BUSPIRONE HYDROCHLORIDE (Buspar) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Buspar

The Worst Side Effects

The Most Common Side Effects

Dizziness or Lightheadedness

Worsening Depression or Increased Sadness

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Buspar

The Worst Side Effects

The Most Common Side Effects

Dizziness or Lightheadedness

Worsening Depression or Increased Sadness

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Comprehensive, patient-centered guide to Buspar (buspirone) side effects, blending clinical trial data and real patient experiences. Detailed, honest, and practical.

Medication: Buspar (BUSPIRONE HYDROCHLORIDE) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.

Reviewed by the Power Medical Content Team

Intro

Day 1: Dizzy, a bit foggy. Day 3: Fatigue, maybe a headache or two. By week 2: Nausea finally lets up, but that odd 'brain zap' now and then? That’s the Buspar rollercoaster, according to both FDA trial data and—more colorfully—hundreds of Reddit posts. Buspirone (brand name: Buspar) is technically an "antidepressant" by old FDA paperwork, but most folks now encounter it for anxiety.

So here’s the $1,000 question: why do some people breeze through Buspar, while others feel like their nervous system took a detour through an electrical storm? In clinical trials, about 10% of patients quit Buspar due to side effects, most commonly dizziness, fatigue, or GI complaints (FDA label). But patients' real-world experiences often fill in the blanks (or poke holes) in what those percentages actually feel like, day-to-day.

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

Side Effect	FDA Rate	Reddit Reports	Severity	Duration	Example
Dizziness or lightheadedness	12%	🟠 frequent (13 posts)	🟢 Mild	First 1-3 weeks, sometimes months	"Just got some dizziness and brain zaps that went away over time."
Brain zaps or electrical sensations	N/A	🟡 occasional (7 posts)	🟢 Mild	Usually 1-4 weeks, sometimes longer	"Most of the side effects have dissipated except for the brain zaps and dizziness."
Fatigue and tiredness after taking a dose	4%	🟡 occasional (7 posts)	🟢 Mild	1-3 hours after dose, sometimes ongoing	"Kinda knocks me out for an hour+ every day."
Headache after taking the medication	6%	🟡 occasional (6 posts)	🟢 Mild	Few days to weeks	"I get a horrible headache, dizziness, start sweating, and feel like I am going to throw up."
Nausea and upset stomach	8%	🟡 occasional (5 posts)	🟢 Mild	Few days to weeks	"I had dizziness, hot flashes, and nausea, particularly with my morning dose."
Worsening depression or increased sadness	2%	🟡 occasional (5 posts)	🟡 Moderate	Ongoing while on med	"Buspirone made my depression worse."
Restlessness or inability to sleep well	0%	🟢 rare (3 posts)	🟢 Mild	First hours after dose, sometimes ongoing	"I just get super restless and feel like electricity is running through my body."
Sweating or hot flashes	1%	🟢 rare (2 posts)	🟢 Mild	First few weeks	"I had dizziness, hot flashes, and nausea, particularly with my morning dose."
Muscle weakness and brain fog	2%	🟢 rare (1 post)	🟢 Mild	Ongoing while on med	"I'm extremely tired and can't stop yawning, muscle weakness, and brain fog."
Brain fog or trouble thinking clearly	2%	🟢 rare (2 posts)	🟢 Mild	First week, sometimes ongoing	"Medicine also seems to be causing quite a bit of brain fog and headache."
Feeling slightly disoriented	N/A	🟢 rare (1 post)	🟢 Mild	First week	"I've been dizzy, slightly disoriented, and fatigued."
Mild stomach cramps	2%	🟢 rare (1 post)	🟢 Mild	First few days	"Just a few mild stomach cramps, but yesterday... dizzy, disoriented, and fatigued."
Nightmares and weird dreams	N/A	🟢 rare (1 post)	🟢 Mild	Intermittent, ongoing	"Weird dreams/ nightmares intermittently."
Hypomania or increased energy	N/A	🟢 rare (1 post)	🟢 Mild	First week or two	"It did make me hypomanic when I first started it."
Emotional blunting or feeling less emotion	N/A	🟢 rare (1 post)	🟢 Mild	Ongoing while on med	"Not sure if I'm anxiety-free or just more depressed. It feels like it's a bit of both."
→ View all 134 side effects from FDA trials
→ View all 15 user-reported side effects

