Multimorbidity: when guidelines add up and collide

An older person has osteoporosis, osteoarthritis, diabetes, high blood pressure and chronic obstructive pulmonary disease. Each of these conditions has a well-founded guideline, written by specialists and supported by clinical trials. A much-cited example in the literature on treatment burden shows what happens when each guideline is followed as if the disease existed on its own: the doctor could end up prescribing up to 12 medications for this same person (Tran, 2015).

This example sums up one of the central problems of primary care. Most people seen by the family doctor do not have one disease, they have several. Guidelines, however, are still written disease by disease. This text shows what the research says about how common multimorbidity is, why adding recommendations together can harm the patient and how to organize care around the person's priorities, and not around the list of diagnoses.

Key points

• Multimorbidity is the presence of two or more chronic conditions in the same person and is the most common situation among adults seen in primary care.
• It is not exclusive to older people: in absolute numbers, there are more people with multimorbidity below the age of 65, and it starts earlier in poorer areas.
• Guidelines written for one disease rarely consider the others; applied together, they generate long lists of medications, interactions and tasks.
• Treatment burden is a clinical problem: the work demanded of the patient can exceed their capacity and lead to non-adherence.
• The way out proposed by the research is to assess the interactions, prioritize with the patient what matters most to them and individualize the plan.
• Structured interventions improve the experience of care, but the effect on clinical outcomes is still uncertain.

Summary

• Multimorbidity is the rule in primary care
• When guidelines add up
• The treatment burden
• Interactions beyond medications
• Prioritizing with the patient
• What the research shows about interventions
• What changes in the consultation
• From prioritization to the medication list
• Frequently asked questions
• Final checklist

Multimorbidity is the rule in primary care

In a study of 980 patients seen by 21 family doctors, about nine in ten had more than one chronic condition. Even in the 18 to 44 age range, about seven in ten were in this situation. The authors concluded that, in family medicine, multimorbidity is the rule, not the exception (Fortin, 2005).

A much larger cohort study used a random sample of 403,985 adults registered in primary care and counted 36 long-term conditions (Cassell, 2018). About one in four people had multimorbidity, more often in women than in men (Cassell, 2018). The frequency rose with age: about one in eight people between 35 and 44, about one in three between 55 and 64 and more than half from 65 onward (Cassell, 2018). This gradient shows that the problem begins well before geriatrics.

The same study found multimorbidity more often among people of lower socioeconomic status (Cassell, 2018). Among adults aged 18 to 44 with multimorbidity, more than half combined a physical illness with a mental illness, and this combination also weighed more in poorer areas, where it affected about four in ten people with multimorbidity, against about three in ten in less poor areas (Cassell, 2018). Multimorbidity is therefore also a marker of inequality.

A systematic review gathered 39 studies carried out in 12 countries and found very different prevalence estimates, from fewer than one person in seven to almost all, depending on how diseases were counted and on the population studied. Despite this variation, the associated factors repeated: age, female sex, lower socioeconomic status and mental health problems. Among the most frequent combinations were osteoarthritis and a set of cardiometabolic conditions (Violan, 2014).

For the clinician, the practical consequence is direct. Those working in primary care rarely meet the guideline patient, the one who has a single disease. The person being seen has several conditions, takes several medications, has limits on time, money and support, and often lives with psychological distress. Age also weighs unevenly: age-related bias can lead the clinician to attribute new symptoms to aging or to an already known disease, without investigating.

When guidelines add up

Clinical guidelines are one of the great achievements of evidence-based medicine. They summarize trials and reviews, grade the strength of the recommendation and the level of evidence and offer a safe path for common decisions. The problem appears when several of them apply to the same person.

Although multimorbidity is common, guidelines are still written, to a large extent, as if each person had a single condition, and the cumulative effect of recommendations from several of them is generally not considered (Dumbreck, 2015). In a person with several diseases, simply applying recommendations from single-disease guidelines can result in complex regimens, with many medications and potentially harmful combinations (Dumbreck, 2015). The same authors note that studies built on a single hypothetical patient, with hand-picked diseases, tend to exaggerate the size of the problem, and for that reason they preferred a systematic examination (Dumbreck, 2015).

