opiates/opioids and depression?

[randomdoc1]

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Just wondering what everyone's experiences with this are. Of course, this type of clinical picture in someone chronically on opiates/opioids is complex as chronic pain worsens mood and those with chronic pain generally tend to be more susceptible to psychiatric symptoms anyways. But I have encountered a share of patients on chronic high dose opioids who seemed to just be refractory to any kind of medication change and sometimes even with therapy optimized. However, on mental status exam, they don't have, I guess, the more typical clinical presentation of someone who is much more clearly in a MDE (e.g. the psychomotor slowing, withdrawn, sometimes very apparent anxious distress, etc.). Which indicates to me a different mechanism of pathology. I've also encountered patients on chronic opiates/opioids who have some personality traits as well including those who are clearly passive in their treatment (psychiatric, or non psychiatric) and just don't engage in therapy which definitely does not help their situation. But anyways, something I've always wondered is, do the opiates/opioids also play a role in potentiating these depressive symptoms further? To my understanding, the literature consensus does not show much benefit of chronic use of these medications and also tendency to increase morbidity and mortality. I found this read as well and am glad to see I'm not the only one who has wondered this.

Prescription Opioid Analgesics Increase Risk of Major Depression: New Evidence, Plausible Neurobiological Mechanisms and Management to Achieve Depression Prophylaxis - PMC

More than 200 million prescriptions are written annually for opioid analgesics despite limited evidence of their long-term efficacy. These medications currently are prescribed to 10% – 15% of Americans with use of long-acting opioids projected to ...

www.ncbi.nlm.nih.gov

 

[Sushirolls]

Chronic opioid use can induce central apneas.
Consider it a risk factor for Sleep Medicine consult to get HST and likely treatment of (O)SA.

 

[mistafab]

I definitely feel like opioids contribute to depression, but can also masquerade as depression.

The way I understand it is the chronic use itself works in the NAC pathway to decrease dopamine-derived behavior rewards due to the intense flood of dopamine occurring naturally with opioid use. This leads chronically to downregulation and to an anhedonic/apathetic picture that is long-lived. We know that even in sobriety, the pathways altered in chronic substance use disorders takes months to begin recovering, and it is thought currently that there may be permanent dysfunction in these regions (VTA/Nac-amygdyla-PFC) that never quite get back to baseline. With that said, it makes sense that some features of depression are apparent in the chronic use of opioids, especially when it comes to behavior/reward (which may present as anhedonia), distress in the amygdyla (fear avoidance w/ withdrawal), and preoccupation in the PFC (anticipating the next dose). These could look a lot like anhedonia, feelings of hopelessness, inattention, or anergia.

Would make sense to me that chronic opioid use could masquerade as depression due to above, and would be less likely to respond to our typical treatments (meds, therapy). It also makes sense that disturbing these pathways could predispose someone who has an underlying depression (or predisposition) to go into an MDE when they get their pleasure circuitry taken away from them by opioids messing up their brain behavior pathways. It makes me wonder if these folks would respond better to an NDRI rather than the SSRIs.

 

[aim-agm]

This depends quite a bit on dosage. At very low doses opioids/mu-opioid agonists are actually quite effective antidepressants (see tianeptine).

 

[Mad Jack]

This depends quite a bit on dosage. At very low doses opioids/mu-opioid agonists are actually quite effective antidepressants (see tianeptine).

The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review - PMC

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are ...

www.ncbi.nlm.nih.gov

Buprenorphine can have some significant impact on depressive symptoms in some patients. The counter to this is that I have seen people develop significant first onset of major depressive disorder that was refractory to SSRIs in the setting of discontinuation of buprenorphine that they were on for opioid use disorder.

 

[aim-agm]

The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review - PMC

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are ...

www.ncbi.nlm.nih.gov

Buprenorphine can have some significant impact on depressive symptoms in some patients. The counter to this is that I have seen people develop significant first onset of major depressive disorder that was refractory to SSRIs in the setting of discontinuation of buprenorphine that they were on for opioid use disorder.

Yes, I've also heard about that with methadone. Overall it's indirect evidence of the antidepressant effect of opioids. I wonder about very slow tapers assisted by clonidine in these cases.
I think the dose matters a great deal. The dosing with tianeptine is IIRC something like 1 MME a day or a little above that. Meanwhile the minimum tablet dose of buprenorphine is 2 mg, which is ~60 MME each dose.

 

[hallowmann]

The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review - PMC

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are ...

www.ncbi.nlm.nih.gov

Buprenorphine can have some significant impact on depressive symptoms in some patients. The counter to this is that I have seen people develop significant first onset of major depressive disorder that was refractory to SSRIs in the setting of discontinuation of buprenorphine that they were on for opioid use disorder.

I have seen both as well. It's difficult to differentiate, but there are definitely some individuals that respond very positively from a mood standpoint to chronic opioids unrelated to pain per se. I don't think we have a good understanding of this mechanism and how to differentiate people that might benefit (or at least I don't).

 

[FrustratedFamDoc]

To me this one is hard to sniff out correlation vs causation. My typical chronic opioid patient (certainly not all), have a lot of not very good stuff simultaneously going on in their lives. They usually don't work and when asked what they see as their purpose, don't really have a good answer for me. Chronic pain definitely has a strong relationship with depression. From what I've seen, the order goes this way:

Fairly normal employed life --> something causing pain/somatic dysfunction/depression/etc mixed with poor coping skills/attitude/outlook --> primary care exhausts all conservative options --> even less activity --> weight gain --> worsening pain/depression --> primary care/pain management begins opiates --> hey doc, I feel great --> hey doc, I don't feel as good as I did 6 mos ago --> weight gain --> medication escalation --> hey doc, feeling better --> doses now as high as doc is comfortable with so tolerance again develops --> discord occurs --> weight gain, worsening depression etc.

Several times in the process, mood meds are sprinkled in to help with various symptoms, probably helping to contribute to the weight gain. Weight gain significantly worsens depression and pain. No one ever feels better packing on an extra 30 pounds.

It's difficult to come along in the middle of the process and truly get a feel for causation and correlation. I've yet to find someone who has no stated purpose in their life that feels fantastic.