Trazodone. What diseases does it treat?

Use trazodone 25–100 mg at bedtime for insomnia; for major depressive disorder, begin at 150 mg/day and titrate toward 150–300 mg/day in divided doses under clinician supervision. Titrate slowly to minimize orthostatic hypotension and daytime drowsiness, and avoid driving or operating machinery until personal response is established. Discuss dose adjustments with your prescriber if you take CYP3A4 inhibitors or hepatic impairment is present.

Mechanism and approved indications: Trazodone acts as a serotonin antagonist and reuptake inhibitor (SARI), which provides both antidepressant effects and sedative properties that can improve sleep continuity. The drug holds FDA approval for major depressive disorder; clinicians commonly prescribe it off‑label for insomnia, insomnia related to PTSD, comorbid anxiety with sleep disturbance, fibromyalgia-associated sleep problems, and certain headache disorders when sleep restoration is a therapeutic goal.

Pharmacokinetics and interaction points: sedative effects typically begin within 30–60 minutes; terminal half‑life ranges roughly 7–13 hours. Metabolism occurs primarily via CYP3A4, so inhibitors (e.g., ketoconazole, some macrolides, protease inhibitors) raise trazodone levels and may require dose reduction. Avoid combining trazodone with MAO inhibitors without an appropriate washout period and monitor for signs of serotonin syndrome when used with other serotonergic agents.

Side effects, rare risks and monitoring: common adverse effects include sedation, dizziness, dry mouth, and orthostatic hypotension; counsel patients about fall risk. Less common but serious events include priapism (seek immediate care), hyponatremia, and QT prolongation at high doses or in susceptible patients. Check baseline blood pressure and reassess within the first 1–2 weeks; monitor sodium in elderly or those on diuretics. Screen for worsening mood or suicidality, especially early in treatment or after dose changes.

Practical prescribing tips: start low and increase based on response and tolerability; use single bedtime dosing for hypnotic effect and divided dosing for antidepressant benefit. Reassess efficacy within 2–4 weeks for sleep and 4–8 weeks for depressive symptoms, and adjust therapy or switch agents if sedation, orthostasis, or sexual side effects limit adherence. Coordinate care with other prescribers to minimize serotonergic overload and drug interactions.

Trazodone for Major Depressive Disorder: Typical Dosing and Expected Timeline for Symptom Change

Start trazodone for MDD at 50–150 mg at night for immediate‑release (IR) formulations or 150 mg once daily for extended‑release (ER); aim for a maintenance dose of 150–300 mg/day (divided for IR, single daily dose for ER), and consider up to 400 mg/day only if tolerated and clinically indicated.

Titrate by 50–75 mg every 3–7 days based on blood pressure, sedation, and orthostatic symptoms; slow the titration in patients over 65 or with hepatic impairment (initial dose 25–50 mg and smaller increments).

Sedation appears within hours and often improves after the first week; sleep continuity commonly improves within 1–3 nights with low nightly doses. Early anxiolytic and sleep benefits may precede mood change; patients typically report first detectable mood improvement at 1–2 weeks, with a clinically meaningful response by 4–6 weeks at an adequate dose. Reassess efficacy at 6–8 weeks; if improvement is <20–25% at therapeutic doses, adjust dose or change strategy.

Monitor blood pressure and orthostatic vitals during titration, and obtain baseline ECG when there is cardiac disease or concurrent QT‑prolonging medications. Check sodium in older adults or those on diuretics because of hyponatremia risk. Warn males about the rare risk of priapism and instruct immediate medical evaluation if an erection persists beyond four hours.

Avoid combining trazodone with MAO inhibitors within 14 days and use caution with other serotonergic agents because of serotonin syndrome risk. Limit alcohol and other sedative co‑use while assessing individual tolerance. Reduce dose by approximately 50% for moderate–severe hepatic impairment and extend titration intervals.

If discontinuing, taper gradually (for example, reduce by ~50 mg every 3–7 days), tailoring speed to dose, duration of therapy, and withdrawal symptoms. For inadequate response after an optimized trial, consider dose escalation toward 300–400 mg/day if tolerated, switching to an alternative antidepressant, or adding a guideline‑based augmentation strategy in collaboration with the patient.

Trazodone for Insomnia: Nighttime Dosing, Sleep Architecture Effects, and When to Use Off‑Label

For adults with insomnia, start trazodone at a low nighttime dose–25–50 mg at bedtime–and increase to 75–100 mg only if sleep benefit is insufficient and adverse effects remain acceptable; reassess within 2–4 weeks.

