uestion: Is this patient severely depressed?
uestion: Is this patient severely depressed?
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Comment
on this question: This question begins the differentiation of melancholic
patients for whom a tricyclic (or comparable agent) might be indicated as first
line. A "yes" answer will lead to another question that will address safety
issues regarding the possible use of a tricyclic in this subgroup.
TCAs may have an edge over SSRIs in cases of severe depression,¹ and from other lines of evidence, TCAs may be superior to SSRIs for melancholia.² These evidences are weak. If full doses of SSRIs are used, i.e. - close to the PDR maximum, several studies show equivalency.³ Nevertheless, the impression remains that tricyclics are superior in some of situations; therefore, the algorithm adopts the position that depressed patients with melancholia and marked severity are appropriate candidates for tricyclic (or equivalent, e.g. - venlafaxine and probably mirtazapine) treatment as the first choice. The definition of 'severe' is deferred to the physician in evaluating the individual situation: usually these will be inpatients, and often they will be elderly.(4) This impression of greater response to a tricyclic in the elderly was not confirmed in some other studies but these studies used inadequate doses of tricyclics and lacked placebo controls.(4)
Those relatively few Dysthymic, Depression NOS, and Subsyndromal Depressed patients who have a non-reactive mood (a marker for melancholia[5-7]), and who are severely depressed are also routed to consideration of a tricyclic (or equivalent). Severely depressed but mood-reactive patients are considered better candidates for first-line SSRI/nefazodone therapy. For example, patients with depressive disorders coborbid with personality disorders such as Borderline may be severely depressed as measured by suicidality, impulsive-angry outbursts, and self-destructive behavior. However, their depressions are typically very mood-reactive and they tend in fact to respond poorly to tricyclics but respond well to SSRI's.(8) The greater risk of such patients taking an overdose also would lead the clinician to prefer an SSRI or nefazodone over a tricyclic.
In summary, the first line recommendation for more mild or moderately depressed melancholic patients will be an SSRI or nefazodone. For the severely depressed group, tricyclics and other drugs with apparently comparable efficacy will be considered.
¹Anderson IM, Tomenson BM. The efficacy of SSRI's in depression: a meta-analysis of studies against tricyclic antidepressants. Journal of Psychopharmacology. 1994;8:238-249.
²Nobler MS, Roose SP. Differential response to antidepressants in melancholic and severe depression. Psychiatric Annals. 1998;28:84-88.
³Hirschfeld RMA. Efficacy of SSRIs and newer antidepressants in severe depression: Comparison with TCAs. Journal of Clinical Psychiatry 1999;60:326-335.
(4)Roose SP, Glassman AH, Attia E, Woodring S. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. American Journal of Psychiatry. 1994;151:1735-1739.
(5)Nelson JC, Charney DS. The symptoms of major depressive illness. American Journal of Psychiatry. 1981;138:1-13.
(6)Maier W, Phillipp M, Schlegel S, Heuser I, Wiedemann K, Benkert O. Diagnostic determinants of response to treatment with tricyclic antidepressants: a polydiagnostic approach. Psychiatry Research. 1989;30:83-89.
(7)Osser DN. A systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia. Journal of Clinical Psychopharmacology. 1993;13:133-144.
(8)Gardner DL, Cowdry RW. Pharmacotherapy of borderline personality disorder: a review. Psychopharmacology Bulletin. 1989;25:515-523.