New medications for treatment-resistant depression: a brief review of recent developments

Thase, Michael E.

doi:10.1017/s1092852917000876

Cited by 14 publications

(10 citation statements)

References 43 publications

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“…Mood disorders are chronic, recurrent, and debilitating mental illnesses that affect the lives of millions of people worldwide and are leading contributors to the global burden of disease 1,2 . Many patients are refractory to conventional therapies and the development of new drugs with novel mechanisms of action is crucial 3,4 …”

Section: Introductionmentioning

confidence: 99%

Regulatory effect of lithium on hippocampal blood‐brain barrier integrity in a rat model of depressive‐like behavior

Taler

Aronovich²,

Hornfeld³

et al. 2020

Bipolar Disorders

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Objectives Recent evidence has associated mood disorders with blood‐brain barrier (BBB)/ neurovascular unit (NVU) dysfunction, and reduction in blood vessels coverage by the water channel aquaporin‐4 (AQP4) immunoreactive astrocytes. Lithium is an established treatment for mood disorders, yet, its mechanism of action is partially understood. We investigated the effects of lithium on BBB integrity and NVU‐related protein expression in chronic mild stress (CMS) rat model of depressive‐like behavior. Methods Male Wistar rats were exposed for 5 weeks to unpredictable mild stressors with daily co‐administration of lithium chloride to half of the stressed and unstressed groups. Sucrose preference and open field tests were conducted to validate the depressive‐like phenotype, and dynamic contrast‐enhanced MRI analysis was utilized to assess BBB integrity in brain regions relevant to the pathophysiology of depression. Hippocampal AQP4 and claudin‐5 expression were studied using immunofluorescence, western blot, and enzyme‐linked immunosorbent assays. Results Lithium administration to the stressed rats prevented the reductions in sucrose preference and distance traveled in the open field, and normalized the stress‐induced hippocampal BBB hyperpermeability, whereas lithium administration to the unstressed rats increased hippocampal BBB permeability. Additionally, lithium treatment attenuated the decrease in hippocampal AQP4 to glial fibrillary acidic protein immunoreactivity ratio in the stressed rats and upregulated hippocampal claudin‐5 and BDNF proteins expression. Conclusions Our findings suggest that lithium administration in a rat CMS model of depressive‐like behavior is associated with attenuation of stressed‐induced hippocampal BBB/NVU disruption. These protective effects may be relevant to the mode of action of lithium in depression.

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Section: Introductionmentioning

confidence: 99%

Regulatory effect of lithium on hippocampal blood‐brain barrier integrity in a rat model of depressive‐like behavior

Taler

Aronovich²,

Hornfeld³

et al. 2020

Bipolar Disorders

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“…The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD [2]. And other way for management of TRD is ketamine that is a new antidepressants with pharmaceutical pipeline [26]. Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that VAP may have better effect for TRD. So many studies were carried out in china [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. This also is the reasons that do meta-analysis to found magnesium valproate and antidepressants for therapy of treatment-resistant depression (TRD) in China is better or not.…”

Section: Discussionmentioning

confidence: 99%

The Role of the Magnesium Valproate in Therapy for Patients with Treatment-Resistant Depression (TRD): Meat-Analysis Results of Chinese Data

