Desyrel
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Desyrel
TrazodoneSystematic (IUPAC) name8-propyl]-6,8,9-triazabicyclonona-2,4,9-trien-7-oneIdentifiersCAS number19794-93-5ATC codeN06AX05PubChem5533DrugBankAPRD00533ChemSpider5332Chemical dataFormulaC19H22ClN5O Mol. mass371.864 g/molPharmacokinetic dataBioavailabilityHighMetabolismHepaticHalf life3-6 hoursExcretion20% feces,80% urineTherapeutic considerationsPregnancy cat.C(US)Legal statusUnscheduled;Rx onlyRoutesOralTrazodone (trade names Desyrel, Molipaxin, Trittico, Thombran, Trialodine, Trazorel) is a psychoactive compound with sedative, anxiolytic, and antidepressant properties. The various manufacturers claim that the antidepressant becomes active 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.Trazodone is chemically and pharmacologically distinct from tricyclic antidepressants and tetracyclic antidepressants (for a review, see PMID: 8019056). Lacking the fused ring structures typical of these compounds, trazodone is a triazolopyridine derivative.// HistoryTrazodone was originally discovered and developed in Italy in the 1960s by Angelini research laboratories as a second-generation antidepressant. This agent was developed according to the mental pain hypothesis, which was postulated from studying patients and which proposes that major depression is associated with a decreased pain threshold. Trazodone was patented and marketed in many countries all over the world. It was approved by the FDA at the end of 1981. It is closely related to Nefazodone. Mechanism of actionTrazodone is not a serotonin reuptake inhibitor; in contrast to the selective serotonin reuptake inhibitors such as fluoxetine (trade name Prozac), trazodone's antidepressant effects may be due to its antagonistic effects at 5-HT2 receptors (PMID 1365657). PharmacokineticsTrazodone is well absorbed after oral administration with mean peak blood levels obtained at approximately 1 hour after ingestion. Absorption is somewhat delayed and enhanced by food. The mean blood 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, some of which such as mCPP may contribute to the side effect profile of trazodone. 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. UsesClinical depression with or without anxietyChronic insomnia (in some countries, this is an off-label use)Fibromyalgia, to control sleeping.Control of nightmares or other disturbed sleepA sleep aid (with a reduced risk of dependency) Other off-label and investigational usesinsomniapanic disorderdiabetic neuropathybulimia nervosaobsessive-compulsive disorderalcohol withdrawalschizophrenia As an SSRI aidTrazodone is often used in conjunction with selective serotonin reuptake inhibitor, like fluoxetine and has been noted to help with the anxiety that can result from beginning treatment with an SSRI anti-depressant. Trazodone has been prescribed to children as an aid to an SSRI. WarningsIf the patient has a known hypersensitivity to trazodone.If the patient is under 18 years of age. (Trazodone use in youth may increase the possibility of suicidal thoughts or actions.) PrecautionsTrazodone 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 occasionally is not likely to have this effect on most people, but drinking large amounts, or drinking it regularly is proven to affect trazodone's clearance.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 suicidal 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.While trazodone is not a true member of the SSRI class of antidepressants, it does still share many properties of the SSRIs, especially the possibility of discontinuation syndrome if the medication is stopped too quickly. Care must therefore be taken when coming off the medication, usually by a gradual process of tapering down the dose over a period of time.A person who abruptly stops taking Trazodone, even in doses as low as 25mg (common for use as a sleep aid for people with anxiety disorders), may experience adverse mental reactions such as emotional instability, depressed mood, and suicidal thoughts. Although such warnings may be included in printed materials supplied with the drug, physicians prescribing Trazodone, particularly those who are not psychiatrists, might not give oral warnings. Pregnancy and lactationPregnancy : 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. Women should not breastfeed while taking Trazodone. Side effectsThe most common adverse reactions encountered are drowsiness, nausea/vomiting, headache and dry mouth. Adverse reactions reported include the following: BehavioralDrowsiness, fatigue, lethargy, psychomotor retardation, lightheadedness, dizziness, difficulty in concentration, confusion, uncontrollable laughter, sex drive increase. (Trazodone is also known to cause a "hangover effect" in patients prescribed the drug as a sleep aid: the "Trazodone hangover" generally ceases with regular use after three or four days.) NeurologicalTremor, headache, ataxia, migraine, akathisia, muscle stiffness, slurred speech, slowed speech, vertigo, tinnitus, tingling of extremities, paresthesia, weakness, complex partial seizures, and rarely, impaired speech, muscle twitching, numbness, dystonia, euphoria, and involuntary movements. AutonomicDry or numb mouth, blurred vision, priapism, diplopia, miosis, nasal congestion, constipation, sweating, urinary retention, increased urinary frequency and incontinence. Cardiovascularhypotension, tachycardia, palpitations, shortness of breath, apnea, syncope, arrhythmias, prolonged P-R interval, atrial fibrillation, bradycardia, ventricular ectopic activity (including ventricular tachycardia), myocardial infarction and cardiac arrest. Rare side effectsRecent clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population. Arrhythmias identified include isolated PVC's, ventricular couplets, and in 2 patients short episodes (3 to 4 beats) of ventricular tachycardia. There have also been several post-marketing reports of arrhythmias in trazodone-treated patients who have pre-existing cardiac disease and in some patients who did not have pre-existing cardiac disease. Until the results of prospective studies are available, patients with pre-existing cardiac disease should be closely monitored, particularly for cardiac arrhythmias. Trazodone is not recommended for use during the initial recovery phase of myocardial infarction. PriapismTrazodone has been associated with the occurrence of priapism. In approximately 33% of the cases reported, surgical intervention was required and, in a portion of these cases, permanent impairment of erectile function or impotence resulted.Priapism is a potentially harmful medical condition in which the erect penis does not return to its flaccid state (despite the absence of both physical and psychological stimulation) within about four hours. It is often painful. Male patients with prolonged or inappropriate erections should immediately discontinue the drug and consult their physician. If the condition persists for more than 24 hours, it would be advisable for the treating physician to consult a urologist or appropriate specialist in order to decide on a management approach.In women, a similar condition of persistent arousal can be caused and is called Persistent genital arousal disorder. GastrointestinalNausea, vomiting, diarrhea, gastrointestinal discomfort, anorexia, increased appetite. LiverRare cases of idiosyncratic hepatotoxicity have been observed, possibly due to the formation of reactive metabolites (PMID 15978881). EndocrineDecrease and, more rarely, increase in libido, weight gain and loss, and rarely, menstrual irregularities, retrograde ejaculation and inhibition of ejaculation.Elevated prolactin concentrations have been observed in patients taking trazodone (PMID 7673654). Allergic or toxicSkin rash, itching, edema, and, rarely, hemolytic anemia, methemoglobinemia, liver enzyme alterations, obstructive jaundice, leukocytoclastic vasculitis, purpuric maculopapular eruptions, photosensitivity and fever. MiscellaneousAching joints and muscles, hypersalivation, chest pain, hematuria, red, tired and itchy eyes. muscle twitches Occupational hazardsSince trazodone may impair the mental and/or physical abilities required for performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned not to engage in such activities while impaired. Laboratory testsIt is recommended that white blood cell and differential counts should be
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Read about trazodone (Desyrel), a drug used for the treatment of depression, panic attacks, agoraphobia, cocaine withdrawal, and agressive behavior.
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