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Journal ArticleDOI

Clinical factors associated with treatment resistance in major depressive disorder: results from a European multicenter study.

TL;DR: The findings provide a set of 11 relevant clinical variables associated with treatment resistance in major depressive disorder that can be explored at the clinical level and show that comorbid anxiety disorder is the most powerful clinical factor associated with TRD.
Abstract: Objectives Very few studies have investigated clinical features associated with treatment-resistant depression (TRD) defined as failure of at least 2 consecutive antidepressant trials. The primary objective of this multicenter study was to identify specific clinical and demographic factors associated with TRD in a large sample of patients with major depressive episodes that failed to reach response or remission after at least 2 consecutive adequate antidepressant treatments. Method A total of 702 patients with DSM-IV major depressive disorder, recruited from January 2000 to February 2004, were included in the analysis. Among them, 346 patients were considered as nonresistant. The remaining 356 patients were considered as resistant, with a 17-item Hamilton Rating Scale for Depression score remaining greater than or equal to 17 after 2 consecutive adequate antidepressant trials. Cox regression models were used to examine the association between individual clinical variables and TRD. Results Among the clinical features investigated, 11 variables were found to be associated with TRD. We found anxiety comorbidity (p 1 (p = .003, OR = 1.6), recurrent episodes (p = .009, OR = 1.5), early age at onset (p = .009, OR = 2.0), and nonresponse to the first antidepressant received lifetime (p = .019, OR = 1.6) to be the factors associated with TRD. Conclusions Our findings provide a set of 11 relevant clinical variables associated with treatment resistance in major depressive disorder that can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated with TRD.
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Journal ArticleDOI
TL;DR: The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders and provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus.
Abstract: Objectives: To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. Methods: Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care.

643 citations


Cites background from "Clinical factors associated with tr..."

  • ...Despite much investigation, consistent empirical associations between melancholic features and superior response to antidepressant medication have not been established (Dodd and Berk, 2004; Georgotas et al., 1986; Mallinckrodt et al., 2005; Nierenberg, 2003; Peselow et al., 1992; Souery et al., 2007; Trivedi et al., 2006; Uher et al., 2011; Uher et al., 2012)....

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  • ...While antidepressant medications have evidence of efficacy in this group, outcomes are often poorer than for subjects without comorbid anxiety (Papakostas et al., 2012; Souery et al., 2007; Tollefson et al., 1994)....

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Journal ArticleDOI
TL;DR: It is suggested that the problem of depression comprises three sub-problems: first episodes in people with low vulnerability ('simple' depressions); an increase in vulnerability and autonomy from stress that develops over episodes of depression (kindling); and factors that confer vulnerability to a first episode (a depressive diathesis).

421 citations

Journal ArticleDOI
TL;DR: Treatment-resistant depression may present an annual added societal cost of $29-$48 billion, pushing up the total societal costs of major depression by as much as $106-$118 billion, and underscore the need for research on the mechanisms of depression, new therapeutic targets, existing and new treatment combinations, and tests to improve the efficacy of and adherence to treatments for treatment- resistant depression.
Abstract: Treatment-resistant depression exacts a heavy price in treatment costs and lost productivity, reaching into the tens of billions of dollars, but its effects on the lives of patients are just as devastating. In this literature review, the authors summarize 62 studies documenting the disease’s toll on quality of life, personal financial resources, and general health. The average patient in the included studies had experienced nearly four earlier episodes of depression, had not responded to 4.7 drug trials, and continued to meet or nearly meet criteria for severe depression.

405 citations

Journal ArticleDOI
TL;DR: In Caucasians 5-HTTLPR may be a predictor of antidepressant response and remission, while in Asians it does not appear to play a major role.

286 citations

Journal ArticleDOI
TL;DR: Preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine.
Abstract: Newer antidepressants are needed for the many individuals with major depressive disorder (MDD) that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine's effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine.

241 citations

References
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Journal ArticleDOI
TL;DR: The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type, used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information.
Abstract: Types of Rating Scale The value of this one, and its limitations, can best be considered against its background, so it is useful to consider the limitations of the various rating scales extant. They can be classified into four groups, the first of which has been devised for use on normal subjects. Patients suffering from mental disorders score very highly on some of the variables and these high scores serve as a measure of their illness. Such scales can be very useful, but have two defects: many symptoms are not found in normal persons; and less obviously, but more important, there is a qualitative difference between symptoms of mental illness and normal variations of behaviour. The difference between the two is not a philosophical problem but a biological one. There is always a loss of function in illness, with impaired efficiency. Self-rating scales are popular because they are easy to administer. Aside from the notorious unreliability of self-assessment, such scales are of little use for semiliterate patients and are no use for seriously ill patients who are unable to deal with them. Many rating scales for behaviour have been devised for assessing the social adjustment of patients and their behaviour in the hospital ward. They are very useful for their purpose but give little or no information about symptoms. Finally, a number of scales have been devised specifically for rating symptoms of mental illness. They cover the whole range of symptoms, but such all-inclusiveness has its disadvantages. In the first place, it is extremely difficult to differentiate some symptoms, e.g., apathy, retardation, stupor. These three look alike, but they are quite different and appear in different settings. Other symptoms are difficult to define, except in terms of their settings, e.g., mild agitation and derealization. A more serious difficulty lies in the fallacy of naming. For example, the term "delusions" covers schizophrenic, depressive, hypochrondriacal, and paranoid delusions. They are all quite different and should be clearly distinguished. Another difficulty may be summarized by saying that the weights given to symptoms should not be linear. Thus, in schizophrenia, the amount of anxiety is of no importance, whereas in anxiety states it is fundamental. Again, a schizophrenic patient who has delusions is not necessarily worse than one who has not, but a depressive patient who has, is much worse. Finally, although rating scales are not used for making a diagnosis, they should have some relation to it. Thus the schizophrenic patients should have a high score on schizophrenia and comparatively small scores on other syndromes. In practice, this does not occur. The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type. It is used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information. The interviewer may, and should, use all information available to help him with his interview and in making the final assessment. The scale has undergone a number of changes since it was first tried out, and although there is room for further improvement, it will be found efficient and simple in use. It has been found to be of great practical value in assessing results of treatment.

29,488 citations

Journal Article
TL;DR: The Mini-International Neuropsychiatric Interview is designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings.
Abstract: The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. With an administration time of approximately 15 minutes, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings. The authors describe the development of the M.I.N.I. and its family of interviews: the M.I.N.I.-Screen, the M.I.N.I.-Plus, and the M.I.N.I.-Kid. They report on validation of the M.I.N.I. in relation to the Structured Clinical Interview for DSM-III-R, Patient Version, the Composite International Diagnostic Interview, and expert professional opinion, and they comment on potential applications for this interview.

19,347 citations

Journal ArticleDOI
TL;DR: The Mini International Neuropsychiatric Interview (MINI) as mentioned in this paper is a short diagnostic structured interview (DSI) developed in France and the United States to explore 17 disorders according to Diagnostic and Statistical Manual (DSM)-III-R diagnostic criteria.

3,143 citations

Journal ArticleDOI
TL;DR: The results supported the validity and reliability of the MINI and the application of short structured interviews in clinical and research settings is discussed.

1,969 citations

Journal ArticleDOI
Maurizio Fava1
TL;DR: An accurate and systematic assessment of treatment-resistant depression is a challenge to both clinicians and researchers, with the use of clinician-rated or self-rated instruments being perhaps quite helpful.

1,143 citations