Recognizing and Treating Major Depression in Fibromyalgia: A Narrative Primer for the Non-Psychiatrist

Abstract

Fibromyalgia (FM) affects 2% to 8% of the general population. FM patients often experience self-stigma and feel rejected by healthcare providers and families, resulting in isolation and distressing symptoms of pain, fatigue, and poor cognitive functioning, increasing the risk of depressive symptoms. Major Depressive Disorder (MDD) is the most common comorbidity in FM patients (Any depression: 43%; MDD: 32%). Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia. Given that even minor symptoms of depression worsen the outcomes of FM patients, clinicians are challenged to identify and manage depression in these patients. However, due to overlapping symptoms, limited screening, and contamination bias, MDD often goes undiagnosed and presents a critical challenge. Unrecognized and untreated MDD in FM patients can exacerbate fatigue, sleep disturbances, and pain, reduce physical functioning, and increase the risk of developing comorbid conditions, such as substance abuse and cardiovascular disease. These comorbidities are associated with a lower treatment response rate, a higher dropout rate, and a greater risk of relapse. Clinicians may effectively identify and treat MDD in FM patients with appropriate pharmacologic agents combined with aerobic exercise and cognitive-behavioral therapies for core FM symptoms, thus significantly reducing symptom severity for both MDD and FM. Such a comprehensive approach will result in a much-improved quality of life. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. In this primer for clinicians caring for FM patients, we describe clinically relevant pharmacologic and non-pharmacologic management approaches for treating MDD in FM patients.

Introduction

Fibromyalgia (FM) is among the most challenging disorders in medicine, not only to diagnose but to effectively treat. ¹ The economic impact of FM can be staggering for patients who often see multiple specialists before receiving a diagnosis, as there are no laboratory investigations to confirm its presence. ¹ In a systematic review of direct medical and non-medical costs and/or indirect costs of FM, annual costs per person were extrapolated from 36 studies after adjusting for inflation in 2019 and ranged from $ 1750 to $ 35 920 in the USA and from $ 1250 to $ 8504 in Europe. ² The presence of comorbid depression in patients with FM may be the critical factor in preventing patients from achieving improvement across domains of functioning, pain, and quality of life. Family-based genome testing has found genetic overlap between FM and MDD.

Depression remains a controversial issue in FM, with diagnostic confusion occurring possibly due to the shared neurobiological pathways of pain and depression as fibromyalgia symptoms improve with certain antidepressants, ³ the overlap in symptoms of FM and depression with one increasing the risk of developing the other,^4,5 the lack of appropriate screening for depression in this population, and the stigma surrounding mental health diagnoses. This paper was designed to provide a roadmap for the identification and effective treatment of depression in FM. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. Data tells us that effective treatment of comorbid depression can profoundly affect the course of the disorder and the response to multicomponent treatment leading to improvements in pain, functioning, and psychological distress. ⁶

What is Fibromyalgia?

Fibromyalgia is a chronic condition marked by widespread musculoskeletal pain, often accompanied by fatigue, sleep, memory, and mood issues. It is thought to result from abnormal pain processing pathways in the central nervous system. Fibromyalgia (FM) is a poorly understood pain disorder occurring in 2% to 8% of the general population, with 80% of those affected being females.^{7 –11} The understanding of FM has undergone a significant evolution. Previously, FM was categorized as a neuropathic pain disorder due to the presence of widespread pain and sensitivity to touch. However, the International Association for the Study of Pain (IASP) has shifted away from classifying FM as neuropathic pain. ¹²

Instead, FM is now recognized as a complex pain disorder with multifactorial origins involving alterations in pain processing, central sensitization, and neuroendocrine dysregulation. Apart from pain and tenderness, FM encompasses various variable symptoms, including fatigue, unrefreshing sleep, and cognitive difficulties, often labeled as “fibro fog.”

