Nonprescription Drugs Recommended in Guidelines for Common Pain Conditions

Abstract

Evidence-based pain guidelines allow recommendation of nonprescription analgesics to patients, facilitating self-care. We researched clinical practice guidelines for common conditions on websites of pain associations, societies, health institutions and organizations, PubMed, ProQuest, Embase, Google Scholar until April 2019. We wanted to determine whether there is a consensus between guidelines. From 114 identified guidelines, migraine (27) and osteoarthritis (26) have been published most around the world, while dysmenorrhea (14) is mainly discussed in developing countries. Specific recommendations to pregnant women, children and older people predominantly come from the UK and USA. We found that acetaminophen and oral nonsteroidal anti-inflammatory drugs (NSAIDs) represent first-line management across all pain conditions in adults and children. In osteoarthritis, topical NSAIDs should be considered before oral NSAIDs. This knowledge might persuade patients that using these drugs first could enable fast and effective pain relief.

Infographic

Infographic: A PDF version of this infographic is available as supplemental material.

Keywords::

• acetaminophen
• children
• clinical guidelines
• nonprescription drugs
• nonsteroidal anti-inflammatory drugs
• older people
• pain relief
• pregnancy

Background

Clinical guidelines are developed to provide evidence-based recommendations aimed at improving healthcare services and optimizing patient outcomes [1–3]. Such guidelines are now an established component of best practice management, and can aid treatment decision-making [4,5].

Practice points

• Patients frequently present with pain to their primary healthcare provider (whether general medical practitioner, practice nurse or pharmacist).

• If – as is usually the case – the pain is not due to serious pathology (i.e., there are no ‘red flags’), the healthcare provider needs to ascertain whether the pain is sufficiently bothersome to require analgesic use, or whether explanation of the benign and time-limited nature of the pain along with expectations of imminent improvement will suffice and thereby avoid analgesic use.

• The next challenge for the healthcare provider is to suggest the most appropriate analgesic for the individual patient, considering their age, gender, comorbidities and concomitant medications. It is important to balance potential pain relief against any risk of harm (adverse effects).

• Currently, the most widely available therapeutic options for simple analgesia, including over-the-counter medications, are acetaminophen (paracetamol), acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs (NSAIDs) – all of which have the major advantage of not causing unwanted sedative, cognitive, addictive or other central effects.

• However, acetaminophen should be avoided in patients with liver disease, while oral NSAIDs may be risky in those with renal, cardiovascular or peptic ulcer disease.

• Importantly, topical NSAIDs are as effective as oral NSAIDs in osteoarthritis, but with fewer systemic adverse effects than oral NSAIDs.

• This summary of national and international evidence-based guidelines of the most common pain conditions should help guide primary healthcare providers as to which nonprescription analgesics are widely recommended, including vulnerable groups such as pregnant women, older people and children.

• The key point from this review is the consistent message for patients, from many national and international groups: acetaminophen and NSAIDs are the best analgesic options for initial, self-treatment of pain.

In the management of pain, clinical guidelines can provide much needed assessment of the relative benefits and harms of available analgesic options. Timely relief of acute pain may help to minimize any negative sequelae [6,7]. The increased availability of analgesics at nonprescription doses makes it easier for patients to take control of their own pain and seek appropriate and effective relief. Nevertheless, patients still seek advice from their doctor or pharmacist regarding the best therapy to use. The sheer number of guidelines that are available for each pain condition can be overwhelming, even for doctors and pharmacists (Figure 1), and is exacerbated by the wide range of prescription and nonprescription options recommended within each guideline. These factors may make it difficult for time-constrained clinicians and pharmacists to recommend initial therapies to their patients.

Figure 1. Number of accessible guidelines per indication per country/region.

The figure shows the total number of guidelines produced worldwide per indication (top), the number of guidelines produced for each indication within each country/region (map, color-coded to those along the top) and the number of international guidelines that have been produced for any indications (bottom).

