Once-Nightly Pregabalin for Co-Occurring Nightmares, Poor Sleep, and Headaches: A Case Series

Nightmares, nonrestorative sleep, and headaches co-occur, are common, underdiagnosed, and contribute to substantial disability. Pregabalin modulates excitatory neurotransmission, increases slow-wave sleep, and suppresses REM sleep, suggesting a potential therapeutic role in nightmares and sleep disturbance. Pregabalin's effect on nightmares has not been systematically studied. Although sedation is a common side effect when prescribed 2-3 times daily according to the package insert, the efficacy and tolerability of once-nightly administration remain poorly characterized.

Our retrospective case series included 23 outpatients seen in the neurology department of a tertiary care center from November 2022 to August 2025. They were prescribed once-nightly pregabalin for nightmares, nonrestorative sleep, and headaches. Clinical data were extracted from medical records, including nightmare frequency, fraction of 24-hour periods with restorative sleep, headache frequency, severity, and duration, and MIDAS scores. Within-subject pre-post comparisons were performed using paired t-tests or Wilcoxon signed-rank tests. All p-values were Holm-Bonferroni adjusted.

Nightmare frequency decreased 81% (17.5 to 3.3/month, p_adj=0.006). Nightmares decreased numerically more for those who transitioned from gabapentin to pregabalin (91%) than for those not initially taking gabapentin (73%). Restorative sleep frequency increased 127% (1.8 to 4.0/week, p_adj=0.006). Headache frequency decreased 50% (17.0 to 8.5/month, p_adj=0.040). Migraine Disability Assessment Questionnaire scores decreased numerically by 34% (38.0 to 24.0) but did not reach statistical significance after correction (p_adj=0.084). Six patients reported side effects, and 19 continued pregabalin at three months.

Once-nightly pregabalin was associated with robust reductions in nightmare frequency, nonrestorative sleep, and headache frequency. The improvement in nightmares validates two prior case reports through systematic cohort evaluation. Nightmares improved even among patients transitioning from gabapentin to pregabalin, suggesting that pregabalin may be superior to gabapentin. No prior studies have addressed these three co-occurring problems simultaneously. Larger controlled studies are needed to test the hypothesis that once-nightly pregabalin may be useful for this patient population.