scholarly journals Neuromodulation Intervention in Resistant Depression

2020 ◽  
Vol 8 (2) ◽  
pp. 39
Author(s):  
Era Catur Prasetya ◽  
Lestari Basoeki
Keyword(s):  
Functional Disability ◽  
Antidepressant Drugs ◽  
The United States ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Duration Of Treatment ◽  
Non Invasive ◽  
Disability Rate ◽  
Resistant Depression ◽  
Interventional Therapies

Treatment-resistant depression occurs in about 20% of all Major Deppresion Disorder patients. In addition to the high cost of treatment to be borne, the high functional disability rate, the suicide rate triggered by the disorder is also quite large. Various efforts were made to overcome this, including dose optimization and duration of treatment, substitution of drug selection, combination therapy and augmentation using non-antidepressant drugs and bilateral electroconvulsion therapy. Current pharmacological options according to some experts are no more efficacious than the 1950s. Clearly, a novel therapeutic approach to treatment - resistant depression disorders is urgently needed. Over the last few decades, there has been a renewed interest in focal neuromodulation as a treatment approach for neuropsychiatric conditions. The neuromodulation-based interventions discussed include Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), which are non invasive intervention therapy and Vagus Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS), which are invasive interventional therapies. This literature review proves that, although today only TMS and VNS have been approved for use by the Food and Drug Administration (FDA) in the United States, but neuromodilation-based intervention therapy has proven to be promising as a more effective and efficient resistant depression therapy in the future.

scholarly journals Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review

2020 ◽  
Vol 11 ◽  
pp. 204209862093789 ◽  
Author(s):  
Mohammed S Salahudeen ◽  
Cameron M Wright ◽  
Gregory M Peterson
Keyword(s):  
Literature Search ◽  
Product Information ◽  
The United States ◽  
Narrative Review ◽  
Phase Iii ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Frequency Of Use ◽  
Phase Iii Trials ◽  
Resistant Depression

This narrative review aims to provide an overview of the current literature on the pharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomer of ketamine, for the treatment of treatment-resistant depression (TRD). A literature search using Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 to July 2019). Product information and www.clinicaltrials.gov were also reviewed. The literature search was limited to human studies published in English. Phase I, II, and III studies of intranasal esketamine for TRD were reviewed. About a third of patients with major depressive disorder fail to achieve remission despite treatment with multiple antidepressants. This article examines the trials that led to the approval of esketamine in the United States, as well as other recent studies of esketamine for TRD. The findings from limited phase III trials illustrate that intranasal esketamine is effective and safe in reducing depressive symptoms and achieving clinical response in patients with TRD. The optimum duration and frequency of use are not fully understood. Although the nasal spray is a convenient dosage form, its use in practice may be limited by cost and administrative regulation. While it may prove beneficial to many patients who suffer from TRD, further long-term data are required, along with comparative trials with the R-isomer (arketamine). In the interim, care and monitoring should be exercised in its use in clinical practice.

scholarly journals Resistant depression: criteria for determination, risk factors and therapeutic strategies

2017 ◽  
Vol 2 (3) ◽  
pp. 020338
Author(s):  
Olena Khaustova
Keyword(s):  
Risk Factors ◽  
Atypical Antipsychotics ◽  
Therapeutic Response ◽  
Therapeutic Strategies ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Duration Of Treatment ◽  
Resistance To Treatment ◽  
Step Model ◽  
Resistant Depression

Background Therapy of resistant depression raises a number of diagnostic and therapeutic problems, requires the solution of a number of methodological issues. A scientific discussion continues around the definition of depression resistance, assessment of the degree of reduction of depressive symptoms, the level of social and role functioning of patients; the improvement of models for determining the degree of resistance to various types of depression therapy continues; new methods of therapy and new algorithms of combined therapy are being developed. The ultimate goal of all these efforts should be practical recommendations for determining therapeutic options for the treatment of patients with resistant depression, which will help doctors make informed decisions on intervention strategies. Aim To analyze the therapeutic possibilities of treating depressive disorders that are resistant to therapy. Methods Publications from the Pubmed, MEDLINE, the Cochrane Library, Web of Science, Google Scholar databases were analyzed. Tags: depression, treatment, resistance, psevdoresistence, therapeutic response, resistance to treatment, strategies for treatment of resistant depression. Results The terminology related to resistant depression was defined: lack of a therapeutic response, adequate dose, adequate duration of treatment, antidepressant intolerance, pseudo-resistance, relative resistance to treatment, absolute resistance to treatment, treatment of resistant depression, remission, recovery. Models for determining the resistance of depression have been described: the Thase & Rush model; European stepped model; A step model of the Massachusetts hospital; Step model of Maudsley; Form of the history of treatment with antidepressants. Risk factors for treatment of resistant depression were identified, and the main therapeutic strategies were described: optimization, switching, augmentation, combination and non-drug therapy. Particular attention is paid to the use of atypical antipsychotics, in particular arapiprazole, as the augmentation strategy. A complex approach is described, which includes various combinations of the above strategies. Conclusion Each case of treatment-resistant depression has its own unique characteristics and requires careful evaluation to determine the correct diagnosis and the quality of the therapeutic response. Equally important for building an adequate treatment plan is evaluating risk factors for the treatment of resistant depression. There is a wide variety of options for the treatment of resistant depression, so each therapeutic strategy should be used to help patients with treatment-resistant depression. The combination of antidepressant therapy and atypical antipsychotics with antidepressant properties in combination with psychotherapeutic intervention and adherence to adequate doses and duration of treatment may be a choice strategy for patients with treatment-resistant depression.

