uestion:
Has the patient had an adequate trial of an SSRI or bupropion?uestion:
Has the patient had an adequate trial of an SSRI or bupropion?
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Help: Given this patient's severe ischemia, the first line drug treatment will be with an SSRI or bupropion. It is assumed that ECT has been considered, since that is a primary option for this severely depressed, melancholic patient. See definition of adequate trial of and SSRI in the "Places to Go" frame. For inpatients, there are always intense pressures to make changes more rapidly. However, shorter trials than the above can not be classified as adequate.
If you choose "no" you will see comments on venlafaxine (Effexor) and mirtazapine (Remeron) as well as the primary recommendations of SSRI's and bupropion.
Recommendations:
Go ahead with your choice of an SSRI or bupropion. Among the SSRI's, a shorter half-life agent such as sertraline or paroxetine would be preferred. If there is a history of bradycardia, bupropion may be preferred. The risk of seizures is greater with bupropion (about 0.44%) compared to an SSRI (about 0.1 to 0.2%). If you choose an SSRI, be aware that there may be a risk of problems with "body sway" and falls secondary to this. Venlafaxine (click here for more information) could be another consideration. Although experience in patients with ischemia is limited, and there is a finite risk of blood pressure elevation, the likelihood is that it is reasonably safe.¹ It could have effectiveness more comparable to a tricyclic and better than an SSRI.² It may also work more rapidly.³ However, many patients do not tolerate nausea and other side effects, which seem particularly common if the patient was recently treated with an SSRI (perhaps due to inhibition of IID6 metabolism of venlafaxine).
The latest addition to the possible options for severe or treatment-resistant depression is mirtazapine (Remeron).* Click on the link for more information. Mirtazapine is related to the antidepressant mianserin (frequently prescribed in England but not available here) and, like some tricyclics and venlafaxine, it enhances both noradrenergic and sertonergic neurotransmission. Efficacy appears comparable to amitriptyline (though the AMI doses were low), with some significant advantages in side effects: a benign cardiac profile** including less orthostasis, apparent safety (including no EKG changes) in the limited number of overdoses recorded, low anticholinergic effects, and very low seizure rate (0.035%). On the other hand, there were significant problems with weight gain, somnolence, and dizziness. Agranulocytosis occurred in 2 of 2,796 patients, which prompted the Food and Drug Administration to require clinicians to warn patients of this possibility (see package insert), although no blood monitoring program is required as is the case with clozapine. The manufacturer reports that in the Netherlands, there were no cases of neutopenia in 13,500 mirtazapine-treated patients in post-marketing surveillance.***
A comparison of 133 severely depressed patients (not necessarily melancholic) is in press which found mirtazapine to be superior to fluoxetine in efficacy with comparable tolerability.**** Mirtazapine certainly appears worthy of further study.
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¹Feighner JP. Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry 1995; 56(12):574-579.
²Clerc GE et al. A double blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. Int Clin Psychopharmacol 1994; 9:139-143.
³Derivan A. Venlafaxine: measuring the onset of antidepressant action. Psychopharmacology Bull 1995; 31(2):439-447.
*Hopkins HS. Mirtazapine. Biol Therapies in Psychiatry 1997;20(1):2-4.
**Tulen JHM et al. Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine. J Clin Psychopharmacol 1996;16:135-145.
***Burrows GD, Kremer CME. Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol 1997;17[suppl 1]:34S-39S.
****Kremer C, Reimitz PE. (Title unknown) International Clin Psychopharmacol 1998 (in press). Also reported in abstract in Biological Psychiatry 1997:42:(Supplement)