What is Pregabalin?
Pregabalin, sold under brand names like Lyrica, is a medication primarily used to treat neuropathic pain, fibromyalgia, epilepsy, and generalized anxiety disorder [1.2.3]. It is a structural analog of the neurotransmitter GABA but exerts its effects by binding to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system [1.2.2]. This action reduces the release of several excitatory neurotransmitters, including glutamate and substance P, which helps to calm overactive nerve signals [1.4.3]. While generally considered effective, it carries a profile of side effects, with the most common being dizziness and somnolence (drowsiness) [1.2.2]. However, more severe neuropsychiatric effects have been documented.
Understanding Delirium
Delirium is an acute and fluctuating disturbance in attention, awareness, and cognition [1.2.2]. It is not a disease itself but a syndrome resulting from an underlying cause, such as illness, infection, or as a side effect of medication [1.5.1]. According to the DSM-5 criteria, its onset is rapid—developing over hours to days—and represents a distinct change from a person's baseline mental state [1.2.2]. Symptoms can include disorientation, memory deficits, perceptual disturbances like hallucinations, and changes in psychomotor activity. Delirium can manifest as a hyperactive state (agitation, restlessness), a hypoactive state (lethargy, reduced motor activity), or a mix of both [1.2.4].
The Link: Does Pregabalin Cause Delirium?
Yes, evidence from numerous case reports and clinical observations confirms that pregabalin can cause delirium [1.2.1, 1.2.5]. This adverse effect can occur even at therapeutic doses and with appropriate, slow titration [1.2.1, 1.7.7]. The delirium is often characterized by confusion, disorientation, and prominent visual hallucinations [1.7.1, 1.2.3]. In most reported cases, the symptoms of delirium resolved promptly after the discontinuation of pregabalin, strengthening the association [1.2.2, 1.2.3]. Delirium has been observed not only during treatment but also as a withdrawal symptom following abrupt cessation of the drug [1.2.6, 1.4.2].
Populations at Higher Risk
Certain factors increase a patient's vulnerability to developing pregabalin-induced delirium:
- Elderly Patients: Older adults are more susceptible to the cognitive side effects of many medications, including pregabalin. They are more likely to experience confusion, dizziness, and both hyperactive and hypoactive delirium [1.3.3, 1.2.4].
- Renal Impairment: Pregabalin is primarily eliminated from the body by the kidneys [1.2.3]. Patients with impaired kidney function may have reduced clearance of the drug, leading to higher plasma levels and an increased risk of toxicity and side effects, including delirium, even at low doses [1.7.4].
- Polypharmacy: The concurrent use of other central nervous system (CNS) depressants, such as benzodiazepines or opioids, can potentiate the sedative and cognitive effects of pregabalin, increasing delirium risk [1.3.1].
- High Doses or Rapid Titration: While delirium can occur at low doses, higher doses and rapid increases in dosage are more frequently associated with adverse neuropsychiatric reactions [1.2.3].
Comparison of Deliriogenic Medications
| Medication Class | Primary Mechanism | Common Delirium Features |
|---|---|---|
| Pregabalin | Binds to α2δ subunit of calcium channels, reducing excitatory neurotransmitter release [1.4.3]. | Confusion, visual hallucinations, both hyperactive and hypoactive states [1.2.3, 1.2.4]. |
| Benzodiazepines | Enhances the effect of the inhibitory neurotransmitter GABA [1.5.7]. | Sedation, confusion, memory impairment, paradoxical agitation, especially in the elderly [1.5.7]. |
| Opioids | Acts on opioid receptors, primarily mu-receptors in the CNS [1.5.5]. | Sedation, cognitive slowing, hallucinations, constipation can contribute to delirium. |
| Anticholinergics | Blocks the neurotransmitter acetylcholine in the CNS and periphery [1.5.5]. | Classic symptoms: "mad as a hatter, blind as a bat, red as a beet, hot as a hare, dry as a bone." |
Managing Pregabalin-Induced Delirium
The most critical step in managing delirium suspected to be caused by pregabalin is to identify and discontinue the offending agent under medical supervision [1.5.1]. In many cases, symptoms resolve completely after the drug is stopped [1.2.3]. Supportive care is crucial and includes:
- Reorientation: Frequent reminders of the date, time, and location [1.5.4].
- Environmental Control: Maintaining a calm, well-lit environment, ensuring the patient has their glasses and hearing aids, and promoting a regular sleep-wake cycle [1.5.3, 1.5.6].
- Avoiding Complications: Ensuring proper hydration and nutrition and encouraging mobility [1.5.4].
Pharmacological treatment for the delirium itself is reserved for cases with severe agitation or psychosis that pose a risk to the patient or others. Low-dose antipsychotics like haloperidol may be used in such instances [1.5.5]. Benzodiazepines are generally avoided as they can worsen delirium, except in cases of alcohol or benzodiazepine withdrawal [1.5.7].
Conclusion
While an effective medication for many, pregabalin carries a clear, though relatively rare, risk of causing delirium. This acute state of confusion, altered awareness, and cognitive impairment is a serious medical condition. Clinicians should be aware of this potential side effect, especially when treating vulnerable populations such as the elderly and those with renal insufficiency [1.2.1, 1.3.3]. Patients and their families should be educated to recognize the signs of delirium—such as sudden confusion, hallucinations, or drastic changes in behavior—and seek immediate medical attention if they occur. Prompt recognition and discontinuation of the medication are key to resolving the episode.
For more detailed prescribing information, consult the FDA drug label.