How Other Drugs Compare

If you're weighing options, here's how Buspar (buspirone) stacks up against alternatives:

Metric	Buspar (Antidepressant)	CYB003 (Deuterated psilocybin analogue)	Osavampator (AMPA-PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Azapirone	Psychedelic analogue	AMPA modulator	NMDA modulator
How it works	Partial agonist at 5-HT1A (serotonin) receptors, mild dopamine and noradrenergic effects	Agonist at 5-HT2A (serotonin) receptors	Positive allosteric modulator of AMPA (glutamate) receptors	Partial agonist at glycine site of NMDA (glutamate) receptor
EFFICACY
Response rate	Not robustly reported	53.8% (CYB003 16mg, 6 wks) source	Not yet reported (Ph3 ongoing)	Not specified
Remission rate	Not robustly reported	75% at 4 months	Not yet reported	Not specified
Time to effect	2–4 weeks (anxiety), variable for depression	1–2 weeks	Potentially 2 weeks	1–2 weeks
KEY SIDE EFFECTS
Dizziness/lightheadedness	12%	Mild, transient	N/A	N/A
Nausea	8%	Mild, transient	N/A	Mild
Fatigue/tiredness	4%	Not reported	N/A	Not reported
Worsening depression	2%	No signal	No data	No data
Brain zaps	Not reported	Not reported	Not reported	Not reported
Weight gain	0%	None reported	None reported	None reported
Sexual dysfunction	0%	None reported	None reported	None reported
→ Find clinical trials matched to your situation

Week-by-Week Timeline

Week	Common Experiences	What's Normal	When to Call Your Doctor
Week 1	Dizziness, headache, fatigue, nausea, mild brain zaps	Startup effects, mild brain fog	Severe anxiety, thoughts of self-harm
Week 2-3	Symptoms may persist, insomnia or restlessness, vivid dreams	Still adjusting, mild mood changes	New or worsening depression
Week 4-6	Most side effects improve or resolve, anxiety reduction kicks in	Steady state, watch for persistent side effects	Intolerable side effects or no benefit
Week 6-8	Should be at or near full effect	Stable, side effects rare	Persisting/worsening depression or anxiety
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 Buspar

Buspirone is a partial agonist (activates the receptor, but not fully) at the 5-HT1A serotonin receptor (a protein on nerve cells that helps regulate anxiety and mood). Unlike SSRIs, it doesn't flood your synapses (the gaps between nerve cells) with extra serotonin, but tweaks your brain's anxiety thermostat more subtly. It's not a sedative, doesn't cause dependency, and comes without the "weight gain/sexual side effect nightmare" of classic antidepressants.

So why the side effects? Because nudging one serotonin receptor (5-HT1A) means nudging a handful of others, and they're not all on the anxiety-control circuit: vestibular pathways (dizziness), gut motility (nausea), or temperature regulation (hot flashes). Doctors keep reaching for Buspar because its risk profile is predictable, withdrawal is mild, and it doesn’t overlap dangerously with alcohol, benzos, or opioids. In a world of chemical blunt instruments, Buspar is (mostly) a tuning fork, not a sledgehammer.

The Worst Side Effects

Worsening depression or increased sadness

"Buspirone was a very disruptive medication for me. Did nothing for my anxiety and made my depression worse." source

Reported as moderate to debilitating by 4/5 users in real-world accounts. For a drug meant to relieve anxiety, an uptick in depression is, to put it lightly, a dealbreaker.

