Bipolar disorder is characterized by episodes of mania, hypomania, and depression. Recurrences of manic or (more frequently) depressive symptoms are common. About 15-20% of patients with bipolar disorder die by suicide.

The oral second-generation antipsychotic drug lumateperone (Caplyta – Intra-Cellular Therapies), which was approved by the FDA in 2020 for treatment of schizophrenia, is now approved for use as monotherapy or as an adjunct to lithium or valproate for treatment of depressive episodes associated with bipolar I or II disorder in adults.

The oral second-generation antipsychotic drug iloperidone (Fanapt – Vanda) has been approved by the FDA for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. First approved in 2009 for treatment of schizophrenia, iloperidone is the eighth second-generation antipsychotic to be approved for acute treatment of manic or mixed episodes of bipolar I disorder (see Table 1).

The FDA has approved Lybalvi (Alkermes), a fixed-dose combination of the second-generation antipsychotic olanzapine (Zyprexa, and generics) and samidorphan, a new opioid antagonist, for treatment of adults with schizophrenia or with manic or mixed episodes of bipolar I disorder. The addition of samidorphan is intended to mitigate the weight gain that occurs with olanzapine. This is the first FDA approval for samidorphan.

The FDA has approved a sublingual film formulation of the alpha-2 adrenergic receptor agonist dexmedetomidine (Igalmi — BioXcel Therapeutics) for acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. It is the first alpha-2 agonist and the only sublingual film to be approved for this indication. Dexmedetomidine has been available for many years in an injectable formulation (Precedex) for sedation in the intensive care unit and to facilitate procedures such as mechanical ventilation.

Three extended-release injectable formulations of second-generation antipsychotic drugs — two of risperidone (Rykindo, Uzedy) and one of aripiprazole (Abilify Asimtufii) — have been approved by the FDA for treatment of schizophrenia in adults. Rykindo and Abilify Asimtufii are also approved for maintenance treatment of bipolar I disorder in adults. Other extended-release injectable formulations of risperidone and aripiprazole have been available in the US for years (see Table 1).

The FDA has approved the second-generation antipsychotic drug cariprazine (Vraylar — Abbvie) for adjunctive treatment of major depressive disorder (MDD) in adults. Cariprazine was previously approved for treatment of schizophrenia and bipolar depression, and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

The FDA has approved an oral extended-release formulation of gepirone (Exxua – Fabre-Kramer), a selective 5-HT_1A receptor agonist, for treatment of major depressive disorder (MDD) in adults. Gepirone was originally developed decades ago for treatment of anxiety and depression, but it was not approved by the FDA for such use. Gepirone is structurally related to buspirone, which is FDA-approved for treatment of anxiety.

The FDA has approved viloxazine extended-release capsules (Qelbree – Supernus) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6-17 years old. Viloxazine is the second selective norepinephrine reuptake inhibitor to be approved in the US for treatment of ADHD; atomoxetine (Strattera, and generics) was approved in 2002.

When used for the appropriate seizure type, antiseizure medications (ASMs) are roughly equivalent in efficacy. In addition to the seizure type, the choice of drug is usually based on factors such as ease of use, spectrum of activity, adverse effects, interactions with other drugs, presence of comorbid conditions, suitability for elderly persons and those with childbearing potential, and cost. Treatment should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally...