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Chronic pain and depression
A Surah MBChB FRCA MRCS
G Baranidharan PG Dip (Anaes) FRCA FFPMRCA
S Morley BSc (Hons) MPhil (Clinical Psychology) PhD FBPsS
Key points
Chronic pain and depression
are common causes of
morbidity.
Coexistence of the two
conditions is underestimated
and poorly understood.
When the two conditions
are comorbid, outcomes are
worse.
Serotonin and
norepinephrine are thought
to play a key role in the
association, but the exact
mechanism is unclear.
Management can be difficult
and a multi-disciplinary
approach is vital.
A Surah MBChB FRCA MRCS
Specialist Registrar in Anaesthesia
Leeds Teaching Hospitals NHS Trust
D Ward, Seacroft Hospital
Leeds LS14 6UH
UK
G Baranidharan PG Dip (Anaes) FRCA
FFPMRCA
Consultant in Anaesthesia and Pain
Medicine
Leeds Pain and Neuromodulation Centre
Leeds Teaching Hospitals NHS Trust
D Ward, Seacroft Hospital
Leeds LS14 6UH
UK
Tel: þ44 113 2063128
Fax: þ44 113 2063144
E-mail: [email protected]
(for correspondence)
S Morley BSc (Hons) MPhil (Clinical
Psychology) PhD FBPsS
Professor of Clinical Psychology
Room 1.13 Charles Thackrah Building
University of Leeds
Leeds LS2 9LJ
UK
85
Chronic pain and depression
Depression and chronic pain are becoming increasingly common and important causes of
morbidity in the Western world. Pain is the most
common complaint in outpatient clinics; with
back pain alone accounting for up to 20% of the
UK’s health expenditure.1 Depression is the
third most common reason for consultation with
a GP and the most common mood complaint.
The prevalence of chronic pain is variably
estimated at 8–60% depending on the definition
of chronic pain used.2 In the UK, 6% of the adult
population per year will experience a depressive
episode and one-third of the population will at
some point experience a depressed mood that
interferes with their daily activities. The prevalence of depression in the primary care setting is
between 5% and 10%.
The conditions are very closely linked, but the
association is complicated and is often underestimated. Between 40% and 60% of patients with
chronic pain have depression, and due to the association, the term ‘pain–depression dyad’ has been
coined.3 When the two conditions coexist, they
are more difficult to treat and outcomes are worse
than when occurring in isolation.4 Both conditions
require expert input from chronic pain specialists
and psychiatrists to effectively manage the conditions, but as the coexistence of the two conditions
is underestimated/unrecognized, appropriate treatment is not always achieved/administered.
2E03, 3E00
are a number of different pain syndromes,
ranging from neuropathic pain to inflammatory pain.
(iii) Depression: Depression refers to a range of
mental disorders where symptoms persist
for longer than 2 weeks. It is a condition
with a cluster of symptoms not all of which
occur in every case. The key features are a
persistent low mood, absence of positive
affect (loss of interest and enjoyment in ordinary things and experiences), and a range
of associated emotional, cognitive, physical, and behavioural symptoms. Depression
is usually defined and classified in severity
according to one of the two classification
systems. DSM-IV (Diagnostic and Statistic
Manual of Mental Disorders) involves five
or more symptoms being present during the
same 2 week period (Table 1).5 One of the
symptoms must be depressed mood or
loss of interest or pleasure. The ICD 10
(International Classification of Diseases)
involves three key symptoms and a further
seven other symptoms. Depression is then
graded according to severity (Table 2).6
(iv) Chronic pain and depression: It is well established that there is an association between
chronic pain and depression. What is unclear
is the strength and mechanism of this association. Undiagnosed and untreated chronic
pain and depression can exacerbate the other
condition, leading to a cycle of worsening
pain and depression.
Definitions
(i) Pain: As described by the International
Association for the Study of Pain (IASP)
‘An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms
of such damage’.