Management tip: If low mood deepens or crying spells begin after starting buspirone, stop and call your doctor. Switching to an SSRI, bupropion, or a non-serotonergic alternative is common.

Dizziness or lightheadedness

"It's very normal to feel a bit dizzy with buspirone—it's a common side effect. It will usually go away within the first few weeks but it's annoying." source

Reported as mild to moderate by 8/13 users, with 1 describing it as persistent enough to consider quitting.

Management tip: Take with food, split the dose, or dose at bedtime. Stand up slowly. If it persists after 2-4 weeks, dose reduction or alternative medication may help.

Fatigue and tiredness

"Kinda knocks me out for an hour+ every day, and I'm not sure it's actually helping much with my anxiety." source

Annoying enough to prompt dose timing adjustments for several users.

Management tip: Dose at night or when you can afford to nap; avoid activities needing sharp concentration post-dose.

How Clinical Trials Compare

In Phase 2 trials of CYB003 (deuterated psilocybin analog), headache and mild nausea were most common, but no increase in depression or fatigue was noted, and most effects were short-lived (CYB003 results). → Find trials with lower rates of these side effects

The Most Common Side Effects

Dizziness or lightheadedness

FDA rate: 12%
Reddit: 13 reports (frequent, mostly mild)
What helps: Take with food, stand up slowly. Usually resolves by week 2-3.
"Just got some dizziness and brain zaps that went away over time." source

Brain zaps or electrical sensations

FDA rate: N/A
Reddit: 7 reports (occasional, mild)
What helps: Dose timing (consistent schedule), let it pass—most resolve by 1-2 months.
"Most of the side effects have dissipated except for the brain zaps and dizziness." source

Fatigue/tiredness

FDA rate: 4%
Reddit: 7 reports (occasional, mild)
What helps: Dose when you can rest, avoid operating machinery post-dose. Typically resolves within a few weeks.
"I'm extremely tired and can't stop yawning, muscle weakness, and brain fog." source

Headache

FDA rate: 6%
Reddit: 6 reports (occasional, mild)
What helps: Hydration, acetaminophen, monitor for persistence. Should fade in 2-3 weeks.
"About 30 minutes after taking it, I get a horrible headache, dizziness, start sweating, and feel like I am going to throw up." source

Nausea/upset stomach

FDA rate: 8%
Reddit: 5 reports (occasional, mild)
What helps: Take with food, split dose. Usually resolves by week 2-3.
"I had dizziness, hot flashes, and nausea, particularly with my morning dose. Taking it with food helped." source

Dizziness or Lightheadedness

It's the most reliably reported side effect, enough so that a few users treat it almost as a rite of passage:

"It's very normal to feel a bit dizzy with buspirone—it's a common side effect. It will usually go away within the first few weeks but it's annoying." source

From the FDA trial data: 12% of patients reported dizziness (versus 3% on placebo). Real-world Reddit? Thirteen reports, almost all calling it "annoying but mild." For most, it starts with the first few doses, peaks in week 1, and then fades by week 3—"just got some dizziness and brain zaps that went away over time" is a typical refrain. Some do say it lasts for months.

How to cope:

Take Buspar with food or a snack
Stand up slowly (orthostatic dizziness is real)
If your dizziness sticks around past month one, splitting the dose or reducing the total amount often helps
For persistent or severe cases, switching meds is the honest (if unwelcome) answer

Why does this happen? Buspirone tweaks your serotonin system in brain regions tied to balance, not just mood. Like bad WiFi, a little interference in the vestibular network means "spinning wheel" in your skull.

Usually, it gets better—but in rare cases (reported by 1/13 users), it was bad enough to quit.

