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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.

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AAN releases recommendations for managing essential tremor
From American Family Physician, 11/1/05 by Amber Huntzinger

The Quality Standards Subcommittee of the American Academy of Neurology (AAN) has released evidence-based recommendations for the initiation of pharmacologic and surgical therapies for patients with essential tremor. The recommendations are based on a systematic literature review and were rated for strength of evidence. The full report was published in the June 28, 2005, issue of Neurology and can be found online at http://www. neurology.org/cgi/content/full/64/12/2008.

Essential tremor is defined as the presence of postural and kinetic tremor. Classic essential tremor most commonly affects the upper limbs, but it also can affect a head, lower limbs, voice, tongue, face, and trunk. Although essential tremor does not reduce life expectancy, and symptoms are limited to tremors, the condition may cause substantial physical and psychosocial disability (e.g., difficulty with writing, drinking, eating, dressing, speaking, and other fine motor skills). Propranolol (Inderal) is the only drug approved by the U.S. Food and Drug Administration for the management of essential tremor. However, an estimated 30 percent of patients will not respond to this medication. Other drugs may be used, and surgical intervention is an invasive alternative to pharmacologic therapy.

Recommendations

PHARMACOLOGIC THERAPY

Table 1 summarizes the evidence for the pharmacologic management of essential tremor.

Level A. Propranolol was effective in managing limb tremor related to essential tremor. The results of treatment with once-daily, long-acting propranolol (Inderal LA) were similar to those of standard propranolol in managing limb tremors. Physicians might consider the use of propranolol, long-acting propranolol, or primidone (Mysoline) to manage limb tremor in patients with essential tremor, depending on concurrent medical conditions and potential side effects. Primidone and propranolol were equally effective for initial treatment of patients with limb tremor.

Trazodone (Desyrel) did not significantly affect postural or kinetic tremor and is not recommended for managing limb tremor.

Level B. Alprazolam (Xanax), atenolol (Tenormin), gabapentin (Neurontin) mono-therapy, sotalol (Betapace), and topiramate (Topamax) may reduce limb tremor associated with essential tremor. Atenolol, gabap-patient's entin monotherapy, sotalol, and topiramate may be used for limb tremor, although data are limited. Alprazolam should be used with caution because of the potential for abuse. Propranolol should be considered for the management of head tremor.

Acetazolamide (Diamox), isoniazid (INH), and pindolol (Visken) probably do not reduce limb tremor and are not recommended for managing essential tremor.

Level C. Nadolol (Corgard) and nimodipine (Nimotop) may be considered to manage limb tremor associated with essential tremor, but clonazepam (Klonopin) should be used with caution because of its potential for abuse and withdrawal symptoms. Clozapine (Clozaril) is recommended only for refractory cases of essential tremor because of the risk of agranulocytosis.

Methazolamide (Neptazane), mirtazapine (Remeron), nifedipine (Procardia), and verapamil (Calan) probably do not reduce limb tremor and are not recommended for managing essential tremor.

SURGICAL THERAPY

Table 2 summarizes the evidence for the surgical management of essential tremor. Surgical intervention should be considered only for patients who do not respond to pharmacologic therapy.

Level C. Sufficient evidence was available only on the effectiveness of chronic thalamic deep brain stimulation (DBS) and thalamotomy for managing essential tremor. Unilateral thalamotomy may be used to manage limb tremor, but bilateral thalamotomy is not recommended because of adverse effects. Thalamic DBS may be used to treat patients with limb tremor, but insufficient evidence exists to make a recommendation regarding its effectiveness in managing head and voice tremor. Although DBS has fewer adverse effects, physicians should choose between DBS and thalamotomy based on the patient's intraoperative complications compared with the practicality of the procedures.

Level U. gamma knife surgery, chronic thalamic DBS (head), chronic thalamic DBS (voice), and unilateral versus bilateral DBS (hand) should be considered unproven therapies at this time.

Conclusion

The committee concludes that research on the management of essential tremor is limited, and additional prospective, double-blind, placebo-controlled trials are needed to better determine the effectiveness and side effects of pharmacologic and surgical therapy for essential tremor.

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