How Iloperidone Rebalances Brain Chemistry
Iloperidone's primary therapeutic effect is achieved by acting on specific receptors in the brain to modulate neurotransmitter activity. Although its exact mechanism is not fully understood, it is believed to be mediated by a combination of receptor antagonisms.
- Dopamine D2 and D3 Receptors: Iloperidone blocks these receptors to help reduce excessive dopamine activity associated with psychotic symptoms. Its moderate affinity for the D2 receptor may help minimize extrapyramidal symptoms.
- Serotonin 5-HT2A Receptors: With a higher affinity for serotonin receptors, iloperidone's blockade of 5-HT2A is thought to help with negative and cognitive symptoms of schizophrenia.
- Alpha-Adrenergic Receptors: Iloperidone has high affinity for alpha-1 and moderate affinity for alpha-2C adrenergic receptors. Blocking these receptors can contribute to both therapeutic effects and the common side effect of orthostatic hypotension.
The Conditions Iloperidone Treats
Iloperidone (Fanapt®) is mainly used for two major mental health conditions in adults:
Schizophrenia
Iloperidone treats schizophrenia in adults, a condition with symptoms like hallucinations, delusions, disorganized thinking, and social withdrawal. Clinical trials show it helps reduce both positive and negative symptoms, though full control may take time.
Bipolar I Disorder
Approved in April 2024, iloperidone is used for acute manic or mixed episodes of bipolar I disorder in adults. Studies have shown it to be more effective than a placebo in reducing manic symptoms.
Potential Side Effects and Risk Profile
Iloperidone can cause a range of side effects and carries several serious risks. Common side effects include dizziness, tiredness, dry mouth, nasal congestion, and a fast heart rate. A notable risk is orthostatic hypotension, a drop in blood pressure upon standing, especially during initial use, which increases the risk of falls.
The medication can prolong the QT interval, increasing the risk of serious heart rhythm problems, particularly when combined with other QT-prolonging drugs. Like other atypical antipsychotics, iloperidone may lead to metabolic changes such as high blood sugar, weight gain, and abnormal lipid levels. Long-term use carries a risk of tardive dyskinesia, characterized by involuntary movements. A rare but severe reaction called Neuroleptic Malignant Syndrome requires immediate medical attention. Iloperidone also has a boxed warning against use in older adults with dementia-related psychosis due to an increased risk of death.
Comparison of Iloperidone to Other Atypical Antipsychotics
Here's a comparison of iloperidone with other common atypical antipsychotics:
| Feature | Iloperidone | Risperidone | Ziprasidone |
|---|---|---|---|
| Mechanism | Antagonist at multiple receptors, with high affinity for 5-HT2A, D2, and α1. | Antagonist at 5-HT2A, D2, and α1. Higher D2 affinity can increase EPS risk. | Similar 5-HT2A and D2 antagonism. Also a serotonin and norepinephrine reuptake inhibitor. |
| EPS Risk | Low propensity for EPS and akathisia. | Higher risk of EPS and prolactin elevation than iloperidone. | Generally low EPS risk. |
| QTc Prolongation | Yes, a notable risk; requires caution. | No significant QTc changes observed in some studies. | Yes, known to cause QTc interval prolongation. |
| Weight Gain | Modest short-term weight gain observed. | Can cause significant weight gain. | Less potential for weight gain compared to iloperidone. |
| Orthostatic Hypotension | High risk, requiring slow dose titration. | Can cause orthostatic hypotension. | Can cause orthostatic hypotension. |
| Prolactin Elevation | Low potential for prolactin elevation. | High potential for prolactin elevation. | Low potential for prolactin elevation. |
The Role of Dosing and Titration
A slow dose titration is crucial when starting iloperidone to minimize orthostatic hypotension. This involves gradually increasing the dose over several days. If doses are missed for over three days, the titration must be restarted. Iloperidone is typically taken by mouth, with or without food. Healthcare providers follow specific guidelines for dosing in schizophrenia and bipolar disorder based on individual patient needs.
Conclusion: A Targeted Treatment Option
Iloperidone is an atypical antipsychotic that targets specific neurotransmitter receptors to manage schizophrenia and bipolar I disorder symptoms. By blocking dopamine D2 and serotonin 5-HT2A receptors, it helps address both positive and negative psychotic symptoms. Its profile, with potentially lower risks of extrapyramidal symptoms and prolactin elevation than some other antipsychotics, makes it an option for some patients. However, the risks of QTc prolongation and orthostatic hypotension require careful monitoring, especially early in treatment. The decision to use iloperidone should be made with a healthcare provider, considering the individual patient's health and potential side effects, as outlined by sources like NAMI.
