Opioid and Tranquilizer Deadly Mix- How Did We End Up That Way? – Bipolar and/or PTSD

It has been said Opioids and tranquilizers can increase risk of overdose death five fold.
In my population, there is a subgroup of cases with bipolar disorder. Indeed, a meta-anlysis found 21 – 25% of Fibromyalgia disorder have it and I suspect more not diagnosed.  In a mixed state, a pain patient gets little sleep and is in considerable distress with agitation and will inadvertently be put on significant doses of tranquilizers to deal with this “pain” when tolerance to atypical anti-psychotics is limited.   March is a good time to see it and I have seen a couple cases already this year.  After the mixed state subsides, they end up continued to take them because they can contend it helped them.

It is also easy to put pain patients that don’t sleep and have restless legs, on Clonazepam which is some cases is dangerous, particularly if subjects are obese and subject to sleep apnea.

Sullivan, Mark.
Dangerously numb? Opioids, benzodiazepines, chronic pain, and PTSD.
Pain (2017). 159(3), 407-8

  • “After these careful controls, the authors were able to demonstrate a 36% increased risk of adverse outcomes in the opioid–benzodiazapine pre-
    scription group.”
    referring to: Gressler LE, Martin BC, Hudson TJ, Painter JT. The relationship between concomitant benzodiazepine-opioid use and adverse outcomes among U.S. veterans. PAIN 2018;159:451–9
  • Article puts co-prescribing of opioids and tranquilizers in PTSD vets at 16% in a 2014 study
  • there are more adverse event on this combo but lack of ability to taper with this combo
  • They describe Chronic Pain – PTSD as a “complex central sensitization” where the numbing effect of Opiod-Benzodiazepine has and alure.
  • dampening pain and hyper arousal needs better measures but they contend none.

What about marijuana in PTSD?

A recent review was not very complementary for PTSD
Steenkamp, Maria M., et al.
Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: a literature review.
Depression and anxiety (2017).

“Of concern, marijuana use has been linked to adverse psychiatric outcomes, including conditions commonly comorbid with PTSD such as depression, anxiety, psychosis, and substance misuse. Available evidence is stronger for marijuana’s harmful effects on the development of psychosis and substance misuse than for the development of depression and anxiety. Marijuana use is also associated with worse treatment outcomes in naturalistic studies, and with maladaptive coping styles that may maintain PTSD symptoms. Known risks of marijuana thus currently outweigh unknown benefits for PTSD…”

Sadly, I can see how Marijuana over-use could be driven by the “pain” of hyperarousal and nightmares

Re Opioid – tanquilizers in Fibromyalgia
20- 25% bipolar risk  as pre:
Wilke, William S., Carmen E. Gota, and David J. Muzina. “Fibromyalgia and bipolar disorder: a potential problem?.” Bipolar disorders 12.5 (2010): 514-520.

Kudlow, P. A., et al. “Prevalence of fibromyalgia and co-morbid bipolar disorder: a systematic review and meta-analysis.” Journal of affective disorders 188 (2015): 134-142.

  • The diagnosis of bipolar is driven by finding episodes of hyomania with
    – happy overactivity – never going to see it in someone who has not slept much for years with chronic pain
    – overspending – not going to see in poor unemployed chronic pain sufferers
    – suicidality – women with children would never accept this option
  • All you are going to see is a mood disorder victim with periods of excessive “worry” that occurs in March, July, and around Xmas. When asked why they are worried they will always have things on there plate but no more than usual (though xmas is always hard on them – partially related with having to deal with toxic bipolar relatives).
  • Associated with this, less sleep and perhaps more agitation & inability to concentrate combined with deepened depression from above issues. This is a mixed state; though irritability and anger are less as well probably related to exhaustion.
  • I would use Quetiapine or Olanzapine and try to ramp former to 300 mg + to get to its anti-depressant dosing. The antidepressant they are on isn’t working anymore and might be holding subject in mixed state and needs to be cut down gradually.
  • They will beg you for tranquilizers but be careful – you may never get them off of them again as they will fear these periods of agitation. – I have had cases with pain 7/10+ tell me they would take the pain rather than the agitation which can have a high suicide rate.


I used to use clonazepam in subjects with chronic pain – sleep disorder and restless legs. However, there is a subgroup of chronic pain subjects that are obese and sleep apnea is a real risk made much worse with tranquilizers. Now, there is good evident that pramipexole helps Fibromyalgia and restless legs and should be used first:
as per http://painmuse.org/?p=5236

If you plan on using clonazepam in someone with risk for sleep apnea (obese, big neck, snores etc) then maybe do sleep study while on..

Lastly, there was a study that found Alprazolam did help Fibromyagia some but this is a slippery slope.


Comment – I have chronic pain victims on Marijuana with benefit. I am working hard to rid may patients of sedatives but this is  not easy.  I have one case that let herself get very sick (beck 41 = extreme depression) before she came in with an agitated depression. 1 week later on 300+ mg quetiapine and cut down antidpressants she is beck 31 (severe) and the agitation is dissipating. I cannot feel more sorry for someone in chronic pain – excessive worry state and would never wish that on anyone.


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