Can the Efficacy of Psychotropic Drugs Be Measured?

Q: What would you say to those who contend that the efficacy of psychotropic drugs cannot be measured, or that the extent of “chemical imbalance” cannot be empirically ascertained?

A: The efficacy of psychotropic medications can be measured. The research design commonly accepted to demonstrate efficacy is the double-blind placebo-controlled clinical trial. A refinement on this design is the addition of an active comparator “arm” that weighs the comparison medication against placebo. If the comparison arm fails to separate the comparison medication from placebo, the study is considered failed.

The research design can also be set up to demonstrate whether the medication under study has equal efficacy with the comparison medication (a so-called non-inferiority study). This usually requires a larger number of patients in each active medication group.

Validated clinical rating scales are used to determine the effect size of each treatment (placebo, medicine under study, and active comparator). Common rating scales used include the Hamilton Depression Rating Scale (HAM-D), the Montgomery Asberg Depression Rating Scale, the Clinical Global Improvement Scale, the Hamilton Anxiety Rating Scale (HAM-A), the Patient Health Questionnaire (PHQ) and Brief Patient Health Questionnaire (PHQ-9), and many others.

Many studies have employed brain-imaging techniques, including PET, fMRI, and SPECT scans, to measure the effectiveness of medication in changing observable brain activity. While brain imaging changes are not accepted by the FDA as an outcome measure proving efficacy for drug approval, they are nevertheless measures that can show relative effectiveness of medication compared to placebo.

“Chemical imbalance” is not a scientific term and is meant to describe the putative underlying pathophysiology of major depressive disorder (MDD) and other psychiatric disorders (eg, anxiety and psychoses). MDD is a heterogeneous disorder, which most likely has many different underlying pathophysiologies. While the pathophysiology of MDD has not been determined, there are hundreds of studies currently being conducted to discover and measure its cause(s). Research shows that MDD is most likely determined by a combination of complex environmental and genetic effects. These findings are expressed by abnormalities of genes, neurotransmitters, neuronal metabolism, gene transcription, inflammatory responses, hormones, brain structure, and brain function.

Psychiatric researchers are optimistic that effective new treatments for psychiatric disorders will become available over the next decade, derived from translational research that is based on an empirical understanding of their underlying pathophysiology.