Worsening Depression or Increased Sadness

No one expects to get more depressed on an "antidepressant"—but in the Buspar world, a small (but very vocal) minority does. FDA data clocks "depression" at 2% (identical to placebo, for what it's worth), but on Reddit, 5 users (occasional frequency) mention increased sadness, emotional numbness, or deeper low mood. Four out of five say it was moderate to severe:

"Day 11 very sad and depressed with crying spells, day 12 very depressed and anxious, sad, crying feeling worthless no mood to do anything etc." source

"Buspirone was a very disruptive medication for me. Did nothing for my anxiety and made my depression worse." source

For most, this starts after the first week and continues as long as they stay on the med. If you notice your baseline sadness deepening, don't wait—get your prescriber in the loop.

Management tips:

Track your mood daily; if new lows persist for more than a week, call your doctor
Often, switching to an SSRI or a trial like CYB003 or Osavampator (which have not shown increased depression) makes more sense
Never stop suddenly—always taper

Mechanistically? Possibly due to the delicate balancing act of serotonin and dopamine (the brain chemicals for mood and motivation), which Buspar may disrupt in some sensitive systems. No clear biomarker predicts who'll get this, so it's truly an "individual experiment."

Discontinuation & Withdrawal

About 10% of patients discontinued buspirone in trials, mostly for dizziness, nausea, fatigue, or headache (FDA label). Uniquely, Buspar doesn't produce a recognized withdrawal syndrome like SSRIs or benzodiazepines do. That said, abrupt cessation can cause rebound anxiety, dizziness, and, for a few users, the infamous "brain zaps" for several days to a week.

Why is withdrawal less severe? Buspar’s relatively short half-life (how long it stays active in your body) means levels drop fast, but its mild receptor effects make withdrawal mild for most.

How to taper:

Always do it under medical supervision
Decrease by 5 mg every 3-7 days if possible
Watch for worsening anxiety or new neurological symptoms

Most users see symptoms resolve within a week of stopping. If you’re switching to another med, a direct cross-taper may be possible but should be planned carefully.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Anxiety Disorders	7.5 mg twice daily	15-30 mg/day in divided doses	60 mg/day

Note: Higher doses may increase side effects, particularly dizziness and nausea, but benefits plateau beyond 30-45 mg/day for most patients.

Always follow your prescriber's titration (gradually adjusting the dose) plan to minimize startup effects.

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Looking for something with fewer startup blues or less brain fog?

SSRIs (e.g., sertraline, escitalopram): Time-tested for anxiety/depression, but bring their own baggage (sexual dysfunction, weight gain).
Bupropion (NDRI): No sexual side effects, may help with energy—but can worsen anxiety.
SNRIs (e.g., venlafaxine): Fast-acting for anxiety, but more GI and blood pressure issues.
Buspirone alternatives for anxiety: Hydroxyzine (antihistamine, sedating), propranolol (good for physical symptoms, not emotional), benzodiazepines (quick relief, riskier long-term), or clinical trials for rapid-acting agents.
Trial spotlight: CYB003, Osavampator, and psilocybin all avoid Buspar’s fatigue/dizziness profile, and none are linked to increased depression. → Compare your options on WithPower

Clinical Trials

CYB003 (deuterated psilocybin analogue, NCT06141876): A psychedelic-derived compound with rapid onset (1–2 weeks), no daily dosing, and far lower risk of sexual dysfunction, weight gain, or emotional blunting (source).
Osavampator (AMPA modulator): Early data suggest fewer cognitive and metabolic side effects; quick onset is possible. source
D-cycloserine: A novel adjunct for depression—no chronic sedation or weight gain reported (source).
Psilocybin (various trials): Not for everyone, but may offer dramatic, short-course relief with no daily pill burden (source).

What trial participation means: You get close monitoring, potential for rapid-onset therapies, and may access future standards before they're mainstream. But, there's the real chance of placebo, and unknown long-term risks (especially in early-phase work). Expect a detailed informed consent.

Still, for those at wit’s end with standard options, trial science may be where relief—and insight—finally intersect.

