Medscape: Pain often is seen concurrently with depression and fatigue such
that the 3 are referred to as a symptom cluster. Are there other symptom
clusters associated with chronic pain?
Bill McCarberg, MD: Yes, anxiety and insomnia are seen with chronic pain.
Depression, anxiety, and insomnia are also seen with substance abuse in the
chronic pain patient. substance abuse is a diagnosis and not a symptom and
has a whole variety of symptoms that come along with it; for example,
inappropriate drug-taking behavior. But if you're just looking for a symptom
complex associated with chronic pain, then anxiety and insomnia would be
very prominent. If you have fatigue, the fatigue relates to the pain itself,
so you can have fatigue without insomnia and you can have fatigue related to
Medscape: How do you typically treat the anxiety and insomnia found with
Dr. McCarberg: If the depression and the anxiety come together, then you
treat the depression and the anxiety often goes away. Treating the pain
frequently relieves the anxiety. A patient who has an underlying anxiety
disorder may be able to control their anxiety through exercise or
maintaining a busy job. Their anxiety may not manifest itself because they
are functional. Once they have a chronic pain condition, the anxiety becomes
more obvious because they cannot use other coping skills to take care of it.
In addition, people who are generally not anxious who develop a chronic pain
problem may become anxious. Chronic pain may lead to unemployment and family
and financial stress that can produce anxiety in a typically non-anxious
With regard to treatment, if a patient has depression and anxiety, then
usually a good treatment for depression, such as an SSRI [selective
serotonin reuptake inhibitor], will take care of the anxiety. If it's
strictly a panic disorder, then you treat the panic disorder, using similar
drugs that are used to manage depression. If, for example, the anxiety is
due to inactivity, getting people active again can release their endorphins
and get the anxiety taken care of.
Cognitive behavioral strategies are often useful in managing depression,
anxiety, or insomnia in a pain patient. For example, if a patient is
complaining of insomnia, you could use a sleeping aid, a sedative hypnotic,
or you could give the patient sleep hygiene measures, which include always
go to bed at the same time, make sure the bed is only for sleeping, not for
watching TV, eating, reading a book, so that the bed becomes a place that
you know you're just going to relax.
If your pain patient is having trouble sleeping, review the sleep hygiene
methods found at
Medscape: This symptom triad we discussed is prevalent in patients with
cancer-related pain, but how prevalent is it in patients with chronic
Dr. McCarberg: Yes, depression, anxiety, and sleep disorders are very common
depending on what clinical setting you're in. If you're in a pain clinic
which is in a tertiary care center, depression can be as high as 80%. If
you're in a primary care clinic and you're seeing the patient for the first
time, there is a 20% chance the patient will have depression. Anxiety would
be very closely paired to that. Almost all patients with chronic pain have a
sleep disorder of some sort, so that can be as high as 100%.
A literature review study by David Fishbain's group[1,2] has shown that
there is a statistical relationship between pain and depression. Depression
is more common in chronic pain patients than healthy controls as a
consequence of the presence of chronic pain. The psychiatric and somatic
comorbidities seen in chronic pain are shown in Table 1
<http://www.medscape.com/viewarticle/572303_Tables#T1> and Table 2
<http://www.medscape.com/viewarticle/572303_Tables#T2> , respectively.
The psychiatric and somatic comorbidities associated with chronic pain are
managed with a psychopharmacologic polypharmacy approach. Polypharmacy is
necessary in this patient population due to the frequency of less than
acceptable response to monotherapy, both for pain and for depression.
Medscape: Some studies have shown that increasing pain causes increasing
symptoms of depression. Can you comment on the impact of pain on depression
and vice versa?
Dr. McCarberg: Pain makes depression worse, depression makes pain worse and
this relationship appears to be independent. Ed Covington's group has
published extensively on this. Many of the symptoms of depression
are seen in chronic pain. Daytime fatigue, insomnia, for example, those are
symptoms of depression and of chronic pain. Anhedonia, (lack of interest) ,
you find that in people who are not depressed, who have chronic pain. So
oftentimes it's difficult to figure out what symptoms are coming from
depression, what symptoms are coming from the chronic pain. Do they
intermix? We know for certain that as depression increases, chronic pain
increases. We know for certain as chronic pain increases, depression
Medscape: How does depression complicate the presentation and clinical
course of chronic pain?
