Ketamine in the Treatment of Depressive Episodes

2019 ◽  
Vol 53 (02) ◽  
pp. 45-50 ◽  
Author(s):  
Philipp Ritter ◽  
Hannelore Findeis ◽  
Michael Bauer
Keyword(s):  
Bipolar Depression ◽  
Controlled Trial ◽  
Repeated Administration ◽  
Precise Position ◽  
Long Latency ◽  
Antidepressant Efficacy ◽  
Insufficient Response ◽  
Year 2000 ◽  
Depressive Episodes ◽  
Fast Acting

AbstractThe treatment of depressive episodes remains complicated by the long latency of antidepressant efficacy, insufficient response, and high risk of suicide. Ketamine and esketamine have been proposed as fast-acting substances able to overcome these impediments.Since the first randomized controlled trial in the year 2000, numerous studies have explored the antidepressant efficacy of ketamine and esketamine. Clear evidence has emerged that a single infusion exerts a significant antidepressant and antisuicidal effect in both unipolar and bipolar depression. A few studies suggest that antidepressant response can be improved and maintained by repeated administration. Although intravenous application has been most common, subcutaneous, intramuscular, and intranasal application has also been successful. There is some evidence that ketamine may accelerate the response to electroconvulsive therapy without improving the overall response rate.The precise position of ketamine and esketamine within treatment algorithms have yet to be defined, and issues surrounding potential toxicity need to be resolved.

scholarly journals Repetitive transcranial magnetic stimulation in the treatment of bipolar disorder

2020 ◽  
Vol 10 ◽  
pp. 204512532097379
Author(s):  
Danielle Hett ◽  
Steven Marwaha
Keyword(s):  
Bipolar Disorder ◽  
Transcranial Magnetic Stimulation ◽  
Side Effects ◽  
Magnetic Stimulation ◽  
Sleep Problems ◽  
Bipolar Depression ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Trial ◽  
Total N ◽  
Depressive Episodes

Bipolar disorder (BD) is a debilitating mood disorder marked by manic, hypomanic and/or mixed or depressive episodes. It affects approximately 1–2% of the population and is linked to high rates of suicide, functional impairment and poorer quality of life. Presently, treatment options for BD are limited. There is a strong evidence base for pharmacological (e.g., lithium) and psychological (e.g., psychoeducation) treatments; however, both of these pose challenges for treatment outcomes (e.g., non-response, side-effects, limited access). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, is a recommended treatment for unipolar depression, but it is unclear whether rTMS is an effective, safe and well tolerated treatment in people with BD. This article reviews the extant literature on the use of rTMS to treat BD across different mood states. We found 34 studies in total ( N = 611 patients), with most assessing bipolar depression ( n = 26), versus bipolar mania ( n = 5), mixed state bipolar ( n = 2) or those not in a current affective episode ( n = 1). Across all studies, there appears to be a detectable signal of efficacy for rTMS treatment, as most studies report that rTMS treatment reduced bipolar symptoms. Importantly, within the randomised controlled trial (RCT) study designs, most reported that rTMS was not superior to sham in the treatment of bipolar depression. However, these RCTs are based on small samples ( NBD ⩽ 52). Reported side effects of rTMS in BD include headache, dizziness and sleep problems. Ten studies ( N = 14 patients) reported cases of affective switching; however, no clear pattern of potential risk factors for affective switching emerged. Future adequately powered, sham-controlled trials are needed to establish the ideal rTMS treatment parameters to help better determine the efficacy of rTMS for the treatment of BD.

scholarly journals Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sanne Y. Smith-Apeldoorn ◽  
Jolien K. E. Veraart ◽  
Jeanine Kamphuis ◽  
Antoinette D. I. van Asselt ◽  
Daan J. Touw ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Treatment Strategies ◽  
Repeated Administration ◽  
Additional Treatment ◽  
Racemic Mixture ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Routes Of Administration ◽  
Antidepressant Efficacy ◽  
Resistant Depression

Abstract Background There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine’s enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. Methods This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. Discussion This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. Trial registration Dutch Trial Register, NTR6161. Registered 21 October 2016.

scholarly journals Antidepressant efficacy of low-frequency repetitive transcranial magnetic stimulation in antidepressant-nonresponding bipolar depression: a single-blind randomized sham-controlled trial

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Arthur D. P. Mak ◽  
Sebastiaan F. W. Neggers ◽  
Owen N. W. Leung ◽  
Winnie C. W. Chu ◽  
Jenny Y. M. Ho ◽  
...  
Keyword(s):  
Bipolar Depression ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Trial ◽  
Low Frequency ◽  
Significant Group ◽  
Time Interaction ◽  
Response Predictors ◽  
Antidepressant Efficacy ◽  
Clinical Trials Registry ◽  
Single Blind

