Iloperidone for Bipolar I Disorder, Principles of Psychodynamic Psychopharmacology, and TMS in Psychiatry

This newsletter provides information about the FDA’s recent approval of iloperidone to treat bipolar I disorder in adults. It discusses the drug’s effectiveness, recommended dosages, and potential adverse effects.

We also share key points from an interview on the principles of psychodynamic psychopharmacology, a presentation on the evidence supporting the application of TMS in the treatment of various psychiatric disorders and its potential side effects, and our practical research summaries of child, adolescent, and adult psychiatry.

Iloperidone Now Approved for Bipolar I Disorder

Iloperidone—an atypical antipsychotic—was approved by the FDA on April 2, 2024, for treating acute manic or mixed episodes associated with bipolar I disorder in adults. Iloperidone has also been approved for the treatment of acute schizophrenia in adults since 2009 and maintenance treatment since 2016.

How does iloperidone work?
- Iloperidone and its metabolite, P88, bind strongly to serotonin 5-HT2A, dopamine D2, and D3 receptors. This inhibition is believed to contribute to the drug’s antimanic effects.
- They are also potent norepinephrine NEα receptor antagonists.
What do we know about its efficacy?
- Its efficacy for bipolar I disorder was confirmed in a phase 3 randomized double-blind, placebo-controlled study.
- Patients were randomly assigned to receive either iloperidone up to 24 mg/day or placebo. The primary endpoint was the change in the Young Mania Rating Scale from baseline to week 4.
- The YMRS total score improved statistically from baseline to weeks 2–4. The secondary endpoints, including the Clinical Global Impressions-Severity score and the Clinical Global Impression of Change, were also improved. Learn more here.
- According to the study, we can expect to see improvements starting from the second week of treatment.
What are the recommendations for dosing?
- To avoid orthostatic hypotensive effects, it is advised to start with a low dose and gradually increase the dose.
- Iloperidone comes with a starter package that enables the dose to be increased from 1 mg twice a day to 6 mg twice a day.
- Although iloperidone can be taken every 24 hours, it is recommended to be given every 12 hours initially to build tolerance.
- The recommended target dosage of Iloperidone is 24 mg/day.
  - For poor metabolizers of CYP2D6, the recommended dosage is 12 mg/day.
What are some potential adverse effects?
- Common adverse effects include tachycardia, dizziness, dry mouth, alanine aminotransferase increase, nasal congestion, increased weight (i.e., 7 pounds over 4 weeks), and somnolence.
- The incidence of akathisia and extrapyramidal symptoms was low.
Does iloperidone affect QTc?
- Iloperidone does impact QTc, as it has been observed to cause an increase. However, some adaptation can occur, and the QTc may reduce after 4 weeks of starting the treatment.
- It is strongly advised not to use iloperidone concurrently with any other drugs known for prolonging QTc.
- Moreover, when prescribing iloperidone alongside other medication that inhibits its metabolism, adjustments in dosages should be considered.
What are the contraindications for using iloperidone?
- History of hypersensitivity to iloperidone, anaphylaxis, and angioedema
How is iloperidone different from existing antipsychotics?
- Among all second-generation antipsychotics, iloperidone has a favorable akathisia profile.
- Its most distinguishing clinical properties include a very low incidence of motor side effects, a low incidence of dyslipidemia, and a moderate incidence of weight gain.
What remains unknown about iloperidone’s effectiveness in treating bipolar I disorder?
- Its long-term effectiveness and its potential to prevent manic or depressive episodes
- Whether it is effective when other psychiatric conditions are also present
- How effective it is compared with other antipsychotics and mood stabilizers

In conclusion, the recent approval of iloperidone by the FDA is a significant milestone in treating adults with manic or mixed episodes associated with bipolar I disorder. It provides another treatment option for patients who have been struggling to find suitable treatment options to manage their bipolar disorder effectively.

Psychodynamic Psychopharmacology With David Mintz, M.D.

In this interview, Dr. Mintz discusses the fundamental principles of psychodynamic psychopharmacology. He highlights the importance of addressing psychological factors for medication resistance and emphasizes the significance of incorporating psychotherapeutic skills in medication management to promote agency and improve adherence. Furthermore, Dr. Mintz explores how transference and countertransference influence management and offers insights into navigating these complexities in patient care.

Interview highlights include the following:

Utilize your therapeutic skills to identify and inquire about ambivalence during the initial assessment, enhancing the efficacy of long-term management strategies.
Encourage active patient participation in their treatment decisions, respecting their preferences for medication when feasible, to reinforce their sense of agency and improve adherence to pharmacotherapy.

Learn more and earn 0.5 CME credits here.

TMS in Psychiatry: Innovations and Best Practices

In this presentation, Dr. Simon Kung immerses us in the world of TMS. He reviews the basis of TMS, the FDA-approved devices and coils, and its potential side effects. Dr. Kung also reviews the evidence supporting the application of TMS in the treatment of depression, obsessive-compulsive disorder, and smoking cessation. To conclude his presentation, he provides insight into insurance companies’ criteria for TMS coverage and presents a clinical case study.

Assessing the Potential Side Effects of TMS

TMS causes physical discomfort at the stimulation site.
Patients tolerate the discomfort better after about 1–2 weeks.
Site pain, headache, and facial twitching are common.
Lowering motor threshold makes TMS more tolerable, but do not underdose it.

Learn more and earn 1 CME credit here.

Quick Takes: Research, Digested

Is High-Dose Olanzapine an Option for Treatment-Resistant Schizophrenia?

A systematic review examines using high-dose olanzapine (>20mg/day) for schizophrenia.
Several older studies suggest it may not be inferior to clozapine. However, clozapine remains the gold standard; high-dose olanzapine is the second-best option.
Use olanzapine cautiously, given its metabolic side effects. Learn more.

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

CAP Smart Takes: Research, Digested

Efficacy of Probiotics in Treating ADHD Symptoms

Current evidence does not indicate a significant difference in therapeutic efficacy between probiotics and placebo in treating pediatric ADHD.
There exists an intriguing nonsignificant trend showing therapeutic efficacy associated with multistrain probiotics or when combined with methylphenidate. Learn more.