Thus, we decided to nonsystematically review all accessible clinical guidelines within each country (English language only) for the most common pain conditions. Our aim was to look at all drugs recommended within the guidelines and descriptively summarize those that are generally available nonprescription. We wanted to determine whether there is a consensus between guidelines regarding preliminary steps that patients can take to relieve their pain. We have tried to present the information clearly and simply so that it can be used more effectively by busy physicians [8]. We believe that this concise summary may aid decision-making for healthcare providers who are trying to determine the first, most effective and evidence-based step to take in the management of pain.

Common pain conditions

Before looking at the guidelines and the recommendations for treatment of pain, it is worth looking at certain pain conditions that are regularly seen by primary care clinicians, to better appreciate their impact and why it is important that patients effectively treat their pain. Pain negatively interferes with many aspects of life, affecting a person’s ability to perform daily activities, changing their overall perception of general health, increasing the risk of depression and affecting relationships with others – all exacerbated by increasing pain severity [9–11]. The following pain conditions are often experienced by patients at some point during their lifetime, and self-treatment is common; accordingly, nonprescription drugs play an important role in their management.

General pain

People of all ages and from all areas of life can experience pain [12], which may affect up to 60% of the global population every month (depending on the methodology used within each study) [12–14]. The consumption of healthcare resources (e.g., direct medical costs such as physical therapy, pharmacological therapy, inpatient services, primary care costs, etc.) is almost double in patients with pain conditions compared with the general population [12]. Overall, pain can lead to decreased quality of life and increased disability [12].

Acute back pain

One of the most common types of pain affects the lower back [15,16], caused by many factors such as strained ligaments or muscles, disc degeneration, traumatic injury, etc. [17]. Low back pain has a worldwide prevalence of 38% over 1 year [18], and lifetime prevalence of 60–85% [19]. Although recovery may be swift in many people, disability is very common in all age groups [20]. In fact, low back pain was the leading global cause of all disability in 2017 (Table 1) [21]. The economic cost of back pain is high; in the US, for example, back pain (along with osteoarthritis and rheumatoid arthritis) is the most common and costly chronic condition in the US, affecting over 100 million people and costing more than US$200 billion every year [22].

Table 1. Disease burden of common pain conditions, estimated in disability-adjusted life-years and global ranking according to life lived with disability.

Pain condition	Proportion of total global DALYs^† (2016), % [23]	Global ranking according to leading causes of total YLD (2017) [21]
Low back pain	2.41	1
Migraine	1.89	2^‡
Oral disorders (± dental pain)	0.79	14 (women) 16 (men)
Osteoarthritis	0.68	38^§
Tension-type headache	0.30	2^‡

† DALY = the sum of years of life lost due to premature mortality and YLD, and a measure of disease burden: one DALY represents 1 year of healthy life lost.

‡ The ranking is for ‘headache disorders’, which mostly comprises migraine, but also includes tension-type headache.

§ Based on 2010 data for global ranking according to DALY [24].

DALY: Disability-adjusted life-year, YLD: Years lived with disability.

Osteoarthritis

Osteoarthritis is the most common form of arthritis, and joint pain is its most commonly reported and limiting symptom [25]. The physical problems caused by osteoarthritis significantly affect daily living [26] and can lead to psychological distress that is greater than that observed in patients with diabetes, for example [27]. The economic costs of the condition are also high [22]. For example, it has been estimated in the UK that direct costs from topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs), NSAID-related iatrogenic events, use of proton-pump inhibitors, hip and knee replacements and arthroscopic surgery were around £1.0 billion (in 2010), while indirect costs (i.e., loss of economic production) were £3.2 billion (in 2002) [28]. As osteoarthritis is mostly found in older people [26], the condition will become an even greater public healthcare problem as the global population ages [29].

Dysmenorrhea

Painful menstruation can affect up to 95% of reproductive-aged women [30], and is a leading cause of absenteeism from school or work [31]. The pain, disruption in daily living and lower quality of life in women with primary dysmenorrhea contributes to a loss of quality-adjusted life years that is comparable with that seen in chronic diseases such as asthma or chronic migraine [32].

Dental pain

Despite increased awareness of the importance of good oral health, oral conditions remain a major global health challenge [33]. One of the most common symptoms associated with many oral disorders is dental pain, and toothache alone has been estimated to affect around 12% of the population in the USA, for example, at any given time [34]. Dental pain is an intensely painful and debilitating experience that has a significant impact on oral health-related quality of life [35], and may account for 40% of pain-related healthcare costs [36].

