When medication side effects get in the way of living life

There are very few people living with chronic pain who gleefully swallow a handful of pills and skip happily off for the day feeling chipper and bright as a button. For the most part, people living with chronic pain don’t seem to enjoy the need to take medications – I’ve heard some say they’re worried about “not being able to tell whether I’m doing damage” when they can’t feel their pain, others say they don’t think medications are very helpful, while still others complain about rattling when they walk. But by far the biggest complaint is the medications for chronic pain have unpleasant side effects – side effects so bad that for some people, it’s just not worth taking the pills at all.

Surprisingly, although there are many studies looking at the side effects of medications, and why they occur, the effect of side effects on doing everyday activities has seldom been examined. Thankfully a group of researchers from Harvard and Johns Hopkins have taken on this task, and we now have some information about just how much side effects can get in the way of life.

What side effects do people experience?

Nausea, dizziness, headaches, constipation, weakness, cognitive fogginess, excessive sleepiness, skin itchiness and rashes, muscle twitching – you get the drift!

Why do they happen?

Many medications for pain, and particularly medications for chronic pain, exert their influence on the central nervous system – where the receptors for neurochemicals important in modulating our experience of pain are found. It would be fabulous if there were some separate receptors that only dealt with “unhelpful” pain that could be targeted, but because pain is an adaptive response designed to protect us – and because in evolutionary terms experiencing pain is crucial to our survival and has been present from early on in our evolutionary development – receptors targeted by many pain medications are found throughout the body. And particularly in the brain – hence the fogginess, sleepiness, and headaches.

What does this mean?

When prescribing medications for chronic pain, clinicians and their patients ultimately go through a process of empirical study. What this means is that because we don’t know which type of medication is most likely to help an individual, each one needs to be tried out. And the trial and error process involves establishing the balance between helpful effects – yes, pain reduction, perhaps some help with sleep – and unhelpful effects – those side effects. The process of deciding which particular combination of medications to take is absolutely personal – only the person with pain can possibly determine whether they find the balance of helpful vs unhelpful effects tolerable.

What about this study?

In this study, Martel, Finan, Dolman and colleagues (2015) sampled a group of 111 people living with chronic musculoskeletal pain. The participants were asked to report once a month, for six months, on their medication use, side effects, and pain and activity levels.  Interestingly, the group selected had to have been prescribed opioids because the larger study of which this one was a small part, was designed to establish ways to improve adherence to medication taking. In addition, this group of people were considered to be at risk of prescription opioid misuse based on an assessment for this problem, but those with a current or past substance abuse problem within the past 12 months. What this means is that while the study has some interesting findings, they will not be representative of all people living with chronic pain, and results need to be interpreted in this light.

OK, OK, I’ll get on with it!

The findings

There were no differences between men and women in terms of pain intensity, mood or pain-related activity interference but women were more likely to describe side effects due to medication. Reports of side effects were no different between those taking opioid medications as well as other pain medications such as antidepressants, anticonvulsants or NSAIDs.

Now for some expected findings: people reporting greater pain-related interference were less likely to be employed, while changes in pain intensity were related to pain-related interference, and similarly, changes in mood were also associated with greater pain related interference.

After some statistical magic (multilevel modeling is horrendously complex!), these researchers examined the unique contribution of medication side effects on pain-related activity interference. What they found was that side effects contributed a unique amount to interference even after controlling for gender, pain intensity and negative mood, and even taking into account individual differences between people.

Now this is important. Medications are prescribed for pain for two reasons: to reduce pain (obviously) and it’s assumed that because pain is then lower, pain-related interference will also be lower. In other words, people will feel less pain and do more things they want to do. What this study suggests is that the burden of side effects from medications can actually ADD to the burden of disability experienced by people living with pain. Now, one way to deal with this is to reduce the number of medications a person takes. That would take care of the side effect burden – but it would also increase the pain. Both distress and disability may then increase. An alternative is to treat the side effects with something else – a bit like taking something to stop constipation when being prescribed opioids. But that in itself can create problems – because, as many people I’ve talked to mention, they really don’t want to rattle like a pill bottle from all the medications they have to swallow.

