Trazodone dosing

Trazodone is an older antidepressant that is associated with significant sedation. Currently, trazodone is not recommended as a first-line antidepressant because of an increased risk of orthostatic hypotension, arrhythmias, and priapism. Also, compared with other available antidepressants, trazodone does not offer an advantage in terms of therapeutic efficacy. However, trazodone may be useful in patients with insomnia. It is currently common practice to use low doses of trazodone (e.g., 50-100 mg) to assist with initial insomnia while starting treatment with one of the newer antidepressants to address the underlying depression. If this strategy is used, we recommend tapering the trazodone dose and discontinuing treatment with trazodone after 4—6 weeks. 

In 6 patients taking trazodone 150 or 300 mg daily, the addition of ear-bamazepine 400 mg daily for 4 weeks deeieased the plasma levels of trazodone by 24%, and of the aetive metabolite of trazodone by 40%. However, the combination was considered clinically useful in three of the cases. In another study, when carbamazepine 400 mg daily was given with trazodone 100 to 300 mg daily, the plasma levels of trazodone and its active metabolite were reduced by 76% and 60%, respectively. The FDA in the US and the manufacturer of trazodone recommend that patients should be closely monitored and trazodone doses increased if necessary when both drugs are given. ... 

A 12-year-old boy taking elonidine 100 mierograms three times daily and dexamfetamine 15 mg twiee daily was preseribed trazodone 50 mg at bedtime. After a few weeks his trazodone dosage was inereased to 100 mg at bedtime. Within 45 minutes of taking his first inereased dose he had a hypotensive episode with bradyeardia and sedation. The trazodone dose was ledueed baek to 50 mg, but the drug was diseontinued 2 weeks later beeause of low blood pressure. ... 

Trazodone and nefazodone cause minimal anticholinergic effects. Sedation, dizziness, and orthostatic hypotension are the most frequent dose-limiting side effects. 

Trazodone (Desyrel). Trazodone was the first of the atypical antidepressants and was actually introduced prior to the SSRIs. It does not have the serious cardiac toxicity or anticholinergic side effects of the TCAs and was the most popular antidepressant until the arrival of the SSRIs. It is approved for the treatment of depression and is also commonly used in low doses to treat agitation in demented patients and insomnia. 

The antidepressant trazodone (Desyrel) is commonly used in low doses to treat agitation or insomnia in dementia patients. However, older patients often do not tolerate the higher doses of trazodone needed to treat depression. 

We recommend trazodone (Desyrel) as a hrst-line treatment for insomnia in dementia patients. It has the added advantage of reducing nighttime agitation due to sundowning. Trazodone should be started at 25-50 mg given at bedtime. It should not be increased above 100 mg as higher doses increase the risk of dizziness and falls. 

Brief Mild Agitation. For the acnte treatment of mild agitation without physical aggression, low doses of trazodone are preferred. If this mild agitation persists, several options are available. Yonr patient s physician may continne to nse trazodone or may prefer sodinm divalproex (Depakote), bnspirone (Buspar), or any of the SSRI antidepressants. These are all well tolerated bnt should be started at low doses and slowly raised npward as needed. 

Brief Severe Agitation. Acute management of severe agitation with physical aggression requires more definitive treatment. The first choice is haloperidol given in low doses (0.25-1 mg) as needed. Lorazepam can also be helpful if used briefly. Risperidone, olanzapine, quetiapine, or trazodone can also be used but are not available in injectable forms. 

One particular variant of the post-TBl behavioral disturbances, nighttime agitation, can be managed successfully with low bedtime doses of sedating antidepressants such as trazodone (25-50mg) or nortriptyline (10mg). These antidepressants may calm the patient and help him/her to sleep while avoiding the potential for confusion or disinhibition posed by other commonly used sleep medicines. 

It is believed that trazodone, in therapeutic doses, inhibits the neuronal reuptake of serotonin. It is not a MAO inhibitor or a CNS stimulator. It has a minor influence on the reuptake of norepinephrine and dopamine. In addition, it does not bind with cholinergic or a-adrenergic receptors. Synonyms of this drag are thrombran, pragmarel, desyrel, and others. 