Tension-type headache

Tension-type headache (TTH) is the most common type of primary headache, with a global age-standardized prevalence of 26.1% in 2016 [37]. It has been estimated that between 30 and 78% of the general population will experience TTH at some point in their lifetime [38]. In 2016, TTH caused 7.2 million years lived with disability (YLDs) [37], compared with 5.9 million YLDs for upper respiratory tract infections, for example [21]. Despite its high socioeconomic impact, it is the least studied of the primary headache disorders [39].

Migraine

Migraine is a recurrent, disabling primary headache disorder [39], with a much lower global prevalence than TTH (14.4% in 2016) [37]. However, migraine is associated with higher disability and is now the second largest cause of YLD (Table 1), causing 45.1 million YLDs in 2016 [37]. Together, TTH and migraine comprise 6.5% of all YLDs globally, mainly because medication overuse headache is now considered a sequela of migraine or TTH [37].

Postoperative pain

More than 80% of surgical patients experience postoperative pain [40], which is moderate-to-extreme in approximately 75% of cases [41]. Inadequately controlled pain negatively affects quality of life and functional recovery, and increases the risk of postsurgical complications, including the risk of persistent postoperative pain [41].

Guideline characteristics

We performed a nonsystematic search of several databases (PubMed, ProQuest and Embase) for national and international guidelines (using terms such as ‘treatment’, ‘guidelines/guidance’, ‘consensus’, ‘recommendations/recommend’, ‘best practices’ and ‘quality standards’) (English language only) for common pain conditions (i.e., general pain, acute back pain, osteoarthritis, dysmenorrhea, dental pain, TTH, migraine and postoperative pain). We also searched websites of pain associations, societies, health institutions and organizations, and conducted open searches on Google and Google Scholar. The search included all guidelines until April 2019 (no specific start date), but only the most updated guideline from any given group was included. We excluded reviews, hospital guidelines and hospital surveys, guidelines that did not include nonprescription drugs, guidelines that are no longer valid or have been withdrawn, or were not written in English; we also excluded guidelines that only discussed diagnostic and surgical procedures for the indications mentioned. Further search details can be found at the end of Supplementary Table 1. Assessing the quality of each guideline was outside the scope of our review.

We identified 114 relevant guidelines in adults, as well as four guidelines specifically written for pain in pregnancy, 11 guidelines that address pain in childhood and five guidelines developed for pain in older people (Supplementary Table 1). Most guidelines that we identified were in acute pain conditions, but some were for chronic pain in osteoarthritis or persisting pain in older people. There were some differences in the guidelines produced by each country or region (Figure 1). For example, developed countries were more likely to produce guidelines for acute back pain, primary headache and dental pain, while guidelines for dysmenorrhea were more prevalent in developing countries.

The methodology used to produce these guidelines varied considerably, and many did not comply with established standards [3,42]. It has been stated that for clinical practice guidelines to be trustworthy, they should be developed by a multidisciplinary panel of experts, based on systematic review of the literature; the evidence should be graded for quality and the strength of the recommendations, and should consider benefits and harms as well as patient values [3,42]. However, in the clinical guidelines that we identified different grading systems were often used to evaluate the quality of the evidence, and drugs were classified in several different ways, for example, using a grade or level, and/or whether they were first or second line and choice. Many did not provide a level of recommendation, but simply recommended a class of drugs based mainly on clinical experience and the reported efficacy and safety. These issues, which are common to many clinical guidelines [43,44], mean that it is difficult to obtain anything other than a general overview of the recommended therapies. Thus, although our summary may be a useful tool, decision makers must also take a closer look at the guidelines specific to their field of expertise.

Nonprescription treatment recommendations for common pain conditions in adults

First-line therapy

Overwhelmingly, acetaminophen and oral NSAIDs represent the first line of management across all pain conditions in adults, particularly for mild-to-moderate pain (Supplementary Table 2 and Figure 2). They are also recommended for severe pain in some cases, such as osteoarthritis [45] and postoperative pain [40,46]. It should be noted that although acetaminophen is recommended throughout all guidelines, recent reviews have questioned its efficacy in some indications [47–50].

