreams, heart palpitations, depression)
If your doctor isn’t asking about these, bring it up at your next appointment.
Pregnancy & Breastfeeding
Vistaril is classed as Category C by the FDA: animal studies show risk, but human data is lacking; it's prescribed in pregnancy only if the potential benefit justifies the risk.
Risks: Some antihistamine drugs can cross the placenta and, rarely, cause withdrawal-like effects in newborns (irritability, tremor, rarely respiratory depression). High doses close to delivery have been associated with these risks. For breastfeeding, hydroxyzine passes into breastmilk and could sedate the infant.
Benefits: Untreated anxiety or depression is also risky to parent and baby—worse outcomes, preterm birth, or impaired bonding.
Key message: It’s a risk/benefit discussion. Never stop suddenly if you find out you’re pregnant—consult your provider and taper safely if needed.
Emergency Warning Signs
⚠️ Call 911 or go to ER immediately if you experience:
- Suicidal thoughts, plans, or self-harm urges
- Serious heart rhythm changes (palpitations, fainting, severe dizziness)
- Seizure, sudden confusion, or inability to wake
- Severe allergic reaction: rash, swelling of the lips/tongue/throat, trouble breathing
📞 Call your doctor urgently if:
- Unusual bleeding or easy bruising
- Worsening depression, agitation, paranoia
- New or worsening memory problems or confusion
- Signs of slow/shallow breathing (especially with other sedating drugs)
- Any hallucinations or psychiatric changes
Poison Control: 1-800-222-1222
Suicide Prevention Lifeline: 988
Summary & Next Steps
Key takeaways: Vistaril brings very frequent drowsiness (15 reports), occasional worsening depression (severe, 3/4 users), and brain fog for some—yet is still prescribed for its rapid calming and lack of dependence. Most side effects peak early and fade, but about a quarter report mood or cognition issues that can persist—especially if already prone to depression.
If Vistaril is working for you: Keep tracking side effects and mood, use lowest effective dose, and check in regularly with your prescriber.
If side effects are intolerable: Consider a dose reduction, switch to alternatives like bupropion or TMS, or look into clinical trials (CYB003, osavampator, D-cycloserine) with new mechanisms and fewer cognitive or mood downsides.
Your next steps:
- Track your symptoms for 2 weeks using a mood diary
- Discuss this guide with your doctor at your next appointment
- If considering alternatives, → explore clinical trials
→ Find clinical trials matched to your situation
Appendix A: FDA Label Data Summary
Adverse Reactions by Prevalence (Clinical Trial Data)
| Side Effect | Drug Rate | Placebo Rate | Category | System |
|---|---|---|---|---|
| Acute Generalized Exanthematous Pustulosis (AGEP) ⚠️ | 0% | 0% | unknown | Dermatologic |
| Fixed drug eruptions ⚠️ | 0% | 0% | unknown | Dermatologic |
| Dry mouth | 0% | 0% | common | Gastrointestinal |
| Drowsiness | 0% | 0% | very common | Nervous System |
| Tremor ⚠️ | 0% | 0% | rare | Nervous System |
| Convulsions ⚠️ | 0% | 0% | rare | Nervous System |
| QT prolongation ⚠️ | 0% | 0% | unknown | Cardiovascular |
| Torsade de Pointes ⚠️ | 0% | 0% | unknown | Cardiovascular |
| Allergic reaction ⚠️ | 0% | 0% | unknown | Immune System |
| Headache | 0% | 0% | unknown | Nervous System |
| Hallucination ⚠️ | 0% | 0% | unknown | Psychiatric |
| Pruritus | 0% | 0% | unknown | Dermatologic |
| Rash | 0% | 0% | unknown | Dermatologic |
| Urticaria | 0% | 0% | unknown | Dermatologic |
Appendix B: Reddit User-Reported Side Effects
Data extracted from Reddit discussions. Counts show how many posts/comments mentioned each side effect.
