Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial.

BACKGROUND: Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. METHODS: Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase. RESULTS: During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression. LIMITATIONS: Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings. CONCLUSIONS: Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.

Efficacy of Ziprasidone Augmentation of Escitalopram for Cognitive Symptoms of Major Depressive Disorder.

OBJECTIVE: To examine the efficacy of adjunctive ziprasidone for cognitive symptoms in adult patients with major depressive disorder (MDD) experiencing persistent symptoms after 8 weeks of open-label escitalopram. METHODS: This post hoc analysis was conducted on a database derived from a previously published study. The parent study was a multicenter, parallel, randomized, double-blind, placebo-controlled trial conducted at 3 academic medical centers in the United States from July 2008 to October 2013. The participant pool consisted of 139 outpatients with persistent symptoms of MDD, according to DSM-IV criteria, following an 8-week open label, flexible-dose trial of escitalopram. Subjects were randomly assigned (1:1, N = 139) to adjunctive fixed-dose ziprasidone (escitalopram + ziprasidone, n = 71) or adjunctive placebo (escitalopram + placebo, n = 68) with 8 weekly follow-up assessments. Primary outcome was clinical response according to the 17-item Hamilton Depression Rating Scale, which was defined as a 50% or greater reduction in scale scores. The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) was used to measure cognitive and executive dysfunction at each study visit. All statistical testing was conducted at the nominal, 2-sided, 0.05 level of significance. RESULTS: Adjunctive ziprasidone therapy did not result in significantly greater improvement in CPFQ scores compared to adjunctive placebo (P > .05). Residual cognitive symptoms were reported in a substantial number of patients who were considered responders to either adjunctive ziprasidone or placebo. CONCLUSIONS: In the present study, ziprasidone used adjunctively with the selective serotonin reuptake inhibitor escitalopram did not demonstrate a greater efficacy for cognitive symptoms in patients with MDD compared with adjunctive placebo. Future, well-designed studies examining the role of atypical antipsychotics or other augmentation versus switch strategies for cognitive symptoms in MDD are warranted.

A case control series for the effect of photobiomodulation in patients with low back pain and concurrent depression.

BACKGROUND AND AIMS: To present incidental findings in patients with low back pain (LBP) who received photobiomodulation (PBM) administered to the back and thighs as an adjunct to physical therapy (PT) and then experienced improvement in concurrent depression. MATERIALS AND METHODS: Five outpatients with LBP and concurrent self-reported depression were treated for LBP over five weeks with PT (5-sessions) and concurrent PBM (final 3-sessions), and retrospectively matched to five control patients treated with PT alone (5-sessions). The PBM device emitted light at 850nm and 660 nm with an irradiance of 100 mW/cm2 and fluence of 3 J/cm2 on 12 symmetrical posterior sites (thoracic, lumbar and thighs) for 30 sec/site. RESULTS: Both groups had non-significant differences in all baseline scores, except for higher functional status (ARGS) in the PBM-group (33.6 ± 12.2 vs.18.6 ± 3.6, t(8) = 2.638, p = 0.030). After treatment, the mean decrease in depression scores (OMSQ-12 item #6) was significantly larger in the PBM-group (43.0 ± 22.0 vs. 8.0 ± 5.7, t(8) = 3.449, p = 0.009). Improvement in functional status (ARGS) in the PBM-group was similar to that in the controls (42.0 ± 13.5 vs. 43.4 ± 11.1, t(8) = 0.179, p = 0.862), suggesting group differences in antidepressant effect were independent of functional status improvement. CONCLUSIONS: This preliminary investigation suggests that an antidepressant effect may result from PBM to the back and thighs in patients with LBP and concurrent depression.

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy [change in Hamilton Depression Rating Scale (HAM-D17) total score at end-point] of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.

Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study.

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.