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Opioids Increase Depression & Depression Increases Opioid Misuse

Opioids Increase Depression & Depression Increases Opioid Misuse
Learn how opioids can lead to depression, how depression worsens pain and what to do when you have both pain and depression.
Depression and pain go hand in hand – pain and disability can cause or worsen depression and depression worsens pain and disability… what a mess!
And to further complicate matters, though depression worsens pain perception and analgesic need, people with depression also get less pain relief from opioid medications.1
Fortunately, it's not all doom and gloom - here’s the good news:
  1. If depression ups your pain, treating the depression will almost certainly reduce pain and disability and improve your quality of life.
  2. If you’re on high-dose opioids and suffer with pain and depression, you might find that reducing your daily dose improves both pain and mood.
  3. If you have an addiction problem, dealing with your substance misuse generally eases pain and depression.
Read on to learn more about how pain and depression interact and about how to deal with this tough co-morbid situation.

Co-Occurring Depression and Addiction

Longer Opioid Use = Increased Depression

An argument for time-limited opioid use.
In one major study of 50,000 military personal, researchers found that compared to people who used opioids for between 1 and 89 days:2
  1. People who used for 180 days or longer were 53% more likely to develop a first or new incidence of depression.
  2. People who used for between 90 and 180 days were 25% more likely to develop a first or new incidence of depression. 
  3. Also, people who used higher doses experienced more depression than people maintained on lower doses.

Depression Ups Opioid Misuse Risk

People with depression – even those with no history of substance abuse, are far more likely to take opioids for reasons beyond pain control than people from the general population.
  • In one study, researchers from Western Illinois University found that people with severe depression were 2.4 times more likely to use opioids for reasons other than pain control and 2.89 times more likely to use more opioids than prescribed than people without depression.3
  • A huge Kaiser Permanente study which looked at the medical records of tens of thousands found that pain patients with a history of depression were three times more likely to receive a prescription for opioids than pain patients without a history of depression.4

Why Are Opioids and Depression So Interlinked?

Opioids systems affect mood – and when things go wrong, this can cause depression.
  • Opioids can produce intense pleasure (highs). Long term opioid use may disrupt reward pathways in the brain, making it harder to feel pleasure from normal everyday events like a good meal or the company of friends. 
  • Opioid receptors are located in areas of the brain that regulate emotion and cognition and opioids play a role in mood and anxiety regulation – for example, the brain releases endogenous opioids to self-soothe social rejection.5 So when opioid systems get dysregulated through over-stimulation, this affects emotional and stress systems as well. 6
  • Chronic opioid use can lead to decreased testosterone, which can cause depression.
  • People experiencing depressive symptoms are more likely to use opioids to self medicate psychological symptoms. This type of misuse ups addiction risks.
  • Depression can worsen the perception of pain, causing a need for greater analgesia and higher opioid doses. Higher opioid doses increase addiction risks and can exacerbate depression.
  • People with depression often have pain that doesn’t respond well to standard pain interventions. This leads to increased medication use - and increased addiction risks.
  • People misusing opioids are less compliant on depression treatment directives. 
  • Opioid abuse may lead to life-consequences that worsen depression.7
Worryingly, opioids increase the lethality of suicide attempts among people with psychiatric disorders.

Guidelines for Using Opioids when Depressed

According to the Canadian Guidelines for the Safe and Effective Use of Opioids for Chronic Non Cancer Pain, people with depression should:1
  • Titrate their opioid dose more slowly at the start of treatment.
  • If you are working with a psychiatrist or psychologist, ask your prescribing physician to consult with this professional on the use, benefits and risks of opioid therapy for your situation.
  • To prevent serious problems (like addiction) ask for frequent doing intervals and other conservative measures that prevent misuse.
  • Monitor your mood and consider how opioids affect your functioning.
  • Stop opioid therapy unless the medications work well – providing more than 30% pain reduction. 

Consider Lower Doses

If you take a high daily opioid dose, you may actually get better pain relief and experience less depression by slowly tapering down to a lower dose.8
  • In one study, doctors in California examined a group of patients who were on a very high daily opioid dose (300 mg per day or higher of morphine equivalent). At the start of the study, the average depression score among the patients was 13.5 on the Patient Health Questionairere-9; a score which indicates major depression.
  • All patients agreed to a very gradual program of dose reduction, reducing at rates from 4% to 16% per 10 days, to a final dosage of 30% the starting dosage.
  • After achieving this final reduced dosage, average patient depression scores dropped to 9.5. Study patients also reported less pain on the lower dose and less pain interference in quality of life.
The results indicate that for some people, chronic high opioid doses may actually worsen pain and depression, rather than alleviate suffering.  

Consider Addiction Treatment

Though lower doses may reduce depression and pain, once addicted, you probably can't control your daily usage. Once addicted, to manage depression and pain, you likely need addiction treatment.
Though the thought of facing withdrawal symptoms, un-medicated pain and depression all at once seems scary and overwhelming, It’s probably not as bad as you think, in fact, most people find that pain and depression get better once they address addiction issues:7
  • On average, addiction treatment causes reduced depression, particularly maintenance treatment with methadone or Suboxone.
  • Results are further improved by supplementing addiction treatment with depression-focused cognitive behavioral therapy. In fact, though reducing opioid use alone can reduce depression, untreated depression ups relapse risks, so it’s important to address both the addiction and the mood disorder at the same time.9

Take Home Messages

  • Since longer opioid use and higher doses are associated with greater depression, be cautious with using opioids for persistent pain. If you must use opioids, make sure to supplement medication with active forms of pain management, such as exercise, relaxation exercises, mindfulness and acceptance techniques. 
  • People with chronic pain and depression commonly use opioids to self-medicate depressive symptoms. However, since depression worsens pain and reduces pain intervention effectiveness, it’s very important to treat the depression and pain at the same time. Simply relying on pain medication to relieve the depression isn’t a good strategy; in fact it’s likely to worsen depression and pain.
  • If you find that pain gets worse, even with increasing opioid doses, you should consider whether depression affects your pain management.
  • People on high opioid doses may experience less pain and depression by reducing daily dosages.
  • Opiate addicted people will generally experience less depression and less pain by getting addiction treatment, especially MAT.

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And, as always, thank you for reading!
All the best to you and yours,


Martin Schoel,
founder of Choose Help
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