Nighttime dosing and practical tips

Typical hypnotic doses range from 25 to 100 mg at bedtime (most common single dose: 50 mg). Trazodone is usually immediate‑release; take 30–60 minutes before sleep. Peak plasma levels occur at ~1–2 hours, and elimination half‑life averages 5–13 hours, which explains potential next‑day drowsiness at higher doses. Start at 25 mg for older adults or those with orthostatic risk, and use 12.5–25 mg starting doses for frail patients when clinically indicated.

Take with or without food; a high‑fat meal delays absorption and can increase total exposure, which may prolong sedation. Reduce concomitant sedatives (benzodiazepines, Z‑drugs, opioids, alcohol) to limit additive respiratory depression and daytime somnolence. Avoid coadministration with MAO inhibitors and use caution with strong CYP3A4 inhibitors, which raise trazodone levels. Monitor blood pressure for orthostatic hypotension during initial titration.

Plan short‑term trials (weeks) for primary insomnia and document sleep latency, total sleep time, and daytime functioning. If benefit is absent after 2–4 weeks or adverse effects are unacceptable, taper off over several days rather than stopping abruptly to limit rebound insomnia.

Sleep architecture effects and off‑label indications

Trazodone improves sleep continuity (reduced awakenings, increased total sleep time) and consistently increases slow‑wave sleep (N3). It tends to have minimal REM suppression compared with SSRIs and may normalize REM when depression‑related REM changes exist. Expect improvements in sleep maintenance more than dramatic reductions in sleep latency at very low doses.

Consider trazodone off‑label for: chronic insomnia when cognitive behavioral therapy for insomnia (CBT‑I) is unavailable or declined; insomnia comorbid with depressive or post‑traumatic stress symptoms; patients with substance‑use disorders who need a non‑habit‑forming sedative alternative; and cases where sleep maintenance is the main problem. Use caution or avoid trazodone in untreated obstructive sleep apnea, severe hepatic impairment, uncontrolled cardiovascular disease, and patients at high fall risk.

Adverse events that warrant stopping or dose reduction include persistent daytime sedation, symptomatic orthostatic hypotension, arrhythmia concerns with other QT‑prolonging drugs, and any sign of priapism (seek emergency care). Reassess ongoing need every 4–12 weeks and prefer behavioral treatments for long‑term insomnia management.

Low‑Dose Trazodone for Anxiety and Panic Symptoms: Indications, Titration, and Monitoring

Consider low-dose trazodone (25–150 mg/day) for patients with anxiety or panic symptoms when nocturnal hyperarousal or sleep disruption amplifies daytime anxiety, or when first-line agents are not tolerated; use as monotherapy for mild anxiety or as an adjunct for insomnia-driven anxiety rather than as a primary treatment for classic panic disorder without sleep disturbance.

Indications and patient selection

• Mild-to-moderate generalized anxiety with prominent sleep disturbance: 25–75 mg at bedtime often reduces nocturnal rumination and nighttime awakenings.
• Situational or acute anxiety with sleep impairment: a single nightly dose (25–50 mg) can be useful short-term while other therapies take effect.
• Adjunct to an SSRI/SNRI when residual insomnia or sleep-related anxiety persists despite daytime anxiolytic benefit; avoid routine combination without monitoring for serotonin effects.
• Not preferred as first-line monotherapy for classic panic disorder with frequent daytime panic attacks; if panic predominates, escalate to guideline-recommended agents or consult psychiatry rather than relying solely on low-dose trazodone.
• Patient factors favoring trial: intolerance to benzodiazepines, desire to avoid dependence, comorbid insomnia, absence of significant cardiac disease or strong CYP3A4 inhibitors in the regimen.

Titration strategies

• Initial dosing:
  • Adults: 25 mg at bedtime for 3–7 days, then increase to 50 mg nightly if tolerated and symptomatic.
  • Daytime anxiety requiring split dosing: 25 mg morning + 25–50 mg evening; increase evening dose first if sleep is a major issue.
  • Elderly or frail patients: 12.5–25 mg nightly, increase every 7–14 days by 12.5–25 mg.
• Up-titration pace: raise dose in 25–50 mg increments every 3–7 days for adults with good tolerability; slow the interval if orthostatic symptoms or excessive sedation appear.
• Target low-dose range: 50–150 mg/day. If panic symptoms persist and higher dosing is contemplated, involve a psychiatrist–panic disorder often requires antidepressant-range dosing and structured therapy.
• Hepatic impairment: reduce initial dose by ~50% and slow titration; adjust further based on response and adverse effects.
• Stopping: taper over at least 1–2 weeks (longer in older adults) to reduce discontinuation symptoms; reduce by 25–50% of the dose every 3–7 days depending on tolerance.

