mCPP levels are only 10% of those of trazodone during therapy with trazodone, but is nonetheless present at concentrations known to produce psychic and physical effects in humans when mCPP has been administered alone. In any case, the actions of trazodone, such as its serotonin antagonism, might partially overwhelm those of mCPP. As a consequence of the production of mCPP as a metabolite, patients administered trazodone may test positive on EMIT II urine tests for the presence of MDMA ("ecstasy"). Elimination
The elimination of trazodone is biphasic: the first phases half-life (distribution) is 3 to 6 hours, and the following phases half-life (elimination) is 4.1 to 14.6 hours. The elimination half-life of extended-release trazodone is 9.1 to 13.2 hours. The elimination half-life of mCPP is 2.6 to 16.0 hours and is longer than that of trazodone. Metabolites are conjugated to gluconic acid or glutathione and around 70 to 75% of 14C-labelled trazodone was found to be excreted in the urine within 72 hours. The remaining drug and its metabolites are excreted in the faeces via biliary elimination. Less than 1% of the drug is excreted in its unchanged form. After an oral dose of trazodone, it was found to be excreted 20% in the urine as TPA and conjugates, 9% as the dihydrodiol metabolite, and less than 1% as unconjugated mCPP. mCPP is glucuronidated and sulfated similarly to other trazodone metabolites. Chemistry
Trazodone is a triazolopyridine derivative and a phenylpiperazine that is structurally related to nefazodone and etoperidone, each of which are derivatives of it.
Trazodone was the second-most prescribed agent for insomnia in the early 2000s, though most studies of trazodone for treatment of sleep disturbances have been in depressed individuals.Systematic reviews and meta-analyses published in the late 2010s, including a Cochrane review, found low-dose trazodone to be an effective medication for short-term treatment of insomnia both in depressed and non-depressed people. Trazodone slightly improves subjective sleep quality (SMD = –0.34 to –0.41) and reduces number of nighttime awakenings (MD = –0.31, SMD = –0.51). Conversely, it does not appear to affect sleep onset, total sleep time, time awake after sleep onset, or sleep efficiency. It appears to increase deep sleep, in contrast to certain other hypnotics. The quality of evidence of trazodone for short-term treatment of insomnia was rated as low to moderate. There is no evidence available at present to inform long-term use of trazodone in the treatment of insomnia.The benefits of trazodone for insomnia must be weighed against potential adverse effects such as morning grogginess, daytime sleepiness, cognitive and motor impairment, and postural hypotension, among others. Quality safety data on use of trazodone as a sleep aid are currently lacking.Trazodone is used at low doses in the range of 25 to 150 mg/day for insomnia. Higher doses of 200 to 600 mg/day have also been studied.The American Academy of Sleep Medicines 2017 clinical practice guidelines recommended against the use of trazodone in the treatment of insomnia due to inadequate evidence and due to harms potentially outweighing benefits.