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

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.

CNS Spectrums ◽  
2002 ◽  
Vol 9 (S14) ◽  
pp. 25-32
Author(s):  
Waguih William IsHak ◽  
Mark H. Rapaport ◽  
Jennifer G. Gotto

ABSTRACTManagement strategies for treatment-resistant depression and anxiety disorders have evolved over the last decade. Our understanding of the factors that impair recovery from an episode of major depression has increased, leading to the development of more precise diagnostic methodology that highlight the presence of comorbid conditions. New medications, creative uses of existing medications, increased empirical data about augmentation strategies, and the development of innovative nonpharmacologic interventions are responsible for a marked expansion in treatment options. Traditionally, augmentations with lithium, thyroid hormones, or electroconvulsive therapy have demonstrated effectiveness in some patients with treatment-resistant mood disorders. Among the promising treatments in both depression and anxiety is augmentation using low-dose antipsychotics medications, combining antidepressants of different classes, and the addition of psychotherapy. Nonpharmacologic interventions that may have potential include transcranial magnetic stimulation, deep-brain stimulation, and vagus-nerve stimulation. This article provides a brief review of the available data summarizing existing and new treatment strategies in depression and anxiety disorders.


Pharmacy ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 118
Author(s):  
Linda Xing Yu Liu ◽  
Marina Golts ◽  
Virginia Fernandes

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.


2020 ◽  
Vol 13 (6) ◽  
pp. 116 ◽  
Author(s):  
Valerie L. Ruberto ◽  
Manish K. Jha ◽  
James W. Murrough

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.


2020 ◽  
Vol 10 ◽  
pp. 204512532092247 ◽  
Author(s):  
Paul Glue ◽  
Natalie J. Medlicott ◽  
Shona Neehoff ◽  
Peter Surman ◽  
Fred Lam ◽  
...  

Background: Ketamine’s defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers. Methods: To assess safety, tolerability, efficacy, and pharmacokinetics of an extended release oral ketamine tablet in patients with treatment-resistant depression/anxiety. This was a multiple dose open-label flexible dose uncontrolled study in seven patients with treatment-resistant depression/anxiety, who had all previously demonstrated mood improvement to subcutaneous ketamine. Assessments included ratings of anxiety, depression and dissociation, safety and tolerability, and blood samples for ketamine pharmacokinetics and brain-derived neurotrophic factor (BDNF) concentrations. Results: Improvements in anxiety and depression ratings occurred gradually over 96 h; all patients had >50% improvements in mood ratings. Ketamine was safe and well tolerated, with no changes in vital signs, and a single brief report of dissociation. Ketamine may induce its own metabolism, as the ratio of norketamine to ketamine increased out to 96 h. Serum BDNF concentrations did not change during the study. Conclusion: Ketamine’s safety/tolerability may be improved with an extended release oral formulation. Onset of mood improvement is slightly delayed compared with parenteral dosing. These data support the further development of extended release ketamine tablets for treatment of resistant depression and anxiety disorders.


2021 ◽  
pp. 1-6
Author(s):  
Emma Pope ◽  
Sabari Muthukrishnan ◽  
James Phillips ◽  
Sarah Phillips

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.


2018 ◽  
Vol 79 (1) ◽  
pp. 17m11475 ◽  
Author(s):  
Sjoerd M. van Belkum ◽  
Hanneke Geugies ◽  
Thom S. Lysen ◽  
Anthony J. Cleare ◽  
Frenk P. M. L. Peeters ◽  
...  

2020 ◽  
Vol 26 (2) ◽  
pp. 244-252
Author(s):  
Kah K. Goh ◽  
Shen-Chieh Chang ◽  
Chun-Hsin Chen ◽  
Mong-Liang Lu

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.


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Erik Roj Larsen ◽  
Rasmus W. Licht ◽  
René Ernst Nielsen ◽  
Annette Lolk ◽  
Bille Borck ◽  
...  

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.


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