(ii) Chronic pain: A continuous, long-term pain
of more than 12 weeks or after the time that
healing would have been thought to have occurred in pain after trauma or surgery. There
Diagnostic difficulties
The association between chronic pain and depression is complex. Each condition can occur independently, but pain and depression may develop
secondarily to each other or may coexist. This
makes diagnosis of the coexisting conditions
difficult.
The existence of chronic pain is a risk factor for the development of depression. Also,
doi:10.1093/bjaceaccp/mkt046
Advance Access publication 8 October, 2013
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 14 Number 2 2014
& The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.
All rights reserved. For Permissions, please email: [email protected]
Chronic pain and depression
Table 1 Depression DSM IV classification
Key symptoms
† Persistent sadness or low mood
† Marked loss of interests or pleasure
At least one of these, most days, most of the time for at least 2 weeks
If any of above present, ask about associated symptoms
† Disturbed sleep (decreased or increased compared with usual) decreased or
increased appetite and/or weight
† Fatigue or loss of energy
† Agitation or slowing of movements
† Poor concentration or indecisiveness
† Feelings of worthlessness, excessive or inappropriate guilt, suicidal thoughts or
acts
Severity is determined by the number of symptoms present
† Subthreshold depressive symptoms: fewer than five symptoms of depression
† Mild depression: few, if any, symptoms in excess of the five required to make the
diagnosis, and symptoms result in only minor functional impairment
† Moderate depression: symptoms or functional impairment are between ‘mild’ and
‘severe’.
† Severe depression: most symptoms, and the symptoms markedly interfere with
functioning. Can occur with or without psychotic symptoms
Table 2 Depression ICD10 classification
Key symptoms
At least one of these must be present for most days for at least 2 weeks
† Persistent sadness or low mood; and/or
† Loss of interests or pleasure
† Fatigue or low energy
If any of the above symptoms are present then ask about associated symptoms
† Disturbed sleep
† Poor concentration or indecisiveness
† Low self-confidence
† Poor or increased appetite
† Suicidal thoughts or acts
† Agitation or slowing of movements
† Guilt or self-blame
The 10 symptoms then define the degree of depression and management is based on the
particular degree
† Not depressed—fewer than four symptoms
† Mild depression—four symptoms
† Moderate depression—five to six symptoms
† Severe depression—seven or more symptoms, with or without psychotic
symptoms
Symptoms should be present for at least 2 weeks and every symptom should be present
for most of every day
Hypotheses: ‘chicken or egg’
A common question in the association between chronic pain and depression is whether depression precedes or follows chronic pain. A
number of theories have been proposed.7
Antecedent hypothesis
In the antecedent hypothesis, depression precedes the development
of chronic pain. Depression can increase pain sensitivity and lower
pain thresholds evoking pain. Approximately half of all depressed
patients have pain, and it can often be a presenting symptom.
Consequence hypothesis
In the consequence hypothesis, depression occurs as a result of
chronic pain. The presence of chronic pain can worsen mood, with
the subsequent development of depression. This is particularly the
case if chronic pain produces an incapacitating physical condition
with a reduction in physical and social activities. This can result in
isolation, a loss of worth, and other psychological symptoms that are
features of depression. In essence, the patient adopts the sick role
and behaviours of chronic invalidism, with depression being part of
a maladaptive response to pain.8
Scar hypothesis
The scar hypothesis implies that there is a genetic predisposition to
the development of depression. An early minor episode lays the foundations for more extensive episodes of depression in later life.
Adverse events that would not normally trigger depression might
become more likely to do so. In circumstances of some stress, such as
pain or a physical illness, these individuals would become depressed.
Cognitive behavioural hypothesis
There are psychological mediators involved in the relationship
between chronic pain and depression and this can be thought of as a
variant of the consequence hypothesis. These mediators, such as life
interference and decreased self-control, mediate the relationship.
