You are absolutely right in terms of most paradoxical reactions - and interestingly they even change during a patient's life. (Everyone working with mental health patients has a good story about a nana on a -pam going totally apeshit, throwing with faeces and definitely not getting any sedation from it).

Nyquil and Nodoz are actually quite common for paradoxical reactions,as are all Benzodiazepines. And there are patients who absolutely do react sensitive to medication. I am a good example for it myself: I am a fairly bulky guy but need minimal dosages for hypnotics like propofol - an amount I would consider barely sufficient for a 50kg nan knocks me out. Give me a Benzo on the other hand and I talk to you when others are already not breathing anymore.

SSRI are a bit different here, though. While I am absolutely sure, that classical paradoxical reactions exist they are extraordinarily rare, simply based on the mechanism of action the SSRI use. A true paradoxical reaction would mean that ones serotonin mechanisms react vastly differently - while this does occur it's extraordinarily rare, most common in already extraordinarily sick patients and would have led to other problems beforehand. There is overwhelming evidence that almost all cases reported are caused by the (almost physiological) initial paradoxical effect, insufficient plasma levels or insufficient adaptation times.

Again, there are patients who still will react strangely to SSRIs (and I am absolutely not a fan of them, I think they are an easy way out for a lot of providers but the cost/risk ratio does not really recommend them). And a lot of patients don't have a good experience with them. But that is not a paradoxical reaction but simply the difference between patients mental reaction to it. Which should be evaluated after proper dosage levels are achieved.

Why I am so particular about that topic? First off we see a lot of patients self therapy with SSRIs lately - changing their dosages, stopping them without any slow reduction,etc. That kills people. And from a broader stance we do see a lot of "self declared reactions" in patients. And that is a huge problem and a huge cost increase for the whole system.

(Buckle up fellas, grandpa is talking about the war again)

To stay with SSRIs: If someone has a proper paradoxical reaction to them we can no longer safely use Triptans against migraine, SNRIs, tricyclic antidepressants, MAOIs, amphetamines, pethidine, tramadol and heaps of other drugs as paradoxical reactions have been linked to Serotonin syndrome. I recently had someone report a penicillin allergy. 10% of all patients report it. Less than 1% of those have it. We couldn't properly interview the patient so we had to use alternative antibiotics. They are more expensive, often less powerful, often reserve-Antibiotics we try to avoid giving directly, have more side effects (in this case they led to the patient needing dialysis for quite some time. This is achieved by putting two finger sized catheters in your vessels. Not pleasant and definitely risky. (This is how I met her, we transferred her to a hospital being able to do that)

Wanna know what happened in reality with the penicillin? The patient took a course of it and suffered from diarrhoea for two days. That's a common side effect from the penicillin killing your gut flora. She told her GP and he explained it to her. When she moved she told her new GP about her "bad Penicillin allergy". Which led to this clusterfuck. There is a good chance the whole shebang she suffered from (Sepsis, Amputation, Dialysis, etc.) could have been avoided as the infection was highly sensitive to... penicillin....

Hope that anecdote explains why I am so critical about this topic. It's absolutely okay and necessary to recognise different drug tolerances (even more so as they are not considering gender, ethnicity,etc. most of the time) - but please do so openly with a healthcare provider and don't self diagnose.