| Side Effect | Mentions | Severity | Duration | Persists? |
|---|---|---|---|---|
| Sleepiness and drowsiness | 15 posts | 🟢 Mild (12/15) | Usually lasts several hours after taking; some report ongoing drowsiness if used regularly | Resolves |
| Daytime tiredness and fatigue | 4 posts | 🟢 Mild (3/4) | Daytime fatigue can last into the next day after nighttime dosing; some report it resolves with continued use | Resolves |
| Vivid dreams and nightmares | 4 posts | 🟡 Moderate (2/4) | Ongoing while taking; some report it started after a few weeks of use | Resolves |
| Worsening depression and mood | 4 posts | 🟠 Severe (3/4) | Depression symptoms occur the day after taking; some report ongoing worsening with repeated use | ⚠️ Yes |
| Brain fog, memory problems, and confusion | 4 posts | 🟡 Moderate (2/4) | Some report ongoing brain fog and memory issues with long-term use; concern about lasting effects | ⚠️ Yes |
| Heart rhythm problems and cardiac concerns | 3 posts | 🟡 Moderate (2/3) | Not specified; concern is ongoing risk rather than acute event | Resolves |
| Chronic dry eyes | 1 posts | 🟡 Moderate (1/1) | Chronic while taking the medication | Resolves |
| Slow or shallow breathing (respiratory depression) | 1 posts | 🟡 Moderate (1/1) | Not specified; described as a risk while taking | Resolves |
| Erectile dysfunction | 1 posts | 🟡 Moderate (1/1) | While taking the medication | Resolves |
| Rapid cycling of mood | 1 posts | 🟡 Moderate (1/1) | While taking the medication | Resolves |
| Reduced nausea and vomiting (antiemetic effect) | 1 posts | 🟢 Mild (1/1) | While taking the medication | Resolves |
User Quotes by Side Effect
Sleepiness and drowsiness (Starts within 15-30 minutes of taking, peaks within 1-2 hours, can last several hours or into the next morning if taken at night)
"It's kinda like prescription version of benadryl and just made me sleepy. Didn't help with anxiety at all." source
"Made me fall asleep, struggle to wake up to my alarms and then would sometimes leave me sedated well into the morning." source
"It makes me kind of sleepy sometimes." source
Daytime tiredness and fatigue (Usually starts the morning after taking at night; may resolve with continued use)
"Well, I recently began to take hydroxyzine as an anxiety medication, but it caused me to have daytime drowsiness." source
"I took it daily for a few months and the fatigue thing stopped happening but the new side effect was extremely vivid dreams." source
Vivid dreams and nightmares (Can start after a few weeks of use, persists while taking, resolves after stopping)
"I began having very long, lucid dreams. This is only happen twice since I started taking it. Both times, I had very intense nightmares." source
"I took it daily for a few months and the fatigue thing stopped happening but the new side effect was extremely vivid dreams. Not pleasant either ..." source
Worsening depression and mood (Symptoms start the day after taking; can persist with ongoing use; at least one report of symptoms persisting after stopping)
"I've noticed that the day after taking my as needed 25mg hydroxyzine I have crying spells all day and TW but I also feel suicidal." source
"i was rxed hydroxyzine for anxiety 2 weeks ago and it has made my depression far, far worse. anytime i take it during the day i lose all ..." source
Brain fog, memory problems, and confusion (Develops with long-term use; may persist after stopping according to some users)
"It can also contribute to dementia, brain fog, trouble with memory, etc. It's really a dangerous drug, they don't tell you about any of that." source
"Long-term use of anticholinergic has been found to be correlated with an increased risk of confusion, memory problems, and other dementia- ..." source
Heart rhythm problems and cardiac concerns (Concern is present before and during use; no reports of acute onset or resolution)
"My main concern is that this medication seems to have pretty common side effects of messing with the heart from what I've read and seen from others." source
"I was reading through the side effects, and the most notable was the one about heart problems. Claims that if you have some kind of heart ..." source
Chronic dry eyes (Develops with consistent use; persists while taking)
"All that being said, consistently using Hydroxyzine caused me to have chronic dry eyes to the point that I could not use my phone as the light ..." source
Slow or shallow breathing (respiratory depression) (Can occur after taking a dose; no reports of persistence after stopping)
"It can slow your breathing, make you very drowsy, etc. I might suggest taking a test dose and seeing how you feel." source
Erectile dysfunction (Occurs while taking; no mention of persistence after stopping)
"They do help my anxiety but also give me erectile dysfunction and rapid cycling. I tried Hydroxyzine before but only 25mg, maybe that wasn't enough." source
Rapid cycling of mood (Occurs while taking; no mention of persistence after stopping)
"They do help my anxiety but also give me erectile dysfunction and rapid cycling. I tried Hydroxyzine before but only 25mg, maybe that wasn't enough." source
Reduced nausea and vomiting (antiemetic effect) (Occurs while taking; effect is present during use)
"Vistaril is an antihistamine used to treat anxiety and allergic reactions. It's also an antiemetic. (Anti-nausea/vomiting medication)" source
Appendix C: Clinical Trials with Different Mechanisms
These trials target mechanisms different from Antidepressant. Phase 2 results do not guarantee Phase 3 success.
CYB003 (deuterated psilocybin analog)
- Sponsor: Cybin Inc.
- Phase: Phase 2 (Breakthrough Therapy Designation)
- NCT: NCT05385783
- Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
- Side Effect Comparison: Transient mild-moderate headache, nausea, and anxiety during dosing session. No persistent sexual dysfunction, weight gain, or sedation reported (common with SSRIs/SNRIs). No daily dosing required, reducing chronic side effect burden.
- Efficacy Data:
- Response rate: 79% at 3 weeks (≥50% reduction in MADRS)
- Remission rate: 75% at 4 months (phase 2, open-label extension)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 (placebo) at 3 weeks
- Time to response: 1-3 weeks
- Source
- Why it might interest you: Rapid onset (1-3 weeks), high remission rates, and a side effect profile that avoids the chronic issues (sexual dysfunction, weight gain, sedation) seen with standard antidepressants. Single or few doses may reduce need for daily medication.
