A double-blind, randomized controlled trial of duloxetine for pain in Parkinson's disease

Iwaki, Hirotaka; Ando, Rina; Tada, Satoshi; Nishikawa, Noriko; Tsujii, Tomoaki; Yamanishi, Yuki; Miyaue, Noriyuki; Yabe, Hayato; Nagai, Masahiro; Nomoto, Masahiro

doi:10.1016/j.jns.2020.116833

Cited by 12 publications

(12 citation statements)

References 22 publications

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“…Usually, a better tolerability can be reached by slow titration. A recent RCT of duloxetine 40 mg for 10 weeks in a group of selected patients with PD-related pains could not replicate the results of this previous study [88]. The study showed positive effects on various aspects of quality of life independently from effects on depression.…”

Section: Duloxetinecontrasting

confidence: 81%

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Diagnosis and Management of Pain in Parkinson's Disease: A New Approach

et al. 2021

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Pain is a frequent and disabling non-motor feature of Parkinson's disease (PD). The recently proposed PD Pain Classification System (PD-PCS) allows for an association of pain with PD to be determined before being allocated to the main pain mechanism (i.e. nociceptive, neuropathic, and nociplastic). In this article, previous studies on treatments for pain in PD are summarized according to the pain mechanisms. A mechanistic approach to treatment is discussed. We suggest that the first step should be optimizing dopaminergic therapy before other therapy is started. When these treatments remain unsuccessful, further causes of pain must be considered. The role of drugs, invasive treatments, and physiotherapeutic interventions are discussed with a focus on older PD patients and considering polypharmacy, altered pharmacokinetics, and comorbidities.

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Section: Duloxetinecontrasting

confidence: 81%

“…When pain does not respond to an optimization of the dopaminergic drug regimen, further pain therapy should be envisaged. To date, only three studies have targeted pain in PD [56,87,88]. In clinical practice, NSAIDs have been prescribed very often [89].…”

Section: Treatment Of Pd-related Pain With Non-dopaminergic Drugsmentioning

confidence: 99%

Diagnosis and Management of Pain in Parkinson's Disease: A New Approach

et al. 2021

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“…Indeed, in a small single-arm, open-label study, the majority of PD patients reported some degree of pain relief noted both on the Short-Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory after 6 weeks of treatment with the SNRI duloxetine [34–36]. However, a recent double-blinded RCT questioned these findings, as it failed to confirm a favorable effect of duloxetine on PD-related pain after ten weeks of treatment (measured as the change from baseline in 24-h average pain severity on a visual analog scale (VAS)) [37 ▪ ]. Another SNRI, venlafaxine, is often prescribed for various pain disorders such as chronic musculoskeletal pain, but its efficacy specifically for the treatment of PD-related pain is yet to be evaluated in a high-quality RCT [38].…”

Section: Noradrenaline and 5-hydroxytryptaminementioning

confidence: 99%

Pain in Parkinson's disease: Mechanism-based treatment strategies

Rukavina

Cummins

Bannister

2021

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewChronic pain, highly prevalent throughout the course of Parkinson's disease (PD), has been ranked as one of the top ten most bothersome symptoms people with Parkinson's (PwP) are experiencing. Yet, robust evidence-based treatment strategies are lacking. This unmet need is partly attributable to the multifaceted nature of PD-related pain, which results in part from a complex and poorly understood interplay involving a range of neurotransmitter pathways. Degeneration of nigrostriatal dopaminergic pathways and alterations of central nervous system extra-striatal dopaminergic, noradrenergic, serotoninergic, glutamatergic, opioidergic and endocannabinoid circuits may all promote a heightened experience of pain in PwP. Thus, the potential targets for mechanism-based pain-relieving strategies in PwP are several. These targets are discussed herein.Recent findingsAn increasing number of clinical trials and experimental studies in animal models of PD are being designed with the aim of addressing the pathophysiological mechanism(s) underlying PD-related pain. Overall, recent research findings highlight the analgesic effects of dopaminergic and opioidergic medication for certain subtypes of pain in PwP, whereas proposing novel strategies that involve targeting other neurotransmitter pathways.SummaryThe origin of pain in PwP remains under investigation. Although our understanding of the mechanisms underpinning persistent pain in PD has improved in recent years, this has not yet translated to clinical alleviation of this most troublesome nonmotor symptom. Patient stratification linked with evidence-based personalized pain-treatment plans for optimal analgesic relief will rely on advances in our understanding of the dopaminergic and nondopaminergic targets outlined in this review.

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“…42 In terms of efficacy in treating pain, mixed results have further been reported on SSRIs and other serotonergic antidepressants, including venlafaxine and duloxetine. 42 Duloxetine has been investigated to treat pain in PD, 37,43 with reports of central pain relief up to 65% of treated people. 43 However, in this study, depressed PwPD were excluded to avoid attributing the beneficial effect of duloxetine in PD pain to the antidepressant properties.…”

Section: Discussionmentioning

confidence: 99%

“…Ten studies [26][27][28][29][30][31][32][33][34][35] (Table 2) were further excluded because of 4 primary reasons: (1) no pain subitem data available because of time lapse since publication and destroyed data (n = 5); (2) no subitem analysis was ever performed on the scales, only overall scores (n = 2); (3) pain subitem questions were not physical PD pain and emotional pain (n = 1); and (4) unable to connect with corresponding authors (n = 2). A final list of only 3 studies [36][37][38] were included in the review (Fig. 1).…”

Section: Identification Of Studiesmentioning

confidence: 99%

Antidepressants Effects on Pain in Parkinson Disease: A Systematic Review

et al. 2021

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ObjectivePain in Parkinson disease (PD) is complex as this symptom can be multifactorial in origin because deficits in dopaminergic but also other neurotransmitters are involved. Pain and depression are increasingly recognized to have clinical importance for the quality of life of people living with PD. This systematic review aims to summarize the existing evidence on the potential benefit of using prescribed antidepressants for decreasing or controlling pain associated with PD.MethodsPubMed databases were searched for relevant studies using keywords and our exclusion/inclusion criteria and targeting only randomized placebo-controlled trials for antidepressants in PD.ResultsAfter screening 108 articles, only 3 focused articles were analyzed. Two of the included studies reported were on nortriptyline and paroxetine antidepressants. Unfortunately, included studies did not align in their outcome measures and did not directly compare the drug groups against each other or the placebo. Therefore, the complex nature of the unaligned outcome measures is inadequate for interpreting the efficacy of antidepressants in treating pain symptoms in PD. The third study focused solely on observing the effects of duloxetine but showed no favorable effects of this drug on pain.ConclusionsProspective studies with a direct comparison of antidepressants and placebo should be conducted, focusing on pain-related scales and questions to understand further the role of antidepressants in treating pain in PD.

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A double-blind, randomized controlled trial of duloxetine for pain in Parkinson's disease

Cited by 12 publications

References 22 publications

Diagnosis and Management of Pain in Parkinson's Disease: A New Approach

Diagnosis and Management of Pain in Parkinson's Disease: A New Approach

Pain in Parkinson's disease: Mechanism-based treatment strategies

Antidepressants Effects on Pain in Parkinson Disease: A Systematic Review

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