Individual responses to psychotropics

By | March 8, 2015

Question. Has there been any research done on individual responses to psychotropics as a predictor of their underlying neurochemistry? For example, when an individual is given Prozac and experiences extreme fatigue, can we use this information in a clinically relevant way? I’d appreciate your comments on this issue as well.

Answer. I am not aware of any published research on this intriguing question, as you have phrased it, but perhaps I can point you in a useful direction. If we come at the question from the opposite direction (i.e., can an individual’s underlying neurochemistry predict response to psychotropics?) there is some affirmative evidence. For example, in the Journal of Affective Disorders, 1990, vol. 18, pp. 59-66, Moller et al. found that major depressed subjects with lower L-tryptophan (an amino acid building block of serotonin, a neurotransmitter) in their blood had a better response to serotonergic antidepressants (e.g., paroxetine) than did depressed subjects with higher tryptophan levels.

This suggests that serotonergic antidepressants may be compensating for an underlying deficit of serotonin in some patients. In the 1970s and 80s, a lot of research was aimed at measuring urinary metabolites of neurotransmitters and correlating those results with response to either noradrenegic or serotonergic agents. But this research hasn’t yielded clinically useful data, perhaps because antidepressants affect so many neurotransmitters, even when they are supposed to be selective.

Can we make inferences about underlying neurochemistry from a patient’s response to a medication? Only in a very limited sense. For example, a calming response to a normally stimulating drug (such as amphetamine) may point to a diagnosis of attention-deficit/hyperactivity disorder, which in turn may tell us something about the patient’s brain structure and function. For example, it turns out that some brain regions normally involved in suppressing aggressive behaviors and maintaining attention may actually be underactive in ADHD, the individual is thus disinhibited. Stimulants may activate those brain regions (e.g., the frontal lobes), allowing them to regain their normal function. Conversely, an aggressive/disinhibited response to, say, a benzodiazepine may suggest underlying structural brain damage.

In a few other areas, response to a psychotropic may tell us something about diagnosis and underlying neurochemistry. For example, some modest evidence indicates that depressed patients who respond well to MAOIs may have low levels of a neuromodulator called PEA (phenylethylamine) and that these individuals tend to have so-called atypical depression (overeating, hypersomnia, mood worse in p.m.). Years ago, M. Liebowitz and D. Klein observed that these same patients often binge eat on chocolate – which contains high levels of PEA! So, perhaps we do have a kind of naturalistic probe, if you believe these data!