In recent years, the 1954 Serotonin Theory of Depression and SSRIs have been thoroughly investigated by scientific researchers. This theory proposed that depression results from a serotonin or nor-adrenaline deficiency, and that increasing levels with antidepressants might cure depression.
“That the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems, and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients”.
This assumption was debunked by a systematic umbrella review of all evidence associated with this theory; from inception until December 2020, and published in Molecular Psychiatry in 2023 by Moncrieff et al.
“This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.”
Serotonin is one of your “feel-good” hormones and neurotransmitters. As a neurotransmitter, it has your brain and spinal cord (your central nervous system) on speed-dial, to transmit and receive crucial chemical messages to and from your nerve cells, muscles and glands; essential for the proper functioning of your brain and body.
It plays a critical role in mood, sleep, memory, digestion, appetite, wound healing, learning ability, and sexual desire. It’s recognised for its positive effect on mood and its protective role in depression. If serotonin signals are disrupted, all lines of communication between the brain and body are disrupted, causing problems in all these areas.
In 1954, a case study observed five hypertensive patients after reserpine was added to their blood pressure medications. The following is a combination of symptoms experienced by all five patients after taking reserpine for 3-4 months. Severe depression, found life was not worth living, reluctant to leave home, inability to enjoy previously pleasurable activities, loss of self-confidence, fear of social interactions, excessive introspection, lost all interest in work, thoughts of alcoholism, wished for death, chronic unhappiness, struggles with daily tasks, fatigue, and suicidal ideation.
When reserpine was discontinued, patient A improved slowly for two months and was depression-free when last seen six months later. Patient B improved dramatically after 48 hours and was depression-free within a week. Patient C returned to a happy, emotional and vigorous physical state within one week. Patient D was given electroshock therapy, improved slowly and returned to work. Patient E improved slowly, but when last seen had not returned completely to his previous personality state.
“In the 1950s, the amine hypothesis of depression was proposed after it was observed that patients treated for hypertension with reserpine developed depression. Since that time, pharmacologic therapy for treatment of depression has focused on increasing concentrations of brain monoamines (neurotransmitters), namely norepinephrine (nor-adrenaline), serotonin, and dopamine”.
In 1954, the medical industrial complex tested reserpine and found that after taking it for 3-4 months, patients became severely depressed. What does reserpine do to the brain?
“Reserpine’s mechanism of action is through inhibition of the ATP/Mg2+ pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines”.
Picture a river (synaptic cleft) with the transmitting (presynaptic) nerve on Bank A and the receiving (postsynaptic) nerve on Bank B. Serotonin must cross the river, find a receiving nerve, connect, and transmit its message to ensure proper brain-body functioning.
Reserpine blocks this process by preventing the ATP/magnesium pump, which powers this process, from switching on. No magnesium, no transmissions. It blocks all speed-dial brain-body communications, causing severe depression and reducing catecholamines, our stress hormones, which also causes depression.
Selective serotonin reuptake inhibitors (SSRIs) hit the market with extensive marketing campaigns in 1987, 38 years ago. In a healthy person, when serotonin is fired from Bank A to Bank B, some do not find receptors and land in the river, which must be cleared of all serotonin to make way for new incoming messages. Thus, the swimmers are guided to SERT, a channel at the side of the river on Bank A, then transported back through SERT to be re-uptaken and recycled by the transmitting (presynaptic) nerve from which they came.
This ends the transmission, signalling the receptors to rest and wait for new incoming messages while maintaining balanced serotonin levels. This process will not stop and allow the receptors to rest until the river (synaptic cleft) is cleared of all swimmers.
In a depressed person, “SSRIs work by blocking ‘inhibiting’ reuptake, meaning more serotonin is available to pass further messages between nearby cells”.
This quote is deceptive; all neurotransmitters only have one way out of the river, and that’s through SERT. SSRIs block SERT and prevent serotonin from being guided back through SERT to be re-uptaken and recycled to deliver future messages from the original transmitting (presynaptic) nerve.
The transmission cannot switch off, preventing receptors from resting, and new incoming messages will not be transmitted or received properly; the river cannot be cleared. The serotonin in the river will pile up and eventually be disposed of (metabolised) by the body. This whole process reduces overall serotonin levels and interferes with the brain-body speed-dial communication pathways.
This explains the symptoms caused by reserpine and experienced by the case study patients, and why 280 million people worldwide suffer from depression today (World Health Organisation, April 2025). How many are on SSRIs, while an army of healthcare professionals, ignorant of the latest science, continue to prescribe these dangerous antidepressants?
Reserpine and SSRIs cause depression by reducing serotonin and other neurotransmitter levels, and blocking crucial brain-body messaging, meant to keep serotonin levels balanced and us depression-free.
The science of depression and antidepressants has changed. The news is not good, but we need to hear it. Why? Because if we don’t know what’s hurting us, we cannot avoid it.