Medication interactions and safety checkpoints

• Avoid coadministration with MAO inhibitors; allow a 14-day washout interval after MAOI discontinuation before starting trazodone, and vice versa.
• Screen for strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole); these raise trazodone levels–reduce dose or choose an alternative.
• Assess concurrent serotonergic drugs (SSRIs, SNRIs, triptans, MDMA); monitor for serotonergic excess and educate patients about symptoms (agitation, hyperreflexia, rapid changes in mental status).
• Review all QT-prolonging drugs and obtain baseline ECG if cardiac disease, known QT prolongation, or multiple interacting agents are present.

Monitoring schedule and clinical markers

1. Baseline: orthostatic blood pressure and pulse, medication reconciliation, brief cardiac history (arrhythmia, syncope), baseline sodium in patients >65 or on diuretics, and review of suicidal ideation risk.
2. Early follow-up: phone or clinic visit at 3–7 days to check sedation, orthostasis, daytime functioning, and fall risk; adjust dose downward if excessive somnolence or symptomatic hypotension occurs.
3. Four-week visit: assess anxiety severity (GAD-7 or PDSS for panic), sleep quality, adverse effects, sexual function, and adherence; check orthostatic vitals again if dose increased.
4. Monthly for first three months, then every 3 months while on a stable low dose: monitor efficacy, mood changes, signs of hyponatremia (confusion, weakness), and any priapism reports (instruct male patients to seek immediate care for prolonged erections).
5. Laboratory and ECG: repeat sodium and ECG only if clinical signs or new interacting medications emerge; order earlier if impaired hepatic function suspected.

When to stop or refer

• Stop immediately and refer to urology for priapism.
• Discontinue if severe orthostatic hypotension, persistent daytime impairment from sedation despite dose reduction, or serotonin syndrome features; seek urgent care for severe reactions.
• Refer to psychiatry if no meaningful symptom reduction after 4–6 weeks at 150 mg/day, if panic attacks persist or worsen, or if comorbid severe mood disorder or suicidality emerges.

Using Trazodone in Chronic Pain and Fibromyalgia: Sleep‑Mediated Benefits and Combination Strategies

Prescribe trazodone to consolidate nighttime sleep in patients with chronic pain or fibromyalgia; improved sleep frequently produces measurable reductions in pain intensity and fatigue within 1–3 weeks.

Start 25–50 mg at bedtime and increase by 25–50 mg every 3–7 days as needed. Typical sleep doses range from 50–150 mg nightly; avoid exceeding 200 mg for sleep because higher doses raise the risk of orthostatic hypotension and daytime sedation. Use immediate‑release trazodone for sleep onset and maintenance; onset of sedation is usually 30–60 minutes and elimination half‑life is roughly 7–13 hours.

Mechanism relevant to pain: antagonism at 5‑HT2A receptors plus H1 and α1 blockade improves slow‑wave sleep and reduces nocturnal arousals, which mediates secondary analgesia and better daytime function. Expect sleep consolidation before major change in pain scores; document sleep efficiency and pain intensity separately.

Combine with gabapentinoids (pregabalin, gabapentin) to target both sleep and neuropathic features of fibromyalgia, but plan for additive sedation–consider starting the gabapentinoid at a lower initial dose (for example, reduce the first titration step by ~25%) and monitor alertness. Combine with duloxetine or other SNRIs only with close monitoring for serotonin excess (watch for agitation, myoclonus, autonomic instability); avoid rapid cross‑tapering between serotonergic agents. Avoid routine co‑prescription with benzodiazepines, high‑dose opioids, or alcohol; if co‑prescribing is unavoidable, use the lowest effective doses and monitor respiratory status and daytime somnolence.

Screen before starting: check current QT‑prolonging medications and obtain baseline ECG in patients with known cardiac disease or electrolyte abnormalities. Measure orthostatic vitals after the first few doses. Reduce starting dose in older adults and in moderate–severe hepatic impairment. Counsel male patients about priapism (seek emergency care for erections >4 hours) and advise all patients to report troubling daytime sedation or falls.

