National Sleep Foundation

Chapter 2: Insomnia

Insomnia Treatment: Other Agents to Treat Insomnia

Other Agents to Treat Insomnia

Other agents are occasionally used off-label to treat insomnia, including: gabapentin, tiagabine, and atypical antipsychotics such as olanzapine and quetiapine. Most of these agents have not been studied in clinical trials in patients suffering from insomnia.

Gabapentin is widely used for chronic pain. It has been studied in clinical trials for some sleep-related disorders such as restless legs syndrome, and has been shown to improve sleep architecture; increase total sleep time, sleep efficiency, and slow wave sleep (SWS); and to decrease stage 1 sleep.i In clinical studies of other neurologic disorders (e.g., epilepsy), gabapentin has been shown to reduce awakenings and increase SWS and REM sleep. Side effects include sedation, dizziness, ataxia, and diplopia.ii

Tiagabine is an anticonvulsant that reduces GABA reuptake into presynaptic neurons by inhibiting the GAT-1 GABA transporter. It has been studied at doses of 4 to 16 mg for the treatment of insomnia, doses much lower than those used for treatment of epilepsy. In studies of non-sleep disrupted individuals, tiagabine improved sleep efficiency and increased SWS. Studies have demonstrated dose-dependent increases in SWS, decreased stage 1 and REM, and inconsistent effects on total sleep time and wake time. Side effects include sedation, dizziness, and nausea.iii

Both olanzapine and quetiapine are atypical antipsychotics with moderate sedating properties. In studies of healthy individuals, olanzapine improves sleep continuity and increases the amount of SWS; quetiapine decreases sleep latency while increasing totals sleep time and reducing REM.iv Both drugs can cause hypotension. Olanzapine may cause weight gain; quetiapine may prolong QTc on EKG.

References

  1. Buysse D, “Clinical Pharmacology of Other Drugs Used as Hypnotics,” In Kryger M, Roth T, Dement WC (eds.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, pages 492-509.
  2. Buysse D, “Clinical Pharmacology of Other Drugs Used as Hypnotics,” In Kryger M, Roth T, Dement WC (eds.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, pages 492-509.
  3. Buysse D, “Clinical Pharmacology of Other Drugs Used as Hypnotics,” In Kryger M, Roth T, Dement WC (eds.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, pages 492-509.
  4. Buysse D, “Clinical Pharmacology of Other Drugs Used as Hypnotics,” In Kryger M, Roth T, Dement WC (eds.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, pages 492-509.