Use of Opioids in Pain Patients with Psychiatric Disorders
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.