Fengpei¹

2018

IJPC

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Background: Major depressive disorder is a prevalent and disabling illnessv, approximately 70% of patients do not remit after first-line antidepressant treatment, and about 20% develop to treatment-resistant depression(TRD). Treatment of TRD have been one of clinical problems. Adjunctive valprovate was a most sued ways for treatment of TRD. The magnesium valproate was common drug for both episode and bipolar disorder in China and also was used for TRD. To systematically evaluate the difference in efficacy of magnesium valproate and antidepressants for therapy of treatment-resistant depression(TRD) in China. Methods: Searches were applied to the following electronic databases in china: Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG and Chinese Social Sciences Citation Index (VIP) databases. A total of 13 RCTs were included. A meta-analysis was performed of all the literatures germane to estimate the treatment-resistant depression patients treated with magnesium valproate combination with antidepressants and only antidepressants randomized controlled trials (RCTs) from 2010 to 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the meta-analysis was conducted with Revman4.2 software. Results: A total of 13 RCTs were included for meta-analysis. The results of meta-analysis demonstrated by effective rate and depressive symptoms change between two groups of combination treatment with magnesium valproate and only antidepressant. The effective rate was higher in magnesium valproate combination with antidepressants group than that in antidepressants group(81/306, 35/298, Z=4.60, P=0.00001). The depressive scale was lower found in magnesium valproate combination with antidepressants group than that in antidepressants group after treatment (Z=16.20, P <0.00001). These results indicated that magnesium valproate combination with antidepressants maybe one better therapeutic way for TRD. Conclusion: The results indicate that magnesium valproate combination with antidepressants was better than antidepressants group in effective rate and improving depressive symptoms during treatment of patients with TRD. So these results may recommend to the patients with TRD though without the differences between groups.

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“…Recently, several potential therapies for TRD have emerged, starting with the discovery of the antidepressant effects of ketamine, and followed by a renewed interest in antidepressant drugs with novel mechanisms of action (eg, esketamine, rapastinel, ALKS-5461 [combination of buprenorphine and samidorphan], and scopolamine) 10,11. However, the long-term benefits and costs of these drugs are unknown, and there remains an unmet need for effective new therapies for patients with TRD.…”

Section: Introductionmentioning

confidence: 99%

<p>Cost-effectiveness model for a hypothetical monotherapy vs standard of care in adult patients with treatment-resistant depression</p>

Wang¹,

Anderson

Mitchell³

et al. 2019

CEOR

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BackgroundPatients with treatment-resistant major depressive disorder (TRD) have limited treatment options. We developed an early stage cost-effectiveness model of TRD to explore the potential value of a hypothetical monotherapy relative to the standard of care (SOC). The relative impacts of the monotherapy’s three differentiating features over SOC are explored: efficacy advantage, tolerability advantage, and price premium.MethodsWe adapted an existing economic model of TRD to evaluate the cost-effectiveness of a hypothetical monotherapy for TRD with a 25% efficacy advantage, a 10% tolerability advantage, and a 50% price premium over SOC (selective serotonin reuptake inhibitor plus atypical antipsychotics [SSRI + AAP]). The model is a hybrid of a decision tree that captures patients’ outcomes after an 8-week acute treatment phase and a Markov model that simulates patients’ depression course through a 10-month maintenance phase. Sensitivity (deterministic and probabilistic) and scenario analyses were conducted to characterize the relative impacts of the monotherapy’s three differentiating features over SOC.ResultsOver the 12-month time horizon, the hypothetical monotherapy is shown to dominate SOC; it generates lower costs and higher quality-adjusted life years in comparison to SSRI + AAP. Sensitivity and scenario analyses showed that this dominance depends largely on the monotherapy’s efficacy and tolerability advantages over SOC. Specifically, a monotherapy with ≥ 12% efficacy or ≥70% tolerability advantage (and a 50% price premium) will always be superior to SSRI + AAP. Between these two extremes, most profiles, nonetheless, generate incremental cost-utility ratios for the monotherapy, which fall below common payer willingness-to-pay thresholds.ConclusionOur adaptation of an existing economic model of TRD provides a flexible platform for researchers to evaluate the efficacy/tolerability improvements required for a successful new TRD product and for decision-makers to assess the cost-effectiveness impact of uncertainties inherent in early stage product development in TRD.

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New medications for treatment-resistant depression: a brief review of recent developments

Cited by 14 publications

References 43 publications

Regulatory effect of lithium on hippocampal blood‐brain barrier integrity in a rat model of depressive‐like behavior

Regulatory effect of lithium on hippocampal blood‐brain barrier integrity in a rat model of depressive‐like behavior

The Role of the Magnesium Valproate in Therapy for Patients with Treatment-Resistant Depression (TRD): Meat-Analysis Results of Chinese Data

<p>Cost-effectiveness model for a hypothetical monotherapy vs standard of care in adult patients with treatment-resistant depression</p>

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