Trazodone chemical structure
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Desyrel

Trazodone (Desyrel®, Trittico®, Thombran®, Trialodine®) is a psychoactive compound with sedative, anxiolytic, and antidepressant properties. The manufacturer claims that the antidepressant activity becomes evident in the first week of therapy. Trazodone has less prominent anticholinergic (dry mouth, constipation, tachycardia) and adrenolytic (hypotension, male sexual problems) side effects than most tricyclic antidepressants. The incidence of nausea and vomiting observed with Trazodone is relatively low compared to SSRIs. more...

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Mechanism of action

Trazodone is a serotonin reuptake inhibitor and is also a 5-HT2 receptor antagonist. However, in contrast to the selective serotonin reuptake inhibitors such as fluoxetine (Prozac®), trazodone's antidepressant effects may be due to the antagonism of 5-HT2 receptors (PMID 1365657).

Pharmacokinetics

Trazodone is well absorbed after oral administration with mean peak plasma levels obtained at approximately 1 hour after ingestion. Absorption is somewhat delayed and enhanced by food. The mean plasma elimination half-life is biphasic: the first phase's half-life is 3-6 hours, and the following phase's half-life is 5-9 hours. The drug is extensively metabolized with 3 or 4 major metabolites having been identified in man. Approximately 70-75% of C14-labelled trazodone was found to be excreted in the urine within 72 hours (PMID 1037253). Trazodone is highly protein-bound.

Uses

  • Depression with or without anxiety
  • Chronic Insomnia (in some countries, this is an off-label use)

Contraindications

  • Known hypersensitivity to trazodone
  • Use in patients below 18 years of age

Precautions

Trazodone is metabolised by CYP3A4, a liver enzyme (PMID 9616194). Inhibition of this enzyme by various other substances may delay its degradation, leading to high blood levels of trazodone. CYP3A4 may be inhibited by many other medications, herbs, and foods, and as such, trazodone may interact with these substances. One drug-food interaction is grapefruit juice. Drinking grapefruit juice is discouraged in patients taking trazodone.

One glass of grapefruit juice once in a while is not likely to have this effect on most people, but drinking large amounts, or drinking it regularly is proven to.

The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. Therefore, the number of tablets prescribed at any one time should take into account this possibility, and patients with suicide ideation should never have access to large quantities of trazodone.

Episodes of complex partial seizures have been reported in a small number of patients. The majority of these patients were already receiving anticonvulsant therapy for a previously diagnosed seizure disorder.

Pregnancy and Lactation

  • Pregnancy : Sufficient data in humans is lacking. The use should be justified by the severity of the condition to be treated.
  • Lactation : Sufficient data in humans is also lacking. Additionally, trazodone may be found in the maternal milk in significant concentrations. The use in breastfeeding women should be carefully weighed against possible risks.

Read more at Wikipedia.org


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Drugs for major depression not much difference in effectiveness
From Healthfacts, 11/1/05

Ever wonder what makes doctors choose one antidepressant drug over another when they all appear to be about the same? Why, for example, would a doctor prescribe Paxil over Zoloft or Prozac or Celexa? All are in the same family of drugs called "second-generation antidepressants," and they work in a similar way. The FDA is no help because the agency requires only that each drug company prove its drug is better than nothing (a placebo). Unfortunately for the public, the FDA does not require the drug companies to prove their drugs are better than the competing drugs.

If any head-to-head comparison trials are done, they are conducted and published years after the drugs have been on the market. In the meantime, the drug companies have plenty of time and money to convince doctors and the public that their products are superior to the competition. Nine drugs make up the second generation antidepressants. In addition to four mentioned above, other brand names are Lexapro, Luvox, Serzone, Desyrel, and Effexor.

To determine whether any of these antidepressant drugs stand out from the rest for the treatment of major depression, a review of all relevant trials was conducted by Richard A. Hansen, PhD, and colleagues at the University of North Carolina at Chapel Hill. The reviewers found 46 head-to-head comparison trials. They also assessed 24 other types of studies, as well as trials in which an antidepressant was compared with a placebo.

When their findings were published recently in Annals of Internal Medicine, Hansen and colleagues showed there are only minimal differences in efficacy between the second-generation antidepressants for the treatment of major depression. In fact, 88% of the comparative trials found no difference between these antidepressants by any outcome measure. There were, however, differences in adverse effects. Also, the trials varied in quality and the length of time spent following the participants.

Since there are minimal differences in efficacy, the decision as to which drug to take should be based on the one with the fewest adverse effects. But the reviewers acknowledged difficulties in making such a determination because only 13% of the trials reported the adverse reactions properly.

96% of all the antidepressant drug studies in this review were sponsored by or had at least one author affiliated with a pharmaceutical company, according to Hansen and colleagues. The review, however, was funded by several government grants.

Suggestions From Worst Pills, Best Pills:

The popular drug-reference book entitled, Worst Pills, Best Pills, advises people to check the side effects of their current medications before going on antidepressant drug therapy. The authors of this book, subtitled, "A Consumer's Guide to Avoiding Drug-Induced Death or Illness," note that depression can be a side effect of numerous prescription medications, including some antihypertension drugs, antibiotics, acne drugs, corticosteroids, and diet drugs.

In 2004, the FDA issued a public health advisory warning that risk of suicidal thoughts and actions are increased in adults and children with the use of Celexa, Prozac, Serzone, Paxil, Zoloft, and Lexapro. Best Pills, Worst Pills advises readers not to use Lexapro because there is no significant difference between this drug and Celexa, and the latter drug is about to be available in a less expensive generic version, citalopram.

Also, there is inadequate information regarding the use of these second-generation drugs in people over the age of 60 years. Because they are underrepresented in the FDA-required clinical trials, older people's risk of adverse effects is unclear and may not be as low as it appears to be for younger adults.

To reduce the adverse effects of any antidepressant, Worst Pills, Best Pills advises people to start with a dose of one-third to one-half the usual adult dose (15-25 milligrams a day at bedtime) and increase the dose slowly, knowing that it may take three weeks for the drug to take effect.

COPYRIGHT 2005 Center for Medical Consumers, Inc.
COPYRIGHT 2005 Gale Group

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