The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States

Zhdanava, Maryia; Pilon, Dominic; Ghelerter, Isabelle; Chow, Wing; Joshi, Kruti; Lefèbvre, Patrick; Sheehan, John J.

doi:10.4088/jcp.20m13699

Cited by 270 publications

(144 citation statements)

References 3 publications

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“…Our study focused on the entanglement of clinical variables and biochemical parameters in the occurrence of TRD in quite a large sample of patients hospitalized for MDD. In line with literature [37,41], TRD was present in slightly more than one-third (35.9%) of the recruited sample. In addition, with regard to rating scales, our sample showed scores that are reliable for inpatients with a diagnosis of MDD (HAM-D and MADRS mean total scores with standard deviations corresponding to a moderate-to-severe major depressive episode) [34,42].…”

Section: Discussionsupporting

confidence: 91%

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression

Buoli

Capuzzi

Caldiroli

et al. 2022

Behavioral Sciences

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Background: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. Aims: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. Methods: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Results: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. Conclusion: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

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Section: Discussionsupporting

confidence: 91%

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression

Buoli

Capuzzi

Caldiroli

et al. 2022

Behavioral Sciences

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“…In Taiwan, 21% of patients treated for MDD were then classified as having TRD [32]. In the USA, 30.9% of treated MDD patients were classified as having TRD [24]. The much lower (8.3% in Hungary and 6.6% in the USA) as well as the much higher (55% in the UK) TRD prevalence reported in the literature can be explained by methodological differences in the inclusion criteria, the definition of TRD, or the source of the data [23,28,33].…”

Section: Trd Prevalencementioning

confidence: 99%

“…Total depression-related costs for TRD patients have been estimated to be 19 times higher than for other depressive patients [22]. In the USA, up to 47% of depression-associated costs are attributable to treatment resistance [2,24]. In Poland, the direct costs of depression exceed 1 billion PLN, while the indirect costs have been estimated at 1-2.6 billion PLN [25,26].…”

Section: Introductionmentioning

confidence: 99%

Treatment-Resistant Depression in Poland—Epidemiology and Treatment

Gałecki

Samochowiec

Mikułowska³

et al. 2022

JCM

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(1) Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. Although several antidepressant drugs have been developed, up to 30% of patients fail to achieve remission, and acute remission rates decrease with the number of treatment steps required. The aim of the current project was to estimate and describe the population of treatment-resistant depression (TRD) patients in outpatient clinics in Poland. (2) Methods: The project involved a representative sample of psychiatrists working in outpatient clinics, chosen through a process of quota random sampling. The doctors completed two questionnaires on a consecutive series of patients with MDD, which captured the patients’ demographics, comorbidities, and medical histories. TRD was defined as no improvement seen after a minimum of two different antidepressant drug therapies applied in sufficient doses for a minimum of 4 weeks each. The data were weighted and extrapolated to the population of TRD outpatients in Poland. (3) Results: A total of 76 psychiatrists described 1781 MDD patients, out of which 396 fulfilled the criteria of TRD. The TRD patients constituted 25.2% of all MDD patients, which led to the number of TRD outpatients in Poland being estimated at 34,800. The demographics, comorbidities, medical histories, and histories of treatment of Polish TRD patients were described. In our sample of the TRD population (mean age: 45.6 ± 13.1 years; female: 64%), the patients had experienced 2.1 ± 1.6 depressive episodes (including the current one), and the mean duration of the current episode was 4.8 ± 4.4 months. In terms of treatment strategies, most patients (around 70%) received monotherapy during the first three therapies, while combination antidepressant drugs (ADs) were applied more often from the fourth line of treatment. The use of additional medications and augmentation was reported in only up to one third of the TRD patients. During all of the treatment steps, patients most often received a selective serotonin reuptake inhibitor (SSRI) and a serotonin norepinephrine reuptake inhibitor (SNRI). (4) Conclusions: TRD is a serious problem, affecting approximately one fourth of all depressive patients and nearly 35,000 Poles.

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“…Given that ~20% of American adults suffer from a mental illness in a given year ( 256 ), the economic burden of these disorders is estimated to be in the hundreds of billions of dollars annually ( 257 , 258 ). Moreover, the current standard of care treatments suffer from slow onset (e.g., 7 week average response time with citalopram) ( 259 ), low efficacy (only 27% of depressed patients achieved remission after 12 weeks of citalopram treatment as measured by HAM-D) ( 259 ), and often intolerable side-effects ( 260 ), it is clear that we need to expand psychiatry's arsenal to include a variety of new approaches.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, all the therapists who participate in the psilocybin and MDMA clinical development programs are required to hold a professional license and demonstrate clinical experience in psychotherapy or mental health counseling ( 288 ). Although institutes such as the California Institute of Integral Study (CIIS), Multidisciplinary Association for Psychedelic Studies (MAPS), and corporate programs from companies like COMPASS Pathways offer short-term training programs for psychedelic-assisted counseling, there is a huge demand and supply gap for competent therapists considering that the estimated prevalence of treatment-resistant depression (TRD) in the U.S. is around 2.8 million people ( 258 ). Moreover, given that set and setting are well-known to influence the subjective effects of psychedelics ( 288 , 297 ), clinical centers with appropriate facilities will need to be established.…”

Section: Introductionmentioning

confidence: 99%

Psychedelics and Other Psychoplastogens for Treating Mental Illness

et al. 2021

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Psychedelics have inspired new hope for treating brain disorders, as they seem to be unlike any treatments currently available. Not only do they produce sustained therapeutic effects following a single administration, they also appear to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorders, substance abuse disorder, and alcohol use disorder, among others. Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health. Here we discuss the importance of structural plasticity in the treatment of neuropsychiatric diseases, as well as the evidence demonstrating that psychedelics are among the most effective chemical modulators of neural plasticity studied to date. Furthermore, we provide a theoretical framework with the potential to explain why psychedelic compounds produce long-lasting therapeutic effects across a wide range of brain disorders. Despite their promise as broadly efficacious neurotherapeutics, there are several issues associated with psychedelic-based medicines that drastically limit their clinical scalability. We discuss these challenges and how they might be overcome through the development of non-hallucinogenic psychoplastogens. The clinical use of psychedelics and other psychoplastogenic compounds marks a paradigm shift in neuropsychiatry toward therapeutic approaches relying on the selective modulation of neural circuits with small molecule drugs. Psychoplastogen research brings us one step closer to actually curing mental illness by rectifying the underlying pathophysiology of disorders like depression, moving beyond simply treating disease symptoms. However, determining how to most effectively deploy psychoplastogenic medicines at scale will be an important consideration as the field moves forward.

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The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States

Cited by 270 publications

References 3 publications

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression

Treatment-Resistant Depression in Poland—Epidemiology and Treatment

Psychedelics and Other Psychoplastogens for Treating Mental Illness

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