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MPN and depression: What is the link?

Oct 22, 2020
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Studies have uncovered an association between myeloproliferative neoplasms (MPN) and depression, and it is believed that over one quarter of patients develop depressive symptoms. What remains unclear, however, is the link between MPN-associated depression and other variables, including symptoms.

Previously, an internet-based survey was created by MPN investigators, patients, and patient advocates with the aim to review fatigue and mood in patients with MPN. Leslie Padrnos et al. analyzed the collected data to assess depressive symptoms in these patients; the outcomes were recently published in Cancer Medicine. The MPN Hub hereby presents a summary.

Study design

A 70-item survey, primarily registered as a study of fatigue in patients with MPN, was circulated on numerous MPN-related websites. The survey was hosted by the Mayo Clinic Survey Research Center and was available for individuals self-identifying as patients with MPN.

Patients were required to report any comorbidities, and answer questions regarding

  • patient demographics
  • disease type and features
  • lifestyle factors
  • co-morbidities
  • MPN complications
  • MPN therapy
  • symptoms

There were several tools used to evaluate mood disorder symptoms among participating patients, including Profile of Mood States-B (POMS-B), Patient Health Questionnaire-2 (PHQ-2), and Mental Health Inventory (MHI-5). Depression was specifically assessed using the PHQ-2 (Table 1), and a score of ≥ 3 was found to be both a sensitive and highly specific screening tool for identifying patients who were at high risk of depression.

Table 1. Patient Health Questionnaire-2 format1

Over the past 2 weeks, how often have you been bothered by

any of the following problems?

Not at all

Several days

More than half the days

Every day

Little interest or pleasure in doing things

0

1

2

3

Feeling down, depressed, or hopeless

0

1

2

3

To assess MPN-related symptoms, the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) in combination with the Brief Fatigue Index (BFI) were applied. The MPN-SAF Total Symptom Score (MPN-SAF TSS; 0 – 100) was used as a quantitative measure of fatigue.

Results

  • Of the 1,788 completed surveys, 1,344 reported an MPN subtype diagnosis and included the responses needed to calculate the PHQ-2.
  • Patient characteristics by PHQ-2 scores are outlined in Table 2.
    • MPN subtype, MPN-directed treatment, and gender did not differ significantly between PHQ-2 scores of ≥ 3 and < 3.
    • Younger age and MPN characteristics, such as history of thrombosis and anemia, were associated with a PHQ-2 score of ≥ 3.
    • Education at a masters or doctorate level was associated with lower levels of PHQ-2 scores.
  • Certain mental disorders and lifestyle factors were associated with increased depressive symptoms (see Table 3).

Table 2. Patient characteristics by PHQ-2 score1

ET, essential thrombocythemia; MF; myelofibrosis; MPN, myeloproliferative neoplasm; PHQ-2, Patient Health Questionnaire-2; PV, polycythemia vera; SD, standard deviation.

Bold font indicates statistical significance between patients reporting PHQ-2 scores of ≥ 3 vs < 3.

Characteristic, % (unless otherwise stated)

PHQ-2 ≥ 3

(n = 309)

PHQ-2 > 3

(n = 1,035)

Total

(N = 1,344)

p

Age, mean (SD)

56.9 (12.2)

59.6 (11.6)

59.0 (11.8)

0.0003

Gender, male

31.7

32.3

32.1

0.85

Race (White)

95.5

96.4

96.2

0.53

Education

 

 

 

<0.0001

Middle school

1.9

1.1

1.3

 

High school

27.9

22.7

23.9

 

Undergraduate

48.4

39.4

41.5

 

Masters or advanced degree

18.8

28.6

26.4

 

Doctorate

2.9

8.2

7.0

 

MPN Diagnosis

 

 

 

0.78

ET

34.6

32.7

33.1

 

PV

39.5

41.4

40.9

 

MF

25.9

26.0

26.0

 

Time since first MPN diagnosis

 

 

 

0.08

< 1 year

11.7

7.1

8.1

 

1–3 years

21.5

19.97

20.1

 

> 3 years

6.8

73.2

71.7

 

MPN characteristics

 

 

 

 

Prior splenectomy

3.9

2.3

2.7

0.13

Thrombosis

23.4

16.6

18.2

0.0071

Cytopenias

 

 

 

 

Anemia

53.5

46.6

48.1

0.04

Received any blood

product transfusion

14.1

12.2

12.6

0.37

Received any blood

product transfusion

in prior 6 months

5.17

5.5

5.4

0.25

Table 3. Mental disorders and lifestyle factors by PHQ-2 score1

PHQ-2, Patient Health Questionnaire-2.

