Opioids and Depression: How Mood Changes Happen and How to Monitor Them

When you’re in chronic pain, opioids can feel like a lifeline. But for many people, that relief comes with a hidden cost: a slow, creeping shift in mood. It’s not just fatigue or irritability. It’s losing interest in things you once loved. Feeling numb. Waking up with no hope. And it’s more common than most doctors admit.

Between 30% and 54% of people with long-term pain also have depression. But here’s the twist: opioids aren’t just treating pain-they might be making the depression worse. A major 2020 study using genetic data found that using prescription opioids doesn’t just correlate with depression-it actually increases your risk. This wasn’t just people who were already depressed taking painkillers. The science points to opioids themselves playing a role in triggering mood disorders.

How Opioids Change Your Brain

Opioids work by binding to receptors in your brain that control pain, but they also touch the same pathways that regulate mood, reward, and emotion. In the short term, this can feel like a double win: less pain, and a little lift in mood. Studies in animals show that drugs like morphine and buprenorphine reduce signs of despair-like giving up in a forced swim test-by 35% to 60%. It’s why some people on opioids say they feel calmer, even happy, at first.

But your brain adapts. Over weeks and months, it starts to rely on the drug to keep those mood pathways running. The natural chemicals your body makes to handle stress and pleasure-like endorphins-slow down. You need more of the opioid just to feel normal. And when the drug wears off, your brain struggles to bounce back. That’s when low mood, apathy, and emotional numbness creep in.

It’s not just about dosage. A 2016 study of burn patients found that the more total opioids someone received, the higher their depression scores climbed-even after adjusting for injury severity. People taking over 50 mg of morphine equivalent per day were more than three times as likely to develop depression compared to those not using opioids at all.

The Vicious Cycle

Depression doesn’t just happen because of opioids-it can also lead to them. People with untreated depression often experience pain more intensely. They’re more likely to seek out pain relief, more likely to be prescribed opioids, and more likely to keep using them long after the injury heals. One study found depressed patients were twice as likely to move from short-term to long-term opioid use.

And once that cycle starts, it’s hard to break. Depression increases the risk of opioid use disorder by 2.5 times. People with both conditions report 37% more interference with daily life and 42% higher mental distress than those with pain alone. It’s not just physical pain-it’s emotional exhaustion, isolation, and hopelessness piling on.

What to Watch For

Depression from opioids doesn’t always show up as crying or sadness. Often, it’s quieter:

• You stop calling friends, even though you used to love talking
• You don’t care about hobbies, meals, or TV shows you used to enjoy
• You feel empty, even when you’re not in pain
• You’re more irritable, or you shut down completely
• You have trouble sleeping-or sleep too much
• You think, “What’s the point?” more often than not

These aren’t just side effects. They’re warning signs. And they often show up before a formal diagnosis. A 2020 study tracking patients on long-term opioids found that 27.3% developed worsening depression within just three months.

How to Monitor Your Mood

The American Pain Society and CDC both say: screen for depression when starting opioids. But in reality, only about 40% of doctors do it regularly. You can’t wait for your doctor to ask. You need to take charge.

Use the PHQ-9-a simple, free, nine-question tool that asks about sleep, energy, appetite, focus, and feelings of worthlessness. You can find it online or ask your doctor for a copy. Fill it out at the start of treatment, then every three months. If your score goes up by 5 or more points, that’s a red flag.

Keep a mood journal. Not a diary. Just a quick note each day:

• How was your energy today? (1-10)
• Did anything feel meaningful or enjoyable?
• Did you feel numb or disconnected?

After a few weeks, patterns emerge. Maybe you feel worse every Friday after your last dose. Maybe you’re more down after sleepless nights. That data is powerful. Bring it to your doctor.

What Can You Do?

Stopping opioids cold turkey isn’t safe-and it won’t fix depression. But there are better paths.

1. Treat the depression, not just the pain. Cognitive behavioral therapy (CBT) for chronic pain has been shown to cut opioid use by 32% when combined with pain management. You don’t need to choose between pain relief and mental health-they can improve together.

2. Ask about buprenorphine. Yes, it’s an opioid. But at low doses (1-2 mg/day), it’s been shown to lift depression in people who didn’t respond to antidepressants. In one study, 47% of treatment-resistant patients felt better within four weeks. It’s not FDA-approved for depression yet, but some psychiatrists prescribe it off-label. If you’re struggling with both pain and mood, it’s worth a conversation.

3. Reduce the dose if possible. High doses (over 50 mg morphine equivalent) are linked to much higher depression risk. Work with your doctor to find the lowest effective dose. Sometimes, adding non-opioid pain treatments-physical therapy, nerve blocks, acupuncture-can help you taper safely.

4. Don’t go it alone. Support groups for chronic pain and mental health are out there. Talking to others who get it reduces shame and isolation. You’re not weak for feeling this way. You’re human.

The Bigger Picture

Scientists are still trying to figure out why short-term opioid use can lift mood, but long-term use crushes it. New research using brain scans is looking at how opioid receptors change over time-how the brain’s natural reward system gets rewired. A $4.2 million NIH study is tracking this in real time.

For now, the message is clear: opioids aren’t just painkillers. They’re mood-altering drugs. And if you’re on them long-term, your mental health needs as much attention as your physical pain.

The goal isn’t to scare you off opioids. It’s to make sure you’re not trading one suffering for another. If you’re on opioids and feel like you’ve lost yourself, you’re not alone. And help is possible-even if it doesn’t look like what you expected.