A double-blind pilot dosing study of low field magnetic stimulation (LFMS) for treatment-resistant depression (TRD).

BACKGROUND: Low field magnetic stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-min session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. OBJECTIVE/HYPOTHESIS: We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. METHODS: In a double-blind randomized controlled trial, 30 participants (age 21-65) with treatment-resistant depression were randomized to three 20-min active or sham LFMS treatments with 48 h between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. RESULTS: Following the 3rd session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F (1, 24) = 7.45, p = 0.03, Bonferroni-Holm corrected; F (1, 22) = 6.92, p = 0.03, Bonferroni-Holm corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. CONCLUSIONS: Three 20-min LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment courses as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.

Attention, Motivation, and Study Habits in Users of Unprescribed ADHD Medication.

OBJECTIVE: Despite the limited effectiveness of ADHD medications on healthy cognition, prescription stimulants' cognitive enhancement use is increasing. This article examines enhancement users' attention, motivation, and study habits. METHOD: A total of 61 users of unprescribed stimulants and 67 controls (no history of prescription stimulant use) completed tests of objectively measured and subjectively reported attention. Self-reports on study habits, as well as motivation during laboratory attention testing, were also administered. RESULTS: Our data replicated previous findings of relatively lower self-reported attention functioning in users. Extending past research, we showed that user-control differences in attention were still present but less pronounced on objective measures than on self-report. In addition, we obtained evidence of lower motivation during cognitive testing and less optimal study habits among users, as compared with their non-using peers. CONCLUSION: Unprescribed stimulant use is more strongly related to compromised study habits, low motivation, and a subjective perception of attention problems than to objective attention performance.

Age-Related Repetitive Transcranial Magnetic Stimulation Effects on Executive Function in Depression: A Systematic Review.

OBJECTIVE: The aims of the current review were to: 1) examine whether the rTMS effects on executive function increase as age advances; 2) to examine the potential of rTMS to remediate executive function in older depressed patients; and 3) to assess the relationship between the executive function and mood benefits from rTMS in depression. METHODS: Randomized or matched-groups, blind, sham-controlled studies (12 studies, 347 participants) on excitatory rTMS applied to left DLPFC in depression were reviewed. RESULTS: A series of meta-regressions found no evidence of greater rTMS effects on executive functions as age advances. Similarly, meta-analyses showed no significant rTMS effects on executive functions in older depressed individuals. However, meta-regression analyses showed that the size of the executive function benefits from rTMS in depression are positively related to the effect size of mood symptom reduction. Despite its correlational nature, this finding is consistent with the idea that improvement in executive function may play a critical role in depression recovery. CONCLUSIONS: The authors consider these findings preliminary because of the modest number of available studies. Based on a qualitative review, the authors describe methodologic modifications that may increase rTMS efficacy for both executive functions and mood in late-life depression.

Does Transcranial Direct Current Stimulation Improve Healthy Working Memory?: A Meta-analytic Review.

Transcranial direct current stimulation (tDCS) has been reported to improve working memory (WM) performance in healthy individuals, suggesting its value as a means of cognitive enhancement. However, recent meta-analyses concluded that tDCS has little or no effect on WM in healthy participants. In this article, we review reasons why these meta-analyses may have underestimated the effect of tDCS on WM and report a more comprehensive and arguably more sensitive meta-analysis. Consistent with our interest in enhancement, we focused on anodal stimulation. Thirty-one articles matched inclusion criteria and were included in four primary meta-analyses assessing the WM effects of anodal stimulation over the left and right dorsolateral pFC (DLPFC) and right parietal lobe as well as left DLPFC stimulation coupled with WM training. These analyses revealed a small but significant effect of left DLPFC stimulation coupled with WM training. Left DLPFC stimulation alone also enhanced WM performance, but the effect was reduced to nonsignificance after correction for publication bias. No other effects were significant, including a variety of tested moderators. Additional meta-analyses were undertaken with study selection criteria based on previous meta-analyses, to reassess the findings from these studies using the analytic methods of this study. These analyses revealed a mix of significant and nonsignificant small effects. We conclude that the primary WM enhancement potential of tDCS probably lies in its use during training.

Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis.

The use of prescription stimulants to enhance healthy cognition has significant social, ethical, and public health implications. The large number of enhancement users across various ages and occupations emphasizes the importance of examining these drugs' efficacy in a nonclinical sample. The present meta-analysis was conducted to estimate the magnitude of the effects of methylphenidate and amphetamine on cognitive functions central to academic and occupational functioning, including inhibitory control, working memory, short-term episodic memory, and delayed episodic memory. In addition, we examined the evidence for publication bias. Forty-eight studies (total of 1,409 participants) were included in the analyses. We found evidence for small but significant stimulant enhancement effects on inhibitory control and short-term episodic memory. Small effects on working memory reached significance, based on one of our two analytical approaches. Effects on delayed episodic memory were medium in size. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets of healthy cognition is probably modest overall. In some situations, a small advantage may be valuable, although it is also possible that healthy users resort to stimulants to enhance their energy and motivation more than their cognition.

Enhancement stimulants: perceived motivational and cognitive advantages.

Psychostimulants like Adderall and Ritalin are widely used for cognitive enhancement by people without ADHD, although the empirical literature has shown little conclusive evidence for effectiveness in this population. This paper explores one potential explanation of this discrepancy: the possibility that the benefit from enhancement stimulants is at least in part motivational, rather than purely cognitive. We review relevant laboratory, survey, and interview research and present the results of a new survey of enhancement users with the goal of comparing perceived cognitive and motivational effects. These users perceived stimulant effects on motivationally-related factors, especially "energy" and "motivation," and reported motivational effects to be at least as pronounced as cognitive effects, including the effects on "attention."