Access to the PPM Journal and newsletters is FREE for clinicians.
11 Articles in Volume 10, Issue #7
Selecting an Antidepressant for Pain Patients
Use of Opioids in Pain Patients with Psychiatric Disorders
Osteopathic Medicine Approach to Pain Management
Cannabis as Medicine
Pain Management in Patients with Pyoderma Gangrenosum
Occipito-Atlanto (C0-C1) Joints as a Source of Spinal Pain
Treat the Pain First—Worry about Psyche Problems Later
Traditional Chinese Medicine for Fibromyalgia
TMJ Condylar Pain From Parapharyngeal Space Tumor
Contraindications for Use of Therapeutic Laser
Platelet-Rich Plasma Prolotherapy for Low Back Pain Caused by Sacroiliac Joint Laxity

Use of Opioids in Pain Patients with Psychiatric Disorders

Opioid medications are a reasonable treatment option for carefully selected patients who suffer from psychiatric endogenous opioid dysfunction syndrome and who have not responded to typical neuropsychiatric medications or other treatments.

Chronic pain patients are known to have a higher prevalence of co-morbid psychiatric disorders,1 and the pain management practitioner can expect to deal with the evaluation and treatment of chronic pain patients displaying a host of various affective, mood, and cognitive syndromes. Nevertheless, for many pain physicians, the thought of treating pain patients with co-morbid psychiatric disorders is disturbing if not terrifying, since they may fear that such patients are more predisposed to overdose or abuse/misuse their prescribed pain medications. Some pain practitioners go so far as to flatly refuse to treat chronic pain patients with psychiatric co-morbidities, in spite of the risk of being successfully sued for not treating pain appropriately. And though there is data indicating that, in this patient population, there may be a decreased likelihood to improve with standard chronic pain treatment,2 the practice of medicine continues to be defined by the management of risk while improving health and easing suffering. The safe and effective use of opioids is no different.3

Common mental health disorders and problem drug use can be associated with the use of prescribed opioids in the general population.4 Nevertheless, the pain practitioner may consider chronic opioid therapy under certain circumstances for patients with chronic non-cancer pain and a history of drug abuse, psychiatric issues, or serious aberrant drug-related behaviors.5 The general medical consensus is that pain patients with psychiatric disorders deserve appropriate pain treatment which can include chronic opioid therapy.

Several questions arise: 1) Why do chronic pain patients have a higher prevalence of co-morbid psychiatric disorders? 2) Why are mental health disorders somehow associated with the prescription of opioid medications? The answers to these and other related questions may be provided by recent brain imaging studies that link several significant psychiatric syndromes to a dysfunctional endogenous opioid system that may respond positively to exogenous opioid administration in the context of chronic opioid therapy. In effect, these new research findings indicate that treatment with opioids is producing a neuro-modulatory effect that is far beyond the consequences of mere analgesia and/or sedation, and clearly crosses over into the territory of practical psychopharmacological treatment found most commonly in the practice of psychiatry/neuropsychiatry.

History of Opioids and Their Use in Psychiatric Disorders

Above and beyond their applicability to analgesia, opioids have been shown to be effective in non-psychiatric, non-chronic pain disorders such as the treatment of restless leg syndrome, which is clinically characterized by a cognitive urge to move associated with sensory sensations deep within the legs and feet.6 But it is the role of opioids in the treatment of psychiatric disorders that deserves more attention.

Opioids demonstrate mood-elevating effects in healthy subjects and they have been used successfully to treat refractory depressed patients.7 The opioid system has been implicated in the mechanism of action of anxiolytic/antidepressant drugs such as benzodiazepines and the SSRI/ SNRIs via opioid neurotransmission pathways which have reciprocal connections with GABAergic interneurons, and with endogenous opioid/5-HT release being modulated by 5-HT signaling.8 But mood stabilization via the use of exogenous opioids is certainly nothing new.

