| Class | Clinical use | Examples | Sleep and wakefulness effects | Alteration of sleep pattern |
| Selective serotonin reuptake inhibitors (SSRIs)* | Depression, anxiety, panic disorder | Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram | Insomnia, daytime sleepiness, akathisia. Exceptions – Paroxetine and fluvoxamine are relatively sedating. | SSRIs may decrease total sleep time and increase awakenings, particularly during initiation of treatment. May also prolong latency to and decrease overall REM sleep[1-4]. Abrupt withdrawal of short-acting SSRIs may worsen insomnia. |
| Serotonin and norepinephrine reuptake inhibitors (SNRIs)* | ADHD, autism, depression, pain | Venlafaxine, duloxetine | Insomnia, daytime sleepiness, akathisia. | SNRIs may decrease total sleep time and increase awakenings, particularly during initiation of treatment. May also prolong latency to and decrease overall REM sleep[1-4]. Abrupt withdrawal of short-acting SNRIs may worsen insomnia. |
| Serotonin-2 receptor antagonists/reuptake inhibitors (SARIs) | Depression, adjunct to SSRI or SNRI to improve sleep | Trazodone, nefazodone, mirtazapine | Sedation, increased sleep time. | SARIs may increase total sleep time and increase deep (N3) sleep[2-4]. |
| Aminoketones* | ADHD, depression, fatigue | Bupropion | Insomnia, agitation. | Aminoketones may alter REM density and activity and cause abnormal dreams¶[2]. |
| Tricyclic and tetracyclics* | Depression, pain, enuresis | More sedating – Amitriptyline, doxepin, nortriptyline, clomipramine | Sedation, daytime sleepiness. Increased total sleep time in non-depressed patients. | When dosed in evening, these drugs can shorten sleep latency, decrease awakenings, prolong REM latency, and reduce REM sleep[2,3]. Clomipramine is a potent suppressor of REM sleep[4]. Antihistaminic and antimuscarinic side effects may cause daytime sedation and altered cognition. |
| More activating – Desipramine, trimipramine, protriptyline | Insomnia, daytime sleepiness, akathisia (motor restlessness). | These drugs may prolong REM latency and suppress REM sleep (potentially beneficial in depressed patients). They also may cause increased wakefulness and decreased total sleep time, particularly during the initial weeks of treatment[2,4]. Antihistaminic and antimuscarinic side effects may cause daytime sedation and altered cognition. | ||
| Monoamine oxidase inhibitors (MAOIs)* | Refractory depression, Parkinson disease | IsocarboxazidΔ, phenelzineΔ, moclobemide, tranylcypromineΔ, selegiline, rasagiline | Insomnia, daytime sleepiness. | MAOIs cause nearly complete suppression of REM sleep, which is potentially beneficial in severely depressed patients. They also cause increased awakenings and decreased total sleep time[2,4]. |
| Benzodiazepines | Seizures, anxiety, muscle relaxant, nausea/vomiting | Lorazepam, diazepam | Daytime sedation. Worsening of sleep-related breathing disorders. Rebound insomnia upon abrupt withdrawal. | Benzodiazepines cause reduced sleep latency, increase total sleep time, reduce awakenings, suppress deep (N3) sleep, and alter REM density[4]. Long-acting agents are associated with more daytime hangover. Short-acting agents are associated with rebound insomnia when withdrawn. |
| Stimulants | ADHD, narcolepsy | Methylphenidate, dextroamphetamine | Insomnia. Increased wakefulness. Rare reports of disturbed sleep, nightmares, hallucinations. | These stimulants prolong latency of sleep onset, reduce total sleep time, and decrease deep (N3) sleep time[4,6]. The negative effects on sleep may be caused by the direct stimulant effect of these medications as well as rebound of ADHD symptoms as the dose wears off. |
| Selective norepinephrine reuptake inhibitor | ADHD | Atomoxetine | Somnolence or insomnia. Increased wakefulness. Sleep disturbance, abnormal dreams. Among pediatric patients in clinical trials, somnolence reported more frequently than insomnia. | Among pediatric patients with ADHD, atomoxetine caused less delay in sleep latency and less reduction in total sleep time than methylphenidate[6]. |
| Antiseizure medications | Epilepsy, bipolar disorder, migraine prophylaxis, neuropathic pain | Phenytoin, valproate, carbamazepine, topiramate, gabapentin | Somnolence. Daytime sleepiness. | This group tends to decrease sleep latency and REM sleep (except gabapentin); they also may increase deep (N3) sleep[4]. |