This group systematically examined the national guidelines for three index conditions, type 2 diabetes, heart failure and depression, and cross-checked their recommendations against those of 11 other common conditions. They identified 32, 6 and 10 potentially serious drug-disease interactions, most involving chronic kidney disease, and 133, 89 and 111 potentially serious drug-drug interactions (Dumbreck, 2015). Very few of these interactions were highlighted in the text of the guidelines themselves.

The numbers show that the conflict is neither rare nor theoretical. It is built into the way knowledge is organized. Each guideline is produced by a group that looks at one disease; the trials that support it usually exclude precisely the people with many conditions; and no one is responsible for putting the pieces together. That task ends up with the family physician, often without time and without tools.

Aspect	Care centered on each disease	Care centered on the person's priorities
Starting point	List of diagnoses and targets from each guideline	What the person wants to achieve and what they want to avoid
How success is defined	Each laboratory or clinical target met	Function, symptoms and goals that matter to the person
Medications	Added with each new recommendation	Reviewed together, with room to withdraw
Interactions	Assessed case by case, when remembered	Actively sought across diseases, treatments and context
Treatment burden	Rarely considered	Treated as part of the clinical decision
Main risk	Over-treatment and non-adherence	Failing to offer an important benefit without discussing it

The table does not propose abandoning guidelines. It shows that, in multimorbidity, guidelines become sources of options, not scripts to be followed in sequence. The final decision depends on how much each recommendation adds for that person and how much it costs them in time, adverse effects and effort.

Treatment burden

Treating chronic diseases takes work, and much of that work is done by the patient. Medications must be taken at different times, drugs bought and stored, glucose or blood pressure measured, diet changed, exercise done, appointments and tests scheduled, different services traveled to, and one's own story repeated to every professional.

A qualitative online study with 1,053 people with chronic diseases from 34 countries organized this experience into a taxonomy of treatment burden. Participants described tasks, such as managing medications, changing habits and keeping up with follow-up; factors that worsen the burden, such as difficulty of access, lack of coordination between services and personal and financial problems; and consequences, such as dropping part of the treatment, financial impact and harm to family and social life (Tran, 2015).

The burden does not depend only on the number of tasks. It also depends on the person's capacity to carry them out. A systematic review of 110 qualitative accounts described this capacity across several dimensions: the person's biography and the meaning they give to the illness, their physical, financial and cognitive resources, the environment they live in, their social support network, and how they manage to organize themselves to complete the tasks. Kindness from professionals and a feasible plan appear as factors that help the person cope (Boehmer, 2016).

This perspective changes how non-adherence is read. When a patient with six conditions does not follow the plan, the problem may lie less in a lack of understanding and more in the imbalance between what is asked and what is possible. Adding one more recommendation in this scenario can worsen the outcome of all the others.

Interactions beyond medications

When interaction is mentioned, the clinician first thinks of one medication that alters the effect of another. In multimorbidity, however, interactions have more layers. An international group of primary care researchers proposed the so-called Ariadne principles, which begin by assessing interactions on several fronts: between conditions, between treatments, and with the person's constitution and life context (Muth, 2014).

Between conditions, one disease can worsen another or mask its symptoms, such as depression that reduces the energy for diabetes self-care. Between treatments, the classic drug interaction adds to competition for time and attention: two recommendations for exercise, diet and monitoring may be incompatible in the routine of someone who works and cares for family. There is also the interaction between condition and treatment: a medication useful for one disease can harm another, as shown by the drug-disease interactions linked to kidney function (Dumbreck, 2015).

