| Drug class |
Anticonvulsant / analgesic (gabapentinoid) |
Hormone / supplement (circadian regulator) |
| Common uses |
• Neuropathic pain (e.g., diabetic neuropathy, post‑herpetic neuralgia)
• Fibromyalgia
• Seizure adjunct
• Generalised anxiety disorder (GAD) |
• Sleep‑related disorders (insomnia, jet lag, shift‑work sleep disturbance)
• Circadian rhythm adjustment |
| Formulation |
Prescription tablets (e.g., 25 mg, 50 mg, 100 mg, 200 mg) |
OTC or prescription (capsules, tablets, liquid, sublingual) – typical doses 1–10 mg |
| Mechanism of action |
Binds to the α2δ subunit of voltage‑gated calcium channels → ↓ calcium influx → ↓ excitatory neurotransmitter release |
Binds to MT1/MT2 melatonin receptors in the suprachiasmatic nucleus → modulates circadian phase, promotes sleep |
| Pharmacokinetics |
• Rapid absorption (≈80 % bioavailability)
• Linear kinetics
• Half‑life ~6.3 h
• Renal clearance (no hepatic metabolism) |
• Rapid absorption
• Short half‑life (20–40 min)
• Metabolised by CYP1A2, CYP2C19, CYP2D6 |
| Typical dosing (adult) |
• Starting: 150 mg/day (split into 2–3 doses)
• Maintenance: 150–600 mg/day (divided)
• Max: 600 mg/day |
• 0.5–5 mg 30–60 min before bedtime
• 5–10 mg for jet lag or shift work (short‑term) |
| Common side effects |
• Dizziness, somnolence
• Periorbital oedema (puffiness)
• Weight gain, increased appetite
• Constipation, blurred vision |
• Drowsiness, grogginess
• Vivid dreams, mild headaches
• Rare: dizziness, nausea, hypotension |
| Contraindications |
• Hypersensitivity to pregabalin
• Severe renal impairment (dose adjustment) |
• Hypersensitivity to melatonin
• Some countries restrict high‑dose OTC use |
| Drug interactions |
• CNS depressants (benzodiazepines, alcohol, opioids, opioids + benzodiazepines) → additive sedation, respiratory depression
• Opioid analgesics may increase risk of sedation and respiratory depression
• Cimetidine, cimetidine, and some antacids can affect absorption slightly |
• Anticoagulants (warfarin, dabigatran) → potential ↑ INR
• Antidiabetics (insulin, sulfonylureas) → may lower glucose
• Cytochrome P450 inhibitors/inducers (e.g., fluvoxamine, rifampin) can alter melatonin levels
• Alcohol → additive CNS depression |
| Safety notes |
• Pregabalin is a Schedule V controlled substance in the US; monitor for abuse potential.
• Renal function must be checked; dose adjustments needed for creatinine clearance <30 mL/min.
• Avoid sudden discontinuation; taper to mitigate withdrawal symptoms. |
• Melatonin is generally safe for short‑term use (<6 months).
• Long‑term safety data limited; caution in pregnancy and lactation (data insufficient).
• Avoid high doses (>10 mg) in children without medical supervision. |
| What to watch for |
• Excessive sleepiness, confusion, or impaired motor skills → reduce dose or discontinue.
• Signs of respiratory depression when combined with opioids/benzodiazepines (e.g., slowed breathing). |
• Excessive daytime sleepiness, vertigo, or headache.
• If used with sedatives, increased drowsiness. |
| When to consult a doctor |
• If you’re on opioids or other CNS depressants
• If you have renal impairment or are pregnant/lactating
• If you experience severe dizziness, visual changes, or swelling. |
• If you have a bleeding disorder or are on anticoagulants
• If you have liver disease, diabetes, or are pregnant/lactating
• If you notice persistent headaches or dizziness. |
| Practical tips |
• Take with food if you experience GI upset.
• Keep consistent dosing times to maintain steady levels.
• Avoid alcohol; it heightens sedative effects. |
• Use in a dark, cool environment for best effect.
• If using a high‑dose formulation, consider a lower dose first and titrate.
• For jet lag, start 4–5 mg 1 h before bedtime on arrival day and taper after 4–5 days. |