As the American College of Rheumatology (ACR) outlines, the current diagnostic criteria for FM are widespread pain lasting at least 3 months and tenderness in at least 11 of 18 specified tender points when pressure is applied. However, the ACR has also recognized the limitations of tender point examination and has proposed an alternative diagnostic method. This alternative method involves a widespread pain index (WPI) and symptom severity (SS) scale, which evaluates the extent of pain and severity of associated symptoms such as fatigue, sleep disturbances, cognitive difficulties, and mood disturbances. ¹³ Fibromyalgia is a diagnosis of exclusion and conditions that mimic FM should be ruled out including rheumatoid arthritis, lupus, polymyalgia rheumatica and cancer. ¹⁴

FM is frequently co-morbid with various psychiatric illnesses, including MDD, persistent depressive disorder, generalized anxiety, and post-traumatic stress disorder. Patients with FM also experience high levels of anger, stress, sadness, fear, guilt,^{15 -18} and pain catastrophizing (exaggerated focus on pain, provoking fear, and increased pain perception). ¹⁹ Patients often feel stigmatized, isolated, misunderstood, and rejected by family, friends, and society because of the illness. These feelings contribute to higher pain perception, somatization, and poorer functioning.^20,21

Treatment of FM

The management of FM requires a comprehensive approach, integrating pharmacological treatments, aerobic exercise, and cognitive-behavioral therapies. Interventions designed to treat FM require a comprehensive and individualized approach. Guidelines from the European League Against Rheumatism (EULAR), Canada, Israel, and Germany on FM management show consensus on the overarching management principles, emphasizing personalized therapy and prioritizing non-pharmacological interventions such as patient education, exercise, and cognitive behavioral therapy (CBT). These guidelines diverge in recommendations about the pharmacological treatment of FM. Serotonin-norepinephrine reuptake Inhibitors (SNRIs), pregabalin, and amitriptyline are commonly recommended, with their endorsement strength varying from strong in some guidelines to weak in others, highlighting differences in evidence interpretation or availability. The Food and Drug Administration (FDA) has approved 3 specific treatments for FM: the antidepressants duloxetine and milnacipran, along with the anticonvulsant pregabalin. The overall approach to pharmacological treatment in FM stresses the importance of tailoring therapy to the individual’s symptoms and needs. There is often a trial-and-error process to identify the most effective and tolerable regimen.

As is the case for most chronic illnesses, treatment of FM is costly, with the need for long-term, individualized medications and therapy. ² Accessibility to specialized care and multidisciplinary teams is crucial but can be limited in some regions. Barriers to effective treatment often include stigma, lack of understanding both from patients and care providers and the challenge of managing a condition with variable symptoms. Strong patient support networks, access to informed healthcare providers, and personalized treatment plans that address the broad spectrum of FM symptoms improve symptoms and quality of life.

The coexistence of FM and major depression presents a complex clinical challenge, as both conditions share overlapping symptoms such as fatigue, cognitive difficulties, and sleep disturbances, making diagnosis and treatment difficult. This comorbidity exacerbates the severity of both conditions, leading to a more significant impact on quality of life and functional capacity. Effective management requires an integrated approach for screening, diagnosing, and managing MDD co-morbid with FM.

Pathophysiology of FM and MDD

The pathophysiology of comorbid FM and MDD is reviewed to assist the primary care provider or specialist in understanding the complexities of addressing depression in this population, as it involves several overlapping mechanisms:

• Neurochemical imbalances: Both FM and MDD are linked to altered levels of neurotransmitters such as serotonin, norepinephrine, and dopamine, affecting mood, pain perception, and sleep.^22,23

• Neuroendocrine dysregulation: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes are observed in FM and MDD, with changes in hormone levels contributing to symptoms of pain, mood disturbance, and fatigue.^24,25

• Neuroimaging Findings: Brain imaging studies show changes in regions involved in pain processing, such as the anterior cingulate cortex and insula, and mood regulation, like the amygdala and prefrontal cortex, which are implicated in both conditions.^{26 -28}

• Genetic studies: Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia using a (GWAS) approach. There is evidence of the serotonin transporter gene (SLC6A4) involvement in both conditions. ²⁹ A family-based GWAS approach to examine the genetic relationship between FM and MDD found a significant genetic overlap between the 2 conditions, with shared genetic variants contributing to the development of both. ³⁰

• Inflammatory markers: Elevated inflammatory markers, including interleukin-8 and TNF-α, are found in patients with FM and MDD, indicating a common inflammatory process that could explain increased pain sensitivity and fatigue.^{31 -33}