Factor, %

PHQ-2 ≥ 3 (n = 309)

PHQ-2 > 3 (n = 1,035)

p

Increased emotional stress

 

66.4

45.0

< 0.0001

New sleep disturbances

33.7

19.9

< 0.0001

Cigarette smoking

10.9

5

0.0003

Regular prescription pain medicine use

24.4

10.6

< 0.0001

Antidepressant use

31.3

11.9

< 0.0001

Anxiety medication use

15.4

8.6

0.0005

Low reports of regular exercise

< 0.0001

 MPN-related treatments

MPN-related treatments reported by patients included phlebotomy, transfusions, radiation, allogeneic stem cell transplants, and medications (including JAK-directed therapy). The number of patients who had received previous MPN-directed treatment was not significantly different between PHQ-2 ≥ 3 vs < 3. Although worse PHQ-2 scores were associated with anemia (Table 1), anemia-directed therapies, including recent transfusions, erythropoietin injections, and iron supplements were not associated with depressive symptoms.  

MPN-related symptoms

  • The following factors differed significantly between patients reporting PHQ-2 of ≥ 3 vs < 3:
    • MPN-SAF TSS (mean 40.8 vs 24.6; p < 0.001)
    • Higher worst fatigue score (mean 7.8 vs 5.8; p < 0.001)
    • Worse overall quality of life (mean 5.7 vs 3.1; p < 0.0001)

Fatigue

  • The period of fatigue differed significantly between patients reporting PHQ-2 of ≥ 3 vs < 3.
    • Patients who reported a PHQ-2 of ≥ 3 were more prone to all-day fatigue (42.7% vs 17.5%; p < 0.0001).
    • Patients who reported a PHQ-2 of < 3 were more prone to fatigue in the evening (35% vs 47%; p < 0.0001).
  • Patients who reported fatigue progression over the previous six months were more likely to report higher rates of depressive symptoms:
    • Very much worse (13% vs 4.2%; p < 0.0001)
    • Moderately worse (29% vs 12%; p < 0.0001)
  • The approaches taken to address fatigue were distinct between patients reporting different PHQ-2 scores.
    • Worse PHQ-2 scores were associated with setting priorities (79.7% vs 73.9%; p < 0.05), postponing non-essential activities (82.9% vs 71.8%; p = 0.0001), and napping (76% vs 68.3%; p < 0.05).
    • PHQ-2 < 3 scores were associated with exercise (77.1% vs 62.5%; p < 0.0001) and volunteering (33.4% vs 24.6%; p < 0.005).

Conclusion

Within a population of patients with MPN, this study reported that nearly a quarter had significant depressive symptoms. MPN-TSS score analysis showed that worse systemic symptoms were associated with significant depressive symptoms in these patients. In particular, increased levels of systemic symptoms of PV and MF, as well as daytime fatigue, were coupled to enhance depressive symptoms. Non-MPN-related factors were also associated with worse depressive symptoms.

When combined with findings from alternative studies, these data suggest that the risk of depressive symptoms is around 20% in patients with MPN and, therefore, similar to patients with high-risk hematological malignancies. Data from this study highlight that heavy symptom burden results in depressive symptoms, and so treating the systemic symptoms may improve or alleviate depression. Additionally, depressive symptoms could heighten systemic symptoms and the risk of cardiovascular events in patients with MPN, and so it becomes important to manage any underlying mood disorders.

Finally, understanding the risk of developing depression is important in the therapeutic decision-making process as certain treatments, such as interferon alpha, are contraindicated for patients with depression.

The authors outlined the main limitations of the study:

  • The PHQ-2 score cannot be used to diagnose depression; this requires confirmation by a physician following an in-person assessment.
  • Survey participants were predominantly White, highly educated, and all lived in the United States, resulting in a lack of racial, socioeconomic, and ethnic diversity.
  • Little information was obtained regarding the time course and effectiveness of mood related therapies (counseling, antidepressants) attempted by patients.
  • The study recorded depressive symptoms at one time point, so it remains unknown as to whether different phenotypes predispose individuals to prolonged symptoms.
  • An additional longitudinal analysis is required to determine the relationship between MPN diagnosis, treatment, symptom burden, and the risk of depressive symptom experience.

  1. Padrnos L, Scherber R, Geyer H, et al. Depressive symptoms and myeloproliferative neoplasms: Understanding the confounding factor in a complex condition. Cancer Med. 2020. Online ahead of print. DOI: 10.1002/cam4.3380

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