This is an egregious violation on many levels. It highlights a massive gap in the clinical trials process (companies can stop trials without reporting negative results) that really should be addressed. I think everyone (outside of drug companies) can agree on that much.

I would like to say a few words on SSRIs (the class of drugs that Paxil is in) and their risks in general, because articles like these tend to cultivate strongly negative feelings toward SSRIs due to the deplorable drug company actions mentioned in this article. I don't blame people for mistrusting the drug companies after reading something like this. I also feel that SSRIs are prescribed too quickly and with too little extra guidance from doctors, although that trend is changing a bit as doctors become more educated.

But my biggest concern is that we're starting to see many people with severe depression who refuse to take SSRIs because they don't trust the drug companies and they've come to believe that their severe depression is still better than the side effects or risks of an SSRI, which couldn't be farther from the truth.

The bottom line is that SSRIs, while far from perfect, are still one of the most effective first-line treatments for severe depression that we have, and they do it with a side effect profile that is head-and-shoulders above previous generation anti-depressants.

Perhaps the biggest problem with SSRI treatment is the delayed onset of action. Unlike short-term rewarding drugs such as stimulants or opioids that may boost one's mood in the short term but quickly develop tolerance, SSRIs work through long-term adaptive changes. These changes are numerous, from increased BDNF and hippocampal growth to HPA axis normalization and restoration of brain connectivity back to a state that more closely matches that of non-depressed patients. However, the problem is that all of this happens as downstream effects of an alteration in how serotonin moves through the brain, which is very disruptive in the short-term while the brain adapts to the changes.

SSRI stands for selective serotonin reuptake inhibitor, which means that it inhibits the ability of serotonin-releasing neurons to take serotonin back up from the synapse after they release it. This doesn't "raise serotonin levels" as many describe it (unfortunately perhaps due to some awful SSRI marketing in the 90s and 00s) but rather alters the dynamics of how serotonin-based circuits operate. Serotonin will now spend more time in the synaptic cleft, activating post-synatpic serotonin receptors and synaptic transmission becomes a bit more smoothed out as the transmission takes longer to terminate via MAO deactivation of the serotonin or via uptake from the ~20% of uninhibited serotonin transporters.

Over time (4-8 weeks on average) the post-synaptic receptors adjust to the "new normal" levels of serotonin that they see in the synaptic space. This adjustment might even be key to some of the therapeutic effects of SSRIs, as some serotonin circuits may be too active in depressed or anxious patients, but the chronic SSRI administration quiets those receptors down, somewhat counter-intuitively. The big problem here is that until those receptors compensate, the patient may actually feel worse in the short-term. (Note that some patients actually feel substantially better during this phase, so please don't take this as a given). In the worst-case, depression or anxiety are actually worsened temporarily, combined with an increased energy due to the SSRI's activating effects. At the extreme worst-case scenario, this can lead to suicidal ideation, and for whatever reason this is more common in teenagers.

I wrote all of this out because the HN crowd tends to want to know how things work behind the scenes or under the hood when making decisions for themselves. My goal is not to suggest that everyone who experiences depression should be on SSRIs, because I actually feel that medication is probably best reserved as a first-line treatment for moderate to severe depression. Instead, my goal is to keep everyone informed such that they can work with their doctor to find the best treatment for themselves without unnecessarily fearing SSRIs due to these deplorable actions of drug companies a few years ago.

If you're feeling depressed, work with your doctor to find a solution. If you question your doctor's decision, see someone else. But it's important to explore all options if depression is taking a toll on your life, and if you choose to go the SSRI route then be aware that therapeutic effects are 4-8 weeks out, at least, and talk to your doctor right away if you're concerned.