Treating mixed states might appear clear-cut in theory, yet overlapping symptoms, risk factors, and side effects turn each plan into a careful balancing act.
If you haven’t read the first essay in this series on mixed states, consider starting there, since this piece focuses on treatment.
In theory, treatment of mixed states in bipolar is simple: Decrease destabilizers or increase stabilizers. Ideally, you’d remove destabilizers first, right? But often, people have already tried to do that on their own and are still struggling with symptoms.
Sometimes a destabilizer simply can’t be reduced or removed. In those cases, we often have to move directly to the stabilizers. I have some favorites, and I’ll tell you why. But first, let’s look at the main players in this tug-of-war.
Destabilizers
- Big stresses
- Erratic sleep patterns
- Street drugs
- Antidepressants
- Steroid medications
- Quickly stopping an antidepressant
- Some antipsychotics, sometimes
Most of this list probably won’t surprise you. Stresses, sure. Erratic sleep, sure — it can lead to too little or too much sleep, both of which are destabilizing.
Street drugs are a common trigger, especially stimulants like cocaine and methamphetamine. Marijuana can be especially risky for young people, since it can bring on psychosis. That said, for at least a few people, it can help with sleep or anxiety (basically functioning as a stabilizer) — so it’s complicated.
Antidepressants can be destabilizers, but oddly, so can stopping one too fast. More on that in a minute.
Also oddly, some antipsychotics can sometimes act too much like antidepressants and cause manic or hypomanic symptoms. The most famous for this are:
- risperidone (Risperdal)
- aripiprazole (Abilify)
- olanzapine (Zyprexa) — rare but reported
- lurasidone (Latuda) — case reports
- quetiapine (Seroquel) — very rare
- Newer ones: cariprazine (Vraylar) and iloperidone (Fanapt) — too new to know
A good rule of thumb: If your symptoms feel more mixed shortly after starting an antipsychotic, sometimes that medication could be responsible.
Stabilizers
Mood stabilizers fall into two groups: the ones that are mostly or purely anti-manic, and those that have antidepressant effects while only infrequently (or never) inducing mania/hypomania or mixed states.
I’ll go deeper into sleep timing and social rhythms in a later essay. For now, here are a few details about mood stabilizers with antidepressant effects (MSAEs). They are a select group. Watch, it gets small quickly.
Antidepressant-Effect Mood Stabilizers
- Cariprazine, Iloperidone These are still far too expensive.
- Lurasidone This is now available as a generic (and may be more affordable). It’s still new, compared with the years of experience we have with everything that preceded it. In my limited experience with it (before retiring from direct patient care a few years ago), it seemed to carry a notable risk of inducing manic or hypomanic symptoms. And it’s not weight neutral, though better than quetiapine.
- Quetiapine This is often listed in guidelines as the best option for bipolar depression. But weight gain is common, and often large. It can lead to serious problems with cholesterol and move people toward diabetes (so-called “metabolic syndrome”).
- Lamotrigine, Lithium, Sleep–Social Rhythm Therapy Thus, in my way of thinking, the list of MSAEs quickly narrows to lamotrigine, lithium, and deliberate timing of sleep and social rhythms. But that’s me.
Another View: Treatment Guidelines
For comparison, here are two recent treatment guidelines for mixed depressions.
As you can see, their recommendations are very different from mine.
The difference? Those guidelines emphasize “efficacy” — how much better a medication performs compared with a placebo.
But in my experience, most people seem to be more concerned about risks and side effects of treatment options, especially those that will be continued for the prevention of further mood episodes. That’s how lamotrigine and sleep regularity became my top recommendations for mixed depressions. They don’t always work, but if they do, they make a good long-term plan.
Dark Therapy: A Low-Risk Option
Speaking of prioritizing low-risk treatments, consider “dark therapy.” Think of it as the opposite of light therapy for depression. Instead, it’s using darkness as an anti-manic tool.
In one key study among patients hospitalized with mania, those who followed dark-therapy protocols improved far faster and required only half as much antipsychotic medication as the control group.
I’ll share more details about how to use dark therapy in the following essay. For now, I mention it as another treatment with limited evidence for “efficacy” that is still worth considering for mixed depression because of its near-zero risk.
One More Trick for Treating Mixed States
Here’s the “ace up my sleeve.” Many people came to me having “tried everything” for their bipolar. Since depression was almost always the remaining problem, they’d almost always be taking an antidepressant, which seems to make sense: They’re “anti-depressants,” right?
But antidepressants can not only cause mania or hypomania and mixed states, but also keep an otherwise effective mood stabilizer from working fully.
So we would talk about stopping the antidepressant and retrying previous mood stabilizers. But it’s tricky: Stopping an antidepressant too fast can make things worse. I’ll present details of antidepressant tapering in the next essay after dark therapy.
The Takeaway
Treating mixed states is straightforward: Decrease destabilizers and, if necessary, add stabilizers, increasing each until you encounter troublesome side effects or safety limits, before adding another. Unfortunately, that’s often easier said than done.
Since most mood-stabilizing treatments need to be continued to maintain that benefit, those with the fewest long-term risks are the best starting place, in my opinion — even if research results on their efficacy are not as good as those for riskier or more expensive approaches.
Next time, we’ll look at a near-zero-risk anti-manic treatment that is probably also a mood stabilizer, but doesn’t get researched as deserved — because it costs about $10!
References
- Barbini B et al. Dark Therapy for Mania: A Pilot Study. Bipolar Disorder. February 2005.