2023 in Review: FDA Approvals in Psychiatry, Tic Disorders in Youth, and Insomnia in Major Depressive Disorder

This newsletter summarizes all the FDA-approved medication in the psychiatric field for the year 2023. It includes treatments for a wide range of conditions, including Alzheimer’s disease, depression, anxiety disorders, and even sexual disorders.

We also discuss the treatment of tic disorders in youth, key points from a presentation on insomnia and major depressive disorder (MDD), and our practical research summaries of adult, child, and adolescent psychiatry (Quick Takes and CAP Smart Takes).

2023 in Review: FDA Approvals in Psychiatry

Neurocognitive Disorders

Leqembi (Lecanemab)

Approval:
- In January 2023, the FDA approved lecanemab through the Accelerated Approval pathway to treat Alzheimer’s disease in mild stages.
Dose:
- Intravenous administration of 10 mg per kilogram of body weight every 2 weeks
Highlights:
- Lecanemab is a humanized monoclonal antibody that binds with high affinity to soluble amyloid-beta (Aβ) protofibrils to reduce the accumulation of amyloid plaques in the brain.
Common side effects:
- Infusion-related reactions, headaches, falls, visual disturbances, dizziness, and confusion
Conclusion:
- Patients eligible for being treated with lecanemab have mild cognitive impairment and good functioning; however, they can be at risk due to serious adverse effects. Learn more here.

Mood Disorders

Zurzuvae (zuranolone)

Approval:
- On August 2023, the FDA approved zuranolone for treating postpartum depression. It is the first oral treatment option for this condition.
Dose:
- 50 mg/day orally in the evening for 14 days
- Dosage may be reduced to 40 mg/day if CNS depressant effects occur.
- It can be used as monotherapy or as an adjunct to oral antidepressant therapy.
Highlights:
- Zuranolone may work within days.
- It can be utilized for a short-term duration of 2 weeks.
Common side effects:
- Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection
Conclusion:
- Zuranolone is a faster and shorter-term treatment for postpartum depression compared with SSRIs. Learn more here.

Exxua (gepirone extended release)

Approval:
- On September 2023, the FDA approved gepirone extended release for the treatment of MDD in adults.
Dose:
- Starting dose: 18.2 mg/day
- Day 4: Dosage may be increased to 36.3 mg/day.
- Day 7: Dosage may be further titrated to 54.5 mg/day.
- After 1 week: 72.6 mg/day
Highlights:
- Gepirone selectively modulates serotonergic neurotransmission by acting as a partial agonist at the serotonin (5HT) 1A receptor.
- It does not have an adverse impact on sexual function.
- Contraindicated in patients with QTc > 450 msec at baseline
Common side effects:
- Dizziness, nausea, insomnia, abdominal pain, and dyspepsia
Conclusion:
- A new treatment for MDD that could provide an effective alternative for patients who suffer sexual side effects from SSRIs
- An electrocardiogram should be performed before starting it. Learn more here.

Anxiety Disorders

Lexapro (escitalopram)

Approval:
- On August 2023, the FDA approved escitalopram for the treatment of generalized anxiety disorder (GAD) in pediatric patients 7 years of age and older.
- Previously, it had only been approved for adult patients.
Dose:
- Initial: 10 mg/day
- Recommended: 10 mg/day
- Maximum: 20 mg/day
Highlights:
- Escitalopram was effective in reducing anxiety symptoms. This was shown by a notable change in the Pediatric Anxiety Rating Scale score for generalized anxiety disorder.
Common side effects:
- Insomnia, ejaculation disorder, nausea, sweating increased, fatigue and somnolence, decreased libido, and anorgasmia
- Side effects are similar to those seen in adults.
Conclusion:
- Escitalopram reduces anxiety symptoms and is well-tolerated in pediatric patients with GAD. Learn more here.

Psychotic Disorders

Uzedy (risperidone extended-release injectable suspension)

Approval:
- Uzedy was approved in April 2023 for the treatment of schizophrenia in adults.
Dose:
- A subcutaneous injection once every month or once every 2 months
- Recommended dosages:

Prior Oral Risperidone Therapy	Uzedy Dosage Monthly	Uzedy Dosage Every 2 Months
2 mg/day	50 mg	100 mg
3 mg/day	75 mg	150 mg
4 mg/day	100 mg	200 mg
5 mg/day	125 mg	250 mg

Highlights:
- It is the first subcutaneous, long-acting formulation of risperidone.
- The initiation of treatment requires no loading dose or oral supplementation.
- Therapeutic blood concentrations are reached within 6-24 hours of a single dose.
- Cost ranges from $1,232–$3,080 per month, depending on dosage strength.
Common side effects:
- Extrapyramidal symptoms, sedation, dizziness, gastrointestinal symptoms, blurred vision, dry mouth, increased appetite, increased weight, and fatigue
- The most common injection site reactions are pruritus and nodules.
Conclusion:
- A new treatment option to address certain treatment challenges and decrease the risk of relapse; however, cost should be taken into account when prescribing it Learn more here.

Substance Use Disorders

Brixadi (buprenorphine extended-release injection)

Approval:
- Buprenorphine extended-release subcutaneous injection was approved in May 2023 for the treatment of moderate-to-severe opioid use disorder.
- It was approved in weekly and monthly subcutaneous injectable formulations at varying doses.
Dose:
- The weekly doses are 8 mg, 16 mg, 24 mg, and 32 mg.
- The monthly doses are 64 mg, 96 mg, and 128 mg.
Highlights:
- It can reduce symptoms of opioid withdrawal and cravings.
- Due to the serious harm resulting from accidental intravenous administration, Brixadi is only available through the Risk Evaluation and Mitigation Strategy (REMS).
Common side effects:
- Injection site pain, erythema, or pruritus; headache, constipation, nausea, insomnia, and urinary tract infection
Conclusion:
- It provides patients with opioid use disorder an opportunity to sustain long-term recovery. Learn more here.

