Trazodone
Is It Right for You?
A complete guide to Trazodone — what it treats, how it works, dosages, side effects, and when a clinician may prescribe it following an online consultation.
What Is Trazodone?
Trazodone is an orally administered antidepressant belonging to the serotonin antagonist and reuptake inhibitor (SARI) class. It has a unique and complex pharmacological profile that distinguishes it from other antidepressant classes, combining moderate inhibition of the serotonin transporter (SERT) with potent antagonism at serotonin (5-HT2A, 5-HT2C), histamine (H1), and alpha-1 adrenergic receptors. This multi-receptor activity produces both antidepressant and anxiolytic effects alongside significant sedation, which accounts for its widespread off-label use as a hypnotic agent for insomnia.
Trazodone was first synthesised in Italy in the 1960s and introduced into clinical practice in the 1970s. It pre-dates the selective serotonin reuptake inhibitors (SSRIs) and was widely used as an antidepressant throughout the 1980s. With the advent of SSRIs, trazodone's use as a primary antidepressant declined in most countries due to its more complex side effect profile. However, it retained significant clinical utility as a sleep aid and is now experiencing renewed interest, particularly as a non-benzodiazepine, non-Z-drug option for insomnia in the context of restrictions on hypnotic prescribing.
Trazodone is available generically and under the brand name Molipaxin. It is supplied in multiple formulations: 50 mg capsules, 100 mg capsules, 150 mg modified-release tablets (Molipaxin CR), and an oral liquid (50 mg/5 ml). A modified-release tablet formulation (Trittico) is available in some markets.
What Conditions Does Trazodone Treat?
Trazodone is prescribed for:
Trazodone is licensed for the treatment of depressive illness, including depression accompanied by anxiety. It is suitable for major depressive disorder (MDD) and may be particularly appropriate in patients where sedation is a desired property — for example, those with agitated depression, depression with significant sleep disruption or insomnia, or depression accompanied by anxiety. It is also used in elderly patients, in whom it is considered better tolerated than tricyclic antidepressants (TCAs).
Antidepressant effect at therapeutic doses requires the full treatment course, as with all antidepressants. Clinical response typically develops over 2 to 4 weeks, and the full benefit may not be apparent for 6 to 8 weeks.
Due to its 5-HT2A and 5-HT2C antagonism and H1 antihistamine properties, trazodone produces meaningful anxiolytic and sedating effects. It is commonly used for generalised anxiety disorder (GAD), particularly when anxiety co-exists with depression or insomnia, and as an adjunct in other anxiety presentations. Unlike benzodiazepines, trazodone does not carry a risk of physical dependence or the rebound anxiety associated with hypnotic discontinuation, making it an attractive option for longer-term anxiety management.
At low doses (25–100 mg), trazodone is one of the most widely prescribed treatments for insomnia in the UK and globally. Its sedative properties at these sub-antidepressant doses are primarily mediated by H1 antagonism and alpha-1 adrenoceptor blockade. Unlike benzodiazepines and Z-drugs (zopiclone, zolpidem), trazodone is not a controlled substance, does not typically impair sleep architecture in the same way (it may actually increase slow-wave sleep), and does not produce the same degree of tolerance, physical dependence, or rebound insomnia. It is therefore used as both short-term and longer-term insomnia management, and is particularly useful for sleep disturbance in the context of depression or anxiety.
Trazodone is used in older adults with dementia-related agitation and disturbed sleep-wake cycles, where it is preferred over antipsychotics and benzodiazepines due to its more favourable safety profile in this population.
Trazodone is used adjunctively in PTSD, particularly for nightmare reduction and sleep disruption. Its 5-HT2A antagonism may help attenuate traumatic nightmares, which are partly mediated by serotonergic dysregulation during REM sleep.
While Trazodone is effective for managing depression and anxiety, it should be used with caution in patients with a history of cardiovascular issues or those taking other medications that may interact.
How Does Trazodone Work?
Trazodone's therapeutic effects arise from its simultaneous action on multiple receptor systems:
Serotonin reuptake inhibition (SERT blockade): At higher therapeutic doses, trazodone inhibits the serotonin transporter, increasing synaptic serotonin concentrations. This contributes to its antidepressant effect, though SERT inhibition is less potent than that seen with SSRIs.
5-HT2A and 5-HT2C receptor antagonism: Trazodone potently blocks postsynaptic serotonin 5-HT2A and 5-HT2C receptors. 5-HT2A antagonism enhances slow-wave (deep) sleep, contributes to anxiolytic effects, and may potentiate antidepressant activity by increasing dopaminergic and noradrenergic neurotransmission in the prefrontal cortex. 5-HT2C antagonism disinhibits dopamine release in the nucleus accumbens and may contribute to the antidepressant effect.
H1 (histamine) receptor antagonism: Potent H1 blockade produces the pronounced sedation that makes trazodone useful for insomnia. This is dose-dependent — more prominent at lower doses relative to SERT inhibition.
Alpha-1 adrenergic receptor antagonism: Contributes to sedation and, at higher doses, to orthostatic hypotension (a fall in blood pressure on standing), which is one of trazodone's most clinically significant side effects.
The net result is a medication that produces antidepressant activity broadly comparable to SSRIs at therapeutic doses, alongside anxiolytic and sleep-promoting properties that are not shared to the same degree by standard SSRIs.
Dosages & Administration
The correct dose depends on the type and severity of infection, age, weight, and kidney function. Always follow your clinician's instructions. The table below is for general reference only.
