Biochemical Aspects of Therapy-Resistant Depression

1988 ◽  
Vol 152 (4) ◽  
pp. 453-459 ◽  
Author(s):  
B. E. Leonard
Keyword(s):  
Affective Disorders ◽  
Clinical Evidence ◽  
Antidepressant Treatment ◽  
Depressed Patients ◽  
High Incidence ◽  
Resistant Depression ◽  
Serotonergic Function ◽  
Definition Of ◽  
Therapy Resistant Depression

Despite the relatively high incidence of therapy-resistant depression, there is little clinical evidence to suggest that there are significant biochemical differences between therapy-resistant and therapy-responsive patients. A major problem for investigators is the lack of an internationally recognised definition of resistant depression. Also, it is possible that depressed patients with delusional symptoms or rapidly cycling affective disorders form subgroups that are more likely to be resistant to tricylic antidepressant treatment and are therefore classified as therapy-resistant. Evidence is presented to show that an abnormality in serotonergic function may characterise some therapy-resistant depressed patients.

scholarly journals Methylome-wide change associated with response to electroconvulsive therapy in depressed patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Sirignano ◽  
Josef Frank ◽  
Laura Kranaster ◽  
Stephanie H. Witt ◽  
Fabian Streit ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Cpg Sites ◽  
Cpg Site ◽  
Depressed Patients ◽  
Resistant Depression ◽  
Functional Pathway ◽  
Regional Analyses ◽  
The Relationship

AbstractElectroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10−8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10−7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák’s p = 0.0031) and 20 (Šídák’s p = 4.2 × 10−5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.

scholarly journals Current perspectives in the management of treatment-resistant depression

2004 ◽  
Vol 6 (1) ◽  
pp. 53-60
Keyword(s):  
Depressive Disorders ◽  
Antidepressant Treatment ◽  
Behavioral Therapy ◽  
Treatment Resistance ◽  
Care Utilization ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Combination Strategies ◽  
Resistant Depression ◽  
Definition Of

Depressive disorders are a leading cause of disability worldwide and greatly impact morbidity, health care utilization, and medical costs. Major depression that does not resolve with adequate antidepressant treatment is termed treatment-resistant depression (TRD), There is no universally accepted definition of TRD and several criteria have been suggested to define it. Multiple factors can contribute to treatment resistance, including unrecognized comorbid medical or psychiatric illness, the use of concomitant medications, noncompliance, and psychosocial stressors. TRD is associated with extensive use of depression-related and general medical services, and poses a substantial economic burden. Current approaches to its management include the use of antidepressant strategies, such as increasing the dose of the antidepressant, augmentation strategies, combination strategies, and switching strategies, electroconvulsive therapy, and cognitive behavioral therapy. Although no definite algorithm exists for treating TRD, research in this area has advanced considerably in recent years. One approach to this is a clinical trial called STAR*D (Sequenced Treatment Alternatives to Relieve Depression). This has the potential to increase our understanding about the diagnostic and therapeutic aspects of TRD, to substantially reduce disability, and to enhance the quality of life in individuals with this condition.

Are bipolar I depressive patients less responsive to treatment with antidepressants than unipolar depressive patients? Results from a case control study

2002 ◽  
Vol 17 (4) ◽  
pp. 200-205 ◽  
Author(s):  
R. Bottlender ◽  
D. Rudolf ◽  
M. Jäger ◽  
A. Strauss ◽  
H.-J. Möller
Keyword(s):  
Affective Disorders ◽  
Acute Treatment ◽  
Antidepressant Treatment ◽  
Specific Treatment ◽  
Unipolar Depression ◽  
Similar Efficacy ◽  
Clinical Impression ◽  
Treatment Regimens ◽  
Depressed Patients ◽  
Depressive Patients

SummaryThe increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were mahed for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in ouome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.

scholarly journals Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: a systematic review and critical analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Juliette Servante ◽  
Gill Swallow ◽  
Jim G. Thornton ◽  
Bethan Myers ◽  
Sandhya Munireddy ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Pregnant Women ◽  
Clinical Evidence ◽  
Case Reports ◽  
Standard Form ◽  
Test Results ◽  
Maternal Deaths ◽  
High Clinical Suspicion ◽  
Increased Risk ◽  
Definition Of

Abstract Background As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Methods Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Results One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. Conclusions Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

scholarly journals The change of gut microbiota in MDD patients under SSRIs treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Shen ◽  
Xiao Yang ◽  
Gaofei Li ◽  
Jiayu Gao ◽  
Ying Liang
Keyword(s):  
Gut Microbiota ◽  
Maximum Dose ◽  
Antidepressant Treatment ◽  
Intestinal Flora ◽  
Alpha Diversity ◽  
The Other ◽  
Control Group ◽  
Depressed Patients ◽  
Metabolic Functions

AbstractThe alterations in the gut microbiota have been reported to be correlated with the development of depression. The purpose of this study was to investigate the changes of intestinal microbiota in depressed patients after antidepressant treatment. We recruited 30 MDD patients (MDD group) and 30 healthy controls (control group). The MDD group received individualized treatment with escitalopram at a maximum dose of 20 mg/day. After depressive symptoms improved to a HAMD scale score > 50%, a fecal sample was collected again and used as the follow-up group. The differences of gut microbiota between patients and controls, the characteristics of gut microbiota under treatment and the potential differences in metabolic functions were thus investigated. The Firmicutes/Bacteroidetes ratio was significantly different within three groups, and the ratio of follow-up group was significantly lower than those of the other two groups. Alpha diversity was significantly higher in MDD group than those of the other groups, and the alpha diversity was not significantly different between control and follow-up groups. The beta diversity of some patients resembled participants in the control group. The metabolic function of gut microbiota after treatment was still different from that of the control group. This study suggests that the intestinal flora of depressed patients has a tendency to return to normal under escitalopram treatment.

FAMILIAL THYROXINE-BINDING GLOBULIN DEFICIENCY IN ASSOCIATION WITH NON-TOXIC GOITRE

1979 ◽  
Vol 91 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Paul Bratusch-Marrain ◽  
Hannes Haydl ◽  
Werner Waldhäusl ◽  
Robert Dudczak ◽  
Wolfgang Graninger
Keyword(s):  
Clinical Evidence ◽  
Autosomal Dominant ◽  
Serum Concentrations ◽  
Dominant Inheritance ◽  
Normal Range ◽  
Thyroxine Binding Globulin ◽  
The Family ◽  
High Incidence ◽  
Total Thyroxine ◽  
Mode Of Transmission

ABSTRACT A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 μg/ml; normal range 12.5–26.0 μg/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.

Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

1995 ◽  
Vol 166 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Cornelius L. E. Katona ◽  
Mohammed T. Abou-Saleh ◽  
Deborah A. Harrison ◽  
Bertrand A. Nairac ◽  
Denzil R. L. Edwards ◽  
...  
Keyword(s):  
Rating Scale ◽  
Antidepressant Treatment ◽  
Controlled Trial ◽  
Depressive Illness ◽  
Controlled Trials ◽  
Major Depressive ◽  
Double Blind ◽  
Primary Care Settings ◽  
Resistant Depression ◽  
Lithium Augmentation

BackgroundThis study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial.MethodLithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10.ResultsResponse was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels ≥ 0.4 mmol/1). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine.ConclusionsOur results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.

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