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Discussion Starter · #1 ·
I've seen a lot of people sticking with completely ineffective or intolerable pills, and there's no reason for it. Thus, here is quick primer on how to get the most from your med trials.

When you visit your psychiatrist/GP, you will most likely receive an SSRI as the first line of attack. During the first few weeks of taking these, you may experience increased anxiety, depression, nausea and other side-effects listed. This is because of several reasons, one being that increased serotonin activates specific receptors in your brain which serve to regulate overall serotonin function (activate them, and the brain thinks it has too much serotonin, and reduces production/release).

If you are on [es]citalopram, venlafaxine, desmethylvenlafaxine or (to a lesser extent) fluoxetine, fluvoxamine or paroxetine, you may experience zero mental [side] effects whatsoever, but maybe some sexual dysfunction and nausea. If this is the case, it's possible a protein called P-glycoprotein is removing the drugs from your brain, leaving them instead merely circulating round the body. If this happens, you may consider switching to sertraline or paroxetine, which both block P-gp.

It takes roughly 2-4 weeks for the control receptors to "down-regulate" to nearer their original state, and this co-incides with the time taken for primary side-effects to diminish. After this stage, serotonin can be effectively "enhanced" in your brain, which brings with it what I call secondary side-effects. These are likely to be the result of serotonin activating certain negative receptors, producing sexual dysfunction, apathy, anhedonia, and more. They are inherent to an across-the-board increase in serotonin, so you'd have to be really lucky to avoid them.

By this point (4-8 weeks) you should be well into positive effects territory, and should notice yourself being more chilled out and happy. You might be getting a bit irritated by the side-effects, well, they're probably not going away without intervention (see later).

You may decide to quit taking the pills, due to side-effects or ineffectiveness. First thing to bear in mind -- just because you (may) get increased anxiety from coming off a drug, doesn't necessarily mean it was effective or even tolerable with side-effects. If an SSRI is not working to significantly improve your life within 3-8 weeks of starting, it probably isn't ever going to. This failure does happen in 2/3 of people (with placebo subtracted), so don't be surprised.

The first thing to consider is raising dose. This is a good choice when both positive and negative effects are low -- raising dose increases temporary (anxiety, nausea, etc.) and secondary (anhedonia, apathy, sexual) side-effects, as well as happiness and the other fun parts. However, if you get minimal mental side-effects but maybe some nausea or sexual problems, it's possible the drug isn't staying in your brain; in this case, a switch to sertraline or paroxetine is recommended.

Your doctor may try you on another SSRI next. This may benefit some patients with dose and/or pharmacokinetic problems, and as a way of simply giving SSRIs longer to alter your brain (as they all do mostly the same thing). However, one more SSRI should be your limit before moving on to a different type of drug, some of which I'll mention.

SNRIs, like venlafaxine, are very similar to SSRIs and only modestly elevate the effect of noradrenaline. You'd expect a noradrenaline increase to worsen anxiety, but the opposite appears to happen for some types (NRIs benefiting panic disorder, for example). I would personally say noradrenaline increase isn't the best idea for social anxiety, as NRIs on their own are not proven effective for this. It may help if you're somewhat lazy and depressed and need the energy.

Some doctors prefer to try drugs separately and hate combinations. This is justified in some cases, but not with mirtazapine and SSRIs. Mirtazapine can be added to SSRIs/SNRIs successfully, giving an enhanced antidepressant effect yet less side-effects (plus helping sleep). Specifically, mirtazapine can block some of the longer-term problems (sexual, apathy, etc.), but not all of the initial ones (anxiety, depression, etc.). I highly recommend the mirtazapine + SSRI combo, though you may have to try each separately first with an unwilling doctor. Mirtazapine can not be combined with MAOIs however; you'll quite likely die. Taking it with SNRIs has been done, but expect increased heart rate and other adrenergic symptoms.

Another class of drug you're probably aware of are benzodiazepines. These give potent relief for anxiety, and are best used sparingly in high-stress situations due to their dependency-forming attributes. You might want to ask the doctor for a small script for a fast acting benzo like alprazolam (Xanax). Even the mental effect of having one in your pocket can be quite empowering, but don't over-use them or you'll end up a million times worse.

If the tolerance and dependency issues scare you, pregabalin (Lyrica) is a relatively new anticonvulsant not believed to form significant tolerance. Moderately effective for SA.

Used for mostly performance purposes are beta-blockers. These don't cause dependency (so can be taken whenever), and mostly relieve physical results of anxiety (such as shaking and nausea). Do not take them if you're on any drug that raises noradrenaline or adrenaline, such as SNRIs, MAOIs or mirtazapine. Clonidine should be okay with those, if you need something to reduce their adrenergic effects (but I only recommend it with mirtazapine, where effects would balance out and cause minimal tolerance/dependency).

