scholarly journals Pharmacological Treatments for Patients with Treatment-Resistant Depression

2020 ◽  
Vol 13 (6) ◽  
pp. 116 ◽  
Author(s):  
Valerie L. Ruberto ◽  
Manish K. Jha ◽  
James W. Murrough
Keyword(s):  
Treatment Options ◽  
Symptom Relief ◽  
Antidepressant Medication ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Qualitative Synthesis ◽  
Course Of Illness ◽  
Effective Strategies ◽  
Increased Risk ◽  
Resistant Depression

Over a third of patients with major depressive disorder (MDD) do not have an adequate response to first-line antidepressant treatments, i.e., they have treatment-resistant depression (TRD). These patients tend to have a more severe course of illness and are at an increased risk of suicide. Next step treatment options for patients with TRD, include switching to a different antidepressant, combining more than one antidepressant, or augmenting an antidepressant with another (non-antidepressant) medication. It is unclear which of these treatment approaches should be applied to a given patient, and in what order. Due to this ambiguity, comparing antidepressants and augmentation agents on the basis of their efficacy, tolerability, and speed of symptom relief would be beneficial for clinicians. To accomplish this, a systematic search was conducted following PRISMA guidelines. Only randomized controlled trials were included in this qualitative synthesis, resulting in 66 articles. This review identified several effective pharmaco-therapeutic strategies that are currently available for patients with TRD. Ketamine and esketamine appear to be effective for the treatment of TRD. Augmentation with certain second generation antipsychotics, such as quetiapine or aripiprazole is likewise effective, and may be preferred over switching to antidepressant monotherapy. While the combination of olanzapine and fluoxetine was one of the first pharmacotherapy approved for TRD, and its use may be limited by metabolic side-effects. Other effective strategies include augmentation with lithium, liothyronine (T3), lamotrigine, or combination of antidepressants including bupropion, tricyclics, or mirtazapine. There is insufficient research to demonstrate the efficacy of ziprasidone or levothyroxine (T4). A shared decision-making approach is recommended to guide treatment selection to address each patient’s individual needs.

scholarly journals Role of the Pharmacist in Managing Treatment-Resistant Depression: A Focus on Ketamine

Pharmacy ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 118
Author(s):  
Linda Xing Yu Liu ◽  
Marina Golts ◽  
Virginia Fernandes
Keyword(s):  
Current Practice ◽  
Quality Care ◽  
Treatment Options ◽  
Critical Role ◽  
Transitions Of Care ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Multiple Treatments ◽  
The Impact

The impact of depression is well described in the literature, and it is most prominent in patients who have trialed multiple treatments. Treatment-resistant depression (TRD) is particularly debilitating, and it is associated with significant morbidity and mortality. Despite this, there seems to be therapeutic inertia in adopting novel therapies in current practice. Ketamine is an N-methyl-D-aspartate receptor antagonist and anesthetic agent which has recently been shown to be effective in the management of TRD when administered intravenously or intranasally. The treatments, however, are not easily accessible due to restrictions in prescribing and dispensing, high costs, and the slow uptake of evidence-based practice involving ketamine within the Canadian healthcare system. Given the limited treatment options for TRD, novel approaches should be considered and adopted into practice, and facilitated by a multi-disciplinary approach. Pharmacists play a critical role in ensuring access to quality care. This includes dissemination of evidence supporting pharmacological treatments and facilitating translation into current practice. Pharmacists are uniquely positioned to collaborate with prescribers and assess novel treatment options, such as ketamine, address modifiable barriers to treatment, and triage access to medications during transitions of care. Extending the reach of these novel psychiatric treatments in both tertiary and primary care settings creates an emerging role for pharmacists in the collaborative effort to better manage treatment-resistant depression.

Treatments for Pediatric Depression

2015 ◽  
Author(s):  
Carolina Biernacki ◽  
Prerna Martin ◽  
Pablo H. Goldberg ◽  
Moira A. Rynn
Keyword(s):  
Positive Response ◽  
Behavioral Therapy ◽  
Antidepressant Medication ◽  
Psychosocial Interventions ◽  
Evidence Base ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Medication Treatment ◽  
Pediatric Depression ◽  
Resistant Depression

