Trazodone (Desyrel®) as Sleep Aid

Trazodone: "off-label" sleeping pill

Trazodone hcl is a sedating antidepressant with significant anxiolytic and sedative activity. In practice it is widely used off-label to treat insomnia. Currently, trazodone is the second most commonly prescribed treatment for insomnia5 because of its effectiveness, proven sedative properties, perceived lack of hazards and serious problems, generic availability, and lack of restrictions for long-term use.

Trazodone is particularly effective for insomnia exacerbated by other antidepressants1. The drug reduces anxiety and insomnia during withdrawal from alcohol14. Also, trazodone is effective for sleep disorders in the elderly with dementia18.

Trazodone is often used as a hypnotic for sleep difficulties even in non-depressed insomniacs. Polysomnographic studies of people with various kinds of insomnia have found that trazodone's main effect on sleep architecture is an increase in deep slow-wave (stages 3 and 4) sleep11,12, which is important for restorative rest. This medication also increases total sleep time and decreases number of awakenings 15.

Comparative efficacy

Trazodone versus Zolpidem (Ambien®)

Only one high quality comparative study with trazodone has been performed.

The clinical trial compared trazodone versus zolpidem (Ambien), a short-acting nonbenzodiazepine hypnotic, in the treatment of primary insomnia in nondepressed patients13. During the first week, both trazodone and zolpidem were similar in improving sleep latency, total sleep time and sleep quality, and decreasing wakefulness after sleep onset. However, at week 2 zolpidem shortened time to fall asleep greater than trazodone.

Trazodone versus Quetiapine (Seroquel®)

The observational study compared and contrasted the efficacy of trazodone and quetiapine (Seroquel), an atypical antipsychotic, for insomnia in persons with with mental illness16. Trazodone was a more effective and less-costly than quetiapine as an alternative sleeping pill. Trazodone prolonged sleep time and decreased the number of nighttime awakenings better than quetiapine.

Trazodone is a better option for persons with depressive disorder. As quetiapine has mood-stabilizing properties, it may be preferable choice for bipolar disorder.

Trazodone dosage for insomnia

When used as hypnotic, the usual starting dose is 25-50 mg of Trazodone at bedtime. If needed, the dose can be increased up to 100 mg. But it is rarely necessary to increase the maximum dose. The sleep promoting effect starts within 1-2 hours and usually lasts about 8 hours.

Important notes:

Take trazodone with food. The absorption of the drug may be up to 20% higher when it is taken with food rather than on an empty stomach.

Trazodone may cause feelings of tiredness and grogginess ("hangover") on the next morning. However its advantage is that unlike most sleeping pills, it is not addictive and not habit forming.

Benefits

Effective sleeping pill. Trazodone has beneficial effects on sleep quality and daytime functioning independently from prior use of sleep medications 17.
Beneficial effects on sleep continuity and duration in primary and secondary insomnia1, 3. Whereas trazodone is not FDA-approved to treat insomnia, several clinical studies and practical experience support its efficacy and safety. This medicine may be of advantage in depressed people with sleep difficulties and for treating insomnia caused by other drugs.
Non-controlled substance.
Has a long safety record, and is relatively safe in overdose.
Low risk of anticholinergic effects, such as dry mouth, blurred vision, bowel movement disturbance, and delayed urine flow9.
Low cost - trazodone is one of the most inexpensive antidepressants. It is considerably cheaper than modern hypnotics like Ambien, Sonata, Lunesta, or Rozerem.
Can be safely used in combination with SSRIs8. It is chemically and pharmacologically distinct from SSRIs.
Trazodone hydrochloride, a triazolopyridine derivative, is the most sedating, and least anticholinergic, of all the currently available antidepressants.

Drawbacks

Not FDA approved specifically for insomnia and the scientific evidence is relatively mixed regarding efficacy of trazodone as a hypnotic. Trazodone has been available as a cheap generic for many years, and there is very little chance that any pharmaceutical company will pay money for studies to gain official FDA approval for an old "off-label" prescription.
Next-day sedation and drowsiness.
Potential for drug interactions with inducers and/or inhibitors of CYP3A47.
Risk of drug-induced priapism due to alpha-adrenergic antagonist properties10.

