This is the 3rd in a series of primers on how psychiatric meds work. The previous posts were on antidepressants and antipsychotics, and upcoming are anti-anxiety meds and sleep meds. These are based on my professional knowledge as a mental health nurse and former pharmacist as well as my own experiencing taking these medications (although with a diagnosis of major depressive disorder I’ve never taken any of the anticonvulsant mood stabilizers).
Mood stabilizers work in a number of different ways to control signalling between nerve cells. They are used to treat and prevent both mania and depression, although some drugs are more effective for one than the other. They fall into 3 broad categories: lithium, anticonvulsants, and atypical antipsychotics.
Lithium has been around for many years. It works via a number of different mechanisms, including regulating genetic expression of various neuron-related factors, and boosting activity of the calming neurotransmitter GABA. GABA counterbalances the excitatory neurotransmitter glutamate. Lithium is effective for both mania and depression, and has been shown to decrease the risk of suicide.
Lithium is a type of salt, so blood levels are affected by kidney function and hydration status. In the past, some people developed kidney damage from long-term lithium use, but that is rare now as we have a better understanding of what levels are safe. People taking lithium need periodic bloodwork to check their lithium and creatinine levels (an indicator of kidney function). Target levels are 0.6-1.2 mmol/L, with higher levels being needed in acute mania. It takes 5 days after a dose change for blood levels to restabilize.
Lithium can potentially cause a lot of side effects: nausea/vomiting/diarrhea, tremor, weight gain, hair loss, acne, frequent thirst, frequent urination, hypothyroidism, and effects on the heart. And if that wasn’t enough, lithium toxicity (levels over 1.5) can cause confusion or even seizures and coma. Yikes. Except lithium works very well, and some people may have no side effects at all.
Lithium has definitely been effective for me. I’m using it for depression, so I aim for levels between 0.65-0.8 depending on how I’m doing. I have side effects, but for me the benefit outweighs the negatives. I have a tremor, which is worse when I’m fatigued or if I’ve had to increase my dose. Taking propranolol (a beta-blocker) helps with this. I’ve gained weight on meds, but I’m on 2 other meds that cause weight gain so it’s hard to tell what’s causing what.
These medications were initially developed as anti-seizure medications, but have since come to be used as mood stabilizers. They affect signalling between nerve cells by acting at voltage-sensitive ion channels that allow sodium/calcium to flow in and out of neurons, and they also boost GABA neurotransmission.
These are essentially the same molecule, but divalproex can be formulated into an enteric-coated tablet that decreases stomach upset. Valproic acid is effective for mania, but it is less clear how effective it is for bipolar depression. Dosing is targeted to reach a blood level of 350-700 µmol/L.
Side effects include nausea, sedation, weight gain, hair loss, tremor, negative effects on the liver, cessation of menstrual periods, and polycystic ovarian syndrome. It is also teratogenic (causes harm to a developing fetus). I talk more about this in my post on mental illness and childbearing.
Carbamazepine is most clearly effective for mania. It affects the liver’s cytochrome P450 system, leading to interactions with a number of different medications. It can also decrease the reliability of oral contraceptives.
Side effects include gastrointestinal upset, sedation, dizziness, impaired coordination, and negative effects on the liver, white blood cells, and platelets.
Lamotrigine is not effective for bipolar mania, and works best for the prevention of bipolar depression. It interacts with both valproic acid and carbamazepine, requiring adjustments in dose. It must be initiated slowly to decrease the risk of Stevens-Johnson syndrome, a type of severe rash.
Other side effects include dizziness, headache, double vision, drowsiness, impaired coordination, nausea, and weight gain.
There are other anticonvulsants that have been tried in bipolar disorder but don’t necessarily have strong evidence to support their use. These include levatiracetam and topiramate. Gabapentin does not appear to be effective.
The mechanism by which atypical antipsychotics have a mood stabilizing effect is not entirely clear, but may be related to their action at the 5HT2a serotonin receptor and resultant effects on glutamate, dopamine, norepinephrine, and serotonin signalling. They are useful for both bipolar mania and depression. Examples include lurasidone, aripiprazole, quetiapine, and olanzapine (which can be combined with the SSRI antidepressant fluoxetine for bipolar depression).
Role of antidepressants
There are two key problems with antidepressants in bipolar disorder: they don’t work particularly well, and there is a risk of triggering mania. The International Society for Bipolar Disorder task force on antidepressant use found that evidence for antidepressant use is limited and weak, and as a result they could not broadly endorse the use of antidepressants in bipolar disorder. An exception is fluoxetine, which is effective when used in tandem with olanzapine.
I hope that this has all made sense and shone some new light on mood stabilizers. If you have any questions please feel free to shoot them my way!