Administration Tips
Trazodone should be taken shortly after food, as this improves absorption and reduces the risk of dizziness associated with its alpha-1 blocking effects. For once-daily dosing (typically used at antidepressant doses), the dose is usually taken at bedtime to take advantage of the sedative effect. If divided doses are used, the larger portion should be taken at night.
Modified-release formulations (Molipaxin CR 150 mg) are taken as a single dose at bedtime and may offer improved tolerability compared with standard-release formulations.
Trazodone should not be stopped abruptly after prolonged use at antidepressant doses. While trazodone's discontinuation syndrome is generally milder than that of SSRIs and SNRIs, gradual tapering over weeks to months is advisable to minimise the risk of discontinuation effects including rebound anxiety, insomnia, dizziness, and irritability.
Side Effects of Trazodone
Trazodone is generally well tolerated, but some side effects may occur.
- Drowsiness or sedation
- Dizziness or lightheadedness
- Dry mouth
- Headache
- Nausea
- Blurred vision
- Priapism — prolonged, painful erection (medical emergency)
- Severe allergic reaction — swelling of face, lips, or throat, difficulty breathing
- Serotonin syndrome — agitation, sweating, rapid heart rate, muscle stiffness
- Heart rhythm disturbances — irregular heartbeat or fainting
- Suicidal thoughts — especially in younger patients at the start of treatment
Patients should be informed about the risk of sedation and the potential for falls, especially when starting treatment or increasing the dose.
Drug Interactions
Inform your clinician about all medications you are taking, as some drugs can interact with Trazodone and affect its efficacy.
Important Warnings
Male patients must be informed of the risk of priapism before starting trazodone. A prolonged, painful erection unrelated to sexual arousal lasting more than 2 hours is a medical emergency requiring immediate attendance at A&E. Delayed treatment can result in permanent erectile dysfunction. Patients should stop trazodone and seek emergency care immediately if this occurs.
Trazodone causes orthostatic hypotension, particularly at initiation and dose increases. Patients should be advised to rise slowly from sitting or lying, especially during the night if getting up to use the bathroom. Falls risk must be carefully assessed in elderly patients.
Never use trazodone within 14 days of stopping an MAOI, and do not start an MAOI within 14 days of stopping trazodone. This combination carries a risk of severe, potentially fatal serotonin syndrome.
Trazodone substantially enhances the sedative effects of alcohol. Patients must be advised to avoid alcohol, particularly during dose titration.
As with all antidepressants, trazodone carries a class warning regarding increased risk of suicidal thinking, particularly in children, adolescents, and young adults during the initial weeks of treatment. Patients and carers should be advised to monitor for worsening mood, agitation, or suicidal thoughts and to seek urgent medical attention if these occur. Trazodone is not licensed for use in children or adolescents.
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Trazodone FAQs
Trazodone is primarily licensed as an antidepressant, but its sedative properties at low doses have led to it being widely prescribed for insomnia — both as a stand-alone hypnotic and as part of depression treatment where sleep disturbance is prominent. At antidepressant doses (150–300 mg), it treats depression and anxiety as well as improving sleep. At lower doses (25–100 mg), it is used predominantly as a sleep aid. Both uses are clinically well-established, though insomnia is technically an off-label indication.
Trazodone's antidepressant efficacy is broadly comparable to SSRIs in clinical trials. Its main clinical advantages over SSRIs are its sleep-promoting properties (which makes it particularly useful when insomnia is prominent), its lack of sexual side effects (SSRIs commonly cause reduced libido and anorgasmia), and its different receptor profile which some patients tolerate better. Its main disadvantages are greater sedation, orthostatic hypotension, the rare risk of priapism in men, and a more complex drug interaction profile compared with most SSRIs.
Trazodone does not produce the tolerance, craving, or withdrawal syndrome characteristic of dependence in the way benzodiazepines or Z-drugs do. It is not a controlled substance. However, after prolonged use at antidepressant doses, abrupt discontinuation can cause discontinuation symptoms similar in nature to (though generally milder than) those seen with SSRIs and SNRIs. Gradual tapering when stopping is advised. For insomnia use at low doses, dependence is not a recognised clinical concern.
Alcohol should be avoided or kept to a strict minimum during trazodone treatment. The combination significantly increases sedation and CNS depression, impairs coordination and judgement, and increases the risk of falls, particularly in older patients. Alcohol also worsens depression and anxiety, undermining the benefits of treatment.
Drowsiness is one of the most common side effects, particularly at the start of treatment and after dose increases. Ensuring the dose is taken at bedtime (rather than in the morning or midday) is the most effective practical strategy. Sedation often diminishes after the first 2 to 4 weeks as the body adjusts. If drowsiness remains problematic, discuss dose timing, formulation (a modified-release preparation may be better tolerated), or dose adjustment with your clinician. Do not drive or operate machinery if you feel sedated.
As with all antidepressants, the sleep-improving and anxiolytic effects of trazodone tend to appear within the first 1 to 2 weeks. Antidepressant effects on mood, motivation, and cognitive function typically develop more gradually over 2 to 6 weeks, with full benefit often not apparent until 6 to 8 weeks. It is important not to discontinue trazodone prematurely if full antidepressant benefit has not yet been achieved.
Trazodone is one of the more commonly used antidepressants in older adults because it lacks the cardiac toxicity of tricyclics and the sexual side effects of SSRIs, and it may help with co-existing insomnia. However, its tendency to cause orthostatic hypotension and sedation creates a meaningful falls risk in this population. It should be started at a low dose (e.g. 50–100 mg) and titrated slowly, with careful attention to blood pressure and falls risk. Regular medication review is important.