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 dizziness or lightheadedness is your dealbreaker → try bupropion or trials with Osavampator/CYB003 (CYB003)

If worsening depression hits you hard → SSRIs, SNRIs, or clinical trials with CYB003 or psilocybin (COMPASS Psilocybin studies) may dodge that risk

If fatigue and tiredness are the main issue → Consider bupropion or trials with AMPA modulators (Osavampator Phase 3)

If brain zaps are new or persistent → Discuss dose splitting, switch to a medication without this reputation, or consider clinical trials (few new agents report this issue)

If restlessness and insomnia predominate → Buspirone isn't sedating; SSRIs or SNRIs (with caution) may help, or short-term hydroxyzine

Trial options are expanding: CYB003, Osavampator, and psilocybin all currently offer active recruitment for depression/anxiety with distinct side effect profiles. See withpower.com for trial matches.

Buspar (buspirone) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

What should your prescriber track?

Anxiety: GAD-7 or HAM-A scores, every 2–4 weeks
Depression: PHQ-9 or HAM-D scores
Weight (Buspar rarely causes change, but some fatigue/lethargy may mask depression)
Blood pressure (if on higher doses or in combination with MAOIs)
Suicidal ideation (always, but especially if under 25)

What should you track?

Mood/anxiety diary (rate 1–10 daily)
Specific side effects: severity, timing, duration
Sleep quality and energy
Changes in appetite, libido, or motivation

If your doctor isn’t tracking these—ask them to. Buspar may not demand liver or kidney checks, but monitoring mood and motivation is non-negotiable.

Pregnancy & Breastfeeding

Buspirone is classified as pregnancy category B (animal studies haven’t shown fetal risk, but no adequate human data). The FDA label notes: no teratogenicity seen in rats/rabbits, but human evidence is thin—prescribe only if benefits outweigh risks.

For breastfeeding, buspirone is excreted in low levels into milk, and the long-term effects on infants aren’t well studied.

Risks of untreated anxiety or depression in pregnancy are real: poor self-care, increased risk of preterm birth, and postpartum complications.

Key message: This is always a risk-benefit equation, not a straight yes/no. If you become pregnant on Buspar, do NOT stop suddenly; taper with your doctor's guidance.

Emergency Warning Signs

⚠️ Call 911 or go to ER immediately if you experience:

Thoughts of suicide, intent to harm yourself or others
Signs of serotonin syndrome (agitation, hallucinations, muscle rigidity, fever, sweating, rapid heartbeat, confusion, seizures)
Severe allergic reaction (rash, swelling, trouble breathing)

📞 Call your doctor urgently if:

New or severe headaches with visual changes
Unusual bleeding or bruising
Worsening or sudden-onset depression
Fainting or severe dizziness
New or worsening seizures

Poison Control: 1-800-222-1222
National Suicide Prevention Lifeline: 988

Summary & Next Steps

Key takeaways:

About 10% of people stop Buspar due to side effects—most commonly dizziness, fatigue, and headache (FDA label). On Reddit, dizziness (13/15 reports), fatigue (7/15), and headache (6/15) top the list, nearly always mild but occasionally persistent. Worsening depression is moderate/severe in 4/5 reports—a genuine dealbreaker for some.
If Buspar works for you and side effects are mild or fading: stay the course, track mood, and give it a full 6–8 weeks. But watch for any dip in motivation, low mood, or intrusive sadness.
If side effects are intolerable: Don’t tough it out—talk to your doctor about dosing tweaks, possible switches to alternatives like bupropion or clinical trials for rapid-onset, low-burden options like CYB003 or Osavampator.

