Altruism, personal benefit, and anxieties: a phenomenological study of healthy volunteers' experiences in a placebo-controlled trial of duloxetine.

OBJECTIVE: The objective of this study was to develop an in-depth understanding of healthy volunteers' experiences of mental health trials. METHODS: A qualitative study was nested within a healthy volunteer placebo-controlled trial of duloxetine, a psychotropic drug used for treating patients with major depression and generalized anxiety disorder. Eight participants were interviewed, and data were analyzed using interpretative phenomenological analysis. RESULTS: Interviewees described volunteering for the trial because they were interested in research, wanted the monetary incentive, wanted to help researchers, and wanted to be part of something. On entering the trial, participants considered the possible risks and described feeling anxious, excited, and determined; they had some clear expectations and some loosely held hopes about what would happen. During the trial, participants were curious about whether they were taking duloxetine or placebo, self-monitored their bodies' reactions, and guessed which treatment they received. On being un-blinded to treatment allocation after completing the trial, some participants' guesses were confirmed, but others were surprised, and a few were disappointed. CONCLUSIONS: Small changes to advertising/consent materials to reflect volunteers' motivations could improve recruitment rates to similar trials; "active" placebos might be particularly useful for maintaining blinding in healthy volunteer trials; and sensitive procedures are needed for un-blinding participants to treatment allocation. Copyright © 2016 John Wiley & Sons, Ltd.

Early effects of duloxetine on emotion recognition in healthy volunteers.

The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants' ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects.

Defensive eye-blink startle responses in a human experimental model of anxiety.

Inhalation of low concentrations of carbon dioxide (CO2) triggers anxious behaviours in rodents via chemosensors in the amygdala, and increases anxiety, autonomic arousal and hypervigilance in healthy humans. However, it is not known whether CO2 inhalation modulates defensive behaviours coordinated by this network in humans. We examined the effect of 7.5% CO2 challenge on the defensive eye-blink startle response. A total of 27 healthy volunteers completed an affective startle task during inhalation of 7.5% CO2 and air. The magnitude and latency of startle eye-blinks were recorded whilst participants viewed aversive and neutral pictures. We found that 7.5% CO2 increased state anxiety and raised concurrent measures of skin conductance and heart rate (HR). CO2 challenge did not increase startle magnitude, but slowed the onset of startle eye-blinks. The effect of CO2 challenge on HR covaried with its effects on both subjective anxiety and startle latency. Our findings are discussed with reference to startle profiles during conditions of interoceptive threat, increased cognitive load and in populations characterised by anxiety, compared with acute fear and panic.