I think there are two more alternatives. One is to look at the timing of medication taking. I’ve seen many people prescribed gabapentin three times a day – but gabapentin is sedating, and people complain of the effects on driving and on concentrating at work. An alternative, and one that I’ve seen carried out very successfully for years at Burwood Pain Management Centre in Christchurch, NZ, is prescribing the same dose of gabapentin, but taking it once a day at night. A good night’s sleep is had, and the hangover effect during the day is minimised. But this requires a change in how the doctor prescribes – and some confidence to fiddle about with the timing of the dose. It also suggests that the person living with pain, his or her doctor and probably the pharmacist need to work together to develop a plan that maximises the effectiveness of medication administration.

The second is to look at reducing reliance on medication as the primary form of coping strategy for chronic pain. This solution is a vexed one. Many people living with chronic pain are afraid to reduce their use of medication. Many doctors are unaware of alternative ways of coping even though it’s evident that as many as three people in four will not obtain any benefit from medication.  Worse still, many communities have few treatment providers available to help people develop nonpharmacological ways of living well with pain. I think that’s a tragedy and I think it’s time that changed.
Martel MO, Finan PH, Dolman AJ, Subramanian S, Edwards RR, Wasan AD, & Jamison RN (2015). Self-reports of medication side effects and pain-related activity interference in patients with chronic pain: a longitudinal cohort study. Pain, 156 (6), 1092-100 PMID: 25782367

Fibromyalgia: an overview

I didn’t intend to get into a theme this week, but this paper arrived in my inbox this morning, and given both the prevalence of fibromyalgia, and the often ‘fuzzy’ management that can be provided, I thought it might be worthwhile taking a look at it.  The paper itself is a pre-print, but has been revised earlier this year and is probably the final version.

The outline of the paper covers diagnostic criteria, and briefly discusses the place of neuroimaging (if only we could get that done readily here!), but notes that many other conditions overlap or mimic FM such as hypothyroidism, tendonitis, ankylosing spondylitis, as well as chronic fatigue, suggesting some sort of common pathway in either the peripheral or central nervous system, raising the possibility of some common treatment approach.  So far though, it’s not clear – and it’s important to rule out these other conditions that all have their own management approach before deciding that FM is what the problem is.

The next section of the paper reviews the current state of knowledge around pathophysiology as a basis for treatment and rehabilitation.  Both peripheral and central sensitisation seem implicated in FM, leading to amplification of sensory impulses that alter pain perception.  Increased excitation of various peripheral structures can in turn lead to neuroplastic changes in the central nervous system – winding up the whole experience for the person in the middle of it!

Imamura, Cassius & Freni, the authors of this paper, briefly review some of the factors thought to play a role in the reduced threshold for neuronal firing, including elevated levels of substance P, calcitonin gene-related peptide, bradykinin, and so on.  Included in their review are CNS factors such as the altered non-REM sleep of people with FM – and that this is associated with the severity of symptoms; the association between depression and FM; and neuroimaging studies showing a change in regional cerebral blood flow to pain-related structures in people with FM.

If these aspects of FM can be explained to people with the pain problem it could make a significant difference to their own attitude toward their pain.  For many people, it can take several years before a diagnosis of FM is made: during this time the beliefs and approaches of many practitioners can influence their understanding of their pain – and sadly, some practitioners are not empathic and can take a somewhat pejorative approach to people with the disorder.  Knowledge can lead to understanding – and understanding can lead to a sense of empowerment.

Moving through the paper, the authors indicate that treatment needs to be based on the proposed model of fibromyalgia.  That is, it needs to address central mechanisms rather than peripheral ones (so, no more NSAIDs, opioids or corticosteroids!), and the overall approach needs to be ‘rehabilitative’ – I’d suggest biopsychosocial as the model!  The shift is from curing the problem to improving health status and health -related quality of life.

There are two arms of management for fibromyalgia:

(1)  pain relief through medication and ‘physical’ strategies to reduce peripheral and central sensitisation

(2)  cognitive behavioural approaches to manage sleep, fatigue, mood, cognitive problems, headache, migraine and other problems associated with FM.

