Showing papers on "Treatment-resistant depression published in 2016"

A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression

Abstract: Objective:Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.Method:In a multicenter, double-blind study, adults (ages 18–64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Asberg Depression Rating Scale (MADRS).Res...

A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression

Abstract: Background: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. Methods: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. Results: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. Conclusions: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

Ketamine for treatment-resistant depression: recent developments and clinical applications

Abstract: Approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants, and those who do generally take weeks to months to achieve a significant effect. There is a clear unmet need for rapidly acting and more efficacious treatments. We will review recent developments in the study of ketamine, an old anaesthetic agent which has shown significant promise as a rapidly acting antidepressant in treatment-resistant patients with unipolar MDD, focusing on clinically important aspects such as dose, route of administration and duration of effect. Additional evidence suggests ketamine may be efficacious in patients with bipolar depression, post-traumatic stress disorder and acute suicidal ideation. We then discuss the safety of ketamine, in which most neuropsychiatric, neurocognitive and cardiovascular disturbances are short lasting; however, the long-term effects of ketamine are still unclear. We finally conclude with important information about ketamine for primary and secondary physicians as evidence continues to emerge for its potential use in clinical settings, underscoring the need for further investigation of its effects.

Ketamine for treatment-resistant unipolar and bipolar major depression: critical review and implications for clinical practice.

Abstract: There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off-label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence-based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract: BACKGROUND To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression. OBJECTIVE This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression. METHODS A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects. RESULTS Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19-3.43; P < .001). This improvement was smaller than the pre-specified clinically important treatment effect. There was a 10% absolute difference between rTMS and sham in the rates of remission or response. This translates to a number needed to treat of 10. Risk ratios for remission and response were 2.20 (95% CI 1.44-3.38, P = .001 and 1.72 [95% CI], 1.13-2.62, P = .01), respectively, favouring rTMS. No publication bias was detected. Trials of rTMS versus ECT showed a statistically and clinically significant difference between rTMS and ECT in favour of ECT (WMD 5.97, 95% CI 0.94-11.0, P = .02). Risk ratios for remission and response were 1.44 (95% CI 0.64-3.23, P = .38) and 1.72 (95% CI 0.95-3.11, P = .07), respectively, favouring ECT. CONCLUSIONS Overall, the body of evidence favoured ECT for treatment of patients who are treatment-resistant. Repetitive transcranial magnetic stimulation had a small short-term effect for improving depression in comparison with sham, but follow-up studies did not show that the small effect will continue for longer periods.

Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study.

Abstract: Background Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).

Sudden gains in cognitive-behavior therapy for treatment-resistant depression: Processes of change.

Abstract: Objective Sudden gains were investigated in cognitive-behavioral therapy (CBT) for treatment-resistant depression (TRD). Client and therapist processes in sessions proximal to sudden gains were examined to better understand the antecedents of sudden gains and potential mechanisms linking them to outcome. Method Participants were 156 adults with TRD in a randomized controlled trial of CBT as an adjunct to pharmacotherapy (Wiles et al., 2013). Depression symptoms were assessed by the Beck Depression Inventory-II at each session. In a subsample of 50 clients, audio-recordings of 125 therapy sessions were rated for hope, emotional processing, and therapist competence in case-conceptualization. Results Sudden gains were experienced by 54% of participants. Those with gains reported significantly lower depression severity at 12-month follow-up and more remission of symptoms than those without gains. Sudden gains also predicted lower depression at follow-up, beyond the slope of linear change in symptoms across treatment. Therapists demonstrated greater competence in case conceptualization with clients who reported sudden gains, and those with gains expressed more hope in sessions prior to a gain. In addition, more hope and emotional processing in the pregain sessions predicted less depression at follow-up, controlling for depression scores in the prior session. Better therapist conceptualization skills and more client hope in the baseline and pregain sessions were also associated with more emotional processing in those same sessions. Conclusion This study extends the phenomenon of sudden gains in CBT for depression to a treatment-resistant population and identified important therapy processes that predicted long-term outcomes: hope and emotional processing. (PsycINFO Database Record

Oral ketamine for the treatment of pain and treatment-resistant depression†.

Abstract: Background Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. Aims To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Method Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Results Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Conclusions Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.

Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

Abstract: Anhedonia, defined as the state of reduced ability to experience feelings of pleasure, is one of the hallmarks of depression. Hedonic tone is the trait underlying one's characteristic ability to feel pleasure. Low hedonic tone represents a reduced capacity to experience pleasure, thus increasing the likelihood of experiencing anhedonia. Low hedonic tone has been associated with several psychopathologies, including major depressive disorder (MDD), substance use, and attention-deficit hyperactivity disorder (ADHD). The main neural pathway that modulates emotional affect comprises the limbic-cortical-striatal-pallidal-thalamic circuits. The activity of various components of the limbic-cortical-striatal-pallidal-thalamic pathway is correlated with hedonic tone in healthy individuals and is altered in MDD. Dysfunction of these circuits has also been implicated in the relative ineffectiveness of selective serotonin reuptake inhibitors used to treat anxiety and depression in patients with low hedonic tone. Mood disorders such as MDD, ADHD, and substance abuse share low hedonic tone as well as altered activation of brain regions involved in reward processing and monoamine signaling as their features. Given the common features of these disorders, it is not surprising that they have high levels of comorbidities. The purpose of this article is to review the neurobiology of hedonic tone as it pertains to depression, ADHD, and the potential for substance abuse. We propose that, since low hedonic tone is a shared feature of MDD, ADHD, and substance abuse, evaluation of hedonic tone may become a diagnostic feature used to predict subtypes of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders.

