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Re: maoi plus wellbutrin

Posted by SLS on June 18, 2003, at 19:15:11

In reply to Re: maoi plus wellbutrin » SLS, posted by shrimp on June 18, 2003, at 17:39:51

Here's an abstract that was sent to me by a friend:


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Bupropion-Tranylcypromine Combination for Treatment-Refractory Depression

Sir: We report the safe and successful use of combined bupropion and tranylcypromine in a case of treatment-refractory depression.

Case report. Ms. A, a 27-year-old woman with chronic major depression (DSM-III-R criteria), was treated in 1990 at age 17 with imipramine up to 150 mg/day. In March 1994, after a suicide attempt by imipramine overdose, paroxetine, 20 mg/day, replaced imipramine. On paroxetine, 30 mg/day, and amitriptyline, 50 mg q.h.s., she experienced only mild improvement at 6 months. By 1995, Ms. A was taking paroxetine, 30 mg/day; nortriptyline, 35 mg/day; and temazepam, 15 mg q.h.s. (with a plasma nortriptyline level of 71 ng/mL). Despite the addition of brief trials of methylphenidate, 5 mg b.i.d., her mood remained depressed.

In August 1995, bupropion was initiated with the gradual withdrawal of nortriptyline and paroxetine. Trazodone, 25 mg q.h.s., replaced temazepam. By October 1995, Ms. A was taking bupropion, 150 mg b.i.d.; trazodone, 100 mg q.h.s.; and lorazepam, 0.5 mg t.i.d., with only a partial response. A trial of adjunctive liothyronine (T3), 25-75 microg/day, failed to yield sustained improvement, and her dysphoria, fatigue, and insomnia instead worsened. Tranylcypromine was added and upon titration to 50 mg/day, Ms. A reported a gradual return to euthymia with resolution of her long-standing depressive symptoms.

Bupropion was tapered and discontinued in March 1996, but within 2 weeks, Ms. A noted a return of depressive symptoms. Bupropion was therefore restarted with good results. On one occasion, Ms. A developed symptomatic hypertension after eating cheese, but it was managed with nifedipine at home. Other than this episode, she was normotensive at all checkups. By the summer of 1996, T3, trazodone, and lorazepam were withdrawn. She remained on a regimen of tranylcypromine, 60 mg/day (40 mg in the morning and 20 mg at noon), and bupropion sustained release (SR), 150 mg b.i.d., with sustained euthymia. Transient and mild periods of stress-related dysphoria or insomnia were manageable with low-dose lorazepam. In November 1997, tranylcypromine was withdrawn in order for Ms. A to undergo a surgical procedure. During the 2 weeks off tranylcypromine treatment, she experienced an acute worsening of mood symptoms that quickly resolved with its reintroduction. Two years later, she remains on tranylcypromine, 60 mg/day, and bupropion SR, 150 mg b.i.d., without relapse of depression. She continues to keep nifedipine in the event of a hypertensive crisis, but aside from her 1 episode associated with ingestion of cheese 3 years ago, she has had no further blood pressure elevations over the course of her treatment.

Ms. A's case is remarkable for chronic depression unresponsive to treatment with a selective serotonin reuptake inhibitor and tricyclic antidepressants, as well as adjunctive methylphenidate and T3. The addition of tranylcypromine to bupropion finally resulted in a sustained remission of her depression. Depressive symptoms returned whenever either antidepressant was withdrawn over the course of treatment, thereby emphasizing the apparent necessity of both antidepressants for treatment response. Ms. A's poor response to multiple antidepressant trials, including both a tricyclic and tranylcypromine alone, classifies her depression at Stage IV resistance as defined by Thase and Rush.1 The treatment of choice for Stage IV resistant depression is electroconvulsive therapy (ECT). 1 ECT was not administered to Ms. A, owing to her desire to continue employment and outpatient management of her depression.

While no controlled double-blind studies support the use of combination antidepressant therapy in treatment-resistant depression,2 this practice is supported by anecdotal evidence and general clinical opinion. Ms. A's case adds to this body of evidence and suggests that combination antidepressant therapy deserves greater study in refractory depression. Although the combination of bupropion and a monoamine oxidase inhibitor is not usually recommended due to the risk of hypertensive crisis,3 the cautious administration of tranylcypromine and bupropion together may be a safe and effective strategy in some cases of treatment-resistant depression.

References

1. Thase ME, Rush AJ. When at first you don't succeed: sequential strategies for antidepressant nonresponders. J Clin Psychiatry 1997;58(suppl 13):23-29

2. Nelson JC. Overcoming treatment resistance in depression. J Clin Psychiatry 1998;59(suppl 16):13-19

3. Kaplan HI, Sadock BJ, eds. Comprehensive Textbook of Psychiatry. 6th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1995

Joseph M. Pierre, M.D.

Michael J. Gitlin, M.D.

UCLA Neuropsychiatric Institute

Los Angeles, California

 

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