In South Korea, an increasing number of people are complaining of depression and requesting antidepressants. The most widely prescribed type of antidepressant is selective serotonin reuptake inhibitor (SSRI). This practice is supported by the ‘serotonin hypothesis’― the belief that depression is caused by serotonin deficiency and can be corrected with SSRIs. With skepticism of such reductionist logic and overprescription of these drugs, I ask whether antidepressants are ‘really’ effective, and if so, why that is the case. The paper first analyses studies critical of antidepressants and shows that each provides only a limited perspective on the drug depending on its academic discipline. On the one hand, scientists attempt to determine SSRI’s unadulterated biological efficacy. On the other hand, social scientists tend to emphasize social forces such as marketing that promote SSRI consumption, or advocate patient agency and choice. I argue that these mutually exclusive analyses turn the debate over effectiveness into a political choice between nature and society. To seek a more relational and nuanced approach to understanding SSRIs, I establish a common premise that all parties can agree upon: when an SSRI is consumed, something unexpected may happen, be it beneficial or harmful. Dualisms of intended effect and side effect, as well as body and mind hinder our interpretation of these changes. Two approaches of New Materialism help move beyond binary thinking about antidepressants. The first is the flat ontology of assemblages, which connects disparate elements such as SSRIs, bodily changes, emotions, serotonin theory, and doctors on a flat ontological plane, and regards therapeutic effects as emerging from their interactions. The second is Elizabeth Wilson’s Gut Feminism. Wilson extends the serotonin hypothesis beyond the brain to the peripheral body and argues that SSRIs transverse and relate bodily substances, emotional states, and the social world. These two approaches are similar in distributing the action of SSRIs across a range of components both inside and outside the body. The curative experience that we attribute solely to the pill arises from attaining an alliance and balance between heterogeneous aspects of life.