The use of opium for “melancholia” and “mania” may be traced to ancient classical medicine. The earliest recorded use of opium was by the Sumerians in Mesopotamia in 3400 BC. They named the poppy the ‘joy plant.’ The antidepressant effects of opium were so beneficial that Hippocrates (460–377 BC), the historic father of medicine, and his successor Galen (AD 129–200) both prescribed opium for the treatment of depression and anxiety, among other ailments. In Europe in the 1700s to 1900s, particularly in Germany, opium was considered the most appropriate remedy against melancholias marked by depression with agitated mood.9

Opium’s use in American psychiatry reached a peak in the middle of the 19th century, when many physicians considered it to be the greatest pharmaceutical aid that psychiatry had available—but also as a cause of mental illness in the form of “morphinomania.”10 Nevertheless, opiates were used to treat major depression in the United States until the mid-1950s.11

But it wasn’t until the 20th century that the true scientific study of the mood and behavioral effects opioids/opiates commenced. Clinical and preclinical studies in this field have included the anti-depressant, antipsychotic, and mood stabilizing effects of enkephalins,12 beta endorphins,13 kappa-opioid ligands,14 and delta-opioid receptor agonists.15 Some of these psychoactive substances provide impractical alternatives for physicians treating psychiatric disorders as they generally involve the use of intravenously-administered opioid peptides. However, studies exist which have examined the use of more commonplace prescription opioids in psychiatric treatment.

The mu-opioid agonists such as morphine, oxycodone, oxymorphone, and hydrocodone have been shown to demonstrate sustained, robust, antidepressant, mood stabilizing, and antipsychotic effects without concomitant opioid abuse/tolerance—or the use of illicit substances.16-18 Buprenorphine has been shown to demonstrate significant im-provement in both subjective and objective measures of depression, including complete remission in subjects with treatment refractory depression.19 Tramadol has been shown to achieve comparable clinical efficacy comparable to antidepressants, without aberrant behavioral implications.20,21 And it has been shown that low dose, long-acting opioids can lessen agitation that is difficult to control in patients with advanced de-mentia, and that this decrease in agitation in these patients persisted after adjusting for sedation.22

The use of morphine for combat-related injuries during early resuscitation and trauma care was found to be associated with a significantly lower risk of developing PTSD after adjusting for injury severity, age, and mechanism of injury. Thus opioid pharmacotherapy in the aftermath of serious physical injury or exposure to traumatic events may be effective for the secondary prevention of PTSD.23

In bipolar disorder patients, opioid analgesics—especially hydrocodone—can precipitate a hypomanic/manic reaction and have an antidepressant effect in others.24 And before the non-psychiatrically-inclined pain practitioner winces at the thought of inducing hypomania in their occult, bipolar pain patients, consider what it would be like to deal with a desperately depressed/anxious bipolar pain patient. They may have come to realize that a touch of hypomania can provide unqualified relief for both the patient and their treating physician.

Unfortunately, the vast majority of patients with treatment-resistant psychiatric disorders will never receive a trial of treatment with an opioid medication for several reasons. The first is that most psychiatrists (and most physicians for that matter) suffer from a lack of knowledge of pain management and/or current research/clinical guidelines for the appropriate treatment of pain25—let alone opioid treatment for psychiatric disorders. Secondly, most pain management physicians may not have the necessary neuropsychiatric expertise/experience or the time necessary to integrate psychiatric and chronic pain aspects into the treatment protocol for their dually-diagnosed patients. Thirdly, and most unfortunately, one of the most significant barriers to adequate treatment with opioids is the fear of punitive action against a physician who prescribes opioids for patients.26

In any event, it must be accepted that in spite of the risks of abuse/addiction, the treatment of patients using opioids for pain relief purposes nevertheless results in neuro-pharmacological modulation that can result in beneficial effects on mood, behavior, and cognition. As such, “morphinomania”—which in all likelihood encompasses the syndromes of addiction, pseudoaddiction, maintenance and “non-medical” use—represents the use of exogenous opioids for the treatment/self-medication of innate neuropsychiatric illnesses and their attendant symptoms.

