Key moments, in order
Rule one: never pick a medication that causes weight gain or appetite increase if you can help it, and minimize side effects. Rule two: pick the most efficacious.
Ask which major depression you mean: true, recurrent, biological major depression (the cousin of bipolar disorder), or dime-store depression from personality and stressors that happens to meet episode criteria.
Methylphenidate is commonly used for geriatric depression, so we cannot write off stimulants in one sweeping blow.
What you feel on a stimulant (meth, cocaine or speed, which is what Adderall is) is an intoxicant effect: the euphoria and energy burst, and you build tolerance to that.
In ADHD plus depression, a stimulant does not treat the depression long term. Irritability and somatic symptoms creep up.
Even for the most biological disorders, treatment works over at least two or three months. A major effect within a few weeks, or a stimulant that seems to stop working and need a higher dose after a few weeks, is the drug effect. Do not fall for that trap.
Sertraline titrates in multiple steps (eight to the FDA maximum), just works, and does not have much in the way of med-med interactions.
Several CYP enzymes metabolize sertraline, while escitalopram is broken down by 3A4 and 2C19, and 2C19 has a lot of variants. Ultra-slow and ultra-fast metabolizers have a really bad response to escitalopram more often than to sertraline.
It has only four titration steps, which feels limiting psychologically and physiologically.
Being the purest SSRI does not mean the fewest side effects. Sertraline is a little better tolerated overall, and some patients tolerate citalopram better than escitalopram, against what we are taught.
The step from 100 to 150 mg gives patients real control: if it does not work out, take the 100 and half of the 50.
Purity is overrated. We like a dirty drug that can do several things at once.
"Major depression" can mean a true, recurrent, biological depression, the cousin of bipolar disorder, or a depression from personality and stressors that happens to meet criteria. Biological depressions can be agitated, with severe insomnia and psychomotor agitation.
With low-dose lithium you do not need the same lab schedule as higher doses, and you would not expect the same kidney dysfunction.
It lasts so long that it is great for patients who forget or skip doses: give a higher dose, and the long half-life still gives an effective serum level when they skip a few doses a week. Start-and-stop patients can get used to it and take it a few times a week (not as a PRN, just whenever they remember).
Many people categorize it as the most weight neutral, and we think a study may even have shown some weight loss in the very short term, but we do not see a significant difference.
Population numbers cannot tell weight gain caused directly by the drug from weight gain as a consequence of treatment. In one analysis, accounting for unhealthy eating made the SSRI weight signal mostly disappear, which is not true for heavy gainers like olanzapine.
They are symptomatic treatments that create habits, build tolerance and stop working. They help people feel better temporarily rather than treating the underlying condition.
They have a role in acute decompensation in a patient whose addiction risk does not worry you, for example a one-week prescription to get through a crisis that is partly depression.
A short-term sleeper can just as easily be high-dose hydroxyzine, low-dose trazodone, higher-dose gabapentin, or mirtazapine if you have to.
It has real strengths: it works quickly, it is a sleeper on top of being an antidepressant, it is easy to dose, and it comes in long- and short-acting forms. A lot of bang for your buck in one tablet.
The old teaching to pick it for poorly adherent patients, so withdrawal reminds them to take it, is outdated. Set an alarm on the phone and use a pill organizer.
Paroxetine is anti-muscarinic, and that organizes everything else about it: it is sedating, and it has bad withdrawal, as any anti-muscarinic medication will.
It is basically escitalopram that makes people sleepier and prolongs the heart rhythm. Not a bad medication, it just has downsides.
If you are on your third medication in a row with no remission, reconsider your diagnosis.
It inhibits CYP1A2 especially, and then basically all the others: 2C9, 2C19 and 3A4.
Famously the worst withdrawal syndrome of all the antidepressants, severe enough to keep it out of a higher tier. An elderly patient was once medically hospitalized from it. It works well, but be careful and taper slowly.
Its improvement over SSRIs is relatively small, so it is not a big-hit medication, and it can raise blood pressure and heart rate.
We reach for it for comorbid pain, diagnosed fibromyalgia or a migraine disorder; otherwise we do not go for the SNRIs. We do not believe in them for apparent ADHD.
Do not combine an SSRI and an SNRI. Stop it. The famous combination in this family is California rocket fuel, which is mirtazapine plus venlafaxine.
Desvenlafaxine theoretically has fewer drug-drug interactions than venlafaxine. No significant difference in efficacy between the two has been noticed.
One of four first-line antidepressants, with escitalopram, sertraline and bupropion, chosen by patient profile. We very rarely deviate from those four.
Incredibly sedating. Warn patients they will feel like a zombie: expect a hangover, usually three to four days of feeling a bit like a zombie the next day, which typically gets better after about a week. Do not start it the night before a big work meeting.
It has a small but statistically significant effect in meth use disorder in some populations, about three fewer meth days a month.
We rank it A tier and add it for almost everyone who does not respond to just one medication. It can put a pep in your step.
If an anxious patient is going to trial it, have them take the first dose on a weekend or when they have nothing to do.
It is a 2D6 inhibitor, so it can be used to raise the effective dose of aripiprazole, including the long-acting injectable forms.
Low-dose trazodone is not a small antidepressant. At 50 mg it is not reuptaking serotonin, which is its antidepressant mechanism, so you have to reach higher doses for that.
Say: this works great for a lot of people, and for some it does not work at all and might even make sleep worse. We do not know which you are, so try it. A small share do have that paradoxical reaction.
Know how to do an AIMS: read the directions and actually do it. A modified AIMS can be done over video with help from a family member or a nurse.
For depression without psychotic features, do not dose it above 5 mg. It is not worth it.
As an antidepressant augmenter it has lower tardive dyskinesia risk than the other antipsychotics and is very well tolerated, so well tolerated that it can be hard to get patients off it once they are stable.
If you are treating major depression and are on your third medication in a row with no remission, reconsider your diagnosis. Make sure you have the right diagnosis: treatment-resistant depression is where personality disorders go to hide.
A perfectly fine medication, but expensive and not particularly more effective than others, the traditional SSRIs included (though we have not used it a lot). For cost reasons we would not go to it first, but someone who has a hard time tolerating medications may tolerate it better than the others, so it is worth a try.
Esketamine is a short-term treatment that helps lift out the depression, and then you have to do hardcore lifestyle changes and psychotherapy on top of that.
Many patients now seek it out as a drug to ignore other problems, while making lifestyle choices that are almost bound to keep stress at unmanageable levels.
Do not underdose it. It is often written off because it was never adequately dosed. Titrate fairly aggressively and do not be afraid to take it to the max, but do not expect the moon and the stars: it gives a modest benefit. We have seen it work better at the higher dose range.
We do see it help patients with emotional dysregulation who report depression, but not MDD proper. Do not use a drug that is not indicated just because its side effect profile matches what you want.
Consider TCAs and MAOIs for true treatment-resistant depression, not for what is really trauma or personality depression, and only if you know what you are doing.
Tailor your tier list to your own patients. Populations differ, your diagnostic pool differs, and so treatment response will too.
Each moment is a point made in the episode, linked to the second it was said. The topic links open everything the podcast has said on that topic.