Polymyalgia rheumatica (PMR) is a common inflammatory condition that leads to pain and stiffness.¹ A feeling of prolonged muscle stiffness in the morning is a typical symptom of PMR, but the condition can also present with several other symptoms including depression.¹ We will look at the associations between these two debilitating conditions. 

What causes PMR?

PMR is related to age and typically occurs in people aged 65 and above; it is rare in people under the age of 50.^1,2 It occurs more commonly in women.¹ PMR is thought to arise from a ‘combination of genetic and environmental factors’, but the exact underlying cause is largely unknown.¹ It is thought to be an autoimmune condition, in which the immune system attacks the body’s healthy cells.² 

PMR – key symptoms

PMR presents with many of the following symptoms:^1,2

• Most commonly, gradually developing pain and stiffness in the muscles of the upper arms, shoulders, neck and hips
  • Muscle stiffness is typically worse in the morning and can last for 45 minutes or longer
• Extreme fatigue/tiredness
• Fever
• Change in weight and appetite (decreased appetite and weight loss)
• Depression 

PMR diagnosis

In 1979, Bird and colleagues set out to define a way in which to standardise the diagnosis of PMR.³ By analysing the symptoms of over 200 patients considered to have PMR, they found 7 criteria that stood out as indicators of the condition. These are:

• Age >65 years
• Erythrocyte sedimentation rate (ESR) of >40 mm/hr
  • ESR is a blood test to measure inflammation which looks at how quickly red blood cells fall in a test tube – the greater the distance in millimetres (mm) per hour (hr), the higher the levels of inflammation⁴
• Bilateral (i.e., on both sides) shoulder pain and/or stiffness 
• Stiffness that lasts for >1 hour
• Onset duration of >2 weeks
• Depression and/or weight loss
• Bilateral upper arm tenderness

PMR can be diagnosed with reasonable confidence if a person presents with 3 or more of these criteria.

Several other blood tests on top of ESR can be performed to examine levels of inflammation in the body and to eliminate other autoimmune conditions that may present similarly to PMR (such as rheumatoid arthritis). Factors such as C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-cyclic citrullinated peptide (anti-CCP) can be investigated.²

But not any one test definitively points to PMR, and the diagnosis must be clinical, based on the signs and symptoms of the individual. Although elevated levels of ESR and CRP have been most implicated in PMR, normal levels of these markers should not preclude PMR diagnosis.⁵

However, assessments for PMR and depression specifically have not been investigated since Bird et al.’s 1979 criteria were set out. Indeed, depression can vary greatly in presentation and severity and is challenging to define in PMR, which itself presents with a variety of symptoms and degrees of severity and impairment.⁵ PMR also presents later in life and may be accompanied by other comorbidities (other conditions) associated with the ageing process, muddying the waters further.⁵

Before we take a closer look at the relationship between PMR and depression in more detail, let’s find out what depression is. 

What is depression?

Depression is a common but serious and debilitating mental health condition, which can drastically impact a person’s ability to manage daily activities. Depression is also known as major depression, major depressive disorder (MDD) or clinical depression, and there are many different types and classifications in the gold standard manual for diagnosing mental health conditions – the DSM-5 (which stands for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). 

For a diagnosis of depression, a person must have symptoms for a minimum of 2 weeks and nearly every day. These symptoms can include:⁶

• Persistent sadness, emptiness, hopelessness, or tearfulness
• Loss of interest or pleasure in activities 
• Weight loss of gain
• Changes in appetite
• Changes in sleep (sleeping too much or too little or suffering from insomnia)
• Loss of energy or fatigue
• Feeling worthless or excessively or inappropriately guilty 
• Poor concentration or indecisiveness 
• And in severe cases, thoughts of death or suicide (known as suicidal ideation), or planning or attempting suicide

Like PMR, depression is thought to be caused by a combination of factors, genetic and environmental. Other risk factors can include stress, family history or traumatic life events. In older adults and the elderly, depression can occur alongside other diseases and conditions. Evidence suggests that those who suffer from depression as well as other medical conditions at the same time will typically experience higher severity of symptoms in both diseases.⁶

PMR and depression – what are the associations? 

