If you're taking primidone for seizures or tremors, and you've noticed you're feeling more down than usual, you're not imagining it. There's a real, documented connection between primidone and depression - one that many patients and even some doctors don't talk about enough. It’s not common for everyone, but when it happens, it can be serious. You need to know the signs, when to act, and what to do next.
What Primidone Actually Does
Primidone is an anticonvulsant drug first approved in the 1950s. It works by calming overactive nerve signals in the brain, which helps stop seizures and reduce essential tremors. It’s often prescribed when other medications like carbamazepine or valproate don’t work or cause too many side effects. About 1 in 5 people with epilepsy use primidone at some point, according to data from the Epilepsy Foundation.
It’s not a quick fix. It takes weeks for your body to adjust, and your doctor will start you on a low dose, slowly increasing it. That’s because primidone affects more than just seizure activity. It changes how your brain handles neurotransmitters - especially GABA, which helps you feel calm, and glutamate, which excites nerve cells. When this balance shifts, it doesn’t just stop seizures. It can also affect your mood.
How Primidone Can Trigger Depression
Depression isn’t just feeling sad. It’s losing interest in things you used to enjoy. It’s waking up tired even after eight hours of sleep. It’s feeling numb, hopeless, or guilty for no clear reason. These aren’t just "bad days" - they’re symptoms that can be directly tied to primidone.
Studies published in the Journal of Neurology, Neurosurgery & Psychiatry found that up to 18% of patients on long-term primidone therapy reported moderate to severe depressive symptoms. That’s nearly 1 in 5 people. The risk goes up if you’re already prone to mood disorders, if you’re older, or if you’re taking other medications that affect the brain, like benzodiazepines or antidepressants.
Primidone breaks down in your liver into two active metabolites: phenobarbital and phenylethylmalonamide (PEMA). Phenobarbital is a barbiturate - the same class of drugs once used as sedatives and sleep aids. Barbiturates are known to slow brain activity, and in some people, that slowdown turns into emotional flatness or deepening sadness. It’s not just psychological. It’s biochemical.
Red Flags: What Depression Looks Like on Primidone
Here’s what to watch for - not just once, but over time:
- Feeling emotionally numb, even during events that used to make you happy
- Withdrawal from friends, family, or social activities you once loved
- Changes in sleep - sleeping too much or not being able to fall asleep
- Loss of appetite or significant weight loss without trying
- Constant fatigue, even when you’ve rested
- Difficulty concentrating, forgetfulness, or feeling like your thoughts are sluggish
- Thoughts of self-harm or worthlessness - even if they’re fleeting
These symptoms don’t always show up right away. Sometimes they creep in after months on the drug. That’s why it’s easy to dismiss them as "just stress" or "getting older." But if you’re on primidone and these signs appear, they’re not normal. They’re signals.
Who’s Most at Risk?
Not everyone on primidone gets depressed. But certain people are more vulnerable:
- People with a personal or family history of depression, bipolar disorder, or suicide attempts
- Those over 65 - older adults process drugs slower, and their brains are more sensitive to neurotransmitter changes
- Patients taking multiple CNS depressants (like alcohol, sleeping pills, or anxiety meds)
- People who’ve had depression before starting primidone
- Those who’ve had sudden dose changes - whether increasing or reducing
If any of these apply to you, your doctor should have flagged this risk before prescribing primidone. If they didn’t, it’s not too late to bring it up.
What to Do If You Suspect Primidone Is Causing Depression
Don’t stop taking primidone on your own. Stopping suddenly can trigger seizures, status epilepticus, or even death. That’s a real danger.
Instead, do this:
- Write down your symptoms. Note when they started, how often they happen, and how bad they feel on a scale of 1 to 10.
- Track your mood and sleep patterns for a week. Use a notebook or a free app like Moodfit or Daylio.
- Call your neurologist or primary care doctor. Say: "I think primidone might be affecting my mood. I’ve noticed [list symptoms]." Don’t downplay it.
- Ask if you can get a blood test to check your primidone and phenobarbital levels. High levels increase depression risk.
- Request a referral to a psychiatrist who understands epilepsy medications. Not all psychiatrists know how anticonvulsants interact with mood.
Some doctors will try lowering your dose first. Others may switch you to a different medication - levetiracetam, lamotrigine, or topiramate - which have lower depression risks. Lamotrigine, in fact, is sometimes used to treat bipolar depression.