It is accepted that neuropsychiatric disorders have a basis in abnormal brain morphology including pathological struc-tural and functional alterations of limbic and cortical/subcortical structures27,28 and, quite clearly, neurotransmitter dysfunction.29 And so what is the scientific evidence that buttresses the contention that the endogenous opioid system is intimately involved with the regulation of mood/behavior? Several exceptional brain imaging studies in this regard are described in the following section.

Brain Imaging Evidence of Endogenous Opioid Regulation of Mood and Behavior

Placebo Effect. The placebo effect in medicine refers to an improvement in function or a reduction of symptoms that occurs with the administration of a “pleasing intervention” – the placebo itself. Placebo analgesia involves the endogenous opioid system, as administration of the opioid antagonist naloxone decreases placebo analgesia.30 Among psychiatric disorders, the placebo effect has been most extensively studied in depression, and it has been demonstrated that improvements which occur as a result of placebo in depression tend to occur early in treatment, be abrupt, and be less likely to persist.31 Nevertheless, the placebo effect has been shown to demonstrate robust beneficial clinical effects in various disease states, albeit for a shorter period of time.

Neuroimaging studies have elucidated how and where in the human brain the placebo effect occurs. Positron emission tomography has demonstrated that both opioid and placebo analgesia are associated with increased activity in the anterior cingulate cortex32 and the dorsal lateral and ventral lateral prefrontal cortices33—all brain regions which are intimately involved in the genesis of psychiatric disorders.

Fibromyalgia Spectrum Disorders. Perhaps no other chronic pain diagnosis bridges the gap between the purely somatic and the psychiatric as much as fibromyalgia. Fibromyalgia is a complex musculoskeletal disorder characterized by widespread and long-lasting pain. The often overlooked yet serious neuropsychiatric symptoms of this disorder can include: marked fatigue, sleep disorders, cognitive disturbances, mood and anxiety disorders, paresthesias, headache, and irritable bowel syndrome. Because of these symptoms, many consider fibromyalgia to be a genuine neuropsychiatric disorder, first and foremost.

Positron emission tomography of mu-opioid receptors in fibromyalgia patients has demonstrated that they exhibit reduced mu-opioid receptor binding potentials within structures typically observed in imaging studies of experimental pain involving healthy controls.34 These structures included the amygdala, the cingulate gyrus, and the nucleus accumbens—all structures vitally important in memory, learning, mood control, and the neuro-behavioral effects of drug abuse.

Depressive Spectrum Disorders. Posi-tron emission tomography (PET) of mu-opioid receptors has also shown that active changes in mu-opioid neurotransmission occur in response to experimentally-induced negative affective states, thus substantiating the role of the mu-opioid receptor system in the neurophysiological regulation of affective experiences in humans. Further, PET imaging has also shown that sustained sadness was associated with a significant decrease in mu-opioid binding potential in the left inferior temporal cortex of patients with major depressive disorder. These findings clearly show that endogenous opioid neurotransmission on mu-opioid receptors is altered in patients diagnosed with major depressive disorder.35 These findings help explain why some of our chronic pain patients report improved mood and/or remission from depression when treated with opioids, above and beyond any reduction of their pain symptoms.

Part of the spectrum of depressive disorder syndromes includes symptoms of social withdrawal resulting in subjective psychological pain. Scientific evidence indicates that the psychic pain resulting from broken social ties may arise from the same neurological substrates that are involved in the unpleasant experience of physical pain. Functional MRI imaging has demonstrated that a particular polymorphism of the mu-opioid receptor gene was associated with individual differences in sensitivity to social rejection. This mu-opioid receptor polymorphism was also associated with differential neural activity in the dorsal anterior cingulate cortex and insula—both areas known to be the principal sites of activation during a social rejection experience.36 These findings help explain why some of our chronic opioid therapy patients maintain that they function better socially while taking their pain medications (again, separate from the effects of analgesia) and is contrary to the notion that that these individuals are simply using the sedative effects of their opioids to cope with stressful social situations or that they are misusing their opioid medications in a social setting.

