Bupropion Side Effects: What You Need to Know About Insomnia, Anxiety, and Seizure Risk

Bupropion is one of the most commonly prescribed antidepressants in the U.S., with over 17 million prescriptions filled in 2022. Brands like Wellbutrin, Zyban, and Aplenzin all contain this drug, and it’s often chosen because it doesn’t cause the sexual side effects or weight gain that many other antidepressants do. But that doesn’t mean it’s without risks. For every person who finds relief without sexual problems or weight gain, another might struggle with sleepless nights, jittery anxiety, or even a seizure they never saw coming. If you’re considering bupropion-or already taking it-here’s what you really need to know about its most serious side effects: insomnia, anxiety, and seizure threshold.

Why Bupropion Is Different From Other Antidepressants

Most antidepressants, like fluoxetine (Prozac) or sertraline (Zoloft), work by boosting serotonin in the brain. Bupropion is different. It targets dopamine and norepinephrine instead. That’s why it’s called an atypical antidepressant. This unique mechanism is why it doesn’t mess with your sex drive the way SSRIs often do. Studies show only 1-6% of people on bupropion report sexual side effects, compared to 30-70% on SSRIs. It’s also one of the few antidepressants linked to weight loss instead of gain-about 23% of users lose weight on it.

But this same mechanism is also why bupropion can cause problems others don’t. Dopamine and norepinephrine are stimulant-like neurotransmitters. Too much of them, especially early in treatment, can overfire your nervous system. That’s the root cause of insomnia, anxiety, and the increased seizure risk.

Insomnia: The Most Common Sleep Killer

About 19% of people taking bupropion report trouble sleeping. That’s higher than most other antidepressants, which typically cause insomnia in 10-15% of users. For some, it’s mild-just a harder time falling asleep. For others, it’s brutal: lying awake until 3 a.m., heart racing, mind spinning. One Reddit user wrote, “I took my last dose at 7 p.m. and still couldn’t sleep until 5 a.m. for three weeks straight.”

The reason? Bupropion’s effects peak in the bloodstream 3-5 hours after taking it, depending on the formulation. If you take it too late in the day, your brain is still buzzing when you’re trying to wind down. The FDA and Mayo Clinic both recommend taking bupropion in the morning, and never within 6 hours of bedtime. If you’re on the extended-release version (XL), take it once in the morning. If you’re on the sustained-release (SR), split the dose-first in the morning, second no later than noon.

Some people find that switching from SR to XL helps. The XL version releases the drug more slowly, so it doesn’t spike as sharply. That reduces the “crash and burn” effect that keeps people up. In clinical practice, about 68% of patients who moved to morning-only XL dosing saw their sleep improve within two weeks.

Anxiety and Agitation: The First Two Weeks Are Critical

Anxiety isn’t just a side effect-it’s a red flag. About 20-25% of people on bupropion report nervousness, restlessness, or agitation, especially in the first 1-2 weeks. This isn’t your usual “I’m stressed” anxiety. It’s a physical jitteriness: trembling hands, racing thoughts, feeling like you’re on edge even when nothing’s happening.

Clinically, this is called “activation syndrome.” It happens because dopamine and norepinephrine levels rise faster than your brain can adapt. Most people get through it. Symptoms usually fade after a week or two as your brain adjusts. But for 1 in 5, it doesn’t. That’s when people quit.

Doctors sometimes pair bupropion with a short-term benzodiazepine like lorazepam for the first 10 days to calm the nervous system. Others reduce the starting dose-from 150mg down to 75mg-and go slower. If your anxiety is severe enough to make you panic, avoid driving, or cause suicidal thoughts, you need to talk to your provider immediately. Don’t wait. This isn’t normal adjustment-it’s a warning sign.

Seizure Risk: The Silent Threat

This is the most dangerous side effect-and the one most people don’t know about. In the general population, the chance of having a seizure is about 0.01% per year. With bupropion at the maximum recommended dose (450mg/day for SR, 400mg/day for XL), that risk jumps to 0.4%. Sounds low? It is-until you realize that risk skyrockets to 2-5% if you go over 600mg/day.

