The FDA has approved Erzofri (Luye), an extended-release injectable formulation of the second-generation antipsychotic drug paliperidone palmitate, for treatment of schizophrenia and schizoaffective disorder in adults. It is the second once-monthly formulation of paliperidone palmitate to be approved in the US for these indications; Invega Sustenna was the first. Longer-acting injectable formulations of paliperidone palmitate are also available (see Table 1).

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).

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.

Invega Hafyera (Janssen), a long-acting, extended-release (ER) formulation of the second-generation antipsychotic paliperidone palmitate, has been approved by the FDA for twice-yearly IM treatment of schizophrenia in adults who have been adequately treated with another injectable ER formulation of the drug (Invega Sustenna or Invega Trinza). It is the first drug to become available in the US for twice-yearly treatment of schizophrenia.

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.

A transdermal formulation of the second-generation (atypical) antipsychotic asenapine (Secuado – Noven) has been approved by the FDA for once-daily treatment of schizophrenia in adults. Asenapine is the first antipsychotic to become available in a transdermal formulation in the US. A twice-daily sublingual tablet formulation of asenapine (Saphris) has been available since 2009.

The FDA has approved lumateperone (Caplyta — Intracellular Therapies), an oral second-generation antipsychotic, for once-daily treatment of schizophrenia in adults. It is the 13th second-generation antipsychotic drug to be approved by the FDA for this indication.

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.

The FDA has approved valbenazine (Ingrezza – Neurocrine Biosciences), a vesicular monoamine transporter 2 (VMAT2) inhibitor, for treatment of tardive dyskinesia in adults. It is the first drug to be approved in the US for this indication; two other VMAT2 inhibitors, tetrabenazine (Xenazine, and generics) and deutetrabenazine (Austedo), were approved earlier for treatment of chorea associated with Huntington's disease.

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.

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.

The FDA has approved two new long-acting injectable formulations of second-generation antipsychotics for treatment of schizophrenia: aripiprazole lauroxil (Aristada – Alkermes), which is given once every 4-6 weeks, and paliperidone palmitate (Invega Trinza – Janssen), which is given once every 3 months. Once-monthly injectable formulations of aripiprazole (Abilify Maintena) and paliperidone palmitate (Invega Sustenna) were approved earlier.

The FDA has approved the oral, once-daily, second-generation antipsychotic brexpiprazole (Rexulti – Otsuka/Lundbeck) for treatment of schizophrenia and as an adjunct to antidepressants for treatment of major depressive disorder (MDD). Aripiprazole (Abilify), a structurally similar second-generation antipsychotic also comarketed by Otsuka (with BMS), recently became available generically.

The FDA has approved an inhalation powder formulation of loxapine (Adasuve – Teva), a first-generation antipsychotic long available in an oral formulation, for treatment of acute agitation related to schizophrenia or bipolar I disorder in adults. Adasuve is the first inhaled drug to be approved for this indication.

An extended-release injectable formulation of the second-generation antipsychotic aripiprazole (Abilify) has been approved by the FDA (Abilify Maintena – Otsuka/Lundbeck) for once-monthly treatment of schizophrenia. It is the fourth second-generation antipsychotic to become available in a long-acting parenteral formulation. Long-acting parenteral antipsychotics, given at intervals of 2-4 weeks, are generally used for patients with a history of relapse due to poor adherence to oral maintenance therapy.

The FDA has approved lurasidone (Latuda - Sunovion), a new second-generation antipsychotic, for oral treatment of schizophrenia in adults.

Glycopyrrolate (Robinul, and others), a synthetic muscarinic receptor antagonist, has been used off-label for many years for treatment of excessive drooling in patients with Parkinson’s disease, in patients taking clozapine for schizophrenia, and in developmentally disabled children.1-3 It has now been approved by the FDA as Cuvposa (Shionogi) for use specifically in children 3-16 years old with severe chronic drooling due to a neurologic condition, such as cerebral palsy. It is being marketed as an oral solution, which will permit more precise weight-based dosing than was possible with the oral tablets used in the past. As with other anticholinergic drugs, dry mouth, constipation, flushing and nasal congestion can occur. Since glycopyrrolate decreases secretion not only of saliva, but also of sweat, overheating due to high ambient temperatures or excessive exercise could be dangerous for patients who take it.

1. ME Arbouw et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74:1203.

2. CS Liang et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. Schizophren Res 2010; 119:138.

3. RJ Mier et al. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154:1214.

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The antipsychotic drugs listed in Table 1 on the next page are more effective for treating the “positive symptoms” of schizophrenia (hallucinations and delusions) than the “negative symptoms” (apathy, social withdrawal, and blunted affect). Some symptoms of schizophrenia and acute psychoses may improve rapidly after treatment with antipsychotic drugs, but chronic schizophrenia improves slowly over many weeks and some patients may continue to improve for months. Most patients with chronic schizophrenia require prolonged maintenance therapy, but the risk of tardive dyskinesia and adverse metabolic effects must be kept in mind.

L-methylfolate (Deplin — Pamlab) is a “medical food” marketed for adjunctive use in depression or schizophrenia in patients with suboptimal folate levels. It is available only by prescription.

The FDA has approved the marketing of iloperidone (Fanapt – Vanda), a second-generation antipsychotic, for treatment of schizophrenia. Iloperidone is chemically related to risperidone (Risperdal, and others).

Paliperidone (Invega - Janssen) has been approved by the FDA in an extended-release formulation for treatment of schizophrenia. It is the primary active metabolite of the second-generation antipsychotic risperidone (Risperdal - Janssen), which is scheduled to lose its patent exclusivity in December 2007.

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.

Aripiprazole (Abilify - Bristol-Myers Squibb/Otsuka), a second-generation (atypical) antipsychotic drug, was approved by the FDA in 2002 for treatment of schizophrenia and more recently for bipolar disorder as well. It has been promoted as causing fewer adverse effects than other antipsychotics, without sacrificing efficacy.

A recent supplement to the Journal of Clinical Psychiatry, titled "The Expert Consensus Guideline Series: Optimizing Pharmacologic Treatment of Psychotic Disorders," concluded that most experts endorsed use of second-generation (atypical) antipsychotics rather than first-generation drugs, with risperidone (Risperdal - Janssen) the top choice for first episodes, multiple episodes or switches from another drug (JM Kane et al, J Clin Psychiatry 2003; 64 suppl 12:5). The supplement was sponsored by Janssen.

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.

Aripiprazole (Abilify - Bristol-Myers Squibb/Otsuka), a quinolinone derivative, has been approved by the FDA for treatment of schizophrenia.

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.

Risperidone (Risperdal - Janssen), a benzisoxazole derivative, is now available in the USA for treatment of schizophrenia and other psychotic disorders.

Clozapine (Clozaril - Sandoz), an antipsychotic drug, was first marketed in the USA three years ago (Medical Letter, 32:3, 1990). Because of its hematological toxicity, the US Food and Drug Administration approved the drug only for patients with schizophrenia who cannot tolerate or do not respond to standard antipsychotic drugs.

Clozapine (Clozaril - Sandoz), a dibenzodiazepine antipsychotic drug that has been available in Europe for many years, was recently approved for marketing by the US Food and Drug Administration. Because of its toxicity, the labeling for clozapine recommends using the drug only for schizophrenic patients who have not responded adequately to standard antipsychotic drugs or have had intolerable adverse effects.