Understanding Ptosis and Its Connection to Medications
Ptosis, the medical term for a drooping upper eyelid, occurs due to a dysfunction of the muscles responsible for lifting the eyelid—the levator palpebrae superioris and the superior tarsal muscle—or the nerves that supply them [1.2.2]. While it is often associated with aging, congenital factors, or underlying neurological conditions, a significant number of cases are iatrogenic, meaning they are caused by medical treatment [1.5.2]. Drug-induced ptosis is a recognized adverse reaction to a wide array of systemic and locally administered medications [1.4.1]. The effect can range from a mild, barely noticeable droop to a severe impairment of vision. Understanding which drugs carry this risk is crucial for both patients and clinicians for proper diagnosis and management.
Pharmacological Mechanisms Behind Drug-Induced Ptosis
The ways in which medications can cause ptosis are varied and depend on the drug's mechanism of action. The primary pathways involve interference with neuromuscular transmission, direct muscle toxicity (myotoxicity), or effects on the nervous system that controls the eyelid muscles.
Neuromuscular Blockade
Some of the most well-documented cases of drug-induced ptosis result from a blockade of neurotransmission at the neuromuscular junction [1.4.1]. The levator palpebrae superioris muscle is controlled by the oculomotor nerve, which uses acetylcholine as its neurotransmitter. Drugs that inhibit the release or action of acetylcholine can lead to muscle weakness and ptosis.
- Botulinum Toxin: Commonly used for cosmetic and therapeutic purposes, botulinum toxin works by inhibiting the release of acetylcholine from nerve endings [1.4.6]. If the toxin diffuses from its intended injection site (e.g., the forehead or glabellar region) to the levator palpebrae superioris, it can cause a temporary but significant droop [1.4.7]. This is one of the most common causes of iatrogenic ptosis, with onset typically occurring 2 to 10 days post-injection [1.6.6].
- Succinylcholine: This muscle relaxant, often used in anesthesia, can also cause ptosis by blocking neurotransmission [1.4.1].
Myotoxicity and Aponeurotic Weakness
Other drugs appear to exert a direct toxic effect on the eyelid muscles or weaken the aponeurosis (the tendon-like sheet that connects the levator muscle to the eyelid structure).
- Topical Steroids: Long-term use of corticosteroid eye drops (e.g., dexamethasone, prednisolone acetate) is a known, though rare, cause of ptosis [1.2.6, 1.5.7]. Research suggests that steroids can induce apoptosis (programmed cell death) in the levator muscle cells and weaken the levator aponeurosis, leading to a gradual drooping of the eyelid [1.2.6, 1.4.4].
- Prostaglandin Analogs: Eye drops used to treat glaucoma, such as bimatoprost and latanoprost, have been linked to ptosis. These medications can cause periorbital fat loss and changes in the eyelid tissue that contribute to drooping [1.4.5].
Central Nervous System Effects
Certain medications that act on the central nervous system can also manifest ptosis as a side effect.
- Opioids: High doses of opioids like morphine, oxycodone, heroin, and hydrocodone can cause ptosis [1.5.2, 1.4.9]. The exact mechanism is not fully understood but is believed to be related to their depressive effects on the central nervous system [1.4.2].
- Anticonvulsants: Drugs such as pregabalin and phenytoin have been reported to cause ptosis [1.5.2, 1.2.4]. Levetiracetam has also been implicated in cases of reversible bilateral ptosis [1.6.2].
- Antidepressants and Antipsychotics: Certain tricyclic antidepressants (like amitriptyline), SSRIs (like fluoxetine), and antipsychotic medications (like chlorpromazine and haloperidol) have been associated with ptosis [1.2.3].
Comparison of Common Drug Classes Causing Ptosis
| Drug Class | Common Examples | Mechanism of Action | Onset & Reversibility |
|---|---|---|---|
| Neurotoxins | OnabotulinumtoxinA (Botox) | Blocks acetylcholine release at the neuromuscular junction [1.4.6]. | Onset 2-10 days post-injection; typically resolves spontaneously in weeks to months [1.3.2, 1.6.2]. |
| Opioids | Morphine, Oxycodone, Heroin | Central nervous system depression; possible selective neuronal toxicity [1.4.2, 1.5.2]. | Associated with high doses; often resolves upon discontinuation or dose reduction. |
| Topical Steroids | Dexamethasone, Prednisolone | Induces levator muscle apoptosis and aponeurotic weakness [1.2.6]. | Gradual onset with long-term use; may be stable or require surgical correction after drug withdrawal [1.2.6]. |
| Glaucoma Drops (Prostaglandin Analogs) | Latanoprost, Bimatoprost | Causes periorbital fat loss and structural changes in eyelid tissue [1.4.5]. | Gradual onset; may persist even after discontinuation. |
| Muscle Relaxants | Baclofen, Succinylcholine | Central muscle relaxation or neuromuscular blockade [1.2.3, 1.4.1]. | Variable; often resolves after stopping the medication. |
| Anticonvulsants | Pregabalin, Phenytoin | Central nervous system effects; unclear mechanism [1.5.2, 1.2.4]. | Often temporary and resolves upon discontinuation of the drug [1.6.2]. |
Diagnosis, Management, and Treatment
Diagnosing drug-induced ptosis begins with a thorough patient history, focusing on the timeline of medication use and the onset of the drooping eyelid. The key to management is identifying and, if possible, discontinuing the offending drug under a doctor's supervision. In many cases, especially with drugs like botulinum toxin or certain anticonvulsants, the ptosis is temporary and will resolve on its own once the drug is eliminated from the system [1.6.2].
For more immediate or bothersome cases, particularly those caused by botulinum toxin, specific treatments can offer temporary relief. Adrenergic agonist eye drops, such as apraclonidine 0.5% or oxymetazoline, can be prescribed [1.6.4, 1.6.3]. These drops work by stimulating the superior tarsal muscle (Müller's muscle), an involuntary muscle that provides a small amount of eyelid lift (1-2 mm), which can be enough to improve vision and appearance [1.6.5, 1.6.7].
In situations where the ptosis is caused by long-term changes, such as with topical steroids, and does not resolve after stopping the medication, surgical correction may be necessary [1.2.6].
Conclusion
A wide range of medications, from cosmetic injectables and glaucoma eye drops to systemic drugs like opioids and antidepressants, can cause ptosis. The mechanisms are diverse, involving neuromuscular blockade, direct muscle toxicity, and central nervous system effects [1.4.1, 1.2.6, 1.5.2]. While often a temporary and reversible side effect that resolves with discontinuation of the drug, drug-induced ptosis can sometimes lead to persistent changes requiring medical or surgical intervention. Awareness and identification of the causative agent are the most critical steps in managing this condition.
For further reading on the prevalence and diagnosis of acquired ptosis, consult authoritative sources such as the National Center for Biotechnology Information (NCBI): A review of acquired blepharoptosis: prevalence, diagnosis, and management [1.3.1].