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

Trazodone is well absorbed after oral administration. It achieves peak plasma levels 1-2 hours following ingestion. The bioavailability of trazodone is 60%-80% with doses between 100 and 200 mg. Trazodone exhibits nonlinear pharmacokinetics because of saturable first-pass metabolism in the liver. Trazodone is metabolized by CYP450-3A4, and its active metabolite, m-CPP, is metabolized through CYP450-2D6. The half-life of the parent compound is 5 to 9 hours, and the half-life of m-CPP is 4 to 9 hours. It is excreted primarily in the urine (Preskorn, 1993). 

Although trazodone has not received an FDA indication for use in children and adolescents, it has enjoyed some success in the treatment of disruptive behavior disorders in this population. An aggressive 15-year-old male inpatient was treated with trazodone at a dosage of 200 mg/day, which resulted in decreased disruptive behavior. Following discharge from the hospital, trazodone was discontinued and the patient s violent behavior resumed. Upon return to his previous dose of 200 mg, the aggressive behavior again remitted (Fras,... 

Trazodone has been used therapeutically, but because of low potency and marked sedative effects, its use has been mostly restricted to a sleeping aid in doses of 50-100 mg at bedtime. It has been routinely used in adults on SSRIs, who develop sleep problems. The concern about priapism even at low doses may reduce enthusiasm for its use in male children and adolescents. 

Similar starting strategies are required for nefazodone and trazodone. However, the dose adjustment of tra-... 

Dose-dependent sustained diastolic hypertension Nausea, dry mouth, dizziness, constipation orthostatic hypotension sedation priapism (trazodone only) mCPP, an anxiogenic metabolite of nefazodone, can accumulate during CYP2D6 inhibition Drowsiness (greater at low doses ) Appetite/weight gain... 

On the basis of the large placebo-controlled studies, mirtazapine has undoubted antidepressant action and is licensed in both Europe and the United States [Claghorn and Lesem 1995 Sitsen et al. 1995). The evidence for superior efficacy is again limited by the failure to set up studies that were large enough to provide an adequate test of two active antidepressants. Nevertheless, mirtazapine has been shown to be more effective than trazodone in hospitalized patients with major depression (van Moffaert et al. 1995) and in a more recent study, mirtazapine was more effective than fluoxetine given in a dose of 20 mg [S. A. Montgomery 1996). 

Studies have been carried out with antidepressants, and trazodone is probably the most studied. These studies contained small samples, and no double-blind design was applied. The general conclusion of these works (Pinner and Rich 1988 D. M. Simpson and Foster 1986) is that trazodone at high doses (200-500 mg/day) helps to control disruptive behaviors. Slight improvement with buspirone was obtained in two studies carried out in small samples of patients with dementia and dismptive behavior (N. Hermann and Eryavec 1993 Sakauye et al. 1993). 

Baxter LR, Phelps ME, Mazziotti JC, et al Cerebral metabohc rates for glucose in mood disorders. Arch Gen Psychiatry 42 441-447, 1985 Baxter LR Jr, Thompson JM, Schwartz JM, et al. Trazodone treatment response in obsessive-compulsive disorder—correlated with shifts in glucose metabolism in the caudate nuclei. Psychopathology 20 (suppl 1 114-122, 1987 Beale MD, Kellner CH, Pritchett JT, et al Stimulus dose-titration in ECT a 2-year clinical experience. Convulsive Therapy 10 171-176, 1994 Beale MD, Kellner CH, Pritchett JT, et al ECT for OCD. J Clin Psychiatry 56 81-82, 1995... 

Wheadon DE, Bushnell WD, Steiner M A fixed dose comparison of 20, 40, or 60 mg paroxetine to placebo in the treatment of obsessive-compulsive disorder [abstract). Paper presented at the annual meeting of the American College of Neuropsychopharmacology, Honolulu, HI, December 1993 Wheatley D Trazodone in depression. International Pharmacopsychiatry 15 240-246, 1980... 

Although benzodiazepines, zolpidem, zaleplon, and eszopiclone are the mainstay of pharmacotherapy for insomnia, other sedating drugs, such as trazodone, diphenhydramine, or chloral hydrate, also may be used. Insomnia should first be addressed diagnostically, and in most cases, nonpharmacological interventions should be attempted before treatment with a hypnotic is instituted. Hypnotic agents should be administered in the lowest effective dose. Medications commonly prescribed for insomnia, along with their recom-... 

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

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