Pathogenetic hypothesis
physical illness can produce symptoms of depression. Chronic pain
patients develop many of the somatic and vegetative symptoms that
form diagnostic criteria for depression according to DSM-IV and
ICD 10. This overlap of symptoms can lead to varying prevalence of
chronic pain and depression.
The relative contribution and effect of each illness on the patient
can be difficult to determine, making management challenging.
Psychiatrists and chronic pain specialists may lack the skills to recognize and manage symptoms, which fall outside of their areas of
expertise.
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The pathogenetic hypothesis suggests that chronic pain and depression share common pathological changes. These are most likely to
be in the form of a neurochemical association, which is discussed
below. In these final two hypotheses, there are common biobehavioural mechanisms in the aetiology of pain and depression.
A simple cause and effect does not explain the relationship
between the two conditions. The fact that numerous theories exist
highlights the issue that the strength of the association between the
two conditions is unclear, and that no hypothesis is a ‘Best fit’.
Many of the studies that have explored this association have also
been cross-sectional studies, with only a few prospective studies
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 14 Number 2 2014
Chronic pain and depression
being performed. This has meant it is difficult to ascertain which
condition occurred first or whether they occurred concomitantly.
Biological models
There are potential models utilizing biological pathways that can be
used to explain the association of chronic pain and depression.
These models may represent the main underlying mechanism for
all the hypotheses described above that are involved in the ‘pain–
depression dyad’. Further research is needed to clarify these
models. These biological models can be either neuroanatomical
or neurochemical.
Neuroanatomical basis
Depression and pain are neuroanatomically linked, which may be
key to the association. Parts of the brain involved in processing of
emotions are also involved with pain processing and modulation.
This overlap of areas involved in processing mood and pain may be
a site for pathological changes that can result in the development of
both conditions.
Emotions are processed in the hypothalamus, the amygdala, and
the anterior cingulate gyrus. These areas relay signals to the periaqueductal grey matter and the ventromedial medulla, which have a
role in pain modulation. The anterior cingulate gyrus in particular may have a key role in depression and pain, as structural and
functional changes have been demonstrated in this area in both
conditions.9
Neurochemical basis
Depression and chronic pain also share commonality with various
neurotransmitters and receptors involved in the conditions. The two
main transmitters are serotonin and norepinephrine (Table 3).
Depression
There is an increasing body of evidence that in depression there is a
reduction in pre-synaptic serotonin (5-HT) release with a compensatory increase in post-synaptic receptors. Studies have shown reduced
levels of serotonin and 5-hydroxyindoleacetic acid (5-HIAA—a metabolite of 5-HT) in post-mortem brain tissue of depressed patients.
All drugs that selectively inhibit serotonin reuptake are effective in
the treatment of depression.10
The evidence supporting the role of norepinephrine in depression
is also extensive with reduction in concentrations in cerebrospinal
fluid (CSF), and its metabolites in plasma and urine. There are
altered neuroendocrine responses to noradrenergic challenges.
Studies performed on post-mortem brain tissue from depressed
patients have shown b-adrenergic receptor up-regulation and
increased density. This is most likely secondary to reduced
synaptic levels of norepinephrine. All antidepressant treatments,
including electroconvulsive therapy, increase synaptic norepinephrine levels by blocking re-uptake, highlighting its importance in
depression.11
Chronic pain
Pain signals are modulated at various levels by descending neurones
involving various neurotransmitters such as serotonin, norepinephrine, and endogenous opioids. In normal circumstances, this descending modulation serves to filter out extraneous signals, allowing
the passage of normal and important signals. Electrical stimulation
of these pathways produces a deep analgesia by inhibiting the
passage of painful stimuli. However, in both chronic pain and depression, neurochemical alterations can affect this inhibition, resulting in disruption of ‘Filtering’ and the passage of abnormal signals.
Depletion of serotonin levels results in increased painful responses
to electrical stimuli in rats, and a functional noradrenergic system is
necessary for this descending modulation.
