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On Antidepressants, Still Anxious

Antidepressants, despite the name, are first-line treatments for anxiety as well as depression.

Choosing the right antidepressant is hard, a topic we’ll come back to frequently. It involves a lot of trial and error, but there is both some science to it and some knowledge to be drawn from practical experiences.

Here are two pieces of practical experience that don’t seem to be as well known as they should be:

  1. Wellbutrin tends to increase anxiety in a lot of people.
  2. Higher doses of SNRI’s (e.g. Effexor, Pristiq, and Cymbalta) tend to increase anxiety in a lot of people.

Usage of Wellbutrin

Wellbutrin, generic name bupropion, can be used by itself to treat depression. It’s also used as a smoking cessation aid, marketed under the name Zyban. But more often, it’s added to another antidepressant to either complement it, or reduce the impact of the first antidepressant’s side effects.

For people who get “slowed down” a bit when taking an antidepressant, sometimes Wellbutrin can help give them a little bit more pep. It’s also very commonly used to combat the dreaded sexual side effects brought on by many antidepressants.

Using Higher Doses of SNRI’s

SNRI’s like Effexor (venlafaxine), Pristiq (desvenlafaxine), and Cymbalta (duloxetine) are commonly prescribed antidepressants that can help with a wide range of anxiety and depressive symptoms.

Everyone is different, but most people start at a low dose of each and may gradually increase. Most people top out around 225mg of Effexor, 100mg of Pristiq, or 60mg of Cymbalta. But you can certainly go quite a bit higher on all of them. After all, if you’ve gotten a good response at a particular dose, maybe you’ll get a better response at an even higher dose?

Taking a Step Back

Before going any further, let’s take a step back and get a refresher on what antidepressants actually do. Your brain has a set of chemicals called neurotransmitters which help control your mood. There are several different neurotransmitters, most notably serotonin, norepinephrine and dopamine, which all affect slightly different aspects of your mood.

Different antidepressants target different neurotransmitters. They don’t actually create more of them, but they make sure that they’re all available right where they are needed. Selective Serotonin Reuptake Inhibitors (SSRI’s) work to maximize the availability of serotonin. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI’s) work to maximize both serotonin and norepinephrine availability. And so on.

Neurotransmitters and Anxiety

For most people, increasing the amount of serotonin available will help improve anxiety symptoms. That is why SSRI’s and SNRI’s tend to be the first meds prescribed for anxiety.

What isn’t most recommended to try first for people with anxiety? Antidepressants that increase the amount of dopamine that is available, which makes many people more anxious, not less.

Guess what neurotransmitter Wellbutrin tends to target? Dopamine.

So what about SNRI’s? The current generation do, as the name suggests, primarily target serotonin and norepinephrine. But they also weakly target dopamine as well. However the larger increase in serotonin tends to more than offset the small increase in dopamine availability for most people.

As you move to higher and higher doses, the amount of extra serotonin made available gets smaller and smaller. That is why increasing the dose of some drugs past a certain point doesn’t greatly improve symptoms. In contrast, at the higher doses of current SNRI’s, the amount of extra dopamine made available does actually get larger.

As an example, somebody taking Cymbalta 60mg will have only a very small amount more dopamine available. That same person taking 90mg or 120mg may have quite a bit more extra dopamine, which can cause nervousness or anxiety.

Every drug has a different behaviour at different doses, which is known as the dose-response curve.

Take Action!

Are you on Wellbutrin and experiencing anxiety? Ask your doctor about reducing or removing the Wellbutrin, and see if it helps your anxiety. If so, will you still need to find something else to replace it?

Are you on an SNRI and experiencing anxiety? Particularly if it’s a higher dose, talk to your doctor about the possibility of going down to a lower dose and seeing it it makes a difference. If it does reduce your anxiety, and the lower dose isn’t enough to help with your other symptoms, you may end up discussing a switch to another antidepressant, or something else to augment the lower dose of your current SNRI.

There are lots of other reasons you may be anxious, which I’ll have more to say about in a future post, but these two kinds of medication-induced anxiety seem to very commonly get missed.

