Table 4.

The most used medications for the pharmacological treatment of insomnia disorders in adolescents.

Drugs	Mechanism of action	Effects on sleep architecture	Side effects	Comments
Benzodiazepines • Clonazepam • Flurazepam, • Quazepam • Temazepam • Estazolam • Triazolam	Agonists of central GABAA receptors	Decreased nocturnal awakenings and suppression of delta sleep	Tolerance, dependence, residual sedation, cognitive or psychomotor disorders, anterograde amnesia, respiratory depression and withdrawal symptoms in case of treatment discontinuation	Short half-life molecules for sleep onset insomnia and long half-life molecules for insomnia maintenance
Alpha-receptor agonists • Clonidine • Guanfacine	Decreased release of norepinephrine	Decreased sleep latency	Dry mouth, hypotension, bradycardia and withdrawal symptoms (shortness of breath, hypertension and tachycardia) in case of treatment discontinuation	They may be used in daytime treatment of attention-deficit/hyperactivity disorder
Benzodiazepines-like • Zolpidem • Zaleplon	Similar action to benzodiazepines but shorter half-life time	Decreased sleep latency	Similar to benzodiazepines	Very few data on their use in adolescents
Atypical antidepressants • Trazodone	Antagonists of serotonin (5-HT2A/c) receptors	Decreased sleep latency, improved sleep continuity, decreased REM sleep and increased delta sleep	Residual sedation, cardiac arrhythmias, hypotension and priapism	They are particularly indicated in cases of comorbid depression
Antihistamines • Diphenhydramine • Brompheniramine • Chlorpheniramine • Hydroxyzine	Antagonists of histamine (H1) receptors	Decreased sleep latency	Residual sedation, loss of appetite, nausea, vomiting, constipation, dry mouth, paradoxical excitation and risk of altered sleep quality	They are well accepted by adolescents and their parents
Melatonin	Targeted action on the circadian regulation of sleep	Reduced sleep latency and correction of some alterations of the circadian rhythm	Largely unknown (hypotension, bradycardia, nausea, headache and possible exacerbations of comorbid autoimmune diseases)	Melatonin may be used in adolescents with mental retardation, pervasive developmental disorders and neurological disorders
Herbal treatments • Passiflora • Valerian • German chamomile • Kava • Lavender	Modulation of central GABA receptors activity and induction of central nervous system depression	Potential sleep-promoting effects without residual daytime drowsiness or performance impairment	Largely unknown	The long-term efficacy and safety of herbal treatments are unknown