Practice guidelines recommend psychosocial interventions for mild or brief cases of pediatric depression. In moderate to severe cases, medication treatment is recommended, with or without cognitive-behavioral therapy (CBT). Fluoxetine and escitalopram are the only antidepressants approved by the U.S. Food & Drug Administration for acute pediatric depression. Among psychosocial interventions, CBT and interpersonal psychotherapy for adolescents (IPT-A) have the largest evidence base for treatment of depressed youth. Combination treatment with CBT and antidepressant medication is superior to treatment with either modality alone. In treatment-resistant depression, a switch in antidepressant is more likely to yield a positive response when medication is used with CBT. Antidepressants should be used judiciously in youths as higher rates of adverse events have been demonstrated, and data from adult trials cannot be systematically extrapolated to youths. Further studies are needed to assess alternative medication and psychosocial treatments as well as factors predictive of treatment response.

scholarly journals PAX-D: study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

2021 ◽  
pp. ebmental-2021-300282
Author(s):  
Sheena Kristine Au-Yeung ◽  
James Griffiths ◽  
Sophie Roberts ◽  
Chloe Edwards ◽  
Ly-Mee Yu ◽  
...  
Keyword(s):  
Decision Making ◽  
Depressive Symptomatology ◽  
Bipolar Depression ◽  
Antidepressant Medication ◽  
Well Being ◽  
Reward Processing ◽  
Self Report ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

IntroductionClinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole vs placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task.Methods and analysisPAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to week 12 post-randomisation measured using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Performance on the decision-making task will be measured at week 0, week 2 and week 12. Secondary outcomes include anhedonia, anxiety and health economic measures including quality of life, capability, well-being and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties.DiscussionPramipexole is a promising augmentation agent for TRD and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with TRD.Trial registration numberISRCTN84666271

scholarly journals A case of treatment-resistant depression in an older adult and a discussion of treatment options

2021 ◽  
pp. 1-6
Author(s):  
Emma Pope ◽  
Sabari Muthukrishnan ◽  
James Phillips ◽  
Sarah Phillips
Keyword(s):  
Personal Experience ◽  
Treatment Options ◽  
Poor Response ◽  
Current Evidence ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Geriatric Population ◽  
Treatment Of Depression ◽  
Resistant Depression ◽  
Careful Assessment

Treatment-resistant depression is a complex condition often requiring specialist psychiatric care. Many different psychiatric, physical and social factors can lead to a poor response to initial treatment of depression, and a careful assessment is required to determine the most appropriate management option. This can be particularly complex in the older population, who often have multiple physical and social comorbidities. We have used a fictional case to illustrate this, alongside an anonymised vignette of someone with personal experience of this condition. We have also provided an overview of the current evidence for treatment options, as well as a discussion of potential aetiological factors. By the end of this article, readers should understand the ambiguity of this diagnostic term, the aetiological factors that need to be assessed and the rationale for the treatment options available. They should be able to recognise how these ideas apply to the geriatric population.

scholarly journals Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245510
Author(s):  
Péter Döme ◽  
Péter Kunovszki ◽  
Péter Takács ◽  
László Fehér ◽  
Tamás Balázs ◽  
...  
Keyword(s):  
Cerebrovascular Diseases ◽  
Poor Quality ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Retrospective Data Analysis ◽  
Real World Evidence ◽  
Increased Risk ◽  
Autoimmune Conditions ◽  
Resistant Depression ◽  
Using Data

Purpose Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD. Patients and methods This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database. Results Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212–1.571]; p<0.001). Patients with TRD had a significantly higher probability of having “Neurotic, stress-related and somatoform disordersˮ, autoimmune conditions, cardio- or cerebrovascular diseases, thyroid gland diseases and self-harming behaviour not resulting in death than non-TRD patients (for all comparisons, p values were less than 0.005). Discussion To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of “Neurotic, stress-related and somatoform disordersˮ and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.

Therapeutic Strategies for Treatment-resistant Depression: State of the Art and Future Perspectives

2020 ◽  
Vol 26 (2) ◽  
pp. 244-252
Author(s):  
Kah K. Goh ◽  
Shen-Chieh Chang ◽  
Chun-Hsin Chen ◽  
Mong-Liang Lu
Keyword(s):  
Antidepressant Treatment ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Treatment Options ◽  
Therapeutic Strategies ◽  
Evidence Based ◽  
Inadequate Response ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Treatment Choices ◽  
Resistant Depression