Second line

If oral NSAIDs or acetaminophen are insufficient when used alone, it is recommended that they be used in combination [51–59] (for example in dental pain, the combination is considered superior to opioids [52,56–59], because it optimizes efficacy while minimizing acute adverse events [60]).

Topical NSAIDs

Topical NSAIDs are currently specifically recommended in osteoarthritis, and in one guideline each for acute back pain and dental pain (specifically myalgia in temporomandibular disorders). They are often recommended first-line before the use of oral NSAIDs because of their comparable efficacy but lower risk of systemic side effects. In fact, in osteoarthritis oral NSAIDs are more likely to be recommended second-line to topical NSAIDs and to acetaminophen for symptom relief (Supplementary Table 2 and Figure 2).

Other analgesic combinations

Some guidelines recommend that topical NSAIDs can be used alongside acetaminophen [26,61–67]. In more severe osteoarthritis pain, it has been recommended that topical NSAIDs be used alongside oral NSAIDs [68]. It is also recommended that glucosamine and chondroitin can be used together to manage osteoarthritis. In primary headache, combinations of acetaminophen and/or NSAIDs with adjunct analgesic caffeine are commonly recommended, and thought to be more effective than any of the active ingredients used alone [69].

Figure 2. Nonprescription pharmacological options recommended in treatment guidelines for the management of acute pain.

First level 1 = grade A, level I or first choice; Second level = grade B, level II or second choice.

APAP: Acetaminophen (paracetamol); ASA: Acetylsalicylic acid (aspirin); NSAID: Nonsteroidal anti-inflammatory drug.

Specific NSAID recommendations

It should be noted that some guidelines recommend use of oral NSAIDs at prescription doses, particularly for severe pain or more difficult to treat pain such as back pain or migraine. Often, no dosage at all is specified, apart from a general recommendation to use oral NSAIDs at the lowest effective dose for the shortest duration of time, to minimize the potential for adverse events. There is little differentiation between the oral NSAIDs recommended, although ibuprofen, diclofenac and naproxen are mentioned most often (including ibuprofen for severe pain in dysmenorrhea [70] and diclofenac for severe acute back pain [71,72]). Acetylsalicylic acid is not specifically mentioned in any guideline for osteoarthritis or postoperative pain. The lack of differentiation is most likely because overall, the available evidence indicates that there is little difference between the mean analgesic efficacy of each NSAID [73]. However, individual patient data suggest that there may be variations between patients [73], and a process of trial and error may be necessary to determine which is the most appropriate for each patient. Figure 3 provides an outline of nonprescription treatment options that both patients and healthcare providers may find useful when determining which nonprescription analgesic may be used based on their type of pain. This knowledge may facilitate self-care and enable patients to treat their pain early and effectively, thus potentially minimizing the impact of pain on their quality of life [74].

Figure 3. Nonprescription acetaminophen and oral nonsteroidal anti-inflammatory drugs can be used initially in all types of acute pain and in vulnerable groups such as children, pregnant women and older people.

Where oral NSAIDs are contraindicated or not tolerated, acetaminophen is the treatment of choice, or topical NSAIDs in osteoarthritis. It should be noted that nonpharmacological options (which vary according to the pain indication, but include measures such as physical therapy, lifestyle changes, etc.) are usually recommended alongside pharmacological therapy, for optimal pain relief.

NSAID: Nonsteroidal anti-inflammatory drug; TTH: Tension-type headache.

Vulnerable groups

Safety concerns are of paramount importance in certain groups of patients, particularly pregnant women, children and older people. Accordingly, guidelines for the management of pain have been specifically developed for these vulnerable groups (Supplementary Table 3), as outlined below.

Pregnant women

There is always concern regarding the use of drugs in pregnant women, mainly because of potential adverse effects on the developing fetus but also because of the risk of adverse drug reactions in the mother [75]. Fear regarding the use of drugs during pregnancy means that some women are at risk of under treatment or no treatment for pain, which can have an adverse impact on health [76]. Nevertheless, nonprescription drugs are used by many pregnant women [75]. Use of the lowest effective dose may be necessary to minimize any risk of maternal, fetal and placental toxicity [75,77].

