From the Guidelines
Promethazine can increase restlessness, also known as akathisia, due to its dopamine receptor antagonist effects, which can disrupt the balance between dopaminergic and cholinergic neurotransmission in the brain. This occurs because promethazine blocks dopamine receptors, particularly D2 receptors, leading to extrapyramidal symptoms including restlessness, agitation, and an inability to remain still 1. The medication's complex effects on the central nervous system can cause this paradoxical reaction, which is more common in certain individuals such as the elderly, children, and those taking higher doses.
Key Points to Consider
- The dopamine blockade caused by promethazine can lead to akathisia, characterized by a state of motor restlessness and an inability to remain still.
- Patients with Parkinson's disease or other movement disorders are particularly susceptible to this paradoxical reaction due to their existing dopamine imbalance.
- The effect is dose-dependent, with higher doses (typically above 25mg) increasing the risk of akathisia.
- If restlessness occurs while taking promethazine, it is essential to contact a healthcare provider, as dosage adjustment or medication change may be necessary to resolve the issue.
Clinical Implications
The potential for promethazine to cause akathisia highlights the importance of careful patient selection, dosing, and monitoring when prescribing this medication. Healthcare providers should be aware of the risk factors for this paradoxical reaction and take steps to minimize its occurrence, such as using the lowest effective dose and closely monitoring patients for signs of restlessness or agitation 1. By understanding the complex effects of promethazine on the central nervous system, healthcare providers can better manage patients and reduce the risk of adverse reactions.
From the FDA Drug Label
Excessive amounts of promethazine HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain
Promethazine (Phenergan) may increase restlessness, also known as akathisia, due to an imbalance between the dose of promethazine and a narcotic, particularly in patients with pain. This suggests that inadequate pain control may contribute to the development of restlessness and motor hyperactivity. The symptoms typically resolve with adequate control of the pain 2.
- Key factors:
- Imbalance between promethazine and narcotic doses
- Inadequate pain control
- Important consideration: Restlessness and motor hyperactivity may disappear with adequate pain management.
From the Research
Promethazine and Restlessness
- Promethazine, also known as Phenergan, is an antihistamine agent used commonly for nausea and allergy, as well as for psychiatric symptoms such as troubling sleep, anxiety, and agitation 3.
- While promethazine is often used for its sedative properties, some studies have reported that it may occasionally elicit acute dystonia in some individuals, especially young children and pregnant women 3.
- In some cases, promethazine has been associated with restlessness, also known as akathisia, although the exact mechanisms are not fully understood.
- A study published in 1997 found that promethazine affected autonomic cardiovascular mechanisms minimally, but reported that most subjects experienced drowsiness, nervous excitation, dry mouth, and fatigue after administration of the drug 4.
- Another study published in 2000 found that promethazine had selective deactivating effects, but also noted that it could induce paradoxical effects, such as anxiety, in some individuals 5.
Possible Explanations
- The antidopaminergic functions of promethazine may contribute to the development of restlessness or akathisia in some individuals 3.
- The anticholinergic properties of promethazine may also play a role in the development of restlessness or akathisia, although the exact mechanisms are not fully understood.
- Individual differences in response to promethazine, such as age, sex, and underlying medical conditions, may also influence the likelihood of developing restlessness or akathisia 3, 4, 5.