The last front, constitution and context, includes age, frailty, cognitive function, social situation and support network. A person who lives alone and has difficulty seeing faces a regimen of several pills very differently from someone with a family member present. This layer usually stays out of guidelines, but it is decisive for knowing whether the plan will work.

Assessing these interactions requires reviewing the complete list of medications, not only those started at the last visit. A medication list review script helps identify what was prescribed by whom, with what goal, and whether that goal still makes sense. Overtreatment is also a form of harm, similar to what is discussed in overdiagnosis: an intervention that would be useful on its own may bring no net benefit when added to all the others.

Prioritizing with the patient

The second Ariadne principle is prioritization. The authors propose asking the person which outcomes they most want to achieve and which they most want to avoid, and using these answers to decide what goes into the plan (Muth, 2014). Prioritization is especially needed in three situations: when treatments may cause more harm than benefit, when goals compete with each other, and when the treatment burden becomes unacceptable.

In practice, this means making room in the visit for a conversation different from the usual one. Instead of starting with tests, the clinician asks what matters most to the person in the coming months: continuing to work, caring for grandchildren, walking again without pain, sleeping better, avoiding hospitalization. These goals usually cut across several diseases at once and help choose which recommendations have the greatest value.

This conversation depends on listening. Patients offer clues about their concerns that do not always appear as the main complaint, and the story told by the person themselves reveals what gives meaning to the treatment. Prioritization is also a form of shared decision, in which the clinician presents the benefits and risks of each option and the person brings their values.

The Ariadne principles also remind us that the steps do not need to follow a fixed order and that preferences change. A person who today prioritizes independence may, after a hospitalization, value comfort more. That is why prioritization is not a single decision: it is reviewed at each important stage of follow-up. When the disease advances, this conversation approaches advance care planning.

The capacity to decide also needs to be considered. Most people with multimorbidity decide for themselves, but cognitive decline is frequent in this population, and the assessment of decision-making capacity helps to know when to include family members or representatives in the conversation without taking from the person what they can still decide.

What the research shows about interventions

If the problem is known, why is there no standard solution? Because the interventions tested so far have had modest results. A Cochrane review gathered 17 randomized trials of interventions for people with multimorbidity in primary care and in the community. The authors found little or no difference in clinical outcomes, improvement in mental health, especially in studies aimed at people with depression, and probably a small improvement in outcomes reported by patients; the certainty of the evidence ranged from low to high depending on the outcome (Smith, 2021).

The largest pragmatic trial in the field tested a person-centered approach in 1,546 patients with three or more chronic conditions, seen at 33 practices. In the intervention group, each person received a broad review every six months, which included the diseases, mood and medications, with a focus on what they considered most important. There was no difference in quality of life, the primary outcome. The median number of medications was 11 in both groups, and the treatment burden did not change (Salisbury, 2018).

The same trial, however, showed consistent improvement in the experience of care. The proportion of patients who said they almost always discussed the problems most important to them went from about one in four to about four in ten. There was a similar increase in the perception of integrated care and in satisfaction, and more people received a written plan (Salisbury, 2018). For those living with several diseases, feeling that care makes sense is a relevant result, even when quality-of-life scores do not change.

A non-randomized study assessed care aligned with the patient's priorities in people aged 65 or older with three or more chronic conditions. Decisions based on health priorities appeared in the clinical notes of 108 of the 163 patients in the intervention group and of none of the 203 in usual care (Tinetti, 2019). The intervention group had a greater reduction in perceived treatment burden, stopped medications more often, about one in two versus about one in three, and received fewer self-care tasks and fewer tests (Tinetti, 2019). Because it was not randomized, the study does not allow firm conclusions, but it indicates that prioritizing does in fact change decisions.

What changes in the consultation

The research does not yet offer a ready protocol, but the studies point to practical changes that fit into the routine of primary care. The first is to set aside time. A consultation dedicated to reviewing the whole, instead of a series of short consultations for each disease, allows one to see interactions and conflicts that go unnoticed when each problem is treated in isolation.