• Central sensitization: FM and MDD involve central sensitization, where repeated episodes increase the likelihood of future episodes through neuroplastic changes. ³⁴

Diagnostic challenges

MDD and FM have a bi-directional relationship. The lifetime prevalence of MDD in FM is 62% to 86%,^{35 -38} with concurrence for both disorders at any given point being 40%. ³⁹

• Overlap of symptoms: Both FM and MDD share common symptoms such as fatigue, pain, and cognitive difficulties, complicating the diagnosis. This overlap can lead to misdiagnosis or underdiagnosis of one or both conditions. ⁴⁰

• Stigma and mental health: Patients with FM might resist acknowledging depression due to the stigma associated with mental health issues. They might feel their physical symptoms are being dismissed or misunderstood as purely psychological. ⁴¹

• Lack of screening: There is often insufficient screening for depression in FM patients due to a lack of awareness about the high comorbidity rate and fragmented care approaches. ⁴²

• Alexithymia: This trait, characterized by difficulty identifying and describing emotions, can hinder patients’ ability to communicate their symptoms effectively, delaying diagnosis and treatment. ⁴³

Risks of unrecognized MDD in FM

• Poor outcomes: Unrecognized MDD can lead to increased pain, decreased physical function, and poorer quality of life for FM patients. ⁴⁴ It can exacerbate FM symptoms like fatigue and sleep disturbances. ⁴⁵

• Healthcare costs and utilization: Comorbid MDD and FM are associated with higher healthcare costs and service utilization. ² Direct healthcare costs for patients with both conditions exceed those for patients with only one. ⁴⁶

• Suicide risk: FM patients have a significantly higher risk of suicidal thoughts and behaviors, especially when comorbid with MDD.^47,48

Treatment strategies for MDD in FM

• Improving diagnosis: Screening tools like the Patient Health Questionnaire (PHQ-9) for MDD and the Fibromyalgia Rapid Screening Tool (FiRST) for FM can help identify early comorbid conditions.^49,50

• Therapeutic alliance: Building a strong, empathetic relationship between patient and provider can reduce stigma, improve treatment adherence, and enhance outcomes.^51,52

• Psychoeducation: Educating patients and their families about FM and MDD can reduce stigma, improve understanding, and promote self-management of symptoms.^53,54

• Psychotherapy: Cognitive behavioral therapy (CBT) and guided imagery can effectively reduce symptoms of both FM and MDD, enhancing patients’ quality of life.^55,56

• Exercise program: Regular physical activity, including aerobic exercise, stretching, and mind-body practices like Tai Chi and yoga, can significantly reduce depressive symptoms and improve FM symptoms.^{57 -65}

• Complementary treatments: Supplements such as 5-HTP and SAM-e, along with acupuncture and dry needling, show potential benefits but require more research for long-term efficacy.^66,67

• Pharmacological treatment: Duloxetine, an SNRI approved for FM and MDD, is the first-line pharmacological treatment. Other medications like milnacipran and pregabalin can help with FM symptoms, though their efficacy in treating comorbid MDD is less clear.

Principles of Pharmacotherapy

Clinicians must consider the overall symptom profile, severity of FM and MDD, other comorbid physical and mental health problems, and drug-drug interactions when choosing antidepressants to treat comorbid MDD in FM patients. Based on current evidence, unless otherwise contraindicated, duloxetine is a reasonable first choice for pharmacological treatment of MDD in FM. If an adequate therapeutic trial of duloxetine is not well tolerated or is ineffective for MDD, a trial of other antidepressants, even if not approved to treat FM, should be considered. In such cases, clinicians can add pregabalin or amitriptyline to address core FM symptoms, wherein the most disabling FM symptom informs the choice.

1. Discontinuation due to adverse effects and ineffectiveness requires balancing starting the medication at a smaller dose and educating and encouraging the patient to gradually increase the dose to therapeutic levels for 6 to 8 weeks to assess the effectiveness of antidepressant medications.