The seizure risk isn’t random. It’s tied to how fast the drug hits your bloodstream. That’s why the immediate-release form (no longer commonly prescribed) had the highest risk. The sustained-release (SR) version is riskier than extended-release (XL) because it releases the drug faster, creating higher peak levels. The FDA approved a new XL formulation in June 2023 specifically to lower these peaks and reduce seizure risk.

Certain people are at much higher risk: those with a history of seizures, head injuries, brain tumors, severe liver disease, eating disorders (like anorexia or bulimia), or those who drink heavily or use stimulants like cocaine or Adderall. Even stopping alcohol cold turkey while on bupropion can trigger a seizure.

One case report from 2023 described a 35-year-old woman who had her first seizure after increasing her SR dose to 300mg. She had no prior history. Her doctor didn’t know she’d been drinking 2-3 beers nightly to sleep. That combination was enough to push her over the edge.

Watch for warning signs: muscle twitching, uncontrolled jerking, staring spells, or sudden confusion. If you feel any of these, stop the drug and get medical help immediately. Don’t wait for a full-blown seizure.

Who Should Avoid Bupropion Altogether?

Bupropion isn’t for everyone. Here are the clear red flags:

• You’ve ever had a seizure
• You have an eating disorder (anorexia, bulimia)
• You’re currently withdrawing from alcohol or sedatives
• You’re taking other drugs that lower seizure threshold (like antipsychotics, stimulants, or certain antibiotics)
• You have severe liver disease
• You’re already on another antidepressant that causes anxiety or insomnia

If any of these apply to you, bupropion is probably not the right choice. There are safer alternatives-mirtazapine, vortioxetine, or even SSRIs if sexual side effects aren’t a dealbreaker.

What to Do If You’re Already on Bupropion

If you’re taking bupropion and having side effects, don’t quit cold turkey. That can cause withdrawal symptoms like headaches, nausea, or mood swings. Instead:

1. Track your doses and timing. Are you taking it too late?
2. Check your daily dose. Are you over 400mg (XL) or 450mg (SR)?
3. Rate your anxiety and sleep on a scale of 1-10 each day for a week.
4. Write down any physical symptoms: twitching, dizziness, palpitations.
5. Schedule a call with your prescriber. Bring your notes.

Many people can stay on bupropion with simple tweaks: moving the dose earlier, switching to XL, or lowering the dose. Others need to switch entirely. There’s no shame in that. Finding the right antidepressant is like finding the right shoe-it has to fit.

Real Stories: What Patients Say

On GoodRx, bupropion has a 6.3/10 rating. The reviews split cleanly:

• Positive: “Finally, an antidepressant that didn’t kill my libido.” “Helped me quit smoking and I lost 12 pounds.”
• Negative: “I couldn’t sleep for 6 weeks.” “I had panic attacks so bad I ended up in the ER.” “I had a seizure at 300mg. Never again.”

Reddit threads are full of similar stories. One user wrote: “I thought Wellbutrin was the miracle drug-until I started shaking at 2 a.m. and couldn’t tell if I was having a panic attack or a seizure.”

The pattern is clear: people who succeed on bupropion tend to be those who took it slow, avoided evening doses, and didn’t ignore early warning signs. Those who struggled often pushed through symptoms thinking it was “just adjustment.”

The Bottom Line

Bupropion is a powerful tool. For the right person, it can change their life-freeing them from sexual side effects, weight gain, or even helping them quit smoking. But it’s not a gentle drug. It’s a stimulant in antidepressant clothing. If you’re considering it, ask yourself: Are you willing to risk sleepless nights and anxiety to avoid weight gain? Are you prepared to stop taking it cold if you feel a twitch in your arm?

Talk to your doctor about your full history: sleep patterns, anxiety, substance use, seizures, liver health. Don’t assume it’s safe just because it’s popular. Millions take it. Thousands have had bad reactions. Your job is to know if you’re in the majority-or the minority at risk.

If you’re already on it and something feels off-trust that feeling. Your nervous system is talking. Listen before it screams.