The second is getting to know the person over time. The physician who follows the same patient for years knows which treatments worked, which were abandoned and why, and can notice when the burden has become too heavy. In the cohort study with 403,985 adults, people with multimorbidity accounted for about half of primary care visits and about eight in ten prescriptions, and the authors concluded that the care of these people needs to improve in quality and efficiency, in practice and in the system (Cassell, 2018).

The third is organizing the consultation agenda. People with several diseases tend to bring many subjects at once, and prioritizing what is serious, urgent, important and deferrable keeps time from being consumed by one item while another more relevant one is left out. The fourth is accepting uncertainty: in multimorbidity, many decisions have no direct evidence, and a planned reassessment helps test a change and return to it with data.

Finally, it is worth recording in the chart the priorities agreed with the person. This record guides the other professionals who see them, keeps each specialist from restarting the reasoning from scratch, and gives meaning to decisions that, seen in isolation, could look like omissions, such as not intensifying a treatment to reach a target.

From prioritization to the medication list

The third Ariadne principle is individualized management: after assessing the interactions and learning the priorities, the clinician and the person choose the treatment options that make the most sense, set realistic goals and agree on how and when the plan will be reviewed (Muth, 2014). This step often involves taking something away, not just adding.

In practice, the review usually follows a simple sequence:

1. Gather the complete medication list, including those prescribed by other professionals and those the person uses on their own.
2. For each item, ask what the goal is, whether it still matches the agreed priorities and whether the expected benefit outweighs the adverse effects and the effort.
3. Identify the relevant interactions among diseases, treatments and context.
4. Agree with the person what to keep, what to adjust and what to remove, one change at a time.

The study of care aligned with priorities showed that, when the person's goals enter the decision, discontinuation of medications becomes more frequent (Tinetti, 2019). This does not mean that less is always better. It means that each medication must justify its presence in relation to the whole, and not only in relation to the guideline for the disease for which it was indicated.

The expected benefits and harms of each treatment also change over time. A preventive medication that makes sense for someone with decades of life expectancy may have little value for someone with other priorities and little time to reap the benefit. This reasoning, applied with care and with the person's participation, is the core of deprescribing, a topic that requires its own method.

Frequently asked questions

What is multimorbidity?

It is the presence of two or more chronic conditions in the same person, without one of them necessarily being the main one. In primary care, it is the most common situation among adults (Fortin, 2005).

Is multimorbidity the same as comorbidity?

Not exactly. Comorbidity describes conditions that accompany an index disease, which serves as the reference. Multimorbidity considers all conditions together, without choosing one as the main one, which is closer to the family physician's view.

Isn't following all the guidelines the safest way to treat?

Not always. Adding up the recommendations of several single-disease guidelines can produce complex regimens, with many medications and potentially serious interactions (Dumbreck, 2015). Guidelines remain sources of options, but the final choice depends on the person's priorities and capacity.

How can I ask the patient about their priorities?

Open questions work well: what matters most to you right now, what would you like to be able to do again, what worries you most about the treatment. Asking also what the person wants to avoid helps identify unwanted outcomes (Muth, 2014).

Is missing a test target an error?

Not necessarily. When the target requires more medications, more adverse effects or a burden the person cannot sustain, not intensifying may be the best decision. What matters is that it is discussed and recorded.

Do structured reviews improve outcomes?

Trials show improvement in the experience of care, but little or no difference in clinical outcomes and quality of life (Salisbury, 2018; Smith, 2021). The evidence is still uncertain.

Final checklist

• Recognize multimorbidity as the usual situation, including in young adults and in poorer areas.
• Set aside one appointment to review the whole picture, not just each disease separately.
• Look for interactions between diseases, between treatments and with the person's life context.
• Ask what the person most wants to achieve and what they most want to avoid, and record the priorities.
• Assess the burden of treatment and the person's capacity before adding any recommendation.
• Review the full medication list and combine gradual changes with planned reassessment.

References

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