is due to an imbalance, most often a deficiency, of the monoamine neurotransmitters, namely serotonin, norepinephrine, and/or dopamine. However, serotonin in particular has been implicated, as in the serotonin hypothesis of depression. The monoamine hypothesis was originally proposed based on observations that reserpine, a drug which depletes the monoamine neurotransmitters, produced depressive effects in people, and that certain hydrazine antituberculosis agents like iproniazid, which prevent the breakdown of monoamine neurotransmitters, produced apparent antidepressant effects. Most currently marketed antidepressants, which are monoaminergic in their actions, are theoretically consistent with the monoamine hypothesis. Despite the widespread nature of the monoamine hypothesis, it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, many people with depression do not respond to monoaminergic antidepressants. A number of alternative hypotheses have been proposed, including hypotheses involving glutamate, neurogenesis, epigenetics, cortisol hypersecretion, and inflammation, among others. In 2022, a major systematic umbrella review by Joanna Moncrieff and colleagues showed that the serotonin theory of depression was not supported by evidence from a wide variety of areas. The authors concluded that there is no association between serotonin and depression, and that there is no evidence that strongly supports the theory that depression is caused by low serotonin activity or concentrations. Other literature had described the lack of support for the theory previously. In many of the expert responses to the review, it was stated that the monoamine hypothesis had already long been abandoned by psychiatry. This is in spite of about 90% of the general public in Western countries believing the theory to be true and many in the field of psychiatry continuing to promote the theory up to recent times. In addition to this review, a 2003 literature review and a 2022 systematic review, both of reserpine and mood, found that there is no consistent evidence that reserpine produces depressive effects. Instead, the results were highly mixed, with similar proportions of studies finding that reserpine had no influence on mood, produced depressogenic effects, or had antidepressant effects. In relation to this, the general monoamine hypothesis, as opposed to just the serotonin theory of depression, is likewise not well-supported by evidence. The serotonin and monoamine hypotheses of depression have been heavily promoted by the pharmaceutical industry (e.g., in advertisements) and by the psychiatric profession at large despite the lack of evidence in support of