Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar Depression

Fawcett, Jan; Rush, A. John; Vukelich, John; Diaz, Shanna H.; Dunklee, Lucas; Romo, Paul E.; Yarns, Brandon C.; Escalona, Rodrigo

doi:10.1176/appi.ajp.2015.15060788

Cited by 71 publications

(50 citation statements)

References 37 publications

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“…As a subset of treatment resistant depressed patients have elevated systemic inflammation that respond to drugs specifically targeting inflammation (Raison et al, 2013), and with recent reports of dopamine agonist medication such as pramipexole being effective in treatment resistant depression (Fawcett et al, 2016), there is further opportunity to systematically use drugs that modulate dopaminergic neurotransmission as antidepressant medication in depressed patients with elevated pre-treatment levels of inflammatory biomarkers.…”

Section: 0 Discussionmentioning

confidence: 99%

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Jha

Minhajuddin

Gadad

et al. 2017

Psychoneuroendocrinology

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161

113

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Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n=51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n=55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient=−0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient=0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder.

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Section: 0 Discussionmentioning

confidence: 99%

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Jha

Minhajuddin

Gadad

et al. 2017

Psychoneuroendocrinology

Self Cite

161

113

View full text Add to dashboard Cite

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“…Hence, our findings are consistent with the potential role of drugs modulating dopaminergic neurotransmission in treatment of depression. For example, application of pramipexole, a dopamine receptor agonist, was reportedly effective in a recent case series of treatment resistant depression patients (46), particularly those patients with elevated IL-17 levels.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection

Jha

Minhajuddin

Gadad

et al. 2017

Brain, Behavior, and Immunity

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Background Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n=166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results There was a significant treatment-arm-by- IL-17 interaction for depression severity (p=0.037) but not for side-effects (p=0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size=0.78, p=0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

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“…Most studies to date have focused on compounds such as cyclooxygenase (COX) inhibitors or minocycline, (Raison et al, 2013b) COX inhibitors Mixed results in psychiatric patients (Köhler et al, 2014;Sommer et al, 2012) Minocycline Reduced negative symptoms in schizophrenia (Köhler et al, 2014;Sommer et al, 2012) DA synthesis L-DOPA Increased motivation in PD (Czernecki et al, 2002) BH4 Case reports: improves depressive/motor symptoms (Pan et al, 2011;Sato et al, 2014) SAMe Evidence of success as adjuvant in MDD (Papakostas et al, 2010;Sarris et al, 2014;Sarris et al, 2015) L-Methylfolate Evidence of success as adjuvant in MDD (Ginsberg et al, 2011;Godfrey et al, 1990;Papakostas et al, 2012;Shelton et al, 2015) DA receptors D2 agonists Successful adjuvant in unipolar and bipolar depression (Cassano et al, 2004;Cusin et al, 2013;Fawcett et al, 2016;Franco-Chaves et al, 2013) Adenosine A2A antagonists…”

Section: Therapies That Block Inflammationmentioning

confidence: 99%

“…In addition to compounds that may increase DA availability and release, adenosine (A2A) receptor antagonists, which are thought to facilitate the activation of DA D2 receptors, are efficacious in reversing decreased effort-based sucrose consumption after DA depletion with tetrabenazine (a vesicular monoamine transporter inhibitor) and after peripheral administration of IL-1β in rats (Chen et al, 2001;Collins et al, 2010;Nunes et al, 2014;Xie et al, 2009;Yohn et al, 2015). The DA receptor agonist, pramipexole, has been shown to block endotoxin-induced degeneration of nigrostriatal DA cells (Iravani et al, 2008), and has also demonstrated the efficacy in unipolar and bipolar patients with treatment-resistant depression (Cassano et al, 2004;Cusin et al, 2013;Fawcett et al, 2016;Franco-Chaves et al, 2013).…”

Section: Strategies To Facilitate Da Packaging and Release Or Da Recementioning

confidence: 99%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

319

237

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Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

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Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar Depression

Cited by 71 publications

References 37 publications

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

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