The powerhouses of anxiety/depression treatment are the MAOIs. Older, unselective MAOIs like phenelzine (Nardil) and tranylcypromine (Parnate) are considered most effective, but do come with some rather severe (but rare) side-effects. These happen when you eat cheese and other food, or a wide range of drugs which interact badly. The risks are very overstated usually, and can be avoided completely by most.

Some newer MAOIs that've been invented are less dangerous. Moclobemide is a RIMA (reversible inhibitor of MAO-A), which appears to be free from "cheese syndrome" (but not drug interactions) when taken after meals, and is proven effective for a range of different disorders. Quite a lot of people don't find it effective though, but I wonder if this is due to insufficient dose (being that people's MAO levels vary widely depending on if they smoke, or other reasons). Smoking inhibits MAO, so would contribute to MAOI action.

A different type of MAOI is selegiline. It blocks only MAO-B, so increases dopamine and noradrenaline. I find it alone to be useless for anxiety and limited for depression, at the selective doses. I only recommend it as an add-on to meds like SSRIs (at low dose, this is not at all dangerous).

Bupropion, AKA Wellbutrin, has similar effects to selegiline. It too is useful as an adjunct to anti-anxiety drugs like SSRIs (works well with sertraline and fluoxetine with dose adjustment and monitoring). On its own, it can make you pretty nervous.

In the same vein, dextromethylphenidate (Focalin) is another highly effective drug for motivation and confidence that can be combined with SSRIs. You may know this as an ADHD drug, well, Adderall (which is amphetamine) is similar and helps a lot of people.

Two rather cool drugs are sulpiride and amisulpride. At 50mg/day and below, these elevate dopamine through two mechanisms. They're useful with or without other meds for depression and anxiety (as they don't really increase anxiety, but rather they help it), but in particular to offset side-effects of serotonergic drugs (e.g. SSRIs) or to boost effects of dopaminergics (bupropion, MAOIs) and preventing tolerance and downregulation happening. It may be possible to make the initial euphoria of Nardil/Parnate last forever with these. I don't think they're available in the US yet.

Pindolol acts in a similar way to amisulpride, but on serotonin receptors. This can make SSRIs and other serotonergics effective immediately rather than after a month or two.

Another way to hit the dopamine receptors is with a dopamine agonist like ropinirone or pramipexole. These are mostly used in Parkinson's, as are COMT inhibitors like entacapone, but both give stimulant effects similar to bupropion. Can be added to some medications, but as with all this (unless stated otherwise), you should look up the interactions yourself and ask a doctor.

If you have sleep difficulties, you can consider adding trazodone or agomelatine (released soon) to your regimen. These don't really have many drug interactions known, except for boosting sedative effects. These two drugs help depression/anxiety too.

It's worth mentioning buprenorphine. It's an opioid with some dependency-forming properties, but not fully. If you're a past opioid addict you may get a maintenance script, and bupe can be combined with proglumide, magnesium/ketamine and/or "ultra low-dose naltrexone" to prevent tolerance, and is one of the most effective drugs ever known for depression and anxiety.

You could have luck adding buspirone or other soon-to-be-developed similarities to your stack, though buspirone is lacking in effectiveness.

There are numerous supplements I could recommend in addition to pharmaceuticals, not limited to: rhodiola, magnesium, niacinamide, St John's Wort, though these are very minimally studied and St John's Wort especially has lots of drug interactions (bad with SSRIs and MAOIs). Tread carefully when combining, and know what you're doing!.

Kava is a herb I can't recommend enough. Just buy the root, and only from vendors that do not use stems or leaves. Those were proven to cause liver damage.

2,661 Posts
Discussion Starter · #2 ·
You also need to have a good diet with lots of protein for the amino acids. It is possible to supplement with aminos such as L-tryptophan, L-tyrosine DL-phenylalanine, L-theanine and L-glutamine, though you need a balance. Closer metabolic intermediates are 5-HTP and L-dopa (+carbidopa!), though I advise restricting 5-HTP dose due to heart valve problems. Of course, take a a multivitamin and vitamin B-complex, and perhaps some antioxidants, inositol, triiodothyronine, phosphatidylserine, L-methylfolate, omega-3 fatty acids, P5P, huperzine A, SAMe, melatonin, taurine, and more.

If you happen to take any drugs which block histamine, ask about modafinil. It does the exact opposite.

Picamilon is a drug/supplement believed to act on GABA receptors, though I haven't tried it myself.

I suppose the most important conclusion of this post is that I cannot be bothered to write any more, so don't take this list to be exhaustive.
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