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Drug update: New antidepressants--beyond SSRIs. (Primary Care).

The newest generation of antidepressants gives physicians some novel options for treating depression that go a step beyond the selective serotonin reuptake inhibitors (SSRIs), but like the SSRIs the new antidepressants are not effective in about 40% of patients with major depression.

Because the SSRIs--citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline--have a longer track record, most experts continue to use them as first-line agents for treating depression. But the newer drugs listed here are generally ranked as comparable to the SSRIs in all other respects.

How would you choose among them? If a patient has been treated successfully in the past, use the same agent. Otherwise, there is no evidence-based way to decide which drug is best for an individual patient.

Some experts recommend matching a patient's symptom complex to the drug's spectrum of effects: for example, using a more sedating agent for a patient whose depression is accompanied by pronounced anxiety. But even this approach has not been supported by study results.

The most significant recent trend in treating depression is to maximize the dosage of whichever drug is used first before switching to a different drug. Also, treatment with the first drug is maintained for up to 12 weeks before it is deemed ineffective and the patient is switched to another drug; in the past, experts recommended sticking with an ineffective drug for only 6 weeks before trying something new The goal of treatment is full remission of symptoms; partial remission is considered inadequate and a reason to switch drugs. When this occurs, some authorities favor picking an agent from a different class, more because it seems sensible than because of any evidence. Others recommend adding lithium or thyroid hormone.

Once remission occurs, treatment should continue for at least 6-9 months. Patients with multiple episodes of depression are likely to require treatment for at least 2 years, and possibly indefinitely.

With depression increasingly viewed as a chronic illness, issues of cost assume more prominence. Fluoxetine is now available in a generic formulation.

All four listed drugs should be used cautiously during pregnancy, in women who are breast-feeding, and in elderly patients. All of the drugs listed here are rated pregnancy category C except bupropion, which is category B. Nefazodone should be started at half the usual dose in the elderly; all others should be started at a low dose and gradually titrated to the most effective dose.
Drug Dosage Cost/Day

venlafaxine 75-225 mg/day $2.61
(Effexor, (Effexor-XR) (150 mg) (*)

mirtazapine 15-45 mg/day $2.61
(Remeron) (30 mg) (*)

nefazodone 300-600 mg/day $2.70
(Serzone) (500 mg) (**)

bupropion 300-450 mg/day $4.48
(Wellbutrin, (Wellbutrin) (400 mg) (*)
Wellbutrin SR)

Drug Comment (+)

venlafaxine Serotonin-norepinephrine reuptake inhibitor. Strongly
(Effexor, inhibits norepinephrine and 5-hydroxytryptamine (5-HT)
 Effexor-XR) reuptake and weakly inhibits dopamine reuptake. Most
 commonly used as a second-line agent or in patients
 with generalized anxiety disorder accompanying
 depression. Treatment is associated with increases
 in blood pressure, so avoid in patients with
 uncontrolled hypertension. Nausea is the most
 frequently reported adverse effect. Contraindicated
 for patients on a monoamine oxidase (MAO) inhibitor
 or within 14 days of treatment with an MAO
 inhibitor. The extended-release formulation
 generally is preferred. The conventional-release
 formulation is used at a dosage of 75-350 mg/day.

mirtazapine Not a reuptake inhibitor; appears to enhance central
(Remeron) noradrenergic and serotonergic activity. The
 drug is associated with significant somnolent
 effects in some patients. Weight gain and dry
 mouth also have been reported frequently.
 Contraindicated for patients on an MAO inhibitor or
 within 14 days of treatment with an MAO inhibitor.

nefazodone This 5-[HT.sub.2] antagonist and reuptake inhibitor
(Serzone) also exhibits [[alpha].sub.1]-adrenergic blocking
 activity. While it has become a common choice for
 patients with anxiety symptoms because of its
 somnolent effects, it is associated with more
 drug-drug interactions than are the SSRIs and
 other post-SSRI antidepressants. Contraindicated
 for patients on an MAO inhibitor or within 14
 days of treatment with an MAO inhibitor. Start
 at half the usual dosage in elderly patients
 and titrate up to the full adult dosage.

bupropion This dopamine reuptake inhibitor exhibits minimal
(Wellbutrin, effects on norepinephrine or 5-HT reuptake. A
Wellbutrin SR) popular second-line agent; also seems to be
 associated with less sexual dysfunction than are
 some SSRIs. Associated with an increased risk of
 seizures with total daily dosages greater than 450
 mg; there are also case reports of hyponatremia,
 extrapyramidal effects, and parkinsonism with such
 higher doses. Bupropion has been reported to
 interact with anticonvulsants and imipramine and to
 cause panic attacks when used in combination with the
 SSRI paroxetine. Contraindicated for patients with
 seizure disorders or a history of bulimia or
 anorexia nervosa. Contraindicated for patients on
 an MAO inhibitor or within 14 days of treatment with
 an MAO inhibitor. Use cautiously in elderly
 patients and those with reduced renal function.
 Bupropion is also marketed as an aid to smoking
 cessation under the name Zyban. Available in a
 sustained-release formulation; dosage of SR
 formulation is 300-400 mg/day.

(*)Cost/day is based on the average wholesale price for a 100-unit
container of the indicated drug in the 2001 Red Book.

(**)Cost/day is based on the average wholesale price for a 60-unit
container of the indicated drug in the 2001 Red Book.

(+)The comments reflect the viewpoints and expertise of the following
sources: Dr. Gregory E. Simon, investigator, Center for Health Studies,
Group Health Cooperative, Seattle.

Dr. Madhukar H. Trivedi, associate professor of psychiatry and director
of the depression and anxiety disorders program, University of Texas
Southwestern Medical Center at Dallas.

Dr. John W. Williams, associate professor of medicine, Duke University
Medical Center, Durham, N.C.
COPYRIGHT 2002 International Medical News Group
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002 Gale, Cengage Learning. All rights reserved.

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Author:Walsh, Nancy
Publication:OB GYN News
Date:Mar 1, 2002
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