I’ve been pouring over textbooks and treatment guidelines, and these four mood stabilizers keep rising to the top.1-6 None of them are perfect, but each has a unique role in bipolar disorder:

  • Lithium
  • Quetiapine (Seroquel)
  • Lurasidone (Latuda)
  • Lamotrigine (Lamictal)

Lithium and quetiapine top the lists for all three phases of the illness: mania, depression, and the maintenance phase. Lurasidone and lamotrigine are either untested (lurasidone) or ineffective (lamotrigine) in mania, but they are essential tools for bipolar depression.


Lithium stands out for its preventative effects in bipolar disorder, but it also has important benefits outside of the manic-depressive symptom lists. It is the only mood stabilizer that significantly reduces the risk of suicide, and it reduces mortality in other ways as well. Although lithium is often avoided out of concerns of toxicity, it actually lowers the risk of cancer, heart disease, stroke, and viral illnesses.7 All of those occur at higher frequency in bipolar disorder. Vascular disease is the leading cause of death in bipolar disorder,8 and viral illnesses are both a consequence (ie, STDs) and cause (ie. inflammatory effects) of bipolar symptoms.9

Patients with classic, “textbook,” bipolar disorder tend to respond best to lithium. They are characterized by full remission between episodes, predominance of manic over depressive symptoms, illness onset in late teens, and a family history of bipolar disorder. They also tend to lack significant mixed states, rapid cycling, and psychiatric comorbidities, although a recent study found that comorbid panic disorder predicted lithium response.10


Quetiapine covers ground that lithium does not. It is more effective against mixed manias, while lithium is preferred for the purer, euphoric highs. It also works better in acute depressive episodes. Quetiapine cannot claim the medical benefits that lithium does, but it does assist with two symptoms that patients find particularly troubling: anxiety and insomnia.11,12 Although its long-term adverse effects give me pause, it did provide the best protection against both poles of the illness in Terrence Ketter’s analysis of the numbers needed to treat (NNT) for long-term maintenance.6

Lurasidone (Latuda) and Lamotrigine (Lamictal)


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