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WHAT IS THE APPROPRIATE ANTIDEPRESSANT?Table 5Other AntidepressantsMedications Initial/Max Dose Comments Adverse EffectsNDRIsBupropion IR (Wellbutrin) 100 mg bid/ Contraindicated in patients with anorexia,150 mg tid bulimia, or seizure disordersBupropion SR (Budeprion SR,Wellbutrin SR, Buproban)Bupropion XL (Wellbutrin XL,Budeprion XL)Mixed-Action Antidepressants150 mg/200 mg bid150 mg/450 mg dailySimilar to SSRIs butwith less 5HT adverseeffects such as nausea,somnolence, andweight gain; no sexualdysfunctionMirtazapine (Remeron) 15 mg/ Blocks alpha 2, 5HT 2a,c, 5HT 3, More weight gain, less45 mg daily and H 1receptors sexual dysfunction,insomniaNefazodone (Serzone) 100 mg bid/ Blocks 5HT 2aand 5HT reuptake; Black box warning =300 mg bid 3A4 inhibitor = many drug hepatotoxicityinteractions will limit useTrazodone (Desyrel) 150 mg/ Blocks 5HT 2and alpha 1receptors Too much sedation600 mg daily limits use5HT: serotonin; IR: immediate release; max: maximum; NDRI: norepinephrine-dopamine reuptake inhibitor; SR: sustained release;SSRI: selective serotonin reuptake inhibitor; XL: extended release. Source: References 4, 10.activity at lower doses and more norepinephrine thanserotonin activity at higher doses, thus having dosedependentadverse effects.Other Antidepressants 4,10 : Several other antidepressantsare available that differ in their mechanism of actionfrom the classes of medications described previously.The norepinephrine-dopamine reuptake inhibitors(NDRIs) such as bupropion immediate-release (IR)branded Wellbutrin (also available in long-acting dosageforms such as Wellbutrin XL, Wellbutrin SR, BudeprionSR, Budeprion XL, and Buproban) may be usedas first-line agents to treat depression (TABLE 5). Theiradverse effects are similar to those of SSRIs, with minimalserotonin effects such as nausea and weight gainand little or no sexual dysfunction. Bupropion has beenshown to exert beneficial effects on Parkinson’s diseasesymptoms in some patients, but it may also induce somepsychotic symptoms, perhaps because of its agonisticaction on the dopaminergic system. 16Finally, there are three more antidepressants withmixed action available: mirtazapine, nefazodone, andtrazodone (TABLE 5). All three agents block differentserotonin receptors, thus having distinct effects. Mirtazapinecauses more weight gain by increasing appetite.Nefazodone has limited uses because of hepatotoxicityand CYP3A4 enzyme inhibition, which leads to druginteractions. Trazodone blocks serotonin receptors toa great extent, with poor binding to muscarinic receptors.Adverse effects such as sedation, headache, memoryimpairment, dry mouth, and constipation may occur.Caution is also advised with trazodone use in men dueto risk of priapism.ConclusionIn general, antidepressant medications have beenshown to be equally efficacious; therefore, medicationchoice should be based on adverse effects, drug interactions,safety, and patient preferences. Several algorithmsare available to guide the clinician during the patient’streatment, particularly the recently updated Texas Departmentof State Health Services algorithm for the treatmentof MDD (updated July 2008). 17 If patients showpartial response, clinicians may choose to increase thedose, change to an alternative agent, or give a combinationof antidepressants. On the contrary, if patients donot respond or cannot tolerate the drug, switching toan alternative agent is also appropriate, taking into considerationthat therapeutic effects will usually occurbetween 4 to 6 weeks, even though adverse effectsmight appear after 1 week of treatment. 4,17 In addition,while the adverse effects appear early in treatment, theygenerally dissipate after 2 to 3 weeks. 4,17 Nonetheless, theantidepressant that will most likely ensure a patient’simprovement and safety may be determined, at least partially,by trial and error. Given the difficulty in predictingwhat medication will be both efficacious for andtolerated by an individual patient, familiarity with a broadspectrum of antidepressants is prudent and useful.References available online at www.uspharmacist.com.39U.S. Pharmacist • November 2009 • www.uspharmacist.com