Opiates, Mood, and Cognition

Today opiate painkillers are prescribed more and more frequently. The Centers for Disease Control (CDC) figures show a 300% increase in prescription opiate pain medications since 1999. The CDC also states that almost 2 million people in the US either abused or were dependent on these agents in 2013. Opiate pain medications include hydrocodone, oxycodone, morphine, codeine, and others. They are sold under familiar brand names such as Vicodin, Norco, Percocet, Oxycontin, and MS Contin. There is absolutely no question that these medications are highly effective in treating acute pain, such as that after trauma or a surgery, and also in treating pain associated with cancer. In fact, in patients with terminal illnesses with significant pain, they may be underutilized, resulting in unnecessary suffering. Yet, in patients with chronic, non-cancer pain (such as low back pain), these medications have significant side effects that may result in changes in mood, memory, coordination, and even basic functions such as breathing and gastrointestinal activity. For this reason, many authorities, including the CDC, are calling for a reassessment of opiate prescribing for chronic, non-cancer pain. I’ll discuss some of the pros and cons of these medications from a psychiatric perspective.

A major psychiatric concern with opiates is their tendency to cause substance induced mood disorder and substance induced cognitive disorder. This means that after taking a “substance” such as a prescription medication, street drug, or even alcohol for an extended period, the person develops a mood disorder, usually depression, or a cognitive disorder, meaning their memory and ability to carry out complex tasks becomes impaired. For opiates, there is striking new evidence from an epidemiologic study that long term use results in depression. Scherrer and colleagues (Ann Fam Med 2016; 14:54-62. doi: 10.1370/afm.1885) studied the records of over 100,000 patients. They found that the longer a person takes opiate pain killers, the greater the risk of depression. Interestingly, the opiate dose was less important than the duration of treatment in predisposing to depression. Sometimes patients with pain experience a temporary improvement in mood when starting opiates, because their pain is decreased. However, these new data show that long term use can readily lead to depression.

How does long term opiate use cause depression? Opiates decrease activity in nervous system overall, and in fact high doses of opiates will cause sedation and even loss of consciousness. Chronic opiate use may decrease activity of key nerve cells involved in regulation of mood and hence lead to depression. To correct this situation, the opiates should be stopped, so the activity of the nervous system can return to normal. This allows the mood to return to a normal, baseline state.

Sometimes antidepressants are prescribed to treat depression in heavy opiate users, without stopped or decreasing the opiates. This approach is unwise. Because opiates alter brain function, antidepressants cannot exert their therapeutic action as they otherwise would do. Further, combining opiates with antidepressants, many of which have side effects such as sedation, can result in potentially dangerous and unpredictable drug interactions. For example, opiates can potentiate the serotonergic actions of common antidepressants such as fluoxetine, leading to a toxic state. In the case of monoamine oxidase inhibiting antidepressants, interactions with opiates can be fatal. In general, “polypharmacy” with drugs acting on the central nervous system is unwise. A far better strategy is to “deprescribe” the opiate, and then see if the mood returns to normal. If not, then an antidepressant, or psychotherapy, or both, may be given.

Another concern with long term opiate use is negative effects on cognition. Cognition encompasses a variety of brain functions including memory, attention and concentration, orientation to place and time, language skills, calculations, planning and foresight, and others. In some patients with significant pain, it appears that opiates can improve cognition by allowing them to focus their thinking rather than being distracted by pain. On the other hand, opiates inhibit awareness and cause sedation, so other patients, particularly elderly ones, may experience a marked decline in cognition with chronic opiate use. Fortunately, this cognitive change is reversible when the opiates are discontinued. Before a patient with cognitive changes were diagnosed as having an irreversible disorder such as Alzheimer’s disease, it is essential that sedated medications such as opiates be discontinued to see if cognition improves.

Even without opiate use, many patients with chronic, non-cancer pain experience depression. There appears to be a two-way vicious cycle: the greater the pain, the more the discouragement and depression. And, the lower the mood gets, the more readily the pain sensations enter into awareness. This is a key point: low mood increases pain awareness. Improved mood results in decreased pain awareness, even if the physical basis for the pain, for example disk disease in the spine, has not changed. When chronic opiate use is added to the mix in a patient with chronic pain and depression, the mood can plummet to dangerous levels – suicidal thoughts may arise, which are particularly concerning when a ready means for self-harm such as opiates are at hand.

Thus, there are definite advantages to discontinuing opiates if you are experiencing depression, forgetfulness or other changes in cognition, or side effects such as chronic constipation or incoordination and falls. Or, if the opiates are no longer alleviating pain, or if you find yourself on a never-ending cycle of increasing pain and increasing dose. However, as many people have found, opiates can induce a psychological and even a physical dependence. Although we may imagine that only users of street opiates like heroin experience an unpleasant withdrawal syndrome when they quit, this also occurs when discontinuing prescription opiates abruptly. Yet, it is possible to gradually wean completely off prescription opiates if you receive the proper support and medical supervision, as well as alternative medical and non-medical means of managing the pain disorder that resulted in the original opiate prescription. I’ll discuss these approaches in a future blog.

Strangely, although there is ample evidence of overprescribing of opiate pain medications for chronic, non-cancer pain, there is also concern that in the case of the terminally ill, particularly those with cancer, in many cases opiates are under-prescribed. This has prompted state medical boards, such as that in California, to mandate education for physicians on end of life issues and appropriate, humane use of opiates in terminally ill patients. It is a paradox that opiates may be under-utilized in terminally ill patients out of concerns for addiction or abuse, whereas for patients with chronic pain, which many times can be adequately treated by non-pharmacologic means, opiates are over-utilized.