Brain functional changes during placebo lead-in and changes in specific symptoms during pharmacotherapy for major depression
Department of Psychiatry and Biobehavioural Sciences, University of California, Los Angeles, Los Ángeles, California, United States Acta Psychiatrica Scandinavica
(Impact Factor: 5.61).
04/2009; 119(4):266-73. DOI: 10.1111/j.1600-0447.2008.01305.x
Brain functional changes during placebo lead-in have been associated with antidepressant response in clinical trials for major depressive disorder (MDD); however, the relationship between such non-pharmacodynamic changes in brain function and changes in specific symptoms is unknown.
Fifty-eight adults with MDD completed a 1-week single-blind placebo lead-in preceding 8 weeks of double-blind randomized treatment with fluoxetine or venlafaxine (n = 30) or placebo (n = 28). Brain functional change during lead-in was assessed using quantitative electroencephalographic (qEEG) prefrontal theta-band cordance. Symptoms were assessed using the Symptom Checklist-90-Revised (SCL-90-R).
The multiple regression model examining the qEEG parameter in relation to SCL-90-R subscales was significant [F(9,9) = 4.27, P = 0.021, R(2) = 0.81] in females, with a significant association for the interpersonal sensitivity subscale (beta coefficient = 1.94, P = 0.001).
Prefrontal neurophysiologic change during placebo lead-in may indicate subsequent antidepressant-related improvement in symptoms of interpersonal sensitivity.
Figures in this publication
Available from: Andrew F Leuchter
- "The 512-point FFT was calculated for artifact-free 2-s epochs with rectangular windowing, 0.5 Hz overlap at the limits of the band, and yielding a frequency resolution of 0.5 Hz. Absolute and relative power were calculated in four frequency bands, corresponding to delta (0.5e4 Hz), theta (4e8 Hz), alpha (8e13 Hz), and beta (13e 20 Hz), for all nearest neighbor bipolar pairs of electrodes (Cook et al., 1998, 2002, 2009; Hunter et al., 2009; Leuchter et al., 1994, 1999). "
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ABSTRACT: Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) enrolled in a multi-site, double-blind placebo-controlled study of the effectiveness of atomoxetine and underwent serial qEEG recordings at pretreatment baseline and one week after the start of medication. qEEG measures were calculated from a subset of the sample (N = 29) that provided useable qEEG recordings. Left temporoparietal cordance in the theta frequency band after one week of treatment was associated with ADHD symptom improvement and quality of life measured at 12 weeks in atomoxetine-treated subjects, but not in those treated with placebo. Neither absolute nor relative power measures selectively predicted improvement in medication-treated subjects. Measuring theta cordance after one week of treatment could be useful in predicting atomoxetine treatment response in adult ADHD.
Available from: David S. Thaler
- "She herself suggested that her practice was akin to cultivating a placebo effect. A key distinction is that a placebo effect is based on deception [7,8] whereas her practice is the opposite: I.e. a critical examination of what the drugs do in her mind and a conscious mimicking of their effects as mediated through the breath. "
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ABSTRACT: A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702–705) offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem.
Whatever the fate of these specific hypotheses, discussion of cognitive enhancing drugs for healthy individuals has the potential to inspire innovative educational and public policy initiatives toward all types of mind-altering drugs and the people who use them.
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ABSTRACT: The placebo response shows pronounced interindividual variability. Placebos are postulated to act through central reward pathways that are modulated by monoamines. Because monoaminergic signaling is under strong genetic control, we hypothesized that common functional polymorphisms modulating monoaminergic tone would be related to degree of improvement during placebo treatment of subjects with major depressive disorder. We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes. Subjects with ValMet catechol-O-methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2 Met alleles) showed a statistical trend toward a lower magnitude of placebo response. These findings support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder.
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