Dr. McCarberg: In primary care it is difficult to sort out depression and
pain. Since the hallmark symptoms for depression (mood, fatigue/sleep, and
anhedonia) are the same symptoms of chronic pain, it is difficult for the
primary care doctor to differentiate the two. The primary care doctor feels
then that depression is causing the chronic pain. It is known that some
patients do not fit the criteria for depression, yet with chronic pain, they
look like they are depressed. It is the chronic pain causing the depressive
symptoms. Treating the pain improves depression; treating the depression can
improve function in pain patients.
Medscape: What is the significance of the pain-depression-fatigue symptom
Dr. McCarberg: Depression and fatigue may be a natural consequence of
chronic pain or there may be a pathophysiologic link to this cluster. If you
do PET [positron emission tomography] scans, depression and chronic pain
light up similar areas of the brain and the same neurotransmitters
(serotonin/norepinephrine) seem to be involved in both. Figures 1 and 2
describe how pain and depression may be linked at the neurochemical level.
<http://images.medscape.com/images/572/303/art-572303.fig1.gif> Click to
Figure 1. (click image to zoom)
Emotional and painful physical symptoms: a shared neurochemical link in
depression? 5-HT = serotonin; NE = neuroendocrine; GABA = gamma-aminobutyric
acid; GLU = glutamate
<http://images.medscape.com/images/572/303/art-572303.fig2.gif> Click to
Figure 2. (click image to zoom)
Depression and chronic pain link. 5-HT = serotonin; NE = neuroendocrine;
GABA = gamma-aminobutyric acid; GLU = glutamate
Dr. McCarberg: There is a whole variety of psychiatric diagnoses, including
obsessive compulsive disorder, clinical depression, bulimia, that are
associated with areas of the brain that are similar. There are a variety of
chronic, not psychiatric, but medical problems, including chronic headaches,
irritable bowel, irritable bladder, fibromyalgia, that light up similar
areas of the brain that are dependent upon serotonin and norepinephrine.
There's this whole theory that maybe these are kind of different
presentations of the same disease. The affective spectrum disorders, which
may all share a neurochemical basis, are listed in Table 3
Medscape: Does the presence of depression or fatigue affect the frequency,
character, and intensity of breakthrough pain?
Dr. McCarberg: There was a study published in 2006 that was done in Denmark,
where they were looking at the rates of breakthrough pain and they realized
that it was significantly associated with higher scores of anxiety and
depression. The average pain intensity is associated with anxiety and
So the important thing is, we've already identified that breakthrough pain
and depression go together. The problem from a clinical point of view is
that we see people who come in and say that they overuse their medication
because something stressful happened in their life. As clinicians we then
judge the patient as inappropriately taking their medicine. When Grandma
comes to visit and there's more disruption in the family, that's not a
reason to be taking more medication for pain. We know that a disruption in a
daily routine, such as a relative visiting, increases pain levels and it
would make sense for people, if their pain level goes up, to take more pain
medicine. Our judgment is that they're treating their anxiety, their
situational stress, with a pain medicine, our judgment is that they're not
taking it for the right reasons. Actually it's not inappropriate to take
more pain medicine when their pain is increasing. Now they should treat the
situational anxiety with other coping skills. They should have family
members help out, they shouldn't do all the work themselves, they should
make sure that all the family stressors are identified early and that
somebody intervenes to help with the stress. So those are all actually very
good reasons not to take a pain medicine. However, in reality, most of these
things are not controllable and people's pain levels do get higher. When we
talk about breakthrough pain, we talk about it being related to overdoing
activities, we talk about it being idiopathic, unpredictable, we talk about
it being "end-of-dose" breakthrough pain. In reality, when people get
stressed and their pain levels go up, that is kind of an incident
breakthrough pain. When people go out and exercise more or do more activity,
we are perfectly willing to give them medications for that, before you go
shopping and you stand all day on your feet, you may want to take some pain
medicine. But if we say, gee, your family is going to come over for the
week, you may need more of your opioid to treat your pain, we're not willing
to do that, which is kind of a conundrum because we know situational stress
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Pain and Depression
Medscape: Pain often is seen concurrently with depression and fatigue such
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