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. 2023 Aug 4;24(Suppl 1):S105-S114.
doi: 10.1093/pm/pnad006.

Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect

Ajay D Wasan  1 , Robert R Edwards  2 , Kevin L Kraemer  3 , Jong Jeong  4 , Megan Kenney  5 , Kevin Luong  1 , Marise C Cornelius  2 , Caitlin Mickles  1 , Bhagya Dharmaraj  1 , Essa Sharif  6 , Anita Stoltenberg  6 , Trent Emerick  1 , Jordan F Karp  7 , Matt J Bair  8   9 , Steven Z George  10   11 , William M Hooten  6
Affiliations

Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect

Ajay D Wasan et al. Pain Med. .

Abstract

Objective: Patients with chronic low back pain (CLBP) and comorbid depression or anxiety disorders are highly prevalent. Negative affect (NA) refers to a combination of negative thoughts, emotions, and behaviors. Patients with CLBP with high NA have greater pain, worse treatment outcomes, and greater prescription opioid misuse. We present the protocol for SYNNAPTIC (SYNergizing Negative Affect & Pain Treatment In Chronic pain).

Design: A randomized comparative-effectiveness study of antidepressants, fear-avoidance rehabilitation, or their combination in 300 patients with CLBP with high NA. In the antidepressant- or rehabilitation-only arms, SYNNAPTIC includes an adaptive design of re-randomization after 4 months for nonresponders.

Setting: A multisite trial conducted in routine pain clinical treatment settings: pain clinics and physical and occupational therapy treatment centers.

Methods: Inclusion criteria include CLBP with elevated depression and anxiety symptoms. Antidepressant and rehabilitation treatments follow validated and effective protocols for musculoskeletal pain in patients with high NA. Power and sample size are based on superior outcomes of combination therapy with these same treatments in a 71-subject 4-arm pilot randomized controlled trial.

Conclusions: SYNNAPTIC addresses the lack of evidence-based protocols for the treatment of the vulnerable subgroup of patients with CLBP and high NA. We hypothesize that combination therapy of antidepressants plus fear-avoidance rehabilitation will be more effective than each treatment alone.

Trial registration: ClinicalTrials.gov ID: NCT04747314.

Keywords: chronic low back pain; comparative effectiveness; negative affect; randomized trial.

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Figures

Figure 1.
Figure 1.
SYNNAPTIC trial schema. AD = antidepressant; AEFAR = application-enhanced fear-avoidance rehabilitation; CPM = conditioned pain modulation; CLBP = chronic low back pain; NA = negative affect.
Figure 2.
Figure 2.
Conditioned pain modulation in low- and high-NA groups. Data presented as group means ± SEM. *Groups differ at P < 0.05 on nonparametric Mann-Whitney U tests. CPT = conditioned pain testing; NA = negative affect; PPTh = pressure pain threshold testing.
Figure 3.
Figure 3.
Pilot study results in 71 subjects with CLBP and high NA. Data presented as proportion of responders ± SE. *AD+FABPT group differs at P < 0.05 on nonparametric Fisher exact tests vs the AD, FABPT, and education-only treatment groups. AD = antidepressants; FABPT = fear-avoidance–based physical therapy; FXN = function; MCID = minimum clinically important difference.
See this image and copyright information in PMC

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