| Lamotrigine, tiagabine, felbamate, levetiracetam | Increased wakefulness. Administer early in day. | This group may increase deep (N3) sleep and improve sleep efficiency (levetiracetam)¶[4]. | ||
| Antipsychotics (first-generation)◊ | Bipolar disorder, psychomotor agitation, schizophrenia | Haloperidol, thioridazine, chlorpromazine | Daytime sedation, especially chlorpromazine and thioridazine. | This drug class tends to decrease sleep latency, cause fewer awakenings, and increase total sleep time. |
| Antipsychotics (second-generation)◊ | Aripiprazole, clozapine, olanzapine, quetiapine risperidone, ziprasidone | Daytime sedation. Aripiprazole is least sedating. Clozapine, quetiapine, and olanzapine are most sedating. | Olanzapine, ziprasidone, and risperidone suppress REM sleep, increase deep (N3) sleep, and improve sleep continuity[1,4]; they may counteract detrimental effects of certain SSRIs on sleep[1]. Sleep improvements are attributed to 5HT-2A/2C receptor blockade. | |
| Alpha-2 agonists | Hypertension, ADHD, pain, migraine prophylaxis | Clonidine, methyldopa | Daytime sedation. | These drugs cause decreased latency of sleep onset and partial suppression of REM sleep[4,5]. |
| Beta-antagonists | Hypertension, heart failure | PropranololΔ, metoprolol, nadolol, atenolol | Disturbed sleep, insomnia, nightmares, hallucinations[5]. | Beta-antagonists tend to suppress REM sleep. The lipophilic beta-antagonists (eg, propranolol, labetalol) may cause more sleep disturbance than hydrophilic agents (eg, atenolol)[4]. |
| Beta-agonists (inhaled) | Inhaled bronchodilator | Inhaled albuterol (salbutamol), salmeterol | Long-acting forms appear to improve sleep in asthmatics. | The long-acting forms of these drugs tend to increase sleep time including deep (N3) sleep in asthmatics due to control of nocturnal asthma symptoms[4,5]. |
| Methylxanthines | Bronchodilation, antiinflammatory (asthma) | Theophylline, aminophylline | Insomnia. Increased wakefulness. | Methylxanthines tend to delay sleep latency, increase awakenings, and decrease total sleep time. They do not improve total sleep time or sleep quality of asthmatics[4,5]. |
| Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors or statins | Hypercholesterolemia | Simvastatin, lovastatin, pravastatin | Reports of disturbed sleep and nightmares. | These effects are limited to case descriptions and are not well documented. |
| Glucocorticoids | Immunosuppression, antiinflammatory, antiemetic | Dexamethasone, prednisone, prednisolone | Insomnia, increased wakefulness, and fatigue. | Glucocorticoids tend to decrease total sleep time and may decrease deep (N3) sleep time. REM sleep suppression is reported with certain glucocorticoids¶[5]. These effects are dose-related, and nighttime dosing may cause greater sleep disturbance. |
| Antihistamines (first-generation) | Allergic rhinitis, pruritus, antiemetic | Diphenhydramine, hydroxyzine, doxylamine, promethazine | Daytime sleepiness may result in decreased night sleep time, increased awakenings. | These drugs are associated with decreased sleep latency and fewer night awakenings in adolescents and adults but may cause paradoxical excitation in young children. |
| Antihistamines (second-generation) | Loratadine, cetirizine, fexofenadine | Few effects on sleep or wakefulness at moderate doses. Daytime sleepiness at higher dosing. | Effects on sleep are minimized because there is little central nervous system penetration with usual dosing for seasonal allergies. Cetirizine may be more sedating. | |
| Opioid analgesics | Analgesia | Morphine, hydromorphone, oxycodone, methadone | Daytime sleepiness and fatigue. Dose-related worsening of sleep-related respiratory disorders. Insomnia and disturbed sleep if abrupt withdrawal. | These drugs increase night awakenings and decrease deep (N3) and REM sleep. Chronic methadone has fewer effects on sleep[4]. |
| Decongestants | Cold and allergy symptoms | Phenylephrine, pseudoephedrine | Insomnia, anxiety, agitation. | These drugs cause decreased total sleep time and increased awakenings. Systemic decongestants are generally not recommended in pediatric patients. |