In this narrative review, we intended to summarize the evidence of pharmacological and somatic treatment choices for treatment-resistant depression (TRD). There are several types of therapeutic strategies to improve inadequate response to antidepressant treatment. The first step for patients with TRD is to optimize the dosage and duration of antidepressants as well as to ensure their drug compliance. The shift to antidepressant and antidepressant combination therapy for patients with TRD cannot be regarded as an evidence-based strategy. Only the combination of a monoamine reuptake inhibitor with a presynaptic α2-autoreceptor antagonist might have better efficacy than other antidepressant combinations. Currently, the most evidence-based treatment options for TRD are augmentation strategies. Among augmentative agents, second-generation antipsychotics and lithium have the strongest evidence for the management of TRD. Further studies are needed to evaluate the augmentative efficacy of anticonvulsants, thyroid hormone, glutamatergic agents, anti-inflammatory agents, and nutraceuticals for TRD. Among somatic therapies, electroconvulsive therapy and repetitive transcranial magnetic stimulation are effective for TRD. Further studies are warranted to provide clinicians with a better recommendation in making treatment choices in patients with TRD.

scholarly journals Transcranial pulsed electromagnetic fields for treatment-resistant depression: A multicenter 8-week single-arm cohort study

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Erik Roj Larsen ◽  
Rasmus W. Licht ◽  
René Ernst Nielsen ◽  
Annette Lolk ◽  
Bille Borck ◽  
...  
Keyword(s):  
Cohort Study ◽  
Antidepressant Treatment ◽  
Treatment Options ◽  
Depression Scale ◽  
Antidepressant Effect ◽  
Hamilton Depression Scale ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Pulsed Electromagnetic

Abstract Background. The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression. Methods. A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group. Results. In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4. Conclusions. The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

scholarly journals Childhood maltreatment and characteristics of adult depression: Meta-analysis

2017 ◽  
Vol 210 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Janna Nelson ◽  
Anne Klumparendt ◽  
Philipp Doebler ◽  
Thomas Ehring
Keyword(s):  
Risk Factor ◽  
Childhood Maltreatment ◽  
Emotional Abuse ◽  
Meta Analysis ◽  
Age At Onset ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Course Of Illness ◽  
Adult Depression ◽  
Resistant Depression

BackgroundChildhood maltreatment has been discussed as a risk factor for the development and maintenance of depression.AimsTo examine the relationship between childhood maltreatment and adult depression with regard to depression incidence, severity, age at onset, course of illness and treatment response.MethodWe conducted meta-analyses of original articles reporting an association between childhood maltreatment and depression outcomes in adult populations.ResultsIn total, 184 studies met inclusion criteria. Nearly half of patients with depression reported a history of childhood maltreatment. Maltreated individuals were 2.66 (95% CI 2.38–2.98) to 3.73 (95% CI 2.88–4.83) times more likely to develop depression in adulthood, had an earlier depression onset and were twice as likely to develop chronic or treatment-resistant depression. Depression severity was most prominently linked to childhood emotional maltreatment.ConclusionsChildhood maltreatment, especially emotional abuse and neglect, represents a risk factor for severe, early-onset, treatment-resistant depression with a chronic course.

scholarly journals Critical review of available treatment options for treatment refractory depression and anxiety - clinical and ethical dilemmas

2016 ◽  
Vol 69 (5-6) ◽  
pp. 171-176 ◽  
Author(s):  
Dusan Kolar ◽  
Michael Kolar
Keyword(s):  
Anxiety Disorders ◽  
Ethical Dilemmas ◽  
Treatment Options ◽  
Depression And Anxiety ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Symptoms Of Depression ◽  
Mood And Anxiety Disorders ◽  
Resistant Depression ◽  
Treatment Refractory

Treatment-resistant mood and anxiety disorders require an intensive therapeutic approach, and it should balance benefits and adverse effects or other potential detrimental effects of medications. The goal of treatment is to provide consistent and lasting improvement in symptoms of depression and anxiety. Benzodiazepines are effective for anxiety symptoms, but with no sustained treatment effects. Other medication treatment options for anxiety disorders are outlined. Ketamine is usually very effective in treating major depressive disorder but without sustained benefits. Long-term use may pose a significant risk of developing tolerance and dependence. Stimulant medication augmentation for treatment-resistant depression is effective for residual symptoms of depression, but effects are usually short-lasting and it sounds more as an artificial way of improving energy, alertness and cognitive functioning. Synthetic cannabinoids and medical marijuana are increasingly prescribed for various medical conditions, but more recently also for patients with mood and anxiety disorders. All of these treatments may raise ethical dilemmas about appropri?ateness of prescribing these medications and a number of questions regarding the optimal treatment for patients with treatment-resistant depression and treatment refractory anxiety disorders.

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