Pain can also cause an increased turnover of serotonin, with a net
reduction in pre-synaptic serotonin release. This would lead to a reduction in the activity of the descending pain control pathways, and
result in more pain. This reduction in pre-synaptic serotonin release
could cause the development of depression as outlined above. The
effectiveness of antidepressants in the treatment of both conditions
supports this theory.
Table 3 Neurochemical changes in depression
Serotonin (5-HT)
Reduced 5-HT and 5-HIAA in post-mortem brain
Reduced CSF 5-HIAA
Increased density 5-HT binding sites in the brain and platelets
Reduced pre-synaptic 5-HT release
Drugs preventing 5-HT reuptake effective in treatment
Reduced 5-HT synthesis produces relapse in treated patients
Norepinephrine
Reduced concentrations of norepinephrine in CSF
Reduced metabolites in plasma and urine
Altered neuroendocrine responses to noradrenergic challenges
Reduced synaptic norepinephrine levels
b-Adrenergic receptor up-regulation and increased density
Antidepressant treatments increase synaptic norepinephrine levels by blocking
re-uptake
Management
The management of both conditions when they coexist can be challenging, and a multi-disciplinary approach is vital. Anaesthetists and
psychiatrists will be comfortable managing parts of the condition
relevant to their area of expertise. Depression in isolation can be
managed by psychiatry services. However, depression with chronic
pain is best managed in the pain clinic with input from psychiatric
services, which commonly involves clinical psychologists. Screening
patients with chronic pain issues for signs of depression may allow
more prompt and successful treatment.
Management can be broken down into non-pharmacological,
pharmacological, and interventional.
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Chronic pain and depression
Non-pharmacological
Psychotherapy
Although analgesic agents can reduce pain, they rarely provide complete relief. With continued use, reduced efficacy can become
evident and there is also the risk of side-effects. Psychotherapy can
be used in conjunction with analgesic agents to allow patients to
more effectively manage their pain. The most common forms of psychotherapy are outlined below. It is often the mainstay in managing
depression and pain.
Cognitive behavioural therapy
This involves managing thought processes and patterns with the aim
of restructuring them to enable patients to better manage their pain.
The theory behind cognitive behavioural therapy (CBT) is that by
changing dysfunctional emotions, maladaptive behaviours, and cognitive processes, a change in affect and mood can be facilitated. An
example of cognitive behavioural therapy would be altering problematic thoughts such as ‘I will always be in pain’ to ‘I can manage
my pain’.
CBT has six phases:12
(i)
(ii)
(iii)
(iv)
(v)
(vi)
assessment,
reconceptualization,
skills acquisition,
skills consolidation and application training,
generalization and maintenance,
post-treatment assessment follow-up.
Assessment identifies the degree of psychosocial impairment and
the most appropriate course of action. The reconceptualization phase
contributes the majority of the cognitive aspect of cognitive behavioural therapy. This seeks to help patients to challenge and question
the rationality of maladaptive thoughts. In the skills acquisition
phase, the therapist teaches patients how to deal with obstacles in
their day-to-day lives, and how to avoid falling into the pattern of
automatic thoughts. In the skills consolidation and application training phase, patients are given homework in an attempt to help them
reinforce the skills that they have acquired during the skill acquisition phase, one of the hallmark methods in CBT. In the generalization and maintenance phase, the therapist and patient discuss the
future, and how the patients are going to cope once they have left
treatment. Finally, patients participate in the post-treatment assessments and follow-up phase in order for the therapist to monitor and
evaluate patients’ application of CBT skills to their lives.
Hypnosis, relaxation, and guided imagery
Hypnosis utilizes a trance-like state to suggest to patients that their
pain is manageable or will improve. Relaxation therapy involves
techniques such as progressive muscle relaxation and deep breathing, which may offset some of the physiological markers of pain. In
guided imagery, the patient is taught to imagine a pleasant, comfortable setting in great detail. By focusing on this setting, patients are
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distracted from their pain, allowing an improvement in their symptoms to occur.