“Endogenous opioid receptors are not only partially responsible for various aspects of cognition and mood control, but endogenous opioids also play a key role in the modulation of temperament and personality.”

Impulse Control Spectrum Disorders. Positron emission tomography studies measuring endogenous opioid neurotransmission have demonstrated that individual differences in the function of the endogenous mu-receptor system predict personality traits that confer vulnerability to, or resiliency against, risky behaviors and that these effects were obtained in the prefrontal and orbito-frontal cortices, anterior cingulate, thalamus, nucleus accumbens, and the amygdale—all regions involved in motivated behavior, cognition, and the effects of drugs of abuse.37 And so now the trend becomes more clearly visible. Endogenous opioid receptors are not only partially responsible for various aspects of cognition and mood control, but endogenous opioids also play a key role in the modulation of temperament and personality. That helps to explain the difficulties we pain practitioners experience with our most difficult chronic pain patients and their seeming proclivity for risk-taking behaviors.

Borderline Personality Spectrum Disorders. In the 2002–2004 National Survey on Drug Use and Health among patients with past-year non-medical prescription opioid use, those with abuse/dependence were more likely to suffer from co-morbid symptoms of panic disorder and social phobia/agoraphobia symptoms.38 Interestingly, it has also been demonstrated that CSF beta endorphin levels are positively associated with anxiety symptoms in normal subjects but not in those with panic disorder,39 further indicating a role for the endogenous opioid system in the modulation of anxiety. And indeed, there are significant neuro-psychiatric similarities between the symptoms of the human opiate withdrawal state and anxiety disorders symptoms in general.

Pain practitioners will have already noticed that the anxious patient can become a desperate patient; and desperate patients have an increased risk of becoming aberrant patients. In pain management we have been ingrained to be on the lookout for the mind numbingly, terrifying individual known as the “aberrant patient.” These patients, by definition, can be anxious, irritable, labile, manipulative, threatening, and even abusive towards the pain practitioner. These patients share many similarities with patients in the opioid withdrawal state who manifest characteristic autonomic and somatic symptoms—including dysphoria, restlessness, hyperirritability, and anxiety. These defining behavioral characteristics are also hallmarks of the borderline personality spectrum of psychiatric disorders which are characterized by a lack of affective regulation of emotional responses. And it is with this spectrum of disorders that some of the most recent neuroimaging findings demonstrate a clear link between endogenous opioid dysfunction and the cognitive and emotional regulation of behavior.

Positron emission tomography of mu-opioid receptor availability in female patients with borderline personality disorder versus controls has demonstrated that borderline patients showed greater regional mu-opioid binding potential than did comparison subjects in a mood-neutral state, especially in the orbito-frontal cortex. In particular, the emotion of sadness was associated with activation of the endogenous opioid system in the anterior cingulate, orbitofrontal cortex, temporal cortex, and the amygdala. En-dogenous opioid system deactivation was seen in the nucleus accumbens, hypothalamus, and hippocampal regions relative to comparison subjects. The conclusion that can be inferred is that differences exist between borderline personality disorder patients and comparison subjects regarding their mu-opioid receptor concentrations and their endogenous opioid system response to negative emotional challenges.40 And it is neuroscientific findings such as this which clearly indicates that a significant proportion of the affective instability displayed by chronic pain patients reflects an endogenous opioid system that is overtaxed and/or dysregulated regarding its innate analgesic and affective control functions.