2. Titrating duloxetine from 30 mg once daily to 60 mg daily after one week can reduce FM pain, anxiety, and depression. Milnacipran’s starting dose is 12.5 mg daily, and clinicians can slowly titrate it up to 50 mg twice daily to improve FM pain. Dosage should be adjusted for individuals unable to tolerate the side effects and those with renal insufficiency.^8,9 Pregabalin dosing starts at 75 mg twice daily and can be titrated up to a target of 225 mg twice daily, depending on an individual’s creatinine clearance.^8,9 In the literature, 450 mg and 600 mg have been cited as having the most significant benefit for reducing pain. Medication management of FM and MDD is summarized in Table 1.

Table 1.

Summary of Medication Management for Comorbid MDD and FM.

Medication	Description
Duloxetine	• First-line pharmacological treatment for comorbid MDD in FM. • Reduces pain severity, improves physical function, and directly and indirectly affects mood. • Starting dosage: 30 mg once daily, max dose 120 mg daily, with 60 mg daily being the usual maintenance dose. • Common adverse effects: Nausea, headache, constipation, dry mouth, dizziness, diarrhea, hyperhidrosis • May be taken with or without food. • Recommend taking with food if experiencing nausea and staying well-hydrated to reduce the risk of constipation and mitigate hyperhidrosis. • Recommend taking at the same time every day. • Approved for treatment of FM with/without MDD by FDA
Milnacipran	• Second-line choice for FM with weaker evidence for improvement of depressive symptoms. • Effective in reducing pain, fatigue, and global perception of improvement. • Starting dosage: 12.5 mg daily, titrated up to 50 mg twice daily. • Common adverse effects: Nausea, constipation, hyperhidrosis, palpitations • May be taken with or without food. • Recommend taking with food if experiencing nausea and staying well-hydrated to reduce the risk of constipation and mitigate hyperhidrosis. • Recommend taking at the same time every day. • Approved for treatment of FM by FDA
Amitriptyline	• Tricyclic antidepressant used off-label in small dosages for FM. • Modest therapeutic response for improvement in pain, sleep, fatigue, and global perception of improvement. • Effective dose: 25 mg/day. • Common adverse effects: Dry mouth, somnolence, gastrointestinal disturbances. • Recommend taking before bedtime to improve sleep and minimize daytime somnolence. • May be taken with or without food. • Higher doses are less effective for FM. • Effective dose for FM is subtherapeutic for MDD.
Pregabalin	• Third-line choice for FM. • Effective in improving pain and sleep quality. • Moderately effective in reducing comorbid anxiety and subsyndromal depressive symptoms. • Starting dosage: 75 mg twice daily, titrated up to 225 mg twice daily. • Common adverse effects: Dizziness, somnolence • Recommend taking at the same time every day. • Recommend taking evening dose before bedtime to improve sleep. • May be taken with or without food. • Approved for treatment of FM by FDA
Selective Serotonin Reuptake Inhibitors (SSRIs)	• Fluoxetine and other SSRIs may reduce pain, depression, fatigue, and overall symptoms. • Combination with other medications or complementary/alternative methods can enhance effectiveness. • Common adverse effects: Nausea, vomiting, diarrhea, headache, somnolence • May be taken with or without food.
Gabapentin	• Antiepileptic effective for neuropathic pain and used off-label for FM. • Effective in reducing pain and sleep quality. • Effective dosages: 1200 to 2400 mg daily in divided doses 2 to 3 times daily; Gralise-Extended-release version which is once daily. • Common adverse effects: Dizziness, somnolence, peripheral edema, clumsiness, or unsteadiness, uncontrolled back-and-forth or rolling eye movements. • Titrate dosage upwards of 300 mg each day until it is an effective dosage. • Recommend taking the evening dose before bedtime or Gralise with the evening meal or before bedtime to improve sleep. • May be taken with or without food. • No improvement in depressive symptoms.

Abbreviations: FDA, Food and Drug Administration; FM, Fibromyalgia; MDD, Major Depressive Disorder; SSRI, Selective Serotonin Reuptake Inhibitor.