Although the authors suggest ‘education’ as a cornerstone – I’d rather suggest helping the person to reconceptualise their problem as one of pain processing.  Education can be seen as simply providing information – reconceptualising is about helping the person see themselves and their pain problem as something they can manage, something only they can do – and something they can do.

The remainder of the paper looks at pharmacological approaches and the rationale for using tricyclic antidepressants and/or serotonin/norepinephrine-reuptake inhibitors, and tramadol because of their effect on reducing afferent transmission at the dorsal horn or increasing the activity of the descending inhibitory pain systems.

It should be noted that even these drugs don’t always reduce the pain and all have their own array of side-effects – so they need to combined with self management.

Nonpharmacological approaches are then reviewed.  This is where the interdisciplinary team can take the lead because these approaches are both effective – and once learned, don’t consume health resources in quite the same way as medications can.

Exercise gets the nod – remembering that exercise can include enjoyable daily activities such as walking, gardening, dancing and playing with the dog, not just going to a gym!

Electrical stimulation – this is suggested, although as far as I know, it’s not readily available – Imamura et al. indicate transcranial direct current stimulation as an effective approach, but I haven’t heard much of this as a strategy available in New Zealand.  (If anyone has, let me know).  I’m also not entirely comfortable with this as a self management strategy – it sounds pretty invasive and requires health care input, at least initially.

Acupuncture – this is less well-documented, and results are, as these authors say, ‘controversial’.  They suggest that ‘clinical benefits seem to be of small magnitude and of short duration’ – my main concern would be that unless the person can ‘do it themselves’, it will involve more appointments, so I’d not be comfortable with it as a self management approach.  I hold a similar view of injections – Imamura et al suggest that ‘concomitant myofascial pain, along with instruction in relaxation techniques, may benefit some patients with an associated mysfascial pain component.’ 

The final area reviews, very, very briefly, cognitive behavioural therapy.  The authors indicate its use for ‘associated psychological and psychiatric comorbidity’, but I’d be inclined to challenge this.  The perception of pain involves thoughts and beliefs about the meaning of pain – and the effect of reconceptualising fibromyalgia as not being a ‘life sentence’ or a ‘constant struggle’, and understanding what some of the mechanism are, will bring about changed perception.  Distress reduction, increased sense of self efficacy and more effective approaches to activity, relaxation, cognitions, as well as effective communication skills and working on relationships – these are all integral to living a good life despite pain.

Overall – this is a nice, brief review especially of some of the pathophysiology of fibromyalgia and the rationale for the treatment approaches suggested.  There are plenty of good references, and while it’s not an ‘easy’ read, it’s quite brief and contains the essentials.


From Imamura, M., Cassius, D., & Fregni, F. (2009). Fibromyalgia: From treatment to rehabilitation European Journal of Pain Supplements DOI: 10.1016/j.eujps.2009.08.011

The impact of pain management on quality of life

What exactly is quality of life? And what is pain management? This article, presented at a 2002 Roundtable on ‘The role of coxibs in successful pain management’ is written by a medical researcher, which should give you a bit of a clue about how pain management is defined for the purpose of this paper (i.e. pain control). Much of the discussion about quality of life measures, however, is useful, and the article itself is reasonably short – and it talks the language of doctors, which I thought gives an interesting slant.

Firstly, the point is made that quality of life involves assessment over multiple dimensions, with the World Health Organisation’s ‘Domains and factors of quality of life’ being used as an example of the domains that can be considered. For those who haven’t reviewed this recently, there are six domains:
1. Physical
2. Psychological
3. Level of independence
4. Social relationships
5. Environmental health
6. Spirituality
and a final ‘general’ facet that evaluates ‘overall perceptions of health and quality of life’.  This link to WHOQOL leads directly to the Seattle Quality of Life Group website.

The point is made that pain affects cognitive, motivational, affective, behavioural and physical components, and quality of life has a similarly all-encompassing nature. Katz points out that ‘quality of life … can be defined as an individual’s ability to perform a range of roles in society and to reach an acceptable level of satisfaction from functionoing in those roles’, but at the same time recognising that quality of life research is relatively new, and the effects of pain on quality of life is only just beginning to be investigated.

