Emerging evidence indicates that treatment context profoundly affects psychopharmacological interventions. We review the evidence for the interaction between drug application and the context in which the drug is given both in human and animal research. We found evidence for this interaction in the placebo response in clinical trials, in our evolving knowledge of pharmacological and environmental effects on neural plasticity, and in animal studies analyzing environmental influences on psychotropic drug effects. Experimental placebo research has revealed neurobiological trajectories of mechanisms such as patients’ treatment expectations and prior treatment experiences. Animal research confirmed that “enriched environments” support positive drug effects, while unfavorable environments (low sensory stimulation, low rates of social contacts) can even reverse the intended treatment outcome. Finally we provide recommendations for context conditions under which psychotropic drugs should be applied. Drug action should be steered by positive expectations, physical activity, and helpful social and physical environmental stimulation. Future drug trials should focus on fully controlling and optimizing such drug × environment interactions to improve trial sensitivity and treatment outcome.

The ability of a trial to detect the potential of a new drug strongly depends on whether the protocol fully controls all the factors that influence treatment success. If expectations, learning processes, and other environmental influences are not controlled, these variables can interact beneficially with the pharmacokinetics in one patient, but these interactions of context factors with psychotropic agents canbedetrimentalinanotherpatient,thus contributing substantially to large variations in treatment efficiency. All treatment arms should therefore controlthese effects as much as possible. The assessment of patient expectancies (e.g., whether to attend study visits) can be adjusted for statistically and may be considered in imputation procedures, which can increase the estimated group differences between treatment conditions (Rabideau et al., 2014). At least one treatment arm of clinical trials should aim to optimize all of these influences, to provide information about the maximal efficiency that is possible in a specific clinical condition. While in the past it was assumed that these effects might be additive, more andmore evidence shows thatthese trajectories caninteract, which invites more complex study designs for clinical trials. However, considering these interactions switches the focus from developing drugs as an environment-independent stand-alone treatment to drugs that optimize the interaction with behavior change, and drugs that amplify learning, expectation modification and further positive environmental stimulation processes.Find full text here:

W. Rief et al. / Neuroscience and Biobehavioral Reviews 60 (2016) 51–64