Duloxetine: Multiple randomized, double-blind, placebo-controlled trials have established duloxetine’s effectiveness in reducing pain severity in FM. ⁶⁸ Several Randomized Controlled Trials (RCTs) have concluded that duloxetine 60 and 120 mg daily reduces fibromyalgia pain more effectively than the placebo.^69,70 The higher dose of 120 mg daily was more effective than a placebo in reducing tender points. Duloxetine at both dosages improved the overall sense of well-being and improved sleep. ⁷¹ In studies specifically investigating a subgroup of FM patients with MDD, duloxetine treatment arms significantly reduced depression scales at both dosages. ⁷² A pooled analysis from 4 double-blind, placebo-controlled RCTs suggested that duloxetine treatment can directly improve pain in patients with both FM and MDD, accounting for 69% of the pain improvement. ⁷⁰ Additionally, the improvement in mood accounted for 31% of the pain response indirectly. ⁷⁰ Therefore, both the direct analgesic properties of duloxetine and the indirect effects on mood appear to be relevant for treating these comorbid patients.

Discontinuation rates due to adverse effects were high in all studies. Treatment-emergent adverse effects were dose-dependent. Studies using a lower starting dose of duloxetine had a lower discontinuation rate. Adverse events occurring significantly more frequently with duloxetine included nausea, headache, constipation, dry mouth, dizziness, diarrhea, and hyperhidrosis. ⁷¹

Overall, duloxetine provides modest improvement in pain, physical function, depressive symptoms, and global well-being in fibromyalgia patients compared to placebo, but adverse effects can limit patient acceptance. ⁷² Starting the medication at lower dosages to improve tolerance but getting to the therapeutic dose for effectiveness is essential for addressing both pain and depressive symptoms.

Milnacipran: Three randomized controlled trials comparing milnacipran to placebo found that milnacipran significantly improved pain, fatigue, and global perception of improvement compared to placebo. Two trials investigated a fixed dose of 200 mg, while the other investigated 100 and 200 mg dosages. Both dosages were effective for composite FM and pain improvement but had minimal effect on sleep quality.^{73 -75} A post hoc analysis revealed that pain improvement was only weakly associated with baseline depressive symptoms and was independent of improvements in depressive symptoms. ⁷⁶ While milnacipran is not FDA-approved for the treatment of major depression, studies have found it more effective than a placebo for the improvement of depressive symptoms in FM. It has also been shown to be as effective as selective serotonin reuptake inhibitors (SSRIs) in treating MDD. ⁷⁷ Nausea, constipation, hyperhidrosis, and palpitations were common treatment-emergent adverse effects. ⁷⁸

Amitriptyline: Multiple small randomized controlled trials have studied the effectiveness of amitriptyline in dosages of 25 to 50 mg/day. Amitriptyline 25 mg/day but not 50 mg/day is associated with modest therapeutic response for improvement in pain, sleep, fatigue, and overall patient impression compared to placebo.^79,80 Of all the medications used for FM, amitriptyline has the most robust sleep improvement data. Discontinuation rates due to adverse effects, most commonly dry mouth, somnolence, gastrointestinal disturbances, and weight gain, were higher at higher dosages.^81,82 Given that dosages of amitriptyline used in these studies were subtherapeutic for the treatment of MDD, we cannot draw any conclusions about its effectiveness in improving core depressive symptoms in FM patients. ⁸³

Pregabalin: Several randomized controlled studies and metanalysis have established the efficacy of pregabalin in improving FM symptoms of pain and sleep quality. The most significant improvement in pain was at dosages of 450 mg and 600 mg for sleep quality. ⁸⁴ Dizziness and somnolence were the most common and dose-dependent adverse effects, reported by about 30% of participants receiving the medication. ⁸⁵ Pregabalin is moderately effective in reducing comorbid anxiety and subsyndromal depressive symptoms. Improvement in pain was independent of baseline mood and anxiety symptoms and any improvement in such symptoms. ⁸⁶

SSRIs: Fluoxetine doses of 10 to 80 mg daily reduced fatigue, pain, depression, and overall symptoms. ⁸⁷ Lower doses are less efficacious but can still provide relief with other medications, such as amitriptyline, or with complementary and alternative methods. ⁸⁵

