Melatonin add-on in manic patients with treatment resistant insomnia

Prog Neuropsychopharmacol Biol Psychiatry. 2000 Feb;24(2):185-91. doi: 10.1016/s0278-5846(99)00097-4.


1. A profound alteration of circadian rhythm of sleep is often a central feature in manic syndrome. Melatonin (MLT) is a main synchronizer of the sleep/wake cycle, playing a role of transduction to brain functioning of informations about periodical environmental changes, i.e. the duration of daylength. 2. In several sleep phase disorders, MLT exerts a therapeutic effect, by normalizing the sleep/wake cycle. 3. Eleven patients, 8 males and 3 females, aged 22-43, meeting DSM IV diagnostic criteria for Bipolar Disorder, Manic Type, were selected for the presence of insomnia not responding to usual hypnotic therapies (benzodiazepine). 4. All the patients were on antimanic treatment. MLT 3 mg per os was administrated at 22.30 h for 1 month, without changing the previous antimanic and hypnotic treatments. All patients showed a significantly longer duration of sleep following MLT add-on. The severity of mania showed a parallel significant decrease. 5. The results of this pilot clinical study suggest that MLT add-on can be useful in antimanic therapy to treat resistant circadian sleep alterations as well as consequently exert a global therapeutic action on the manic state.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Benzodiazepines
  • Bipolar Disorder / complications*
  • Bipolar Disorder / psychology
  • Drug Resistance
  • Female
  • Humans
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacology*
  • Melatonin / therapeutic use
  • Pilot Projects
  • Recurrence
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / etiology
  • Sleep Initiation and Maintenance Disorders / psychology
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Anticonvulsants
  • Benzodiazepines
  • Melatonin