Medications for Anxiety and Sleep in the Hospital Setting
For hospitalized patients with sleep disturbances, first-line pharmacologic treatment should be short-to-intermediate acting benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon, temazepam) or ramelteon, with trazodone (25-100 mg at bedtime) as an effective alternative, particularly when comorbid depression or anxiety is present. 1
Sleep Disturbances in Hospitalized Patients
First-Line Pharmacologic Options
Short-to-intermediate acting benzodiazepine receptor agonists (BzRAs) are the recommended initial approach:
Zolpidem 5 mg at bedtime - very short half-life, reduces sleep latency with minimal residual sedation 1, 2
Temazepam - medium duration of action, improves both sleep onset and maintenance 1, 3
- Suitable for patients needing help with sleep maintenance, not just initiation 1
Zaleplon - ultra-short half-life, primarily for sleep initiation with minimal morning effects 1
Eszopiclone - longer half-life, effective for sleep maintenance but higher risk of residual sedation 1
Ramelteon - non-DEA scheduled alternative, particularly appropriate for patients with substance use history 1
Effective Alternative: Sedating Antidepressants
Trazodone 25-100 mg at bedtime is specifically recommended for hospital settings and is particularly useful when treating comorbid depression or anxiety 1, 4
- Most popular second-choice treatment among clinicians after melatonin 1
- Caution: Avoid concurrent use with MAOIs (contraindicated), monitor for serotonin syndrome with other serotonergic drugs 4
- May prolong QT interval - avoid with other QT-prolonging medications 4
Other sedating antidepressants for refractory cases:
Second-Line Options for Refractory Insomnia
Atypical antipsychotics should be reserved for specific situations:
Olanzapine 2.5-5 mg at bedtime - effective for refractory insomnia 1
Quetiapine 25 mg at bedtime - sedating, less likely to cause extrapyramidal symptoms 1
- Should not be prescribed for sleep disturbances alone due to significant metabolic side effects 1
Chlorpromazine 25-50 mg at bedtime - for refractory cases, particularly in palliative care 1
What NOT to Use
Avoid these medications for hospital insomnia:
OTC antihistamines (including hydroxyzine) - not recommended due to lack of efficacy and safety data for chronic insomnia 1
- If used: Hydroxyzine carries QT prolongation risk, causes CNS depression, and increases fall risk in elderly 5
Barbiturates and chloral hydrate - explicitly not recommended 1
Herbal supplements (valerian, melatonin) - insufficient efficacy and safety data for chronic insomnia 1
Anxiety in Hospitalized Patients
Acute Anxiety Management
For acute anxiety or agitation, benzodiazepines remain first-line:
Lorazepam 0.5-1 mg (oral, sublingual, subcutaneous, or IV) 1
Midazolam 2.5 mg subcutaneous or IV - for severe agitation and distress 1
- Use lower doses (0.5-1 mg) in elderly or when combined with antipsychotics 1
Duration of Benzodiazepine Use
Critical prescribing principles to prevent dependence:
- Limit prescriptions to a few days, occasional/intermittent use, or courses not exceeding 2 weeks 6
- Short-term use (1-7 days or 2-4 weeks maximum) is justified for acute stress reactions and episodic anxiety 6, 7
- Long-term use (>4 weeks) should be rare and only for severe refractory anxiety where benefits outweigh dependence risk 6, 7, 8
Choice of benzodiazepine by anxiety pattern:
- Sustained/chronic anxiety: Long-acting agents (diazepam, clorazepate) 7
- Episodic/acute anxiety: Shorter-acting agents (lorazepam, oxazepam) 7
Antipsychotics for Anxiety with Agitation
When benzodiazepines are contraindicated or ineffective:
- Olanzapine 2.5-5 mg (oral or subcutaneous) 1
- Quetiapine 25 mg 1
- Risperidone 0.5 mg 1
- Haloperidol - traditional option but higher risk of extrapyramidal symptoms 1
Critical Safety Considerations
Universal Precautions for All Sedative-Hypnotics
Patient education must include: 1
- Treatment goals and realistic expectations
- Safety concerns and fall risk (especially elderly)
- Potential side effects and drug interactions
- Risk of dosage escalation
- Rebound insomnia upon discontinuation
Monitoring requirements:
- Follow patients every few weeks initially to assess effectiveness and side effects 1
- Use lowest effective maintenance dose 1
- Attempt medication tapering when conditions allow 1
High-Risk Populations
Elderly patients require special consideration:
- Start with lowest doses of all sedative-hypnotics 1, 5
- Higher risk of falls, confusion, oversedation, and memory impairment 5, 2, 8
- Benzodiazepines with half-lives >16 hours likely cause impaired performance the next day 3
Patients with respiratory compromise:
- Extreme caution with benzodiazepines due to respiratory depression risk 1
- Consider non-benzodiazepine alternatives first 1
Drug Interactions
CNS depressant combinations increase risk significantly:
- Avoid combining multiple sedative-hypnotics 2
- Reduce doses when combining with opioids, alcohol, or other CNS depressants 4, 5, 2
- Fatal outcomes reported with olanzapine plus high-dose benzodiazepines 1
QT prolongation concerns:
- Avoid combining trazodone, hydroxyzine, or quetiapine with Class 1A/III antiarrhythmics, certain antipsychotics, or antibiotics 4, 5
Practical Algorithm for Hospital Use
Step 1: Assess sleep disturbance type using validated tools (Epworth Sleepiness Scale) 1
Step 2: Rule out and treat contributing factors (pain, delirium, medication side effects, primary sleep disorders) 1
Step 3: Initiate pharmacotherapy:
- Sleep onset difficulty: Zolpidem 5 mg or zaleplon 1
- Sleep maintenance difficulty: Temazepam or eszopiclone 1
- Comorbid anxiety/depression: Trazodone 25-100 mg 1
- Substance use history: Ramelteon 1
Step 4: If initial agent unsuccessful after 2-3 nights, switch to alternative within same class 1
Step 5: For refractory cases, consider sedating antidepressants or atypical antipsychotics 1
Step 6: Limit duration to <2 weeks when possible, taper upon discharge 1, 6