According to the FDA the question they want to answer at a new drug approval is: "Does this drug work for the proposed use?"
To answer that question the FDA requires the drug company to submit studies that prove the drug to be safe and effective for the proposed use.
There are a host of criteria's such as preregistration that the FDA takes into account but the main criteria for effectiveness is that there are two drug trials that show statistically significant effects for the drug.
Drug design usually starts with a Pharma company deciding that there a target where they believe that a drug that binds to the target will have a positive effect on a condition. Then the Pharma company tries lot of different molecules in High Throughput Screening (HTS).
When it finds molecules that bind to the target they test the drug in animal to see what it does. The test the dosage that's required to kill animals.
If that step is promising they move on to human studies and go through the 4 phases of the the FDA process.
The drug company usually has a theory of how their drug works but in most cases the theory will be proven wrong and the drug is not shown to be safe and effective in the clinical trials.
But even if the drug is shown to be safe and effective, that doesn't mean that the theory of the Pharma company is right. Drugs usually do more than one thing. In the case of SSRI the theory based on which they were developed in that they are supposed to affect serotonin levels in the brain.
Further research found out that they also have effects in the gut. The gut also uses the neurotransmitter serotonin. It even uses 95% of the serotonin in the body. Chronic inflammation is linked to depression. In vitro SSRI have been shown to exert significant immunoregulatory effects.
Nobody knows for certain whether the clinical effect of SSRI's on depression shown in the studies that were submitted to the FDA are due to effects fo the drugs in the gut or effects in the brain. It would also be possible that the effects are due to a process that's yet to be uncovered.