Trazodone MAOIs

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... 

Many commonly used medications also contain substances that are eliminated by the MAOIs and must not be taken by these patients. The list of medications to be avoided inclndes the narcotic pain reliever meperidine (Demerol), and many over-the-connter cold remedies containing dextromethorphan or pseudoephedrine. Finally, patients taking MAOIs must also avoid medications that elevate serotonin levels. This inclndes certain appetite snppressants and antidepressants including the SSRIs, venlafaxine, duloxetine, mirtazapine, nefazodone, and trazodone. Medications that interact with the MAOIs cannot be taken until at least 2 weeks after the MAOI has been stopped. 

Drugs that may affect trazodone include carbamazepine, phenothiazines, and venlafaxine. Drugs that may be affected by trazodone include alcohol, barbiturates, CNS depressants, digoxin, MAOIs, phenytoin, and warfarin. 

Drugs that may affect venlafaxine include cimetidine, cyproheptadine, and MAOIs. Drugs that may be affected by venlafaxine include clozapine, desipramine, haloperidol, indinavir, St. John s wort, trazodone, sibutramine, sumatriptan, and warfarin. 

There is a great disparity of current knowledge regarding the effects of antidepressants on GYP enzymes. There have been almost no studies to test the potential effects of TCAs, MAOIs, and trazodone on GYP enzymes. There has only been one study with bupropion but it demonstrated that bupropion produces substantial inhibition of GYP 2D6 comparable with the effect of fluoxetine and paroxetine. In contrast to studies in these antidepressants, there have been extensive in vitro and in vivo studies of SSRIs, nefazodone, and venlafaxine. 

Clinical experience with trazodone has indicated unpredictable efficacy for depression though it has proved very useful as a hypnotic, sometimes being combined with MAOIs, which disturb sleep. 

Trazodone + SSRIs, buspirone, MAOIs —> serotonin syndrome possible due to additive serotonergic effects. 

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. 

MAOIs should be for fhe expert, especially if combining with agents of potential risk (e.g., stimulants, trazodone, TCAs)... 

For the expert psychopharmacologist, trazodone can be used cautiously for insomnia associated with MAO inhibitors, despite the warning - must be attempted only if patients closely monitored and by experts experienced in the use of MAOIs... 

An alternative categorisation of antidepressants is based solely on mechanism of action (Fig. 19.1). The majority of antidepressants, including TCAs, SSRIs and related compounds are reuptake inhibitors. Certain novel agents including trazodone and mirtazapine are receptor blockers while MAOIs are enzyme inhibitors. 

The novel compounds nefazodone and trazodone usually require titration to a minimum therapeutic dose of at least 200 mg/day. Response to reboxetine, venlafaxine and mirtazapine may occur at the starting dose but some dose titration is commonly required. Venlafaxine is licensed for treatment-resistant depression by gradual titration from 75 to 375 mg/day. There is some need for dose titration when using MAOIs although recommended starting doses (e.g. phenelzine 15 mg t.d.s.) may be effective. Unlike other drug classes, reduction to a lower maintenance dose is recommended after a response is achieved. 

TCAs (especially imipramine and clomipramine)—contraindicated with MAOIs (trazodone may be used cautiously with MAOIs) Increased TCA levels s3mdrome of excitation, very high temperature, mania, seizures, coma, death... 

Antidepressant drugs A major class of psychotropic drugs with diverse chemical configurations including the monoamine oxidase inhibitors (MAOIs), the heterocyclic drugs (composed of mono-, di-, tri-, and hetero-cyclics), the serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, trazodone, and venlafaxine), and bupropion are more recent innovations. Antidepressants usually must be taken for several weeks to have the desired effect and they often have a low therapeutic index, so they must be closely monitored. 

DA agonists levodopa, bromocriptine, ropinirole, pramipexole, selegiline AAAD inhibitor carbidopa M-blockers benztropine, trihexiphenidyl MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone... 

MAOi (most studied with pheneizine), oianzapine, SSRi with ciomipramine (combined), trazodone,... 

Nefazodone is a phenylpiperazine antidepressant structurally related to trazodone, but it differs pharmacologically from trazodone, the SSRIs, the MAOIs, and the TCAs (Fig. 21.22). When compared with trazodone, nefazodone displays approximately twice the affinity potency for SERT. Nefazodone therapy, however, was associated with life-threatening cases of idiosyncratic hepatotoxicity, and as a result, nefazodone was withdrawn from both the North American and European markets in 2003. The mechanism of hepatotoxicity remains unknown, but nefazodone, being structurally similar to trazodone (Fig. 21.23), is metabolized to p-hydroxynefazodone, m-CPP, and phenoxyethyltriazoledione. In turn, p-hydroxynefazodone is thought to be oxidized to an iminoquinone and/or an epoxide reactive metabolite, which may play a role in the initiation of nefazodone-mediated hepatotoxicity (76). 

An isolated report describes a woman who developed marked and acute hypotension and weakness when desipramine, fluoxetine and venlafaxine were replaced by nefazodone. Isolated cases describe the serotonin syndrome in patients given nefazodone together, or sequentially, with another serotonei c drug (amitriptyline, paroxetine, St John s wort, or trazodone). The manufacturer recommended that nefazodone should not be used with an MAOI or within 14 days of discontinuing an MAOL Note that, due to adverse hepatic effects nefazodone was widely withdrawn from the market. 

Trazodone and fluoxetine have been used concurrently with advantage, but some patients develop increased adverse effects. There have been isolated reports of the serotonin syndrome in patients receiving trazodone and MAOIs, usually in association with... 

A case report describes a patient treated with trazodone, isocarboxazid and methylphenidate who developed symptoms of the serotonin syndrome. The US manufaeturer says due to the absence of clinical experience, if MAOIs are diseontinued shortly before or are to be given concurrently with trazodone, therapy should be initiated cautiously with a gradual increase in dosage until optimum response is achieved. However, the UK manufaeturer of trazodone says possible interactions with MAOIs have occasionally been reported they do not recommend concurrent use, nor should trazodone be given within 2 weeks of stopping an MAOI. MAOIs should not be taken within one week of stopping trazodone. ... 

Major drug interactions trazodone interacts with MAOIs with the risk of serotonin syndrome. When switching between trazodone and an MAOI, a 2-week no-trazodone no-MAOI gap is necessary to safely stop and start treatment Trazodone should not be stopped abruptly. Trazodone interacts with alcohol with worsening sedation. Tegretol decreases blood levels while Nizoral and Norvir increase blood levels of trazodone. Co-administration of trazodone can increase blood concentrations of digoxin and phenytoin. Trazodone may also pass into breast milk and affect a nursing baby. 

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