Other antidepressants: Mirtazapine is an antidepressant with noradrenergic and specific serotonergic activity that has been used for FM symptoms. One group reviewed 3 studies with 606 participants that compared mirtazapine to placebo over 7 to 13 weeks. ⁸⁸ There was no difference between mirtazapine and placebo for pain relief of 50% or greater, Patient Global Impression of Change (PGIC), improvement in health-related quality of life (HRQOL) of 20% or greater, reduction in fatigue, or improvement in mood. ⁸⁸ A systematic review of venlafaxine found only one RCT (randomized clinical trials) and a few small open-label studies for the treatment of FM. While venlafaxine was well tolerated in these studies, its effectiveness for core FM symptoms was not established. ⁸⁹

Gabapentin: In an RCT, gabapentin in dosages of 1200 to 2400 mg was found to significantly reduce pain and improve the quality of life for fibromyalgia patients. Gabapentin was also positively associated with improving sleep quality. However, there was no improvement in depressive symptoms. ⁹⁰

Comparative effectiveness: A large systematic review ⁹¹ and network meta-analysis comparing the effectiveness and tolerability of amitriptyline, pregabalin, duloxetine, and milnacipran in reducing fibromyalgia symptoms reported that duloxetine at 120 mg was most effective in reducing pain and depressive symptoms, and amitriptyline in improving sleep, fatigue, and quality of life. Another network meta-analysis ⁹² comparing duloxetine, pregabalin, and amitriptyline reported that 25 mg of amitriptyline was most effective for a 50% reduction in pain. In contrast, a Bayesian network meta-analysis ⁹³ reported pregabalin and duloxetine to be most effective in the overall impact of FM as measured by the Fibromyalgia Impact Questionnaire (FIQ).

Non-pharmacological treatments for MDD in FM

Psychoeducation

Educating patients and family members about depression and FM and helping them recognize the symptoms reduces catastrophic thinking, improves the sense of control, and reduces stigma. Psychoeducation provided individually or in a group setting can reduce depression and anxiety symptoms and improve pain and overall quality of life. A recent systematic review found psychoeducation beneficial in reducing anxiety and depression levels, pain, fatigue, and improved functional status. ⁵⁴

• Explain the relationship between fibromyalgia and depression: It is essential to explain to patients that fibromyalgia and depression are often linked and that having one condition can exacerbate symptoms of the other. This approach can help patients understand why they may be experiencing both conditions and reduce any confusion or frustration they may be feeling.

• Discuss treatment options: There are various treatment options for both fibromyalgia and depression, and it is essential to discuss them with patients. Treatment for depression may include therapy and/or medication, while treatment for fibromyalgia may include medications, exercise, and other lifestyle changes. A combination of treatments may be necessary to manage both conditions effectively.

• Stress the importance of self-care: Clinicians should remind patients suffering from fibromyalgia and depression of the importance of self-care. These recommendations include getting enough sleep, eating a healthy diet, and engaging in regular physical activity. (“Maintaining a healthy emotional state is crucial to living a healthy life.”) Stress reduction techniques, such as meditation or yoga, may also be helpful.

• Provide resources: Patients with fibromyalgia and depression may benefit from additional resources, such as support groups or educational materials. Primary care providers can provide patients with information on these resources or refer them to a mental health specialist or support group.

• Encourage regular follow-up: Regular follow-up appointments can help ensure patients get the care they need for both conditions. Primary care providers should encourage patients to keep appointments and discuss any changes in symptoms or side effects of medications.

Psychotherapy

Cognitive behavior therapy (CBT) and guided imagery have been effective for FM. CBT focuses on identifying negative automatic thoughts, cognitive distortions, and maladaptive behavioral patterns. CBT has become a cornerstone of treating mild to moderate MDD. There is increasing evidence of its effectiveness in reducing depressive and anxiety symptoms, catastrophic thinking, decreased healthcare utilization, and improved quality of life for patients with FM. ⁵⁵

Guided imagery helps the patient create an internal image to promote adaptive emotional and behavioral changes. Meta-analysis and systematic reviews have consistently shown up to 50% improvement in pain with guided imagery. ⁵⁶

Exercise program

Active FM patients display lower rates of moderate to severe depression than their inactive counterparts. One study reported noticeable differences in depressive symptoms between inactive and active patients with FM, with a positive correlation between the severity of depression and physical inactivity in FM patients. ⁵⁷