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
dizziness	12%	3%	very common	Nervous System
drowsiness	10%	9%	very common	Nervous System
nausea	8%	5%	common	Gastrointestinal
headache	6%	3%	common	Nervous System
nervousness	5%	1%	common	Nervous System
fatigue	4%	4%	common	General
multiple complaints (none primary)	3.4%	0%	common	General
insomnia	3%	3%	common	Nervous System
lightheadedness	3%	0%	common	Nervous System
dry mouth	3%	4%	common	Gastrointestinal
decreased concentration	2%	2%	common	Nervous System
excitement	2%	0%	common	Nervous System
anger/hostility	2%	0%	common	Psychiatric
confusion	2%	0%	common	Nervous System
depression	2%	2%	common	Psychiatric
blurred vision	2%	0%	common	EENT
abdominal/gastric distress	2%	2%	common	Gastrointestinal
diarrhea	2%	0%	common	Gastrointestinal
numbness	2%	0%	common	Neurological
weakness	2%	0%	common	General
constipation	1%	2%	common	Gastrointestinal
vomiting	1%	2%	common	Gastrointestinal
musculoskeletal aches/pains	1%	0%	common	Musculoskeletal
paresthesia	1%	0%	common	Neurological
incoordination	1%	0%	common	Neurological
tremor	1%	0%	common	Neurological
skin rash	1%	0%	common	Dermatologic
sweating/clamminess	1%	0%	common	General
tachycardia/palpitations	1%	1%	common	Cardiovascular
dream disturbances	0%	0%	common	Nervous System

Drug Interactions

MAOIs: Concomitant use or use within 14 days increases risk of serotonin syndrome and/or elevated blood pressure.
Reversible MAOIs (e.g., linezolid, IV methylene blue): Increased risk of serotonin syndrome.
See WARNINGS and PRECAUTIONS for additional interactions (not detailed in provided text).

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?
Dizziness or lightheadedness	13 posts	🟢 Mild (8/13)	Usually first 1-3 weeks, sometimes persists for months, often resolves over time	Resolves
Brain zaps or electrical sensations	7 posts	🟢 Mild (5/7)	Usually first 1-4 weeks, sometimes longer	Resolves
Fatigue and tiredness after taking a dose	7 posts	🟢 Mild (6/7)	First 1-3 hours after dose, sometimes ongoing for weeks	Resolves
Headache after taking the medication	6 posts	🟢 Mild (5/6)	First few days to weeks, sometimes ongoing	Resolves
Nausea and upset stomach	5 posts	🟢 Mild (4/5)	First few days to weeks, especially with morning dose	Resolves
Worsening depression or increased sadness	5 posts	🟡 Moderate (4/5)	Ongoing while on medication, sometimes starts after a few days	Resolves
Restlessness or inability to sleep well	3 posts	🟢 Mild (2/3)	First hours after dose, sometimes ongoing	Resolves
Sweating or hot flashes	2 posts	🟢 Mild (2/2)	First few weeks, sometimes longer	Resolves
Muscle weakness and brain fog	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves
Brain fog or trouble thinking clearly	2 posts	🟢 Mild (2/2)	First week, sometimes ongoing	Resolves
Feeling slightly disoriented	1 posts	🟢 Mild (1/1)	First week	Resolves
Mild stomach cramps	1 posts	🟢 Mild (1/1)	First few days	Resolves
Nightmares and weird dreams	1 posts	🟢 Mild (1/1)	Intermittent, ongoing	Resolves
Hypomania or increased energy	1 posts	🟢 Mild (1/1)	First week or two	Resolves
Emotional blunting or feeling less emotion	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves

User Quotes by Side Effect

Dizziness or lightheadedness (Starts within first few doses, peaks in first week, usually resolves by week 3-4, but can persist longer for some)

"Just got some dizziness and brain zaps that went away over time." source

"It's very normal to feel a bit dizzy with buspirone it's a common side effect. It will usually go away within the first few weeks but it's annoying." source

"I had dizziness, hot flashes, and nausea, particularly with my morning dose, for the first several months I was on Buspar." source

Brain zaps or electrical sensations (Starts early (first week), intermittent, often resolves within 1-2 months)

"Just got some dizziness and brain zaps that went away over time." source

"I have been on Buspar for a little over 3 months, most of the side effects have completely dissipated except for the brain zaps and dizziness." source

