last updated 11/16/2024
Depression is the main symptom in the middle of the mood spectrum: either episodic, or with brief ups, or Mixed with anxiety, anger and attention problems. But antidepressants can make things worse, increasing the frequency of depressive episodes, adding or intensifying Mixed symptoms, or causing an agitated hypomania or mania.
So the treatment goal is simple: ease the depression and stabilize mood at the same time. Thus the main tools are “Mood Stabilizers with Antidepressant Effects”.
Step 1 is not a pill
Too much sleep can cause or add to depression. Too little sleep can push mid-spectrum people toward an agitated hypomania. The right amount, 7-8 hours for most people, can be a mood stabilizer, if it comes on a regular schedule. And it can be an antidepressant, sometimes. Read on!
Mid-spectrum people tend to feel worst in the morning. So why get up early, just to feel miserable, right? Maybe just sleep some more until later in the day, when mood is often a little better. The best time of day is often at night, so why not stay up later to enjoy it (or finally get some work or chores done)? But see what happens: you stay up later and later, and get up later.
The good news is that shifting your sleep hours earlier (earlier bedtime, earlier rise time) can have an antidepressant effect. The bad news, which I’m sure has already occurred to you: making this shift can be really hard. You’re going against the tide of your own biological clock.
How about some help? How about a “therapy” that helps you get to bed just a little bit earlier every night, and wake up — and get up — a little earlier each morning. Pretty simple. It’s sort of silly to call this a “therapy”, but that making this change can be really challenging. So here’s some help:
- Social Rhythm Therapy: the complete version of this treatment
- Simpler, just the key step: make sleep hours regular (not as easy as it sounds…)
Don’t skip this step completely. If it’s too hard now, come back to it later. Really working toward regular sleep may help you need less medication (my experience talking; that’s not been really tested).
Pill options
Mood stabilizers with antidepressant effects: as of 2024, there are 4 medications routinely recommended for this role: lamotrigine, low-dose lithium, lurasidone and quetiapine. They each have their pro’s and con’s.
Lamotrigine has almost no long-term risks, and usually no side effects, so it’s my top recommendation for most patients. But it’s good to know a little about all of them.
A quick comparison
| Medication | Pro’s | Con’s |
| lamotrigine | Almost no long-term risks Usually no side effects | Doesn’t always work 1-in-2,000 dangerous allergy risk |
| low-dose lithium | Often has anti-suicide effect No side effects (none allowed) | Doesn’t always work 1-in-20 decrease in thyroid |
| quetiapine | More likely to work Strongly helps get to sleep | Major weight gain common Slow to get going in a.m. |
| lurasidone | Good evidence for benefit Less weight gain | Newest so less well known Have to time it with meals |
Why lamotrigine is usually first
Why start with lamotrigine? Two reasons. First, it has no long-term risks. (Or very close; it depends on who’s counting and what’s counted. Certainly much less risk than other medication options).
Second: most people can take it with no side effects at all. This is essential because you’re likely to take it for quite a while. (Not necessarily “lifelong”: when things have been going really well for several years, you can talk with your provider about slowly tapering it off. Other mood stabilizing effects may be in place by that time. But never taper off by yourself!).
But lamotrigine doesn’t always work?
No medication always works. But some have better evidence for benefit than others. Lamotrigine’s evidence is a little mixed. Quetiapine’s evidence is much better, for example.
But most of my patients are prefer “no weight gain, no significant long term risks, usually no side effects” over “good evidence for benefit”. Lamotrigine definitely has enough evidence to support trying it first.
Why consider others
One potential exception to the “lamotrigine first” approach would be if your symptoms are really severe right now. You might need to go straight to the medications with the highest chances they’ll work. Another exception would be if you’re thinking about suicide a lot. Very low doses of lithium can often make that thinking just stop (even if depression doesn’t get much better; it’s interesting).
Quetiapine is often considered when insomnia has been a big problem. It almost always helps get to sleep and stay asleep. The problem is getting going in the morning; and the biggest risk with quetiapine is weight gain, like 10 pounds right away and often more. Few people do not gain weight on quetiapine.
Lurasidone only recently became available as a generic. I don’t have much experience with it. Just enough to see it frequently cause weight gain, even though it’s supposed to do that much less than quetiapine. Otherwise I won’t comment further. There are more medications coming but for now they’re far more expensive and we have far less experience with them (what risks will be discovered 10 years from now, for example).
More information on each
Read more about lamotrigine and then if you are not certain that’s the best option, learn about low-dose lithium next. Then to complete your knowledge of mood stabilizers with antidepressant effects, there’s a page comparing quetiapine and lurasidone.
lamotrigine, or an antidepressant?
The crucial choice, for people in the mid-mood spectrum who want a pill approach, is: lamotrigine, or an antidepressant? My suggestion: carefully compare potential risks. Here’s a direct comparison (which leads to this graph):
Links
References
Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, Hopwood M, Lyndon B, Mulder R, Porter R, Singh AB. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Australian & New Zealand Journal of Psychiatry. 2021 Jan;55(1):7-117.