Follow a practical monitoring plan: use a 1–2 week sleep diary and pain numeric rating scale during the first month; reassess dose if sleep efficiency improves but pain persists. If daytime sedation occurs, lower the dose or consider splitting a low daytime dose plus bedtime dose only with careful supervision. Taper by decreasing dose over 1–2 weeks when discontinuing after prolonged use to reduce rebound insomnia or withdrawal symptoms.

Simple algorithm: optimize sleep hygiene → start trazodone 25–50 mg HS → reassess sleep and pain at 1–2 weeks → increase to 75–150 mg HS if needed → add or adjust gabapentinoid/SNRI only after accounting for interactions and sedation → refer to pain specialist if pain remains refractory despite combined pharmacologic and behavioral strategies.

Trazodone for PTSD‑Related Nightmares and Sleep Disturbance: Dosing, Evidence, and Safety Considerations

For patients with PTSD who have nightmares and fragmented sleep, prescribe trazodone as a bedtime adjunct starting at 25–50 mg and titrate to an effective nocturnal dose, commonly 50–150 mg nightly; if nightmares persist despite an adequate trial, switch or add an agent with stronger evidence for nightmares (for example, prazosin) and prioritize trauma‑focused psychotherapy.

• Dosing and titration (PTSD‑focused):

  • Initial: 25–50 mg orally 30–60 minutes before bedtime.
  • Titrate: increase by 25–50 mg every 3–7 days as tolerated to target 50–150 mg at night for sleep/nightmares.
  • Maximum for nocturnal use: generally 150 mg nightly; higher total daily doses are antidepressant regimens and require split dosing and careful monitoring.
  • Assess response after 2–4 weeks at a stable dose; if partial response, maintain for 6–8 weeks before declaring inadequate.
  • If daytime sedation or orthostatic symptoms occur, reduce dose or shift timing earlier in the evening; consider divided dosing only when treating mood symptoms rather than isolated nocturnal disturbance.

• Evidence summary:

  • Controlled trial data specific to PTSD nightmares are limited; most support comes from open‑label studies, chart reviews, and small trials showing improved sleep continuity and reduced nocturnal awakenings.
  • Mechanism likely combines 5‑HT2A antagonism and antihistaminic/sedative effects that improve sleep maintenance; effects on REM and nightmare frequency are variable between patients.
  • Expect heterogeneous responses: some patients report clear reduction in nightmare frequency and intensity, others improve sleep continuity without marked change in dream content.

• Safety and baseline checks:

  • Assess blood pressure and orthostatic symptoms at baseline and after dose increases; trazodone can cause orthostatic hypotension, especially during titration and in older adults.
  • Screen medication list for interactions:
    • Avoid combined use with MAO inhibitors.
    • Watch for additive serotoninergic effects with SSRIs/SNRIs, triptans, linezolid, and other serotonergic agents; monitor for signs of serotonin syndrome.
    • Expect higher trazodone levels with strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, clarithromycin); reduce dose as needed.
  • Consider baseline ECG if the patient has cardiac disease, uses other QT‑prolonging drugs, or has electrolyte abnormalities; trazodone can prolong QT at high doses or with interacting medications.
  • Warn about rare but serious adverse event priapism; instruct patients to seek urgent care for prolonged erections.
  • Advise about next‑day sedation and impaired driving; recommend trying the first therapeutic dose on a night without obligations and avoiding alcohol or concomitant sedatives.
  • In older adults, use lower starting doses and monitor gait/fall risk closely.
  • Pregnancy/breastfeeding: data are limited; weigh maternal benefit against potential neonatal/infant exposure and consult obstetrics when appropriate.
  • For patients under 25, monitor for new or worsening suicidal ideation per standard antidepressant precautions.

• Monitoring and follow‑up:

  • Reassess sleep quality, nightmare frequency/intensity, daytime functioning, orthostatic symptoms, and adverse effects within 1–2 weeks of dose changes and at 4–8 weeks for treatment response.
  • If insomnia improves but nightmares persist, consider trialing or adding an agent with stronger nightmare data and coordinate with a trauma specialist.
  • Taper over 1–2 weeks when discontinuing a maintenance nocturnal dose to limit rebound insomnia or withdrawal symptoms; for very low short‑term doses a shorter taper may suffice.

• Practical prescribing tips:

  • Start at home on a night without planned driving; take 30–60 minutes before intended sleep.
  • Combine with trauma‑focused psychotherapy and basic sleep measures (consistent sleep schedule, limiting stimulants) to maximize benefit for nightmares and sleep consolidation.
  • Document rationale for off‑label use and obtain informed consent discussing limited PTSD‑specific trial data and known risks.