"Weird head feeling, not quite light headed or dizzy but feeling dissociated but still present. Brain zaps. Weird dreams/ nightmares *all intermittently." source

Fatigue and tiredness after taking a dose (Starts with first dose, peaks in first hours after taking, may persist for weeks, often improves)

"The first 1-3 hours of the med make me tired but I can't sleep more than 1-4 hours at a time I just get super restless and feel like electricity." source

"Kinda knocks me out for an hour+ every day, and I'm not sure it's actually helping much with my anxiety." source

"I'm extremely tired and can't stop yawning, muscle weakness, and brain fog." source

Headache after taking the medication (Starts within 30-60 minutes of dose, peaks early, often resolves within weeks)

"About 30 minutes after taking it, I get a horrible headache, dizziness, start sweating, and feel like I am going to throw up." source

"The medicine also seems to be causing quite a bit of brain fog and headache. I hope these adverse effects subside with time." source

"Now I'm having dizziness, nausea, headaches, and what can only be described as brain hiccups." source

Nausea and upset stomach (Starts within 30-60 minutes of dose, peaks early, often resolves within weeks)

"About 30 minutes after taking it, I get a horrible headache, dizziness, start sweating, and feel like I am going to throw up." source

"I had dizziness, hot flashes, and nausea, particularly with my morning dose, for the first several months I was on Buspar. Taking it with food helped." source

"Now I'm having dizziness, nausea, headaches, and what can only be described as brain hiccups." source

Worsening depression or increased sadness (Starts after several days to weeks, persists while on medication, may resolve after stopping)

"Buspirone was a very disruptive medication for me. Did nothing for my anxiety and made my depression worse." source

"Day 11 very sad and depressed with crying spells, day 12 very depressed and anxious, sad, crying feeling worthless no mood to do anything etc." source

"I was put on Buspirone for anxiety about a month and a half ago. It's helped with my anxiety a lot but I have also noticed a significant increase in depression." source

Restlessness or inability to sleep well (Starts within hours of dose, may persist, often improves)

"The first 1-3 hours of the med make me tired but I can't sleep more than 1-4 hours at a time I just get super restless and feel like electricity." source

"I just get super restless and feel like electricity is running through my body." source

Sweating or hot flashes (Starts within 30-60 minutes of dose, may persist for weeks, often resolves)

"About 30 minutes after taking it, I get a horrible headache, dizziness, start sweating, and feel like I am going to throw up." source

"I had dizziness, hot flashes, and nausea, particularly with my morning dose, for the first several months I was on Buspar." source

Muscle weakness and brain fog (Starts after first few doses, persists while on medication)

"I'm extremely tired and can't stop yawning, muscle weakness, and brain fog." source

Brain fog or trouble thinking clearly (Starts in first week, may persist, often improves)

"The medicine also seems to be causing quite a bit of brain fog and headache. I hope these adverse effects subside with time." source

"I'm extremely tired and can't stop yawning, muscle weakness, and brain fog." source

Feeling slightly disoriented (Starts in first week, usually resolves quickly)

"I've been dizzy, slightly disoriented, and fatigued." source

Mild stomach cramps (First few days, resolves quickly)

"First few days were surprisingly fine, just a few mild stomach cramps, but yesterday and especially today, I've been dizzy, slightly disoriented, and fatigued." source

Nightmares and weird dreams (Intermittent, can occur at any time)

"Weird head feeling, not quite light headed or dizzy but feeling dissociated but still present. Brain zaps. Weird dreams/ nightmares *all intermittently." source

Hypomania or increased energy (Starts in first week, resolves after 1-2 weeks)

"It did make me hypomanic when I first started it, but I evened out after a week or two." source

Emotional blunting or feeling less emotion (Ongoing while on medication)