When we’re choosing any assessment tool, there are some practical things to consider – quite apart from the psychometric properties of the instruments we may think of. Katz nicely identifies some considerations:
1. Which is more applicable – a disease-specific or generic instrument? He identifies that there are both advantages in specific measures (for example, able to detect more subtle change) as well as disadvantages (difficulty comparing across patient groups). The SF-36 (Medical Outcomes Study Short Form 36) is suggested as a general health status measure that combines the ‘best’ of both worlds.
2. What dimensions of quality of life need to be measured? Katz acknowledges that quality of life measures are multi-dimensional since ‘an instrument that does not include several dimensions will make it impossible to determine the nature of a score change’. The areas of physical, psychological, social, somatic, and spiritual are thought to be important, and again the SF-36 is identified as a key contender because of the breadth of dimensions included.
3. How much responder burden is acceptable? This refers to the amount of work needed to complete the questionnaires – an important consideration when we recognise that many people don’t like paperwork, or have relatively low reading levels.
4. What administrative issues need to be considered? Ahhh, now that’s an excellent point! A very comprehensive database that I know of has been abandoned from time to time because of difficulty obtaining clerical time to score and enter questionnaires, and in the mists of time, some of the original scoring ‘rules’ have been lost… Questionnaires used in pain outcome measurement need to be applied at least twice, more appropriately three or four times – and ‘compliance’ or the number of people who complete all of the measures all of the time reduces over time…
5. Has the instrument been validated, and is it reliable? Well, this goes without saying… and should be a ‘given’ for people working in the area of pain management.

There are a number of issues that this paper does not cover well.
Firstly, there is an assumption that if quality of life is reduced when pain is experienced, an individual’s quality of life should improve simply by reducing pain intensity. While this intuitively makes sense, it assumes that pain intensity alone is responsible for loss of quality of life. Reports of pain intensity are influenced by things like psychological distress, fear of injury, fear of being out of control, low mood, health anxiety and so on (e.g. Severeijns, Vlaeyen, van den Hout & Weber, 2001). When analgesia is used, while it may reduce pain intensity it may not address underlying issues such as low mood, health anxiety, and most especially fear of injury. The latter is one reason some patients tell me they don’t want to take medication, because it ‘masks’ pain!

Katz suggests that ‘analgesic agents should be compared … incorporating the use of symptom distress scales, which may be the most sensitive way of discriminating among analgesics in effects of quality of life’. I suggest that distress scales may not be the most appropriate measure of effectiveness in quality of life, and in fact changes across several domains such as Physical, Psychological, Level of Independence, and Social Relationships should be observed before an intervention should be considered ‘successful’.

Another issue is that although Katz indicates that taking repeated measures is important, he makes little mention of the need for longer-term followup. At least part of the initial response from any intervention is likely to be due to the ‘meaning response’, or expectancies or placebo response that people have simply from having been given a treatment. As a result, it’s important to measure changes in quality of life (and any other outcome measure) some months or even years later after the treatment is first initiated. The risk otherwise is that an initial lifting of mood, sense of hope, even physiological changes secondary to placebo can subside over time – and in the end, it’s the effects that are sustained that are important.

However, it’s difficult to argue with Katz on this: quality of life measures should be included as a key variable in future pharmacological research. Personally, I think it should be included as an outcome measurement of any pain management intervention.

For further information on a broader range of outcome measures that are being considered for pain management, this article by Dworkin and colleagues provides some insights into the areas that the IMMPACT group recommend: (1) pain; (2) physical functioning; (3) emotional functioning; (4) participant ratings of improvement and satisfaction with treatment; (5) symptoms and adverse events; and (6) participant disposition.  Worth a read – and they’re continuing to publish more on this area.

Katz, N. (2002). The Impact of Pain Management
on Quality of Life. Journal of Pain and Symptom Management, 24(1S), S38-S47.

Severeijns, R., Vlaeyen, JWS., van den Hout MA., & Weber, JWA., (2001)Pain catastrophizing predicts pain intensity, disability, and psychological distress independent of the level of physical impairment. The Clinical journal of pain vol. 17, no2, pp. 165-172