Clinical Management of Chronic Pain and Psychiatric Disorders

Why do chronic pain patients have a higher prevalence of co-morbid psychiatric disorders and why are mental health disorders associated with the prescription of opioid medications and “opioid abuse” in general? The answer may have something to do with the interesting scientific finding that chronic pain, in and of itself, can cause degenerative brain changes41 and that chronic pain may play a role in the genesis of certain cognitive and behavioral disorders.42

The major reason chronic pain patients have a higher prevalence of co-morbid psychiatric disorders is because opioid ligands and receptors are neuro-anatomically located in essential central nervous system locations that are responsible for controlling the expression of anxiety, cognition, and emotional regulation. Furthermore, their role in the regulation of affect has been demonstrated via brain imaging and other scientific studies that have shed light on the role of endogenous opioid functioning during the experience of various affective states in humans including depression, anxiety, panic, PTSD, obsessive-compulsive disorder, psychotic disorders, impulse control disorders, and substance abuse disorders.

The idea that dysregulation of the endogenous opioid system underlies the propensity to exhibit aversive emotional responses or specific dysfunctional personality traits has arrived. The pain practitioner may have previously come to this conclusion after conscientious reflection regarding the range of dysfunctional affective and behavioral symptoms exhibited by his/her chronic pain patients and the beneficial effects that prescribed opioids have had on those symptoms—with and without the concomitant administration of anti-depressant and/or mood stabilizing agents.

As such, the careful and knowledgeable pain practitioner has the unique opportunity to “lead the way” medically regarding the amelioration of a host of neuropsychiatric disorders. These include syndromes associated with a dysfunctional endogenous opioid system that may respond to exogenous opioid administration in the context of chronic opioid therapy. The benefits of the use of opioid medications for the management of psychiatric disorders in chronic pain patients should obviously outweigh the risks and, practically speaking, this risk/benefit analysis should be the same as that for any other chronic pain patient. The question then becomes how to appropriately implement this treatment modality.

Guidelines for the Treatment of Psychiatric Disorders Utilizing Opioid Medications

If opioids are to be used to treat psychiatric disorders alone—and/or those patients with concomitant chronic pain disorders—then several guidelines should be followed by those treating physicians and allied health professionals that go beyond those recommended singularly for chronic pain patients.


The pain practitioner must educate himself/herself regarding the neuroscience of opioids so that they can competently prescribe these medications for use in psychiatric and chronic pain syndromes. At a minimum, the treating health care professional should be aware of some of the more common medical side effects of the opioids including the neuroendocrine effects (i.e., low testosterone via chronic opioid administration is a known cause of depression), and general medical side effects—such as cardiac dysrhythmias which may or may not be a risk factor for methadone and seizures (i.e., meperidine). Basic knowledge of the neuropsychiatric effects of the exogenous and endogenous opioids is a mandatory prerequisite.


This goes without saying. The most common risks, benefits, and alternatives of the opioid medications—for any use—must be addressed and documented with the patient. With opioids, the risks for opioid induced hyperalgesia (if it can ever truly be clinically significant), physical dependence, pseudo-addiction, addiction (though the risk is statistically small), and misuse/abuse must be strongly communicated to the patient in an ongoing yet non-judgmental manner. Of course, any anxieties the patient may have regarding the issues of physical dependence, pseudo-addiction, and addiction can be greatly alleviated by educating them about the wealth of scientific knowledge regarding the existence of, and the role that endogenous opioids play in the manifestation of these syndromes—and how the careful administration of exogenous opioids can effectively ameliorate their associated symptoms.

Risk Factors

Of the many risk factors that must be addressed with patients for proper consent to be achieved is the potential for hazardous drug interactions between the patient’s prescribed opioids and/or other medications and substances of abuse, including alcohol. Patients must be warned about the cumulative sedating effects that can occur when opioids are concomitantly ingested with many different substances—especially the psycho-tropic medications. For instance, even though the benzodiazepines are not, and should not be, contraindicated for use with opioid medications—as the anxiolytic affects of benzodiazepines and the muscle relaxants, in many cases, can reduce the need for higher doses of opioid medications in certain chronic pain patients—it must be stressed that intoxication with these medications, alone or used together, is always a possibility. And, of course, the risks of concurrent heavy alcohol use/abuse or the use of any legal or illegal substance concurrently with prescribed opioid medications always includes the possibility of accidental overdose/death.

