Trazodone toxicity

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

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 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. 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

Although severe disruption in the sleep-wake cycle is a common feature of dementia, the use of BZDs in such cases may also produce significant behavioral toxicity. Alternative drug approaches include bedtime use of olanzapine in nondepressed patients or trazodone in depressed patients. 

Nefazodone Inhibition of 5- 2 receptor nefazodone also blocks SERT weakly Trazodone forms a metabolite (m-cpp) that blocks 5-HT2A,2C receptors Major depression sedation and hypnosis (trazodone) Relatively short half-lives active metabolites Toxicity Modest receptor blockade (trazodone) Interactions Nefazodone inhibits CYP3A4... 

Trazodone Hydrochloride Trazodone overdose causes severe toxic effects. These effects are severe if taken along with benzodiazepines or alcohol. Trazodone interacts with MAOIs, cardiovascular drugs, CNS depressants, and antiepileptics. 

Experience with therapeutic and toxic dose ranges of trazodone has thrown much doubt on earlier claims for its greater safety, and some unanticipated problems have surfaced. 

DIGOXIN TRAZODONE Reports of two cases of t plasma concentrations of digoxin after starting trazodone Uncertain at present Watch for digoxin toxicity check levels and 1 the dose of digoxin as necessary... 

SSRIs DULOXETINE, ST JOHN S WORT, SSRIs, TCAs, TRAZODONE T risk of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive effect. In addition, TCAs inhibit CYP2D6-mediated metabolism of SSRIs Caution with co-administration with TCAs or trazodone. Specialist advice should be sought and alternatives considered. Avoid co-administration of two SSRIs, and SSRIs with duloxetine or St John s wort... 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

Because this group as a whole engages in frequent suicidal acting out, it is advisable to treat borderline patients with medications that have been found to have a low degree of toxicity when taken in overdose. These include antipsychotics and the following antidepressants fluoxetine, paroxetine, bupropion (note above caution), trazodone, and sertraline. Most other antidepressants are quite toxic when taken in overdose. 

High suicide risk Less toxic antidepressants (fluoxetine, trazodone, paroxetine, sertraline, bupropion, venlafaxine, nefazodone)... 

Trazodone Concurrent use may cause serotonin syndrome. SSRIs may inhibit the metabolism of trazadone resulting in increased toxicity. 

Trazodone may be viewed as a triazolopyridine (left portion of the molecule) or as a phenylpiperazine. It is not to be easily categorized. It is inactive in most of the usual animal screens used. Its pharmacology is complex and not well understood. It shows weak serotonin uptake inhibiting ability and may also increase release of NE by blocking 02-adrenoceptors. The major metabolite is m-chlorophenylpiperazine. Toxicities are low and some patients respond well others obtain little benefit. 

ABBREVIATIONS O, oral tablet or capsule I, injectable NE, norepinephrine DA, dopamine 5-HT, 5-hydroxytryptamine, serotonin 0, negligible 0/-I-, minimal +, mild 2+, moderate 3-H, moderately severe 4+, severe. " Nefazodone additional side effect of impotence (-H) and some risk of hepatic toxicity. Trazodone additional side effect of priapism (-H). 

Fluoxetine at a dose of 20-60 mg/day, may cause a 2-4-fold increase in plasma concentration of tricyclic antidepressants (TCAs), possibly associated with signs of toxicity, including decreased energy, psychomotor retardation, sedation, dry mouth, and memory loss. The mechanism of this interaction may be attributed to the potent inhibitory effect of fluoxetine and norfluoxetine on the CYP2D6-mediated hydroxylation of TCAs. When given in combination with the heterocyclic antidepressant trazodone, fluoxetine was found to produce a significant elevation in plasma levels of both trazodone and its metabolite m-cbloropbenylpiperazine (mCPP)... 

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