This series is based on my professional knowledge as a mental health nurse and former pharmacist as well as my own experience 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’re 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 the genetic expression of various neuron-related factors and boosting the activity of the calming neurotransmitter GABA. GABA counterbalances the excitatory neurotransmitter glutamate. Lithium is effective for both mania and depression, and it can decrease the risk of suicide.
Lithium is chemically very similar to sodium, and blood levels depend on 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. You can find out more in this Quick Guide to Lab Tests on the Resources page. Maintaining adequate hydration is important, as dehydration can cause your kidneys to retain more lithium, leading to an increase in blood levels.
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 I’m willing to tolerate, as the benefit outweighs the negatives. I have a tremor that gets worse with fatigue or dose increases. Taking propranolol (a beta-blocker) as needed is helpful. 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 originally used to treat seizure disorders, but over time, it became clear that they also worked as mood stabilizers. They affect signalling between nerve cells in a number of different ways, including effects on ion channels that control the movement of chemicals like sodium and calcium in and out of nerve cells.
Valproic acid can also be taken in the form of divalproex, which is an enteric-coated tablet that decreases stomach upset. It’s effective for mania, but it’s less clear how effective it is for bipolar depression. Dosing is targeted to reach a blood level of 350-700 µmol/L. Regular blood tests will also include liver function tests.
Side effects include nausea, sedation, weight gain, hair loss, tremor, negative effects on the liver, cessation of menstrual periods, and polycystic ovarian syndrome. It’s also teratogenic (causes harm to a developing fetus); for more on this, see Medication Use in Pregnancy.
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. Regular blood tests are done to monitor drug levels and blood cell counts.
Side effects include gastrointestinal upset, sedation, dizziness, impaired coordination, and negative effects on the liver, white blood cells, and platelets.
Lamotrigine hasn’t demonstrated effectiveness for bipolar mania; it works best for the prevention of bipolar depression. It interacts with both valproic acid and carbamazepine, requiring adjustments in dose. Dose increases need to happen slowly to decrease the risk of Stevens-Johnson syndrome, a type of severe, dangerous rash.
Other side effects include dizziness, headache, double vision, drowsiness, impaired coordination, nausea, and weight gain.
Other anticonvulsants have been tried in bipolar disorder but the research to support their effectiveness just isn’t there. These include levetiracetam, topiramate, and gabapentin.
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 concluded 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!
The rest of the Psych Meds 101 series covers:
You may also be interested in this post on Bipolar Disorder Treatment Guidelines.
Ashley L. Peterson
BScPharm BSN MPN
Ashley is a former mental health nurse and pharmacist and the author of four books.