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Trazodone (Desyrel) Brief Information

Active ingredient: trazodone hydrochloride
Brand names: Desyrel, Sideril, Trazalon; Trazonil
Drug class: Antidepressant, Phenylpiperazine derivative
Pregnancy Category: C
Dosages: 50 mg, 100 mg, 150 mg, 300 mg tablets
FDA approved: 1982
Habit forming? No
Avalable as generic? Yes
Trazodone medical info

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Detailed Information

Trazodone (brand names: Desyrel, Trazon, Trialodine) is a psychoactive compound with sedative, anxiolytic and antidepressant properties. Trazodone is used to relieve symptoms of depression such as feelings of sadness, worthlessness, or guilt; loss of interest in daily activities; changes in appetite; tiredness; insomnia. It decreases the insomnia caused by selective serotonin reuptake inhibitors and is a good choice for depressed patients with difficulty sleeping.

Trazodone is chemically unrelated to the serotonin reuptake inhibitors (SSRIs), the tricyclic antidepressants (TCAs) or the monoamine oxidase inhibitors (MAO inhibitors). It is chemically related to nefazodone and shares its actions. The drug possesses antidepressant, and also some anxiolytic and hypnotic activity.

Trazodone is a relatively safe, non-habit-forming medication that is technically considered to be an antidepressant, but is actually used more often simply to help the individual get a good night?s sleep. It is also a good short-term alternative treatment for anxiety or when a mild sedative is needed.

Trazodone is best taken with food, so take it after dinner, or dessert, to ensure a quality night's rest.

Off-label Uses

insomnia (3, 5, 6)
panic/anxiety (2)
obsessive-compulsive disorder (7)
depressive phase of bipolar (manic-depressive) disorder.
attention-deficit/hyperactivity disorder
opiate withdrawal (11)
pain syndromes (8, 9)
essential tremor
chronic fatigue
irritable bowel syndrome (IBS)
bulimia nervosa (4)
enuresis (bed-wetting)
aggression

Advantages:

good choice for insomnia combined with mild depression or anxiety
not addictive or habit forming
the most sedating and least anticholinergic of all the currently marketed antidepressants
very well tolerated in geriatric patients
has an advantage over traditional hypnotics in that it does not depress respiration, an attribute that could be relevant in persons with sleep apnea
in cases of overdose, trazodone alone has not caused a single death
no restrictions on long-term prescription
good safety and efficacy for patients with chronic depression when used up to 5 1/2 years
low cost

Disadvantages:

some evidence of tolerance (after 1-2 weeks) especially for primary insomnia
risk of priapism and drug-induced penile erections (incidence 1:6000, usually in the first 4 weeks)
risk of orthostatic hypotension
risk of drug interactions due to cytochrome metabolism

Trazodone for insomnia:
Trazodone is commonly used in the treatment of insomnia at doses of 25 mg to 150 mg. This medication may be especially useful in persons with associated anxiety, depression, or psychosis. Trazodone can significantly improve insomnia, with little tolerance developing to its hypnotic effect. Its actions on sleep have been hypothesized to be mediated through 5-HT2 serotonergic receptor antagonism or through alpha-adrenergic antagonism. Polysomnographic studies of patients with various kinds of insomnia have found that trazodone's main effect on sleep architecture is an increase in slow-wave (stages 3 and 4) sleep. Trazodone improves sleep not only in major depressive disorder and dysthymic disorder but also in chronic primary insomnia and in insomnia associated with other antidepressant medications such as SSRIs and monoamine oxidase inhibitors (MAOIs).

Trazodone is an effective hypnotic for persons with antidepressant-associated insomnia. (Trazodone for antidepressant-associated insomnia)
Trazodone is effective for the treatment of insomnia and nightmares associated with chronic PTSD. (Survey on the usefulness of trazodone)

How long does it take to work:
The therapeutic effects of trazodone, like other antidepressants, appear slowly. It is considered it may take up to 4 weeks for Trazodone before you begin to feel better.
However, unlike most reuptake inhibitors, Trazodone works for 75% of people within 2 weeks. If it is going to work at all, that is.

Average time to clear out of your system:
It takes about 3 days for Trazodone to clear out of your system.
Approximately 60 to 70% of C14-labelled trazodone was found to be excreted in the urine within 2 days and 9 to 29% in feces over 60 to 100 hours.

Dosage
The dose of trazodone will be different for each patient. Treatment should be started with low initial doses of 75 to 150 mg daily in divided doses or in an evening single dose. The dose may be increased slowly to a maximum of 300 mg daily in ambulatory patients and to 600 mg daily in hospitalized patients. Geriatric and emaciated patients should begin with 100 mg daily, but may be slowly increased to 300 mg. This medication is usually taken with a meal or light snack two or more times a day.