Parenthetically, many pain practitioners are already secondarily modulating their patient’s neuro-psychiatric symptoms while treating their pain when they prescribe pain-modulating psychotropic medications such as the anti-depressants (i.e., milnacipran, duloxetine, amitriptyline, nortriptyline etc.) and the anti-convulsants (i.e., pregabalin, gabapentin, valproate, etc.). The careful pain practitioner must always be aware of the risk for suicide with any of the psychotropic medications—but especially in their chronic pain patient population that is already at risk for symptoms of dysphoria and desperation.

Risk Management of Abuse/Misuse

The safe and effective use of opioids for improving health and easing suffering of psychiatric and/or pain management patients is inextricably intertwined with the management of risk and the careful pain practitioner will, at all times, consider the risk of abuse/misuse with each and every chronic pain and/or psychiatric patient.

Abuse monitoring can only be accomplished by frequent contact with the patient. In these days of economic hardship and skyrocketing fuel costs, bimonthly and even monthly visits may be very difficult for most patients—not just those in rural areas. In high-risk patients, the hardship of frequent visits such as these may still be required. However, in those patients who have (for the time being) proven their trustworthiness/ responsibility regarding their opioid medications, comprehensive visits every month, two months or rarely three months, are prudent.

It is important during these visits to be non-judgmental and certainly non-accusatory—unless the circumstances warrant. However, recurring inspection of medication bottles and the identification and tabulation of their contents is an excellent idea. Patients receiving chronic opioid therapy can have pill counts that meander from their prescription instructions as they experience peaks and valleys regarding their pain and neuropsychiatric symptoms. However, adulteration of medication bottle contents to pass the pain practitioner’s pill count is intolerable and warrants discharge.

Random urine drug screens are also important. Although they cannot tell us about the serum levels of particular prescribed medications, they can obviously inform the pain practitioner about patient compliance with their treatment medications and the presence of any unauthorized legal or illegal substances. The pain practitioner must remember, however, that urine drug screen results are certainly not infallible, and unusual findings must be confirmed or repeated and then addressed with the patient—before they are summarily discharged.

When possible, the involvement of family and/or friends of the patient is extremely desirable. It is they who will usually provide the pain practitioner with the first early warning signs of untoward opioid effects on the patient, and/or signs of opioid abuse/misuse. Sometimes this family/friend interaction in the pain practitioners’ office can be heated, uncomfortable, and even confrontational but this type of communication with the patient receiving chronic opioid therapy and their significant others is always educational. And, in this way, the pain practitioner can more objectively assess the positive and negative effects of the opioid treatment, and concurrently monitor the patient for the continuous possibility of abuse/misuse/diversion.

“The safe and effective use of opioids for improving health and easing suffering of psychiatric and/or pain management patients is inextricably intertwined with the management of risk and the careful pain practitioner will, at all times, consider the risk of abuse/misuse with each and every chronic pain and/or psychiatric patient.”

Finally, the pain practitioner must take every report of abuse/misuse regarding their chronic opioid treatment patients seriously. Some of these reports can be malicious in nature, such as when the chronic opioid therapy patient refuses to give another individual some of their medication causing that individual to retaliate by contacting the pain practitioner with a fallacious report of medication abuse/misuse. Nevertheless, the careful pain practitioner must remember that sometimes where there’s smoke, there is indeed fire.

