Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis

Abstract

Objective: Duloxetine is a treatment approved by the US Food and Drug Administration for both osteoarthritis (OA) pain and depression, though uptake of duloxetine in knee OA management varies. We examined the cost-effectiveness of adding duloxetine to knee OA care in the absence or presence of depression screening.

Methods: We used the Osteoarthritis Policy Model, a validated computer microsimulation of knee OA, to examine the value of duloxetine for patients with knee OA who have moderate pain by comparing 3 strategies: 1) usual care, 2) usual care plus duloxetine for patients who screen positive for depression on the Patient Health Questionnaire 9 (PHQ-9), and 3) usual care plus universal duloxetine. Outcome measures included quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Model inputs, drawn from the published literature and national databases, included annual cost of duloxetine ($721-937); average pain reduction for duloxetine (17.5 points on the Western Ontario and McMaster Universities Osteoarthritis Index pain scale [0-100]), and likelihood of depression remission with duloxetine (27.4%). We considered 2 willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY. We varied parameters related to the PHQ-9 and the cost of duloxetine, efficacy, and toxicities to address uncertainty in model inputs.

Results: The screening strategy led to an additional 17 QALYs per 1,000 subjects and increased costs by $289/subject (ICER = $17,000/QALY). Universal duloxetine led to an additional 31 QALYs per 1,000 subjects and $1,205 per subject (ICER = $39,300/QALY). Under the majority of sensitivity analyses, universal duloxetine was cost-effective at the $100,000/QALY threshold.

Conclusion: The addition of duloxetine to usual care for knee OA patients with moderate pain, regardless of depressive symptoms, is cost-effective at frequently used WTP thresholds.

Figure 1

Panel A. The usual care (UC) treatment sequence for knee OA in the OAPol Model. Subjects are initialized based on specific cohort characteristics and progress through the regimens outlined, including corticosteroids, tramadol, oxycodone (for some subjects, others skip opioid regimens), total knee replacement, and revision total knee replacement. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence. Panel B. The depression screening treatment sequence for knee OA in the OAPol Model. Subjects are initialized based on specific cohort characteristics and are screened for depression using the Patient Health Questionnaire 9 (PHQ-9) at initialization. If they screen positive, they receive duloxetine before UC, consisting of corticosteroids, tramadol, oxycodone (for some subjects, others skip opioid regimens), total knee replacement, and revision total knee replacement. If they screen negative, they proceed directly to UC. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence. Panel C. The universal duloxetine treatment sequence for knee OA in the OAPol model. Subjects are initialized based on specific cohort characteristics and receive duloxetine before progressing through the rest of the UC treatments, including corticosteroids, tramadol, oxycodone (for some subjects, others skip opioid regimens), total knee replacement, and revision total knee replacement. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence.

Figure 2

Panel A. Univariate sensitivity analyses of parameters related to duloxetine, prevalence of depressive symptoms, and the Patient Health Questionnaire 9 (PHQ-9) for the screening strategy. Incremental cost-effectiveness ratios (ICERs) for the screening strategy are presented in relation to variations in the pain and depression efficacy of duloxetine, the prevalence of depressive symptoms, and the sensitivity and specificity of the PHQ-9. All parameters were held at base case values except for the parameter listed on the vertical axis, which was varied according to the values listed. The orange line represents the base case. Panel B. Univariate sensitivity analyses of parameters related to duloxetine, prevalence of depressive symptoms, and the PHQ-9 for the universal duloxetine strategy. ICERs for universal duloxetine compared to the screening strategy are presented in relation to variations in the pain and depression efficacy of duloxetine, the prevalence of depressive symptoms, and the sensitivity and specificity of the PHQ-9. All parameters were held at base case values except for the parameter listed on the vertical axis, which was varied according to the values listed. Parameters presented are the same as those presented for the screening strategy, with the exception that the lowest value of pain efficacy presented is 50% of base case, as the no pain efficacy scenario was dominated. The orange line represents the base case.

Figure 3.

Tipping point sensitivity analysis of the cost of duloxetine. The incremental cost-effectiveness ratios (ICERs) for depression screening and universal duloxetine are presented in relation to relative increases in the cost of an annual prescription of 60 mg of generic duloxetine. Solid lines represent base case toxicity values; dotted lines represent the increased toxicity parameters, which includes an increased risk of falls and sexual dysfunction. Red lines represent the $50,000 and $100,000/QALY willingness-to-pay thresholds.

Figure 4.

Probabilistic sensitivity analyses were conducted varying the toxicity rates, pain and depression efficacy of duloxetine, the sensitivity of the PHQ-9, and prevalence of depressive symptoms. 500 iterations of probabilistic inputs were run. Incremental cost-effectiveness ratios (ICERs) were calculated for each iteration comparing UC (grey dashed line), the depression screening strategy (blue), and universal duloxetine (green). The ICERs for these strategies were compared to a range of willingness-to-pay (WTP) thresholds, and that which produced the greatest quality-adjusted life expectancy while remaining below the WTP threshold was termed the preferred strategy. The probability of being the preferred strategy is plotted against various WTP thresholds.