Pharmacological characteristics

Elimination half-life: 3-6 hours
Metabolism: Hepatic via CYP3A4 to an active metabolite (mCPP)
Excretion: Primarily urine (80%); secondarily feces (20%)

Mechanism of action

Trazodone is a serotonin reuptake inhibitor and is also a 5-HT2 receptor antagonist. However, in contrast to the SSRIs, trazodone's antidepressant effects may be due to its antagonistic action at the 5-HT2 receptor site. It causes adrenoreceptor subsensitivity, and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. This agent also blocks histamine (H1) and alpha1-adrenergic receptors.

Trazodone's hypnotic properties are due to its antihistaminergic effects at the histamine-1 receptor, alpha 1-adrenergic receptor antagonism, and serotonin 5-HT2 receptor antagonism.

Trazodone alternatives

Antidepressants with sedative properties, which can substitute for trazodone include:

Amitriptyline (Elavil)
Mirtazapine (Remeron)
Trimipramine (Surmontil, Rhotrimine, Stangyl) is very popular in Germany
Doxepin (Sinequan, Silenor)

References

1. Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994 Jul;151(7):1069-72. PubMed
2. Mavissakalian M, Perel J, Bowler K, Dealy R. Trazodone in the treatment of panic disorder and agoraphobia with panic attacks. Am J Psychiatry. 1987 Jun;144(6):785-7. PubMed
3. Bossini L, Coluccia A, Casolaro I, Benbow J, Amodeo G, De Giorgi R, Fagiolini A. Off-Label Trazodone Prescription: Evidence, Benefits and Risks. Curr Pharm Des. 2015;21(23):3343-51.
4. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. 1994 Apr;4(4):331-55. PubMed
5. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry. 2005 Apr;66(4):469-76. PubMed
6. Dossier Trazodone. 15/03/2007: Angelini.it
7. Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metabolism Disposition 1998 Jun;26(6):572-5.
8. Prapotnik M, Waschgler R, Konig P, Moll W, Conca A. Are there pharmacokinetic interactions involving trazodone and SSRIs? Int J Clin Pharmacol Ther. 2004 Feb;42(2):120-4.
9. Gershon S, Newton R. Lack of anticholinergic side effects with trazodone. J Clin Psychiatry. 1980 Mar.
10. Abber JC, Lue TF, Luo JA, Juenemann KP, Tanagho EA. Priapism induced by chlorpromazine and trazodone: mechanism of action. J Urol. 1987 May;137(5):1039-42.
11. Parrino L, et al. Trazodone in chronic insomnia associated with dysthymia: polysomnographic variables and sleep quality. Psychopharmacology 1994;116:389-395.
12. Montgomery I, et al. Trazodone enhances sleep in subjective quality but not in objective duration. Br J Clin Pharmacol 1983;16:139-144. PubMedCentral
13. Walsh JK, Milton E, Erwin CW, et al. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII-R primary insomnia. Hum Psychopharm Clin. 1998;13:191–198.
14. Arnedt JT, Conroy DA, Brower KJ. Treatment options for sleep disturbances during alcohol recovery. J Addict Dis. 2007;26(4):41-54. PubMed
15. Kaynak H, Kaynak D, Gözükirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004 Jan;5(1):15-20. PubMed
16. Doroudgar S, Chou TI, Yu J, Trinh K, Pal J, Perry PJ. Evaluation of trazodone and quetiapine for insomnia: an observational study in psychiatric inpatients. Prim Care Companion CNS Disord. 2013;15(6). PubMed
17. Wichniak A, Wierzbicka A, Sobańska A, Szatkowska E, Czasak K, Musińska I, Jernajczyk W. The effectiveness of treatment with trazodone in patients with primary insomnia without and with prior history of hypnotics use. Pol Merkur Lekarski. 2007 Jul;23(133):41-6. PubMed
18. Camargos EF1, Pandolfi MB, Freitas MP, et al. Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study. Arq Neuropsiquiatr. 2011 Feb;69(1):44-9. PubMed

By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018

Trazodone HCl (Desyrel®) for Insomnia