Opvee (nalmefene hydrochloride) nasal spray

Approval:
- In May 2023, the FDA approved nalmefene for the emergency treatment of known or suspected opioid overdose in adults and pediatric patients 12 years of age and older.
Dose:
- It is administered as a single spray intranasally: 2.7 mg of nalmefene in 0.1 mL.
- Additional doses may be administered every 2–5 minutes (using a new nasal spray with each dose) if the patient does not respond or responds and then relapses into respiratory depression.
Highlights:
- Nalmefene is 6-methylene analogue of naltrexone, a well-established opioid antagonist.
- It is the first over-the-counter opioid reversal agent.
- It is intended for immediate administration as emergency therapy.
- It can reverse the effects of opioid overdose, including respiratory depression, sedation, and low blood pressure.
Common side effects:
- Nasal discomfort, headache, nausea, dizziness, hot flush, vomiting, anxiety, fatigue, nasal congestion, throat irritation, rhinalgia, decreased appetite, dysgeusia, erythema, and hyperhidrosis
Conclusion:
- It is not a substitute for emergency medical care, but it can prevent drug overdoses and reduce deaths. Learn more here.

Sleep Disorders

Lumryz (sodium oxybate)

Approval:
- Sodium oxybate was first approved by the FDA in July 2002 for the treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy.
- However, Lumryz—an extended-release formulation—was approved in May 2023.
Dose:
- Recommended starting dose is 4.5 g/night, increased by 1.5 g/night weekly; do not exceed 9 g/night.
- Before ingestion, the dose of Lumryz should be suspended in approximately 80 mL of water.
- It is important to take it at least 2 hours after eating.
Highlights:
- It is a central nervous system depressant and the sodium salt of gamma-hydroxybutyrate (GHB).
Common side effects:
- Drowsiness, dizziness, nausea, vomiting, confusion, or hallucinations may occur.
Conclusion:
- Lumryz is the first and only FDA-approved once-at-bedtime oxybate for patients with narcolepsy. Learn more here.

Sexual Disorders

Eroxon (alprostadil)

Approval:
- In June 2023, the FDA approved alprostadil—a nonmedicated topical formulation—for the treatment of erectile dysfunction in adult males aged 22 years and over.
Dose:
- Topical application of the content of 1 tube on the penis for each use.
Highlights:
- It stimulates the nerve endings by inducing a temperature change, leading to tumescence and erection.
- It has shown to be effective in achieving an erection within 5–30 minutes of application.
- Available over the counter
Common side effects:
- Local irritation or rash at the application site
Conclusion:
- An alternative with minimal side effects and quicker effectiveness than phosphodiesterase-5 (PDE5) inhibitors for erectile dysfunction Learn more here.

Tic Disorders in Youth With David Rosenberg, M.D.

In this interview, Dr. David Rosenberg discusses treatments for tic disorders in children and adolescents, highlighting the effectiveness of methylphenidate for ADHD and tics, SSRIs and therapy for OCD and tics, and clonazepam for tics with anxiety. The discussion also emphasizes the importance of screening for comorbid psychiatric conditions and considering family history in treatment decisions.

Interview highlights include the following:

Tic disorders often coexist with other psychiatric conditions. In a patient with a tic disorder, it is best to screen for other mental disorders, such as ADHD and OCD.
When considering treatment options, consider family history and patterns of treatment response among family members with similar conditions.

Learn more and earn 0.5 CME credits here.

Navigating Insomnia in MDD

In this video lecture, Dr. Chopra discusses the assessment and management of insomnia in patients with MDD. He begins by outlining the sleep architecture and establishing the criteria for diagnosing insomnia. Then, he explores nonpharmacologic interventions and FDA-approved pharmacologic treatments. Dr. Chopra further expands on the impact of innovative depression treatments, such as ketamine and neurostimulation therapies, on insomnia.

Pharmacologic Interventions for Insomnia: Benzodiazepines and Nonbenzodiazepine Hypnotics

Benzodiazepines and nonbenzodiazepine hypnotics are recommended for treating insomnia disorder.
Benzodiazepines enhance the function of GABAA receptors.
Nonbenzodiazepine hypnotics specifically act at alpha-1 subunit of GABAA receptor.
Triazolam and zaleplon are effective for sleep initiation insomnia.
Zolpidem, eszopiclone, and temazepam are effective for sleep initiation and sleep maintenance insomnia.

Learn more and earn 1.25 CME credits here.

Quick Takes: Research, Digested

Risk for Suicide Attempts and Suicide Associated With Benzodiazepines

There is a significant increase in the prescription of benzodiazepines in the month preceding suicidal acts.
This highlights the necessity for rigorous suicide risk assessment when prescribing these medications, especially for patients with no recent psychiatric history. Learn more.

Listen to or read the full volume and earn 0.5 CME credits here.

CAP Smart Takes: Research, Digested

Effect of Methylphenidate on Pain Perception Thresholds in Children With ADHD

Methylphenidate remains the most common pharmacotherapy for children and adolescents with ADHD worldwide. This study suggests that it may increase the pain threshold in pediatric patients with ADHD. Learn more.