Abstract Background To examine the antidepressant efficacy and response predictors of R-DLPFC-LF rTMS for antidepressant-nonresponding BD. Methods We conducted a single-blind randomized sham-controlled trial for 54 (28 sham, 26 active) patients with antidepressant-nonresponding BD (baseline MADRS ≥ 20). Patients received 15 daily sessions of active or sham neuronavigated rTMS (Figure-of-8 coil, five 1 Hz 60 s 110% RMT trains). Outcome measures included depressive response (≥ 50% MADRS reduction, CGI ≤ 2) and remission (MADRS < 7, CGI = 1) rates, treatment emergent hypo/mania (YMRS), depressive and anxiety symptoms (HAM-A). Results 48 patients (25 sham, 23 active) completed treatment, with 3 drop-outs each in active and sham groups. Active rTMS did not produce superior response or remission rates at endpoint or 6 or 12 weeks (ps > 0.05). There was no significant group * time interaction (ps > 0.05) in a multivariate ANOVA with MADRS, HAMA and YMRS as dependent variables. Exploratory analysis found MADRS improvement to be moderated by baseline anxiety (p = 0.02) and melancholia (p = 0.03) at week 3, and depressive onset at weeks 6 (p = 0.03) and 12 (p = 0.04). In subjects with below-mean anxiety (HAMA < 20.7, n = 24), MADRS improvement from active rTMS was superior to sham at week 3 (ITT, t = 2.49, p = 0.04, Cohen’s d = 1.05). No seizures were observed. Groups did not differ in treatment-emergent hypomania (p = 0.1). Limitations Larger sample size might be needed to power subgroup analyses. Moderation analyses were exploratory. Single-blind design. Unblinding before follow-up assessments due to ethical reasons. Conclusions 1-Hz 110% RMT (5 × 60 s trains) R-DLPFC-LF rTMS was not effective for antidepressant non-responding BD but may be further investigated at increased dosage and/or in BD patients with low anxiety. Trial registration CCRB Clinical Trials Registry, CUHK, CUHK_CCT00440. Registered 04 December 2014, https://www2.ccrb.cuhk.edu.hk/registry/public/279

scholarly journals Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maximilian Pilhatsch ◽  
Thomas J Stamm ◽  
Petra Stahl ◽  
Ute Lewitzka ◽  
Anne Berghöfer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Phenotypic Expression ◽  
Anxiety Symptoms ◽  
Controlled Study ◽  
Double Blind ◽  
Comorbid Anxiety ◽  
Depressed Patients ◽  
Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

scholarly journals Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

2014 ◽  
Vol 44 (16) ◽  
pp. 3455-3467 ◽  
Author(s):  
A. Peters ◽  
L. G. Sylvia ◽  
P. V. da Silva Magalhães ◽  
D. J. Miklowitz ◽  
E. Frank ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Collaborative Care ◽  
Bipolar Depression ◽  
Age At Onset ◽  
Number Needed To Treat ◽  
Systematic Treatment ◽  
Illness Duration ◽  
Bipolar Patients ◽  
Depressive Episodes ◽  
Intensive Psychotherapy

Background.The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.Method.Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.Results.Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.Conclusions.Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

P.2.e.029 Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo controlled trial

2009 ◽  
Vol 19 ◽  
pp. S465
Author(s):  
A. Saricicek ◽  
K. Maloney ◽  
B. Lorberg ◽  
A. Muralidharan ◽  
B. Ruf ◽  
...  
Keyword(s):  
Bipolar Depression ◽  
Controlled Trial ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Rumination-focused cognitive–behavioural therapy for residual depression: phase II randomised controlled trial

2011 ◽  
Vol 199 (4) ◽  
pp. 317-322 ◽  
Author(s):  
Edward R. Watkins ◽  
Eugene Mullan ◽  
Janet Wingrove ◽  
Katharine Rimes ◽  
Herbert Steiner ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Cognitive Behavioural Therapy ◽  
Controlled Trial ◽  
Behavioural Therapy ◽  
Control Group ◽  
Specific Content ◽  
Cognitive Behavioural ◽  
Randomised Controlled ◽  
Major Depressive Episodes ◽  
Depressive Episodes

BackgroundAbout 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive–behavioural therapy (CBT).AimsTo test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression.MethodForty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150).ResultsAdding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination.ConclusionsThis is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.

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