Key moments, in order
Kraepelin defined manic-depressive illness by recurrent mood episodes, not by polarity, so today both recurrent major depression and the bipolar disorders would fall under it. What resembles a bipolar disorder genetically and biologically is less the strict DSM definition than a recurrent, episodic, primary mood disorder.
People with real bipolar disorder can genuinely lack memory of past manic, hypomanic or mixed episodes once they are out of them. We lean toward a state-dependent memory explanation.
Start the sleep history with a memorable question: "Have you ever had at least three days in a row where you were not your normal self and didn't sleep, didn't need it or couldn't sleep, yet still had energy?"
Reduced sleep is neither necessary nor sufficient for an episode. What is necessary is a marked change in mood (irritable, elevated, overconfident) with increased or preserved activity.
Gather substances and then sleep: sleep disruption, with decreased sleep and preserved or increased activity.
Draw a timeline of DSM-defined major depressive episodes with the patient: first onset, length, time between and recurrence. Early onset and recurrent episodes should raise your suspicion.
Do not attribute every episode to a substance or medication. People who are hypomanic or manic are more likely to use substances (cannabis and nicotine use often rises during mood episodes) even when those are not the trigger. Some people do have medication-induced episodes, but if you take the substance away and watch them, they may not have another.
Do not feel pressure to make a diagnosis at the end of a first appointment. Say what is on your differential and why, and that time is the only thing that will tell.
When there is not enough evidence to say what is causing it, stay agnostic: watch, and use the minimum amount of the safest medications you can.
Akiskal's definition: at least one major depressive episode, no spontaneous hypomanic or manic episodes, and either a first-degree relative with bipolar disorder or antidepressant-induced mania or hypomania.
Lithium has evidence as an augmenting agent in unipolar depression. Some clear-cut but severe unipolar depressions probably have something a little more bipolar in them, and Europe is much more willing than the US to add lithium to what looks like unipolar depression.
In bipolar disorder, avoid antidepressants like the plague unless you cannot get away without them. If someone is already on one and rock-solid stable, that is fine.
Mood stabilization is king. Labs are a headache and the side effects sound scarier, but do the mood stabilization first.
What turns a novice into an experienced bipolar clinician is focusing on maintenance. Treatment has three parts, maintenance, acute mania and acute depression, and maintenance is understated in a lot of practice.
Warn patients they may feel tired and depressed at first. Without that warning, they conclude the mood stabilizer is the problem and stop it.
Lamotrigine is the weakest but probably the best tolerated. Lithium is the gold standard. Depakote works great but has problems, especially with male and female fertility.
It is not a mood stabilizer. The evidence is not there for primary mood stabilization, and on its own it just doesn't really work. Think of it as an adjunct: relatively safe, apart from a small risk of withdrawal and tolerance.
The evidence is old and mixed and people say they do not like it, but there is at least some, and its action is meaningfully close to carbamazepine.
A decline in kidney function is not renal failure. Given the choice of 30% worse kidney function or 30% less brain function over 20 years, take the better brain every time.
The two major adverse effects in practice are thirst with increased urination (more common, and different from the rarer diabetes insipidus) and acne. Increased urine can alarm clinicians who are new to lithium.
For adjunctive lithium or mild bipolar disorder, levels of 0.4 to 0.7 are fine. The traditional target of about 0.75 comes from literature on severe, hospitalized bipolar I.
It is a salt. Too much salt lowers the level and too little raises it; dehydration raises it and overhydration washes it out; NSAIDs hold lithium in and can make it toxic.
The ER does not have to be given twice a day; you can dose it all at once. But level studies used immediate release two or three times a day, drawn 12 hours after a dose and before the next, so time your draws accordingly.
We used to start lithium at a dose tolerable for outpatients of usually 450 to 600 mg, and as much as 900 mg, before calling a 900 mg start too high for outpatients.
The labs look at kidney function, thyroid function and calcium. Within the first month, check a lithium level, thyroid panel, CBC and comprehensive metabolic panel.
It takes at least two weeks to start working, and in an acute state it will not kick in until the dose is adequate. Set expectations; wanting instant gratification is part of why clinicians and patients skip mood stabilizers.
It is for prevention, not acute states. It helps prevent episodes of mania, but if a patient is already manic or hypomanic it will not work.
It is better for significant irritability and aggression, for people with some TBI history, and for people with a legitimate migraine condition, where it prevents headaches.
Tardive dyskinesia risk is higher in mood disorders than in schizophrenia, and abrupt withdrawal can cause dyskinesias that may go away or persist. Use antipsychotics sparingly and only as the clinical picture requires.
If you give an antipsychotic in bipolar disorder, choose one that works for every phase, such as lurasidone, though it carries the most akathisia.
It is approved and effective for bipolar depression. We do not use it much because of the side effect profile, but if someone does not gain weight and is not oversedated on it, it is a good choice.
Many choose antipsychotic-only maintenance because it is one pill, and that is their choice. Still ask them to give the mood stabilizers a fighting chance for long-term body and mind health.
Aripiprazole's acute approval studies started at 15 mg, went quickly to 30 mg, and had PRN lorazepam on board.
Trial placebo is not inert; it is a holding environment with check-ins, almost psychotherapy. Trials also rely on professional patients, so trial populations may differ from community ones.
We usually use combination treatment built on three main things. Start a mood stabilizer, whichever one the patient can get on, knowing it will take time to work.
A go-to combination is lithium, lurasidone and gabapentin: lurasidone is effective quickly and at low doses, and lithium is most effective long term.
It is a really great medication, especially in bipolar. It was only studied in bipolar depression and never tested in acute mania, likely because it was sold as the bipolar depression drug; given how it acts, it makes no sense that it would work in acute schizophrenia but not acute mania.
Wait for at least two or three months of euthymia, then go by patient comfort; sooner is usually better.
Lifestyle is the third major pillar of treatment: regulate sleep and the daily cycle. It is its own psychotherapy, interpersonal and social rhythm therapy.
For a bipolar depressive episode, the best thing to do is go temporarily to the second-generation antipsychotics with proven efficacy for bipolar depression. We like those the most.
The community idea that bupropion is the safer antidepressant in bipolar disorder is a myth; we do not think there are data to show it.
Beyond medication, TMS seems to help while the mood is stabilized, and esketamine can be considered for some patients.
In depression we usually wait at least six months of remission before changing medications. In bipolar disorder we are willing to move a little earlier.
Call it whatever you want, but give the right treatment. If a mood stabilizer is helping, maybe they do need a mood stabilizer.
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.