Alternatives to Primidone With Lower Depression Risk
If depression is a major concern, here are other seizure medications with better mood profiles:
| Medication | Depression Risk | Common Side Effects | Notes |
|---|---|---|---|
| Primidone | High | Dizziness, fatigue, nausea, depression | Barbiturate metabolite increases risk |
| Lamotrigine | Low to neutral | Rash (serious if not monitored), headache, dizziness | May improve mood; used for bipolar disorder |
| Levetiracetam | Low | Drowsiness, irritability, mood swings (in some) | Generally well-tolerated; no liver metabolism |
| Topiramate | Low | Cognitive slowing, weight loss, tingling | Can cause word-finding trouble |
| Valproate | Medium | Weight gain, hair loss, liver stress | Higher risk in women; not for pregnancy |
Switching meds isn’t simple. It takes weeks to taper off primidone safely and build up the new one. But if depression is stealing your life, it’s worth the effort.
What Your Doctor Should Be Monitoring
A good doctor won’t just check your seizure control. They should also ask about your mood - regularly. Here’s what proactive care looks like:
- Initial mood screening before starting primidone
- Follow-up appointments every 4-6 weeks during the first 3 months
- Use of simple tools like the PHQ-9 depression screening questionnaire
- Checking blood levels of primidone and phenobarbital
- Asking directly: "Have you felt down, depressed, or hopeless in the past two weeks?"
If your doctor never asks about your mood, ask them. You have the right to be monitored for side effects - not just seizure frequency.
Real Stories: What Patients Have Experienced
A 58-year-old teacher in Christchurch started primidone for tremors. Within three months, she stopped teaching her art class - she said she didn’t care anymore. She didn’t cry. She just didn’t feel anything. Her doctor thought she was grieving her husband’s death. It wasn’t. It was primidone. After switching to lamotrigine, she painted again within six weeks.
A 32-year-old nurse in Auckland had seizures since her teens. She was on primidone for 10 years. She started feeling like a ghost in her own life. She didn’t want to see her kids. She thought they’d be better off without her. Her neurologist dismissed it as "stress." She found a new doctor who ran blood tests - her phenobarbital level was double the safe range. She switched meds. The dark cloud lifted slowly, but it lifted.
These aren’t rare cases. They’re warnings.
When to Seek Immediate Help
If you’re having thoughts of harming yourself or ending your life, call a crisis line right away. In New Zealand, contact Lifeline on 0800 543 354. In the U.S., call or text 988. You don’t have to wait for your next appointment. This is an emergency.
Depression from primidone can be reversed. But only if you speak up.
Final Thought: Your Mental Health Matters as Much as Your Seizures
Seizures are dangerous. So is untreated depression. You don’t have to choose between them. There are options. You deserve to feel alive, not just safe.
Don’t let silence keep you stuck. Talk to your doctor. Track your mood. Ask about alternatives. You’ve fought hard to control your seizures. Now fight for your mind, too.
Can primidone cause suicidal thoughts?
Yes, primidone can increase the risk of suicidal thoughts, especially in people with a history of depression or bipolar disorder. The FDA issued a warning in 2008 about all antiepileptic drugs carrying this risk. If you’re having thoughts of self-harm, contact a crisis line immediately - don’t wait. This is a medical emergency.
How long does it take for depression to go away after stopping primidone?
It varies. For some, mood improves within a few weeks after switching meds. For others, especially those who were on high doses for years, it can take 2-3 months. The body needs time to clear phenobarbital, which has a long half-life. Therapy and support can speed up recovery.
Is depression from primidone permanent?
No. Depression caused by primidone is not permanent. Once the drug is safely tapered and replaced with a better-suited medication, most people see significant improvement. In rare cases, if depression was already developing before starting primidone, it may need ongoing treatment - but that’s not because of the drug. It’s because the underlying condition was there.
Can I take antidepressants with primidone?
Some antidepressants can be used safely with primidone, but not all. SSRIs like sertraline or escitalopram are often preferred because they don’t interfere with liver enzymes that process primidone. However, combining medications increases the risk of side effects like dizziness or drowsiness. Always work with a psychiatrist who understands both epilepsy and mood disorders.
Should I avoid primidone if I have a history of depression?