In all clinical guidelines, acetaminophen is generally considered relatively safe to use in pregnancy and is recommended for use during all stages. It is recommended to avoid oral NSAIDs if possible, but that they may be used if greater analgesia is required; in that case, caution is advised during the first trimester and use should be discontinued by week 32 [78].

Children

Children suffer from many of the same painful conditions as adults, including headaches, sprains and strains, dental pain, cold and flu symptoms and postvaccination pain. For optimal safety, dosing errors in children should be avoided by basing the dose used on their weight and not on their age [79]; weight has been shown to have a greater influence than age on pharmacokinetics and consequently on systemic exposure [80]. However, some guidelines still provide dosages based on age.

For all common painful conditions, acetaminophen and oral NSAIDs are recommended in children, but at lower doses than in adults. If either class of drug is insufficient when used alone, it is recommended that they should be used in combination, for example in children with dental pain [81] or postoperative pain [82]. Acetylsalicylic acid has been recommended in one guideline in France for migraine in children [83]; all others warn against its use in children younger than 12 or 16 years old (depending on the guideline) because of the potential risk of Reye’s syndrome (particularly if recovering from a viral infection [84]).

Older people

Pain is common in older adults (>60 years of age) [85–87]. But treatment of their pain requires careful consideration of various factors, such as age-related physiologic changes, concomitant drug use and comorbidities (e.g., cardiovascular disease and cognitive impairment), which can potentially increase the risk of adverse drug reactions [88,89]. Thus, treatment of pain in older people can be challenging and complex [90,91].

In the guidelines for the management of pain in older adults, acetaminophen is recommended as the first-line treatment. Oral NSAIDs may also be used, but caution is recommended because of the greater risk for drug-related adverse events. It is recommended that oral NSAIDs be used at the lowest possible dose for the shortest duration of time, always monitoring and managing side effects. These recommendations are reflected in the guidelines for adults in general that also mention older people. In the case of osteoarthritis, topical NSAIDs are recommended before the use of oral NSAIDs in older people, to minimize any systemic side effects [64,92].

Conclusion

A review of all accessible national and international clinical guidelines for various pain conditions indicates that acetaminophen and oral NSAIDs are initially recommended to relieve mild-to-moderate pain in adults and in children, although oral NSAIDs should be used with caution in pregnant women and older people. Where oral NSAIDs are contraindicated or not tolerated, acetaminophen is the initial treatment of choice. If either class of drugs is insufficient alone, they may be tried in combination in adults and children but not in pregnant women. In osteoarthritis, topical NSAIDs should be considered before the use of oral NSAIDs to minimize the risk of systemic side effects, particularly in older people. Topical NSAIDs may also be used in combination with acetaminophen in osteoarthritis. All of these analgesics are available nonprescription, which should facilitate self-care by patients and enable them to appropriately treat their pain.

Future perspective

Greater internet access means that patients will be better informed about their disease and available treatment options. Furthermore, healthcare systems will become increasingly expensive, so patients will need to pay for their own treatment. As a result, nonprescription medications will become more common – highlighting the importance of providing evidence-based data not only to clinicians, but also to patients.

Author contributions

M Hagen was involved in the search for the pain treatment guidelines. Both authors contributed to the interpretation of the data and development of the manuscript throughout every stage, and both authors reviewed and approved the final manuscript.

Supplementary data

An infographic accompanies this paper at the end of the references section. To download the infographic that accompanies this paper, please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pmt-2019-0057

Financial & competing interests disclosure

M Hagen is an employee of GlaxoSmithKline Consumer Healthcare. J Alchin is an employee of the Canterbury District Health Board, Christchurch, New Zealand, and a member of the GlaxoSmithKline Global Pain Forum, but otherwise declares no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The draft manuscript was prepared by Deborah Nock (Medical WriteAway, Norwich, UK), with full review and approval at all stages by the authors. The services of the medical writer were funded by GSK Consumer Healthcare S.A.