Several studies have shown diverse types of exercise (aerobic, resistance, and stretching) of 3 to 4 week duration^58,59 contribute to improved quality of life and enhance pain reduction in patients with FM,^{60 -62} with aerobic exercise, even at low-intensity benefiting FM patients. ⁶³ This is why a multidisciplinary Delphi consensus considers aerobic exercise a core treatment for all FM symptoms. ⁶⁴ However, it is important that the quantity and intensity of aerobic exercise be adapted to an individual’s physical condition and disease symptoms. ⁵⁴ Initiating aerobic exercise below an individual’s physical capacity and gradually increasing to a moderate intensity as tolerated can improve acceptability. ⁶⁵

Depressive symptoms are a barrier to engaging in exercise, ⁹⁴ but studies have consistently shown that exercise benefits depressive symptoms. Research demonstrates that aerobic and pool-based exercises effectively reduce depressive symptoms in patients with fibromyalgia.^54,95,96 A 30-minute exercise program, 3 days a week for 23 weeks, significantly reduced depression levels. ⁹⁶ A 12-week Tai Chi ⁹⁷ and 8-week yoga program ⁹⁸ reduced depressive symptoms in patients with FM.

These studies indicate core FM symptoms and depressive symptoms responding to several types of exercises. Further research is necessary to determine the most effective individualized regimes to ensure maximum adherence and long-term sustainability of exercise regimens in depressed FM patients.

Complementary treatment

There is limited evidence for the use of various supplements and over-the-counter medications for addressing depressive symptoms in FM. Natural supplements L-5 hydroxytryptophan (5-HTP) and S adenosylmethionine (SAM-e) may improve depression ⁶⁶ ; 5-HTP, derived from the amino acid tryptophan, is an immediate precursor of serotonin, a neurotransmitter that regulates mood, sleep, and appetite. SAM-e is involved in neurotransmitter production such as serotonin, which may help reduce depression. Dry needling and acupuncture have been reported to improve pain, anxiety, depression, fatigue, stiffness, quality of sleep, and quality of life in FM patients. Both interventions were noted to be beneficial in the short term, but the techniques still need to be sufficiently studied for long-term effects. ⁶⁷

Conclusion and recommendations

The effective identification and treatment of comorbid MDD in FM patients requires a comprehensive and individualized approach. Clinicians must be vigilant in screening for depression in FM patients and employ a combination of pharmacological and non-pharmacological treatments to improve patient outcomes. Addressing the limitations and barriers to treatment can enhance the quality of life for patients suffering from both FM and MDD.

Effectively treating depression in FM is an important goal for providers to gain improvement in pain, functioning, and psychological distress. This paper reviewed important concepts and challenges in approaching patients for evaluation and treatment of depression.

1. Due to the high comorbidity of MDD in patients with FM, the presence of depression should be evaluated in every patient diagnosed with FM.

2. Education is essential to reduce stigma and improve compliance.

3. Non-pharmacological treatment, especially exercise, should be a component of any treatment plan to address depression in FM.

4. Pharmacologic treatment includes 3 FDA-approved medications for FM. Duloxetine is the only one approved for MDD and FM and should be considered a first-line choice.

5. Multicomponent treatment programs that include cognitive behavioral therapy have shown effectiveness in reducing pain, improving the level of functioning, and improving psychological distress, including depression.

6. Patients with fibromyalgia may benefit from modifications to their treatment plan after initial clinical evaluation and consideration should be given by the clinician to regular follow up of these patients if necessary. ⁹⁹

Limitations

• Generalization of findings: The discussion in the paper is broad and may not account for individual variations in symptom presentation and response to treatment, nor does it consider demographic factors such as age, gender, or cultural differences.

• Limited discussion on screening tools: While screening tools like PHQ-9 and FiRST are mentioned, their potential limitations or challenges, such as false positives/negatives or applicability in diverse populations, are not discussed.

• Insufficient evidence for complementary treatments: While the paper mentions complementary treatments like supplements and acupuncture, it acknowledges limited evidence for their use but does not critically evaluate the quality of existing studies or potential side effects.