Not necessarily, but you need extra care. If you’ve had depression before, your doctor should consider alternatives like lamotrigine or levetiracetam first. If primidone is the only option that controls your seizures, they should monitor you closely - with regular mood checks and blood tests. Never assume you’re safe just because you’ve been on it for years.
Dana Dolan
November 20, 2025 AT 06:25I was on primidone for 2 years for essential tremors and didn’t realize my constant fatigue and crying at commercials was the drug. My doctor never asked about my mood. I just thought I was "getting old." Switched to lamotrigine and felt like I’d been asleep for a decade. I’m crying again now-but it’s because I finally remembered how to laugh.
Thank you for writing this.
Nick Lesieur
November 21, 2025 AT 13:52lol so now we’re blaming meds for being sad? next thing you know, people will say their breakup was caused by low serotonin and not just being a clingy mess.
just take an antidepressant and stop whining. everyone’s depressed these days.
Angela Gutschwager
November 22, 2025 AT 16:31Same. Took primidone for 8 months. Mood crashed hard. Doctor said "it’s just stress." I said "I haven’t left the house in 3 weeks." He shrugged.
Switched to levetiracetam. Life came back. 🙃
Andy Feltus
November 23, 2025 AT 06:28It’s not that primidone causes depression-it’s that modern medicine treats the brain like a toaster. You plug in a voltage, you get a result. But the brain isn’t a circuit board. It’s a symphony. And when you start messing with GABA and glutamate like you’re tuning a radio, you don’t just silence seizures-you silence joy.
They didn’t invent primidone to help people live. They invented it to stop convulsions. The rest? Collateral damage.
And yet, we’re supposed to be grateful it works. Meanwhile, the person inside the body? Still screaming.
It’s not medical progress. It’s medical compromise.
Dion Hetemi
November 24, 2025 AT 11:08Let’s be real-18% depression rate? That’s not a side effect, that’s a feature. Pharma knows this. They just bury it in the fine print. You think they want you to know your meds are turning you into a zombie? No. They want you to keep taking it. Because a depressed patient is a loyal patient.
And don’t even get me started on phenobarbital. That’s not a metabolite-that’s a time machine to 1950s psychiatric wards.
Stop glorifying this drug. It’s a relic with a body count.
Kara Binning
November 25, 2025 AT 01:24AMERICA NEEDS TO STOP LETTING FOREIGN DRUGS DESTROY OUR MINDS. This stuff is banned in 12 countries for mood risks. Why are we still giving it to our veterans, our teachers, our mothers? Because Big Pharma owns Congress. And if you’re depressed because of primidone? That’s just collateral damage in the war on seizures.
Wake up. This is a national crisis. And no, I won’t stop yelling until we ban this poison.
Zac Gray
November 25, 2025 AT 03:51I hear you, Dana. I’ve been there. I was on primidone for seizures after a traumatic brain injury. Started feeling like I was watching my life through a foggy window. No motivation. No joy. Just… numb.
My neurologist didn’t blink when I mentioned it. Said, "That’s just part of the package." So I went to a different doctor. Got blood tests. My phenobarbital was at 28 mcg/mL-way over the 12 limit. Switched to lamotrigine. Took three months to feel human again. But I did.
Don’t let a doctor dismiss you. You’re not being dramatic. You’re being honest. And honesty saves lives.
Also-track your mood. I used Daylio. It saved me. Not because it cured me-but because it proved to my doctor I wasn’t imagining it.
Steve and Charlie Maidment
November 26, 2025 AT 19:55Everyone’s so quick to blame the drug, but have you considered maybe you’re just… not coping? I’ve been on primidone for 15 years. I’m 67. I get tired. I get moody. I lost my wife last year. Is it the meds? Or is it life?
Don’t let the internet turn every gray day into a medical emergency. Sometimes, you just need to get out of bed and walk the dog. Not switch meds.
Michael Petesch
November 28, 2025 AT 16:08Interesting. I’m from the U.S. but currently living in India. I’ve observed that in Western medical practice, the pharmacological model dominates-every mood change is a neurotransmitter imbalance. In contrast, Ayurvedic practitioners often view such symptoms as a disruption in prana or vata dosha, linked to lifestyle, digestion, and emotional suppression.
Could it be that primidone exacerbates pre-existing imbalances rather than directly causing depression? Or is this simply a cultural bias in how we interpret side effects?
I’d love to see a cross-cultural study on this.