Opioids: Start Low and Work-Up Slow

The rule of thumb with opioid medications is to start low and, only if needed, increase the dose slowly. Obviously, because of the many complicated neurochemical actions that the opioids modulate within the human central nervous system, the chance of untoward or idiosyncratic reactions is always possible. The greatest step one can take to mitigate these possible outcomes is to start with low doses of any opioid medication. With non opioid-naïve patients, sudden, sizeable increases or decreases in medication dosages should also be avoided. In any event, in most cases, the mood stabilizing effects of opioids tend to occur at the lower end of the dosing spectrum. It is usually the frequency of administration of the opioid medication that may vary from patient to patient, and the experienced pain practitioner will know that more frequent dosing may be required for efficacy in some patients due to the vicissitudes of individual opioid receptor polymorphisms and unique cytochrome P450/2D6-modulated opioid responses, among other factors.

Document the Efficacy of Treatment

Documentation of the patient’s psychiatric and/or pain symptom responses to the prescribed opioid medication(s) is a must. Listen to the patient carefully. This takes significant face to face time. Ask about the patient’s mood and cognitive responses to their opioid medications. Listen for clues regarding abuse such as the patient (hopefully) being honest and admitting to the fact that they are only taking their medication to “get high” or to “party.” Look for the physical signs of substance abuse and keep in mind that these abuse “behaviors,” in and of themselves, also represent complex neurobehavioral aspects of the endogenous opioid system within the human brain. The ultimate treatment goal is mood and cognitive stabilization. As such, the feedback that the pain practitioner is looking for from psychiatric patients—with or without chronic pain disorders—would be more akin to: “Doctor, I feel more psychologically normal when I am taking my pain medicine.”

Don’t Panic!

This is a phrase from Douglas Adams’ popular science fiction novel, “The Hitchhiker’s Guide to the Galaxy.” Chronic opioid therapy for the management of pain and/or psychiatric disorders is fraught with risk. But so is the practice of medicine in general. If the pain practitioner does not feel comfortable managing psychiatric symptoms due to endogenous opioid dysfunction, then they should not do so. However it is their responsibility to refer that patient to where they can receive appropriate evaluation and treatment for their con-dition(s). Second opinions can always be obtained, but for the pain practitioner who is aware of endogenous opioid dysfunction with psychiatric co-morbidities and is amenable to treat it, there is no better course of action for the initiation of patient treatment than to fully educate oneself on the topic of endogenous opioid dysfunction and its implications for the treatment of psychiatric syndromes in both psychiatric and chronic pain patients. Doing this will significantly mitigate any disabling pain practitioner anxiety; hence the phrase, “Don’t Panic!”

A Final Thought

Always keep in mind the words of the late president, Ronald Reagan, who regularly stated, “Trust but verify.”


The scientific principles of endogenous opioid dysfunction are now a clear reality. Therefore the pejorative mislabeling and mischaracterization of those chronic opioid therapy patients who experience positive mood/cognitive stabilizing effects from their opioid medications, is distasteful, unethical and unacceptable. As such, the paradigms of addiction, non-medical use, pseudoaddiction and maintenance regarding opioid therapy will have to be re-evaluated in the future. In the meantime, psychiatric endogenous opioid dysfunction syndrome (PEODS)—having predominantly depressive, anxious, obsessive/compulsive, impulsive or mood instability features—can be used to document the diagnosis or presence of neuropsychiatric disorders that arise in whole, or in part, due to endogenous opioid dysfunction.

Opioid medications can therefore be considered reasonable treatment options in carefully selected patients who are psychiatrically desperately ill and who have not responded to typical neuropsychiatric medications or other treatments. Of course, confounding factors such as gene polymorphisms predicting individual sensitivity to opioids, peculiar individual cytochrome P450/2D6-modulated opioid responses, pharmacokinetic differences among individual opioid medications reflecting their respective molecular idiosyncrasies, or potential manifestation of drug abuse behaviors—whatever their final neurological/neuropsychiatric origins may be—must all be considered when the mood and cognitive stabilizing effects of opioids are put into practical medical use. Nevertheless, functional neuroimaging techniques are further substantiating the age-old use of opioids for the treatment of disorders arising from psychiatric endogenous opioid dysfunction syndrome.

Last updated on: January 5, 2012
close X