Trazodone versus Other Antidepressants

Comparison with Imipramine
A 6-week double blind non-crossover study have shown that trazodone may have an earlier anxiolytic effect than imipramine and a greater antidepressant effect. With respect to side effects Imipramine has significantly greater frequency of impaired visual accommodation. (Comparison of the efficacy and safety of trazodone and imipramine in endogenous depression)

Comparison with Amitriptyline
A double-blind study was conducted to determine the efficacy and safety of trazodone vs. amitriptyline and placebo for neurotic depression. Trazodone was found to be significantly better than placebo on almost every rating scale. Trazodone was superior to amitriptyline in some patients while amitriptyline was only occasionally better than placebo. Significant improvement was noted in trazodone patients within the first seven days of therapy. Trazodone produced a low level of side effects compared to amitriptyline. (A double-blind study)

Comparison with Bupropion (Wellbutrin)
In a two-center, double-blind clinical trial of outpatients with moderate to severe major depression the overall efficacy for each of the two drugs was similar. Improvement in the trazodone treatment group was significantly greater on day 7 because of the effects on sleep. At the end of treatment, 58% of the bupropion-treated patients and 46% of the trazodone-treated patients were considered much or very much improved. Anorexia and anxiety were reported significantly more often with bupropion, whereas somnolence, appetite increase, and edema were reported significantly more often with trazodone. (Comparison of bupropion and trazodone)

Comparison with Zolpidem (Ambien)
In placebo controlled trilal subjective sleep latency and duration showed significant improvement with both trazodone and zolpidem vs. placebo. However, effect was greater with zolpidem.

Comparison with Fluoxetine (Prozac)
The efficacy and safety of fluoxetine and of trazodone were compared in a trial in outpatients with major depressive episode. With regard to efficacy both medications were similarly effective.
More fluoxetine-treated patients reported rhinitis and tremor, while more trazodone-treated patients reported somnolence and dizziness. More combined events suggesting activation (agitation, anxiety, nervousness, insomnia) were reported with fluoxetine than with trazodone, while more combined events suggesting sedation (somnolence, asthenia) were reported with trazodone than with fluoxetine. (Fluoxetine versus trazodone)

Fluoxetine has a slower onset of antidepressant action than does trazodone. (A comparative trial of fluoxetine versus trazodone)

Comparison with Gabapentin (Neurontin)
Alcohol-dependent outpatients with persisting insomnia were treated with either gabapentin or trazodone. Both medications were significantly effective on the Sleep Problems Questionnaire. But patients treated with gabapentin improved significantly more than the patients treated with trazodone (1).

Comparison with Venlafaxine (Effexor)
A double-blind, placebo-controlled trial compared the safety and efficacy of venlafaxine and trazodone for major depression. Venlafaxine produced more improvement in the cognitive disturbance and retardation factors on the Hamilton Rating Scale for Depression. Trazodone was more effective against the sleep disturbance factor. Patients on venlafaxine were most likely to enter the long-term phase and to remain in the trial longest. Venlafaxine was most likely to cause nausea, whereas trazodone was associated with the most dizziness and somnolence (10).

Comparison with Mirtazapine (Remeron)
In a double-blind controlled study in hospitalized patients with major depression mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability. (Mirtazapine is more effective than trazodone)

References

1. Karam-Hage M, Brower KJ. Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients. Psychiatry Clin Neurosci. 2003 Oct;57(5):542-4. 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. 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
4. Pope HG Jr, Keck PE Jr, McElroy SL, Hudson JI. A placebo-controlled study of trazodone in bulimia nervosa. J Clin Psychopharmacol. 1989 Aug;9(4):254-9. PubMed
5. Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Gruber G, Mandl M, Strobl R, Gollner D, Prause W, Saletu B. Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):249-60. PubMed
6. Scharf MB, Sachais BA. Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. J Clin Psychiatry. 1990 Sep;51 Suppl:13-7. PubMed
7. Prasad A. Efficacy of trazodone as an anti obsessional agent. Pharmacol Biochem Behav. 1985 Feb;22(2):347-8. PubMed
8. Schreiber S, Backer MM, Herman I, Shamir D, Boniel T, Pick CG. The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms. Behav Brain Res. 2000 Sep;114(1-2):51-6. PubMed
9. Ventafridda V, Caraceni A, Saita L, Bonezzi C, De Conno F, Guarise G, Ramella G, Silvani V, Tamburini M, Toscani F. Trazodone for deafferentation pain. Comparison with amitriptyline. Psychopharmacology (Berl). 1988;95 Suppl:S44-9. PubMed
10. Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, Fischer DE, Hearst E. A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994 Apr;14(2):99-106. PubMed
11. Pozzi G, Conte G, De Risio S. Combined use of trazodone-naltrexone versus clonidine-naltrexone in rapid withdrawal from methadone treatment. A comparative inpatient study. Drug Alcohol Depend. 2000 Jun 1;59(3):287-94. PubMed

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