This question was originally posted on Quora.com and was answered by David Moore , studied Bachelor of Medicine and Bachelor of Surgery Degrees at University of Sydney This is a very important question, and the largest and most appropriate study I am aware of has just been published on this topic. Association of Antidepressant Use With Adverse Health Outcomes Key Points Question: Is antidepressant use associated with adverse health outcomes, and how credible is the evidence behind this association in published meta-analyses of real-world data? Findings: In this systematic umbrella review of 45 meta-analyses of observational studies, convincing evidence was found for the associations between antidepressant use and suicide attempt or completion among individuals younger than 19 years and between antidepressant use and autism risk among the offspring. However, none of these associations remained at the convincing evidence level after a sensitivity analysis that adjusted for confounding by indication. Meaning: This study’s findings suggest that claimed adverse health outcomes associated with antidepressants may not be supported by strong evidence and may be exaggerated by confounding by indication; no absolute contraindication to the use of antidepressants was found to be currently supported by convincing evidence. This study thankfully confirms a common-sense suggestion that has been difficult to support with evidence before now: that is that the effects of medications used to treat a condition and the effects of the illness that they are intended to alter can be difficult (if not impossible) to differentiate. All commonly used antidepressants act via Brain-Derived Neurotrophic Factor (BDNF - a key transducer of antidepressant effects.). Regardless of their synaptic mechanisms, it is the structural effects on dendritic development that underly their longer-term therapeutic effects. I usually use the analogy of ‘grass growing’. It’s why we’re often waiting a month to see real efficacy, and it’s why antidepressants are best used for at least the medium term (I often suggest 12 months of treatment at least) in order for stability to be more likely to persist. BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo Unsurprisingly, people who experience symptoms that they attribute to medication are more likely to discontinue them, and given the slowness of the ‘infrastructure building’ underlying their effects it is more likely that people suffering such symptoms may not derive any positive effects but rather see the perpetuation (and/or worsening) of the conditions the medications are intended to treat. It’s quite ironic. The key point regarding antidepressant action is this: complexity is good. Where stimuli are applied over and over the brain adapts - synaptic pruning simplifies neural structures such that repetitive responses increase in likelihood. The model of reduced complexity in response to recurrent exposure is one of the best models to explain learning. I joke (darkly, and with respect) that the World gives us all PTSD to various degrees, it’s just that some of the entrained behaviours are helpful. So, where complexity is lost then perpetuation is more probable. This can lead to the infinitely self-critical phenomenon of suicidality, which may be reflected by a sort of cerebral auto-phagy, if I am allowed some poetic licence to describe it as such. Chronic stress decreases synaptic connections and produces depressive-like behavior: rapid reversal by ketamine. https://www.researchgate.net/public...n_in_Depression_Potential_Therapeutic_Targets In summary, problems and possible solutions can look similar, just as ‘dendritic growth’ is neither good nor bad (and could represent maladaptive alterations!) however the effect of antidepressants is generally to reverse some of the specialisation that occurs in synaptic structures, thus allowing something of a ‘second chance’ - like adding marble to a sculpture that has a mistaken chip on its shoulder. I say all this as both a clinician and a patient. I feel that (if nothing else) my money is where my mouth is. For further reading I suggest the RANZCP Guidelines and resources for practice | RANZCP Source