It was found that a majority of research looks at depressive symptoms (rather than fully diagnosed cases of depression) in the context of PMR,⁵ and that much of the research that looks at comorbidities in PMR including depression are small-scale and of low methodological quality.⁵ Studies and reviews have also focused more on other conditions that co-occur with PMR, such as cancer, stroke and vascular disease, rather than mental health.⁷ 

Patient-reported outcomes (PROs) can be used to screen for depression but again present a risk of showcasing symptoms that may be related to depression or that may be related to other conditions, for instance, physical health problems.^5,8 Interestingly, one study found that depression was indeed higher in PMR patients with other comorbid conditions.⁸ The tools used to assess PMR, such as short-form questionnaires, are important to consider, as they typically only ask about elements of depression rather than screening for the condition as a whole.⁵

Whether depression is actually ‘mimicking’ PMR is hard to know. Evidence shows elevated levels of depression in many elderly patients referred for rheumatological support suffering from chronic conditions, and this can be regardless of whether it’s PMR or another rheumatic or musculoskeletal ailment such as fibromyalgia.^9,10

The role of inflammation in PMR and depression has been reviewed⁵ but no studies have found a link between depression and inflammation and its potential causal role in the onset of PMR.⁵ Although evidence has shown that patients with higher levels of one anti-inflammatory marker (interleukin 10, or IL-10) had considerably fewer PMR symptoms (including depression), and another showed some links to prolactin (PRL), depression was not being assessed in a robust and standardised way to make these findings reliable.⁵

As we will learn about later (in the ‘Treatment’ section below), PMR patients are treated with anti-inflammatory drugs (known as steroids, glucocorticoids, or corticosteroids).^1,5 It is well established that glucocorticoids can lead to adverse events – physical, cognitive, behavioural and psychological. 

Glucocorticoids have been shown to increase the prevalence of depression in older persons, through mechanisms that alter the production of brain chemicals such as neurotransmitters (e.g., dopamine, serotonin).^5,11 As PMR patients are treated with glucocorticoids, it is possible they develop depression secondary to taking the medication, as well as many other side effects (such as increased risk of infection, high blood pressure, stomach ulcers, osteoporosis, and weight gain).¹

The NHS states that ‘1 in 20 people experience changes in their mental state when they take prednisolone’. To complicate matters further, most antidepressant drugs used for the treatment of depression can alter the activity of glucocorticoids.¹²

However, study designs need to be made more robust for any firm conclusions to be drawn about the complex interactions of these disease states and the medications used to treat them. The paucity of robust research means we cannot determine the prevalence of depression in PMR patients, making it harder to understand which populations are affected (and potentially why), and what support they need.⁵

Treatment

The most common treatment for PMR is a glucocorticoid medicine called prednisone (or prednisolone). Patients are treated over 12-24 months and doses can be reduced over this timeframe.^1,5 Prednisone is usually offered as a tablet. It is an effective treatment for inflammation and can help relieve many of the symptoms of PMR (though it cannot cure it).¹

Patients are typically given moderate doses to start with, and this can be reduced over time if symptoms improve. Low doses should be taken for about 2 years to help prevent relapse; steroids should never be stopped abruptly.¹ Painkillers (e.g., paracetamol) can be taken to reduce pain over time.

Active follow-up every 3 months with your GP will enable a better recovery and ensure the right dose of prednisone is being taken at any given time. You can also discuss how you are responding to treatment and any side effects you are experiencing with your healthcare practitioner. Blood tests may also be carried out to examine inflammatory markers in your body. Anyone taking steroids for 3 weeks or more should be given a steroid card which gives details of the medication and dose.¹

Prednisone is also used to help symptoms of another condition, called temporal arteritis (or giant cell arteritis, GCA); about 20% of people with PMR are at risk of developing this serious and dangerous condition.¹ GCA is characterised by inflammation of the blood vessels (arteries) of the head and back, and presents as new and persistent headaches, with scalp tenderness, changes in vision and jaw pain.^1,2 Anyone experiencing these symptoms should seek immediate medical attention.

Summary

PMR is a common inflammatory disease of unknown cause. As a condition that can be easily mistaken for other chronic pain conditions (such as rheumatoid arthritis), PMR has been subject to diagnostic criteria defined in the late 1970s, which includes the presence of depression.

Treatment for PMR is using a steroid medicine called prednisone. Symptoms can improve in a few days, but steroid doses are adjusted over time to help prevent relapse. However, prolonged use of glucocorticoids can lead to many adverse effects such as weight gain, infection, and depression. However, this medicine should never be stopped abruptly. The complex interplay of PMR and depression is not fully understood and more research is needed to clarify this link.

If you, or anyone you know, experience symptoms mentioned in this article that concern you, please seek advice from a healthcare professional. If you experience new and persistent headaches, it is advisable to seek immediate medical attention.