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.

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 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.

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 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.

Monitoring adherence of psychiatric patients to oral medication may be especially difficult. The FDA has approved Abilify MyCite (Otsuka/Proteus), an aripiprazole tablet with an embedded sensor that tracks when patients take the medication. It is indicated for treatment of adults with schizophrenia, bipolar disorder, or major depressive disorder. Abilify MyCite is the first drug with a digital ingestion tracking system to be approved in the US.

Oral antipsychotic drugs used for treatment of schizophrenia, schizoaffective disorder, delusional disorder, and other manifestations of psychosis or mania are listed in Table 1. Parenteral antipsychotic drugs used for treatment of these disorders are listed in Table 2.

Bipolar disorder is characterized by intermittent episodes of mania and/or depression. Even with maintenance treatment, recurrences of manic or (more frequently) depressive episodes are common. Some of the drugs and dosages recommended here have not been approved by the FDA for use in bipolar disorder.

The FDA has approved cariprazine (Vraylar – Actavis), an oral, once-daily, second-generation antipsychotic, for treatment of schizophrenia and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) can be used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

Drugs are not the only treatment for mood disorders. Psychotherapy remains an important component in the management of these disorders, and electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective, poorly tolerated or cannot be used. Some drugs are recommended here for indications that have not been approved by the FDA.

The FDA has approved a delayed-release capsule formulation of valproic acid (VPA; Stavzor - Noven Therapeutics) for all of the indications for which divalproex sodium (Depakote, and others; Depakote ER) is approved: monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures, and adjunctive therapy in patients with multiple seizure types that include absence seizures; acute treatment of manic episodes associated with bipolar disorder; and prophylaxis of migraine headaches. In addition, valproate (valproic acid or divalproex sodium) is considered a drug of choice for treatment of other types of seizures including generalized tonic-clonic, myotonic and atonic seizures.

Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) is used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

An extended-release formulation of carbamazepine, available since 1997 for treatment of epilepsy, has now been approved under a new name, Equetro, for acute mania and mixed episodes of bipolar disorder. Although the drug was effective in some patients for up to 6 months, it has not been approved for maintenance treatment. Carbamazepine has not been shown to be more effective than lithium or valproate, and it can cause serious adverse effects.

Gabapentin (Neurontin - Pfizer), which has been available in the US since 1994, is approved by the FDA only for treatment of partial epilepsy and postherpetic neuralgia, but is widely used off-label for a number of other indications, especially neuropathic pain syndromes. According to one report, among Medicaid recipients in Florida receiving gabapentin, 71% of prescriptions were for chronic pain and 8% for seizures and neuralgia ("The Pink Sheet" February 2, 2004; 66:30).

The fixed-dose combination of olanzapine and fluoxetine (Symbyax - Lilly) has been approved by the FDA for treatment of depressive episodes associated with bipolar disorder. Olanzapine alone (Zyprexa), which is mainly used as an antipsychotic (Medical Letter 2003; 45:102), is FDA-approved for treatment of acute manic episodes and for maintenance treatment of bipolar disorder. Fluoxetine alone (Prozac, and others), which is mainly used as an antidepressant (Medical Letter 2003; 45:93), has no specific approval for use in bipolar disorder.

The number of drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Anticonvulsants are now widely used for treatment of psychiatric illnesses, particularly bipolar disorder. Lithium is the standard drug for treatment of bipolar disorder, but it can cause severe toxicity, serum concentrations must be monitored, and it is not effective in some patients.

The number of new drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 1997.

Although lithium (Eskalith, and others) is the standard treatment for bipolar (manic-depressive) disorder, 20% to 40% of patients do not respond adequately or cannot tolerate its adverse effects (Medical Letter, 33:43, 1991). Results of recent studies suggest that valproate (Depakene - valproic acid; Depakote - divalproex sodium), a widely used anticonvulsant (Medical Letter, 31:1, 1989), might be an effective alternative. Other anticonvulsants, particularly carbamazepine (Tegretol, and others), have also been used as second-line drugs for treatment of mania and other psychiatric disorders (C Van Valkenburg et al, Drugs, 44:326, 1992; PE Keck, Jr et al, J Neuropsychiatry Clin Neurosci, 4:395, 1992).