scholarly journals Animal models of major depression: drawbacks and challenges

2019 ◽  
Vol 126 (11) ◽  
pp. 1383-1408 ◽  
Author(s):  
Barbara Planchez ◽  
Alexandre Surget ◽  
Catherine Belzung
Keyword(s):  
Major Depression ◽  
Animal Models ◽  
Poor Response ◽  
Treatment Resistant Depression ◽  
Recurrent Depression ◽  
Treatment Resistant ◽  
Neuronal Populations ◽  
Future Challenges ◽  
Resistant Depression ◽  
Depression Subtypes

Abstract Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to poor response to antidepressant therapy. Progress in this area requires valid animal models. Current models are based either on manipulating the environment to which rodents are exposed (during the developmental period or adulthood) or biological underpinnings (i.e. gene deletion or overexpression of candidate genes, targeted lesions of brain areas, optogenetic control of specific neuronal populations, etc.). These manipulations can alter specific behavioural and biological outcomes that can be related to different symptomatic and pathophysiological dimensions of major depression. However, animal models of major depression display substantial shortcomings that contribute to the lack of innovative pharmacological approaches in recent decades and which hamper our capabilities to investigate treatment-resistant depression. Here, we discuss the validity of these models, review putative models of treatment-resistant depression, major depression subtypes and recurrent depression. Furthermore, we identify future challenges regarding new paradigms such as those proposing dimensional rather than categorical approaches to depression.

scholarly journals A Review of the Conceptualisation and Risk Factors Associated with Treatment-Resistant Depression

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jenifer A. Murphy ◽  
Jerome Sarris ◽  
Gerard J. Byrne
Keyword(s):  
Major Depression ◽  
Poor Response ◽  
Clinical Problem ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Rank One ◽  
System Activation ◽  
Resistant Depression ◽  
Staging Model ◽  
Inflammatory System

Major depression does not always remit. Difficult-to-treat depression is thought to contribute to the large disease burden posed by depression. Treatment-resistant depression (TRD) is the conventional term for nonresponse to treatment in individuals with major depression. Indicators of the phenomenon are the poor response rates to antidepressants in clinical practice and the overestimation of the efficacy of antidepressants in medical scientific literature. Current TRD staging models are based on anecdotal evidence without an empirical rationale to rank one treatment strategy above another. Many factors have been associated with TRD such as inflammatory system activation, abnormal neural activity, neurotransmitter dysfunction, melancholic clinical features, bipolarity, and a higher traumatic load. This narrative review provides an overview of this complex clinical problem and discusses the reconceptualization of depression using an illness staging model in line with other medical fields such as oncology.

Toward Optimal Treatments for Major Depression

CNS Spectrums ◽  
2002 ◽  
Vol 7 (2) ◽  
pp. 148-154 ◽  
Author(s):  
Pierre Blier ◽  
Herbert Ward
Keyword(s):  
Major Depression ◽  
Therapeutic Response ◽  
Antidepressant Drug ◽  
Treatment Resistant Depression ◽  
Antidepressant Response ◽  
Controlled Clinical Trials ◽  
Treatment Resistant ◽  
Ongoing Research ◽  
Resistant Depression ◽  
First And Second Generation

ABSTRACTThe treatment of major depression remains problematic for several reasons. In particular, the therapeutic response to medications usually does not manifest itself until a week after administration has begun, and more than half the patients will not experience a full recovery with the first antidepressant drug administration. There are, however, some pharmacologic strategies that can accelerate antidepressant response. When facing a treatment-resistant depression, combination therapy offers a more time-efficient approach to achieve remission than drug substitution. These interventions have been devised on a better understanding of the basis for the therapeutic response obtained with the first- and second-generation antidepressants, and evidence derived from controlled clinical trials of their superior effectiveness is growing. The rationale for such approaches will be described in this article, as well as their advantages and potential inconveniences. Ongoing research in this field continues to fuel the development of novel, better-tolerated, and more effective pharmacotherapies for depression.

142. Levels of Immune Factors in Depression Subtypes of Treatment Resistant Depression

2017 ◽  
Vol 81 (10) ◽  
pp. S59
Author(s):  
Sun Yu ◽  
Xuejun Liu ◽  
Jaskaran Singh ◽  
James Palmer ◽  
Giacomo Salvadore ◽  
...  
Keyword(s):  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Immune Factors ◽  
Depression Subtypes

Pharmacogenomic testing for treatment resistant depression

2014 ◽  
Vol 4 (5) ◽  
pp. 236-239
Author(s):  
Susan G. Leckband
Keyword(s):  
Genetic Testing ◽  
Genetic Factors ◽  
Poor Response ◽  
Trial And Error ◽  
Treatment Resistant Depression ◽  
Antidepressant Response ◽  
Treatment Resistant ◽  
Dose Selection ◽  
Multiple Trials ◽  
Resistant Depression

The percentage of patients who have failed to completely or partially respond to multiple trials of antidepressants at adequate doses and for an adequate duration of therapy has varied in the literature and is considered substantial. Numerous strategies exist to treat poor antidepressant response, but often medications are selected on a “trial and error” basis. Genetic factors may play a role in poor response or intolerance to treatment with antidepressants which lead to treatment failures. Currently, available genetic testing as well as genetic testing currently under research may help guide clinicians with proper medication and dose selection.

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 A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Eduardo Jorge Muniz Magalhães ◽  
Luciana Maria Sarin ◽  
Lorena Catarina Del Sant ◽  
Ana Cecília Lucchese ◽  
Carolina Nakahira ◽  
...  
Keyword(s):  
Sexual Abuse ◽  
Adult Population ◽  
Positive Family History ◽  
Poor Response ◽  
Depression Symptom ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
History Of ◽  
Resistant Depression ◽  
The Impact

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD).Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients.Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction.Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine.

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