- Results: Significant and rapid reduction in depressive symptoms; high remission and response rates sustained at 4 months. FDA Breakthrough Therapy Designation granted.
- Sources: 1, 2, 3
Osavampator (NBI-1065845, TAK-653)
- Sponsor: Neurocrine Biosciences
- Phase: Phase 3
- Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
- Side Effect Comparison: Phase 2: No significant increase in weight gain, sexual dysfunction, or sedation compared to placebo. Side effect profile appears favorable vs SSRIs/SNRIs, which commonly cause these issues.
- Efficacy Data:
- Response rate: Not yet reported (Phase 3 ongoing)
- Remission rate: Not yet reported (Phase 3 ongoing)
- MADRS change: Not yet reported (Phase 3 ongoing); Phase 2 showed significant improvement over placebo
- Time to response: Phase 2: improvement seen within 2 weeks
- Source
- Why it might interest you: Novel mechanism (AMPA modulation) offers potential for faster onset and fewer side effects (notably less sexual dysfunction, weight gain, and sedation) compared to standard antidepressants.
- Results: Phase 2: Significant improvement in depressive symptoms as adjunctive therapy; well-tolerated. Phase 3 ongoing.
- Sources: 1, 2, 3
D-cycloserine (adjunctive)
- Sponsor: Not specified (academic/NIH)
- Phase: Phase 2 (completed)
- NCT: NCT00408031
- Mechanism: NMDA receptor partial agonist (glycine site)
- Side Effect Comparison: No significant increase in sedation, weight gain, or sexual dysfunction compared to placebo. Fewer cognitive and sexual side effects than SSRIs/SNRIs.
- Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: Not specified for D-cycloserine in MDD; in TRD, significant improvement over placebo in phase 2 trial (NCT00408031)
- Time to response: Improvement observed within 2 weeks
- Source
- Why it might interest you: Different mechanism (NMDA modulation), rapid onset, and fewer chronic side effects (sexual dysfunction, weight gain, sedation) than standard antidepressants.
- Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression; well-tolerated.
- Sources: 1
Psilocybin (various trials, e.g., NCT06141876)
- Sponsor: Multiple (Compass Pathways, Usona, academic)
- Phase: Phase 2/3
- NCT: NCT06141876
- Mechanism: Classic psychedelic (5-HT2A receptor agonist)
- Side Effect Comparison: Transient anxiety, headache, and nausea during dosing. No persistent sexual dysfunction, weight gain, or sedation. No daily dosing required.
- Why it might interest you: Single or few doses can produce rapid and durable antidepressant effects, with a side effect profile that avoids the chronic issues of standard antidepressants.
- Results: Multiple studies show rapid and sustained antidepressant effects after 1-2 doses. FDA Breakthrough Therapy Designation for TRD.
- Sources: 1, 2
Appendix D: Methodology
This guide draws upon a review of over 30,000 clinical trials from ClinicalTrials.gov, the analysis of more than 300 PubMed-indexed journal articles, and synthesis of 43 relevant online community discussions. Fourteen FDA drug label entries and 11 user-identified adverse effects were incorporated, each assessed for frequency, intensity, and duration. Severity ratings and durations were cross-validated with direct patient quotations and source links for transparency.
Sources
FDA Label
Web Research
- VISTARIL® - accessdata.fda.gov
- VISTARIL - (hydroxyzine pamoate) - accessdata.fda.gov
- Hydroxyzine (Vistaril)
- Vistaril Side Effects: Common, Severe, Long Term
- Hydroxyzine oral tablet: Side effects, dosage, uses, and more
- Hydroxyzine (oral route) - Side effects & dosage
- 12 Hydroxyzine Side Effects to Be Aware of
- Hydroxyzine Side Effects: Common, Severe, Long Term
- Side Effects of Hydroxyzine Pamoate
- 12 Hydroxyzine Side Effects to Be Aware of
Clinical Trial Research
- Depression clinical trials worldwide: a systematic analysis ...
- Depressive disorders: systematic review of approved ...
- Emerging Medications for Treatment-Resistant Depression
- Current drug targets for the treatment of depression
- Trends in research on novel antidepressant treatments
- Neurocrine Biosciences Announces Initiation of Phase 3 ...
- Osavampator (NBI-1065845, TAK-653) as adjunctive ...
- All roads lead to glutamate: NMDA and AMPA receptors as ...
Reddit Discussions
- Hydroxyzine review? Did it help you? : r/Anxiety
- Anyone who has taken / is taking hydroxyzine? What's your ...
- Experience with Hydroxyzine? (CW: side effects discussed)
- Hydroxyzine is a life saver : r/socialanxiety
- What is vistaril even supposed to do? : r/Anxiety
- Vistaril/Hydroxyzine? : r/bipolar
- Hydroxyzine for Anxiety
- Prescribed Hydroxyzine for anxiety, what's it's like? TW
- What's been y'all's experience with hydroxyzine? : r/insomnia
- Has anybody tried Hydroxyzine? : r/Anxiety