Biofeedback
Biofeedback can be used to help patients control their physiological
state associated with their pain. Pain and stress can cause an involuntary physiological response in the form of muscle tension, increased
heart rate, increased arterial pressure, and an increased respiratory
rate. When this response is controlled and modified, an improvement
in symptoms can be seen. Multiple studies on biofeedback and depression have found that this therapy can have significant positive
effects.
Different types of biofeedback are used to monitor different
body systems, then various techniques are used to help the patient
control the physiological response. Techniques utilized by biofeedback include:
† deep breathing,
† progressive muscle relaxation—alternatively tightening and
then relaxing different muscle groups,
† guided imagery—concentrating on a specific image to focus
the mind,
† mindfulness meditation—focusing thoughts and letting go of
negative emotions.
Acupuncture
Acupuncture can be used to improve pain. It is thought to release endogenous opioids and also stimulate descending inhibition of pain
pathways via norepinephrine and serotonin.
Exercise
Exercise can play an important role due to its beneficial effects on
both chronic pain and mood. It can also take various forms from
stretching, strengthening, and aerobic exercise to Tai Chi. Recent
Cochrane reviews have shown a moderate effect on patients with
fibromyalgia, and a small to moderate effect on depression.4 Regular
exercise is also recommended as an adjunct in treatment of depression. The reasons for the beneficial effects are multi-factorial. Regular
physical activity can cause physiological changes with increased
levels of endorphins and monoamines, while also reducing cortisol
levels. This can improve the mood of patients. The process of exercising can also act as a distraction from negative thoughts due to their
condition and result in an improvement in function, management of
symptoms, and quality of life.
Pharmacological
The pharmacological management of chronic pain and depression in
isolation is well established and documented in other literature. A
number of drugs that are used to treat depression can also be used
as analgesics in an altered dose. Appropriate choice of agents to
cover both conditions avoids the issue of polypharmacy, reduces
side-effects, and improves compliance with treatment. In-depth
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Chronic pain and depression
pharmacology is beyond the scope of this article. Pharmacological
management involves the use of antidepressants, mood stabilizers,
and anticonvulsants and analgesic agents.
Antidepressants
Tricyclic antidepressants (TCAs) work by increasing synaptic cleft
monoamine levels, in particular serotonin and norepinephrine. They
have a well-documented role in the treatment of neuropathic pain
and depression. Serotonin and norepinephrine reuptake inhibitors
(SNRIs) have a similar mechanism of action as TCAs and have been
used in the treatment of chronic pain. SNRIs have less anticholinergic, antihistaminic, and adrenergic side-effects than TCAs and are
also relatively safer in overdose. Selective serotonin reuptake inhibitors (SSRIs) due to their lack of effect on norepinephrine are thought
not to have independent analgesic properties. Their use in chronic
pain has had varied results.
Summary
The coexistence of depression and chronic pain is important to appreciate in the successful and appropriate management of both conditions. The underlying mechanism for the association remains
unclear with a number of potential explanations. Successful management involves expert input from a multi-disciplinary team.
Declaration of interest
None declared.
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pain is widespread. Drugs such as pregabalin and gabapentin can
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Interventional
Interventional treatments can be considered on carefully selected
patients with pain and depression. They can take the form of nerve
blocks, spinal cord stimulators, or surgery. Interventions can help
avoid using pharmacological agents with side-effects. A multidisciplinary team (MDT) should carefully select the patients to
avoid further deterioration in depression secondary to treatment
failure.
11. Baker GB, Greenshaw AJ. Effects of long-term administration of antidepressants and neuroleptics on receptors in the central nervous system.
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12. Turk DC, Flor H. The cognitive-behavioral approach to pain management. In: McMahon SB, Koltzenburg M, eds. Wall and Melzack’s Textbook
of Pain, 5th Edn. London: Elsevier Churchill Livingstone, 2006
Please see multiple choice questions 29–32.
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