Deep Transcranial Magnetic Stimulation (dTMS) - Beyond Depression.

Abstract: Introduction: Deep transcranial magnetic stimulation (dTMS) utilizes different H-coils to study and treat a variety of psychiatric and neurological conditions with identifiable brain targets. The availability of this technology is dramatically changing the practice of psychiatry and neurology as it provides a safe and effective way to treat even drug-resistant patients. However, up until now, no effort was made to summarize the different types of H-coils that are available, and the conditions for which they were tested.Areas covered: Here we assembled all peer reviewed publication that used one of the H-coils, together with illustrations of the effective field they generate within the brain. Currently, the technology has FDA clearance for depression and European clearance for additional disorders, and multi-center trials are exploring its safety and effectiveness for OCD, PTSD, bipolar depression and nicotine addiction.Expert commentary: Taken together with positive results in smaller scale experi...

Seizure Adequacy Markers and the Prediction of Electroconvulsive Therapy Response.

Abstract: Objectives Electroconvulsive therapy (ECT) is the most effective therapy for patients with treatment-resistant depression; however, some patients do not respond or relapse in a short time. Electroconvulsive therapy stimulus parameters may be related to the outcome. We carried out a retrospective study review to investigate various ECT parameters in relation to the outcome, clinical variables, and pharmacological treatments. Our aim was to understand which factors could be considered putative seizure quality markers and which are relevant to clinical practice. Methods Two physicians evaluated the seizure length, the postictal suppression index, the wave amplitude, tachycardia, and hemispheric brain wave synchronicity in a double-blind manner for 45 treatment-resistant depression patients receiving ECT. Results The analysis showed a significant association between the outcome and the ECT seizure quality measured by the parameters (P = 9.9 × 10−5). Among patients with poor-quality seizures, 61.5% relapsed after approximately 1 month from the last ECT session. Particularly, there was an association between higher symptomatology decrease and higher quality of hemispheric brain wave synchronicity (P = 5.0 × 10−6), as well as a higher wave amplitude (P = 0.01). Conclusions Our results confirm that ECT seizure quality was strongly correlated with the decrease of depressive symptomatology.

Therapeutic Efficacy of Neurostimulation for Depression: Techniques, Current Modalities, and Future Challenges.

Abstract: Depression is the most prevalent debilitating mental illness; it is characterized as a disorder of mood, cognitive function, and neurovegetative function. About one in ten individuals experience depression at some stage of their lives. Antidepressant drugs are used to reduce the symptoms but relapse occurs in ~20% of patients. However, alternate therapies like brain stimulation techniques have shown promising results in this regard. This review covers the brain stimulation techniques electroconvulsive therapy, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, which are used as alternatives to antidepressant drugs, and elucidates their research and clinical outcomes.

Stimulants for depression: On the up and up?

Abstract: The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes.

Assessing the risk factors for difficult-to-treat depression and treatment-resistant depression.

Abstract: Depression is the leading cause of disability among people across the globe, according to the World Health Organization Among those who have been diagnosed, many fail to achieve remission after following recommended antidepressant medication and psychosocial therapies In particular, difficult-to-treat and treatment-resistant depression may cause severe impairments for patients, including diminished cognitive functioning, increased medical bills, and decreased workplace performance, as well as an increased risk of developing comorbid illnesses However, many tools are available to clinicians for identifying treatment-resistant depression, including rating scales such as the 9-question Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-SR16), as well as clinical evidence related to risk factors for difficult-to-treat or treatment-resistant depression Accurately identifying treatment-resistant depression is the first step toward changing treatment regimens to help patients achieve remission

Is treatment-resistant depression a useful concept?

Abstract: The term treatment-resistant depression (TRD) is widely used in the context of managing mood disorders, but defining it, both conceptually and in practice, has proven difficult. Most definitions have focused on pharmacotherapy but even these have struggled to capture the complexity of varying response and duration of treatment. Both clinically and for research studies a meaningful definition of TRD is necessary because it may lead to the development of 'therapy-defined depressive subtypes' and the discovery of novel antidepressants. This brief perspective critically reviews the concept of treatment resistance and how it can be more clearly defined so as to achieve a better understanding of depression and facilitate clinical treatment trials.

Ketamine Anesthesia, Efficacy of Electroconvulsive Therapy, and Cognitive Functions in Treatment-Resistant Depression.

Abstract: ObjectivesElectroconvulsive therapy (ECT) is the most effective treatment for drug-resistant depression (DRD). Because a single infusion of ketamine may exert both a rapid antidepressant effect and a quick improvement of cognition, the aim of the present study was to assess whether ketamine, as an a