Get your Ferritin and B12 Levels

If I could only give out one piece of advice when it comes to people suffering from depression or anxiety, it’s this: find out your ferritin (stored iron) and Vitamin B12 levels.

If every family doctor checked just these two things before putting someone on an antidepressant, it would save an incredible amount of grief. Such a simple thing, but not having recent ferritin or B12 levels, or them being too low, is one of the most commonly-missed and easily treated causes of depression and anxiety.

Why Ferritin and B12 are Important

Iron and B12 are used for a variety of things in the body, including assisting in the process of creating neurotransmitters like serotonin which help regulate your mood. If you don’t have enough iron and B12 available, you don’t produce enough neurotransmitters. You can end up severely fatigued, with low energy, poor concentration, bad memory, more anxious, etc.  In other words, low iron or B12 mimic many of the usual symptoms of anxiety and depression.

Antidepressants are designed to keep the number of neurotransmitters available in your brain at a high enough level. But no antidepressant is going to help you if you don’t have enough neurotransmitters to begin with. Experimenting with antidepressants under these circumstances is an incredible waste of your time and money.

What Causes Low Ferritin and B12?

There are lots of causes. For example, excessive bleeding can reduce iron. Inadequate dietary intake can be an issue, as can inadequate absorption of what you eat. Many medications can decrease absorption, as can some foods. Many people gradually lose the ability to absorb B12 as they get older, and develop all kinds of cognitive problems as a result. Too many, whose B12 isn’t checked, may be mistakenly assumed to have some kind of dementia. If the low B12 is corrected (e.g. via injections), the cognitive problems often quickly go away.

What you Need to Check

There are multiple different blood tests to check for iron levels, but for this purpose you need to make sure your serum ferritin is checked. This is a measure of the amount of iron stored in your blood that’s not already part of other things like blood cells, and so is available to help create neurotransmitters. Vitamin B12 levels are more straightforward. So ask your doctor if you’ve recently had a ferritin and a B12 level done, and if not, get them to order it. Then ask for the actual result of each.

Within Normal Range Isn’t Good Enough

You probably know that different blood tests have a range that’s considered normal, and anything above or below that range gets flagged in the lab reports that go back to your doctor.

Here’s the problem: for people with mental health symptoms, the normal ranges are too low.

The normal range for ferritin is 12–300 ug/L. That’s good enough to make sure there’s enough iron for building blood cells, but not enough for neurotransmitters. To avoid problems with fatigue, memory, concentration, etc. your ferritin level must be at least 50.

Similarly, the recommended level of Vitamin B12 is a minimum of 150 pmol/L, but for optimal mental health your B12 level should be at least 240.

Consequences in Practice

Many doctors, if they’ve ordered these tests at all, see them come back normal, and that’s the end of it. This is not good enough. The clinical difference between the official normal range and the optimal range for people with mental health symptoms can be substantial. I’ve seen many people have their symptoms improve, in some cases dramatically, simply by correcting these deficiencies.

Becoming deficient can happen anytime too. Some people are on antidepressants for years, with good effect, when they gradually start developing symptoms again, which worsen over time. Too many doctors are quick to assume that their antidepressant has “pooped out” and try to switch them to something else, instead of first checking if there is a new or worsening ferritin or B12 deficiency.

There is so much research and evidence behind this, that it is one of the few things that I would recommend truly pushing with your doctor if they are hesitant. Too many doctors (and pharmacists) are reluctant to treat low ferritin or B12, as long as the numbers are close to the normal range. Unless they can offer a good reason that supplementation to these higher minimum levels would be harmful, this is one worth fighting for.

Take Action!

Go to your doctor, check if you’ve had recent ferritin and B12 levels measured. If not, get them to order it. Ensure your ferritin is at least 50, and your B12 at least 240. If not, ask them how best to correct it. Make sure it gets checked again several months later.

Further Reading

Effect of iron supplementation on fatigue…  Canadian Medical Association Journal, August 7 2012.

It Could Be Old Age, or It Could Be Low B12. New York Times, November 28 2011.