"I'm not sure if I'm anxiety-free or just more depressed. It honestly feels like it's a bit of both." 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: NCT06141876
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: CYB003 showed mostly transient, mild-moderate side effects (e.g., headache, nausea, mild anxiety) with no serious adverse events. No sexual dysfunction, weight gain, or cognitive blunting reported, which are common with SSRIs/SNRIs. No daily dosing required, reducing chronic side effect burden.
Efficacy Data:
- Response rate: 53.8% (CYB003 16mg) vs 19.2% (placebo) at 6 weeks
- Remission rate: 75% at 4 months (CYB003)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 points (placebo) at 6 weeks
- Time to response: 1-2 weeks
- Source
Why it might interest you: Rapid onset (1-2 weeks), high remission rates, and a side effect profile that avoids sexual dysfunction, weight gain, and cognitive dulling make this attractive for those intolerant to standard antidepressants.
Results: Significant and rapid reduction in depressive symptoms; 75% remission at 4 months; well-tolerated with transient, mostly mild-moderate side effects.
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: AMPA modulators like osavampator are not associated with sexual dysfunction, weight gain, or sedation typical of SSRIs/SNRIs. Early data suggest a favorable side effect profile, with low rates of cognitive impairment or metabolic effects.
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: Potentially within 2 weeks (based on AMPA modulator class)
- Source
Why it might interest you: Novel mechanism (AMPA modulation) with potential for faster onset and fewer side effects (no sexual dysfunction, weight gain, or sedation) compared to standard antidepressants.
Results: Phase 2 data showed significant improvement in depressive symptoms as adjunctive therapy; Phase 3 underway to confirm efficacy and safety.
Sources: 1, 2, 3

D-cycloserine (adjunctive)

Sponsor: Not specified (academic/NIH)
Phase: Phase 2 (completed)
NCT: NCT00408031
Mechanism: NMDA receptor glycine-site partial agonist (D-cycloserine)
Side Effect Comparison: D-cycloserine is not associated with sexual dysfunction, weight gain, or sedation. Side effects are generally mild and transient, with no significant cognitive impairment or metabolic effects reported, unlike SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not specified
- Remission rate: Not specified
- MADRS change: Not specified; significant improvement in depressive symptoms in TRD (Phase 2)
- Time to response: Within 1-2 weeks (based on NMDA/glycine-site modulator class)
- Source
Why it might interest you: Different mechanism (NMDA/glycine-site modulation), rapid onset, and minimal side effects make it appealing for those who cannot tolerate standard antidepressants.
Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression and bipolar depression.
Sources: 1

Psilocybin (various trials, including COMPASS Pathways)

Sponsor: Multiple (COMPASS Pathways, Usona, academic centers)
Phase: Phase 2/3 (multiple ongoing)
Mechanism: Classic psychedelic (psilocybin, 5-HT2A receptor agonist)
Side Effect Comparison: Psilocybin is not associated with sexual dysfunction, weight gain, or chronic sedation. Side effects are typically transient (e.g., headache, mild anxiety, nausea) and resolve within hours. No daily dosing required, reducing chronic side effect risk.
Efficacy Data:
- Response rate: Not specified
- Remission rate: Not specified
- MADRS change: Not specified (review article)
- Time to response: 1-2 weeks (based on psilocybin class)
- Source
Why it might interest you: Rapid, robust effects after 1-2 doses, with a side effect profile that avoids the most common and bothersome issues of standard antidepressants.
Results: FDA Breakthrough Therapy Designation for treatment-resistant depression; multiple studies show rapid, robust antidepressant effects after 1-2 doses.
Sources: 1, 2

Appendix D: Methodology

To create this guide, we reviewed more than 30,000 clinical trial listings from ClinicalTrials.gov, over 300 journal articles indexed in PubMed, and 54 online discussions, integrating insights with 134 adverse reaction entries from the OpenFDA Drug Label data set. Our team identified and ranked 15 unique side effects by user report frequency. Severity ratings, duration, and real patient quotes with sources were analyzed to capture both clinical and lived experience.