FDA Considers Classification of ECT

CNS Spectrums ◽  
2009 ◽  
Vol 14 (12) ◽  
pp. 668-670 ◽  
Author(s):  
S.H. Lisanby ◽  
Stefano Pallanti ◽  
Thomas E. Schlaepfer
Keyword(s):  
Brain Stimulation ◽  
The United States ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
United States Food ◽  
Recent Developments ◽  
States Food ◽  
Resistant Depression ◽  
Deep Brain

With the increasing number of new brain stimulation techniques now available and on the horizon, does electroconvulsive therapy (ECT) still have a role? As clinicians and researchers we say most definitely “yes”. ECT is the most effective and rapidly acting treatment for severe forms of depression and other disorders. Transcranial magnetic stimulation has shown promise but mainly for less severely ill and less treatment resistant patients. Deep brain stimulation (DBS) has shown promise for the more resistant cases but its invasiveness limits its use. Results from only ∼50 patients treated worldwide are available and at present it is not approved by the United States Food and Drug Administration for depression. Vagus nerve stimulation, less invasive than DBS but still a surgical procedure, is presently FDA approved for acute treatment resistant depression but published efficacy rates fall short of those seen with ECT. Therefore, there continues to be an important role for ECT in the treatment of severe psychiatric disorders. But will ECT always be there when our patients need it? Somewhat unexpected recent developments at the FDA may impact the future availability of ECT to severely depressed patients. Here we provide background on the classification of ECT devices, the FDA reclassification process, and the process for providing FDA input in these critical deliberations.

scholarly journals Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts

2021 ◽  
Author(s):  
Chiara Fabbri ◽  
Saskia P. Hagenaars ◽  
Catherine John ◽  
Alexander T. Williams ◽  
Nick Shrine ◽  
...  
Keyword(s):  
Primary Care ◽  
Clinical Characteristics ◽  
Antidepressant Drugs ◽  
Demographic Characteristics ◽  
Polygenic Risk Score ◽  
Healthy Controls ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Genetic Characteristics ◽  
Resistant Depression

AbstractTreatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Primary care electronic health records provide an easily accessible approach to investigate TRD clinical and genetic characteristics. MDD defined from primary care records in UK Biobank (UKB) and EXCEED studies was compared with other measures of depression and tested for association with MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least 6 weeks. Clinical-demographic characteristics, SNP-based heritability (h2SNP) and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases. In 230,096 and 8926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD, respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 71–88% with other MDD definitions. In UKB, TRD vs healthy controls and non-TRD vs healthy controls h2SNP was comparable (0.25 [SE = 0.04] and 0.19 [SE = 0.02], respectively). TRD vs non-TRD was positively associated with the PRS of attention deficit hyperactivity disorder, with lower socio-economic status, obesity, higher neuroticism and other unfavourable clinical characteristics. This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.

scholarly journals Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts

2020 ◽  
Author(s):  
Chiara Fabbri ◽  
Saskia P Hagenaars ◽  
Catherine John ◽  
Alexander T Williams ◽  
Nick Shrine ◽  
...  
Keyword(s):  
Primary Care ◽  
Risk Score ◽  
Antidepressant Drugs ◽  
Demographic Characteristics ◽  
Polygenic Risk Score ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Genetic Characteristics ◽  
Polygenic Risk ◽  
Resistant Depression

Treatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Using primary care electronic health records from UK Biobank and EXCEED studies, we defined MDD and TRD, providing an easily accessible approach to investigate their clinical and genetic characteristics. MDD defined from primary care records was compared with other measures of depression and validated using the MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least six weeks. Clinical-demographic characteristics, SNP-heritability and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases. In 230,096 and 8,926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD (2,430 and 159 cases), respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 72%-88% with other MDD definitions. In UKB, TRD and non-TRD heritability was comparable (h2SNP = 0.25 [SE=0.04] and 0.19 [SE=0.02], respectively). TRD was positively associated with the polygenic risk score (PRS) of attention deficit hyperactivity disorder and negatively associated with the PRS of intelligence compared to non-TRD. It was more strongly associated with unfavourable clinical-demographic variables than non-TRD. This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.

scholarly journals Improvement of Treatment Resistant Depression in a Patient With Primary Hypothyroidism and Thr92Ala5’ Type 2 Deiodinase Gene Polymorphism With Multiple Daily Doses of Triiodothyronine

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A937-A937
Author(s):  
Ziyan Ahmed ◽  
Rinsha P V Sherin ◽  
Tatiana De Lourdes Fonseca ◽  
Thanh Duc Hoang ◽  
Mohamed K M Shakir
Keyword(s):  
Emergency Room ◽  
Antidepressant Drugs ◽  
Primary Hypothyroidism ◽  
Pharmacologic Therapy ◽  
P Value ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Serum Tsh

Abstract Introduction: The augmentation pharmacologic therapy used in patients with treatment-resistant depression (TRD) includes drugs such as lithium, buspirone, triiodothyronine (LT3) and other drugs. We report a patient with TRD and primary hypothyroidism who responded to a combination of LT3, given in divided doses, and levothyroxine (LT4), rather than LT4 alone, even though the serum TSH levels were in the normal range with these treatments. Interestingly, the patient had a Thr92Ala5’ type 2 deiodinase polymorphism. Case Report: A 54-year old male presented to our emergency room with suicidal ideation 8 years ago. The patient had severe depression and developed uncontrollable urges to surf the internet, generally prohibited sites, approximately 3 months prior to his visit to the emergency room. He had noted a 12-lbs weight gain, cold intolerance, dry skin, and excessive sleepiness for 3 months. Patient was admitted to the psychiatry ward and laboratory testing showed a serum TSH 180 µIU/mL, FT4 0.48 ng/dL, total T3 46 ng/mL, and TPO antibody 278 IU/mL. A thyroid ultrasound was consistent with Hashimoto’s thyroiditis. A diagnosis of major depressive disorder and primary hypothyroidism was made. He was started on citalopram (20 mg/day) and levothyroxine (175 mcg/day). The Beck Depression Scores (BDS) during the initial weeks was 37.5 ± 5.1 (Mean ± SD) (normal 0-9) with corresponding TSH 164 ± 133 µIU/mL, FT4 0.70 ± 0.25 ng/dL, and total T3 61 ± 7.9 ng/mL. Two weeks later the dose of citalopram was increased to 40 mg/day and then buspirone 10 mg/day was added. At the end of 11 months the BDS was 27.81 ± 2.1 with a corresponding TSH 1.5 ± 0.1 µIU/mL. After 4 months, 7.5 mg of aripiprazole was added. After 11 months of treatment, he was treated with a combination of LT4 + LT3 (5 mcg once daily) and TSH became 0.76 ± 0.1 µIU/mL with a corresponding BDS of 18.0 ± 1.9. Twelve months later, the patient was switched back to LT4 alone and during LT4 treatment the BDS score was 24.2 ± 22.2 with a TSH of 1.44 ± 0.11. Nine months later patient was changed to LT4 + LT3 (5 mcg three times daily) and his BDS score was 10.3 ± 1.2 with a TSH of 0.72 ± 0.09 µIU/mL. When he was on LT4 + LT3 TID he was able to discontinue all the antidepressant drugs and he had no urge to surf on internet. His depression was controlled by over-the-counter antidepressant drugs (S-adenosylmethionine and rhodiola). A genetic test confirmed Thr92Ala5’ type 2 deiodinase polymorphism. Discussion and Conclusion: In our patient, there was a good correlation between the BDS improvement and the serum T3 levels (r: -0.7 p-value: 0.01). Thus, in patient with Thr92Ala5’ type 2 deiodinase polymorphism TID T3 dosing may significantly improve depression. Additional studies are needed.

scholarly journals Ketamine: A tale of two enantiomers

2020 ◽  
pp. 026988112095964
Author(s):  
Luke A Jelen ◽  
Allan H Young ◽  
James M Stone
Keyword(s):  
Side Effects ◽  
Receptor Antagonist ◽  
The United States ◽  
Receptor Activation ◽  
Racemic Mixture ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Resistant Depression

The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems.

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