This chapter describes the growing use of atypical antipsychotics as mood stabilizers for bipolar disorder. Some of these agents are FDA-approved for bipolar depression, mania, or maintenance treatment. Others have hypothetical efficacy in the treatment of bipolar disorder but are less well studied. The broad therapeutic effects of these agents as mood stabilizers likely derive from their similarly broad spectrum of pharmacologic actions. This chapter presents the fourth step in the symptom-based treatment algorithm, namely, an in-depth presentation of pharmacologic mechanisms of eight different mood stabilizers from the atypical antipsychotic drug class. As in Chapter 4, drug introductions are followed by particular mechanisms of action hypothesized to contribute to each drug's potential efficacy. The various atypical antipsychotics are discussed in terms of the present understanding of each agent's mechanism and function. This chapter continues to build on neurobiology presented in Chapter 3 to describe the dopamine agonist spectrum and its potential role in treating the symptoms of bipolar disorder.

Partial agonists that lie closer to the antagonist side of the spectrum are favored for acute mania and for psychotic mania, and some exhibit good antipsychotic efficacy. Other agents, such as amisulpride and sulpiride (not available in the United States), may exhibit partial agonist properties at very low doses.

D2 partial agonists that are closer to the full agonist end of the spectrum include pramipexole and ropinirole (see also Fig. 5.7). These agents are in testing for bipolar depression and treatment-resistant depression but are not yet approved for these uses.

Asenapine has been developed as a sublingual formulation. Doses of 5 and 10 mg have been tested for mania and schizophrenia. Asenapine shows only mild metabolic risk and little prolactin elevation.