Opposite effects of the same drug

Abstract

Several studies have shown that psychological factors such as learning, expectation, and emotions can affect pharmacological treatment and shape both favorable and adverse effects of drugs. This study investigated whether nocebo information provided during administration of an analgesic cream could reverse topical analgesia to hyperalgesia. Furthermore, we tested whether nocebo effects were mediated by negative emotional activation. A total of 142 healthy volunteers (73 women) were randomized into 6 groups. A topical analgesic cream (Emla) was administered together with suggestions of analgesia in 1 group, whereas another group received Emla with suggestions of hyperalgesia. Two other groups received a placebo cream together with the same information as the groups receiving Emla. A fifth group received Emla with no specific information about the effect, and the sixth group received no treatment but the same pain induction as the other groups. Heat pain stimulation (48°C) was administered during a pretest and 2 posttests. Pain was continuously recorded during stimulation, and measures of subjective stress and blood pressure were obtained before the pretest, after the application of cream, and after the posttests. The results revealed that pain was significantly lower in the group receiving Emla with positive information and highest in the groups receiving suggestions of hyperalgesia, regardless of whether Emla or the placebo was administered. Mediation analyses showed that stress and blood pressure mediated hyperalgesia after nocebo suggestions. These results suggest that nocebo information can reverse topical analgesia and that emotional factors can explain a significant proportion of variance in nocebo hyperalgesia.

Placebo and Active Treatment Additivity in Placebo Analgesia: Research to Date and Future Directions

“…Fig. 4 shows the results of this search, in which only seven studies were found to have used one of these designs in placebo analgesia (Aslaksen, Zwarg, Eilertsen, Gorecka, & Bjørkedal, 2015; Atlas et al, 2012; Berna et al, 2017; Butcher & Carmody, 2012; Kam-Hansen et al, 2014; Lund, Vase, Petersen, Jensen, & Finnerup, 2014; Schenk, Sprenger, Geuter, & Buchel, € 2014). …”

“…Four of the seven studies used the balanced placebo design (Aslaksen et al, 2015; Butcher & Carmody, 2012; Kam-Hansen et al, 2014; Schenk et al, 2014), while two used the balanced open-hidden design (Atlas et al, 2012; Lund et al, 2014). The final study conducted by Berna et al (2017) used a novel design here described as a “balanced active placebo design.” In this variation of the balanced placebo design, receipt of an active treatment or placebo are factorially crossed with administration of an active placebo or placebo, with the second factor replacing the instructions of treatment allocation typical of the balanced placebo design.…”

“…Three studies examined lidocaine, a sodium channel blocker (Aslaksen et al, 2015; Lund et al, 2014; Schenk et al, 2014), two examined NSAIDs, namely diclofenac and ibuprofen (Berna et al, 2017; Butcher & Carmody, 2012), one examined maxalt, a triptan used to treat migraines (Kam-Hansen et al, 2014), and one examined the opioid remifentanil (Atlas et al, 2012). …”

“…The time course of the treatment relative to outcome assessment was reported in most studies and varied between 13.5 min and 4 h (Aslaksen et al, 2015; Atlas et al, 2012; Berna et al, 2017; Butcher & Carmody, 2012; Kam-Hansen et al, 2014). The two exceptions were Lund et al (2014) and Schenk et al (2014), who did not report the time course of treatment administration and outcome assessment.…”

Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus

“…Importantly, placebo and nocebo effects can substantially modulate the efficacy and tolerability of active pharmacological or other medical treatments [15, 16]. This empirical evidence from experimental and clinical studies challenges health-care professionals to translate and implement the findings of placebo and nocebo research into practice.…”