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Letter to the Editor   |    
Dr. Mamdani and Colleagues Reply
MUHAMMAD M. MAMDANI, PHARM.D., M.A., M.P.H.; SAGAR V. PARIKH, M.D.; PETER C. AUSTIN, PH.D.; ROSS E.G. UPSHUR, M.D., M.SC., M.A.
Am J Psychiatry 2001;158:329-330. doi:10.1176/appi.ajp.158.2.329

To the Editor: Drs. Flint and Silveira have raised several important issues that warrant further consideration. As discussed in our study, the use of tricyclic antidepressants in the elderly should be limited to secondary amine tricyclic antidepressants, such as nortriptyline, given their favorable adverse effect profile relative to tertiary amine tricyclic antidepressants, such as amitriptyline. Unfortunately, findings from studies primarily based on tertiary amine tricyclic antidepressants are often generalized to include secondary amine tricyclic antidepressants, which may not be appropriate. The evidence for inadequate tricyclic antidepressant prescribing, to which Drs. Flint and Silveira refer, is based primarily on tertiary amine tricyclic antidepressants. These conclusions may not be generalizable, since prescribing practices may be much more favorable for secondary amine tricyclic antidepressants (1). Furthermore, numerous studies have demonstrated that treatment with nortriptyline is not associated with a higher dropout rate than with SSRI treatment (2).

Although we concur that SSRIs possess more favorable dosing characteristics and may be more suitable for select groups of patients, such as those with ischemic heart disease(3), much more information is needed to determine the appropriate role of SSRIs and justify such dramatic shifts in prescribing practices. For example, recent evidence suggests that nortriptyline may be significantly more effective than fluoxetine in the treatment of poststroke depression (4). The Danish University Antidepressant Group found better remission rates with tricyclic antidepressants than with SSRIs, raising further questions about the true efficacy of SSRIs versus tricyclic antidepressants (5, 6). Similarly, emerging literature on the superiority of newer agents, such as venlafaxine, to SSRIs has invoked the "dual-mechanisms" explanation that is applicable to many of the tricyclic agents as well (7). With respect to adverse events, SSRI use may be associated with a substantially greater risk of major gastrointestinal bleeding, particularly in those taking nonsteroidal anti-inflammatory drugs (8). Although the frequency of adverse events associated with secondary amine tricyclic antidepressants and SSRIs is well documented, the burden of side effects and their longer-term, clinically relevant implications for patient well-being is poorly understood. Such issues, which may be even more relevant to an elderly population, warrant further consideration and more stringent analyses of the risks, benefits, and costs associated with treatment alternatives, rather than speculative conclusions and strong opinions.

Although clinicians have traditionally ignored the cost of medical treatment, a growing understanding that costs are indeed an important consideration in routine medical decision making is emerging. The allocation of a fixed budget, which must constantly weigh the benefits of newer and often more expensive treatments against the cost of denying other beneficial therapies, makes a strong case for judicious prescribing.

Jerling M: Dosing of antidepressants: the unknown art. J Clin Psychopharmacol1995; 15:435–439
 
Roose SP, Suthers KM: Antidepressant response in late-life depression. J Clin Psychiatry 1998; 59(suppl 10):4–8
 
Roose SP, Laghrissi-Thode F, Kennedy JS, Nelson JC, Bigger JT Jr, Pollock BG, Gaffney A, Narayan M, Finkel MS, McCafferty J, Gergel I:. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA  1998; 279:287–291
[PubMed]
[CrossRef]
 
Robinson RG, Shultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, Curdue K, Petracca G, Starkstein S: Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry2000; 157:351–359
 
Danish University Antidepressant Group: Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disorder  1990; 18:289–299
[CrossRef]
 
Danish University Antidepressant Group: Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study. Psychopharmacology  1986; 90:131–138
[PubMed]
 
Ferrier IN: Treatment of major depression: is improvement enough? J Clin Psychiatry 1999; 60(suppl 6):10–14
 
de Abajo FJ, Rodriguez LA, Montero D: Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. Br Med J 1999; 319:1106–  1109
 
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References

Jerling M: Dosing of antidepressants: the unknown art. J Clin Psychopharmacol1995; 15:435–439
 
Roose SP, Suthers KM: Antidepressant response in late-life depression. J Clin Psychiatry 1998; 59(suppl 10):4–8
 
Roose SP, Laghrissi-Thode F, Kennedy JS, Nelson JC, Bigger JT Jr, Pollock BG, Gaffney A, Narayan M, Finkel MS, McCafferty J, Gergel I:. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA  1998; 279:287–291
[PubMed]
[CrossRef]
 
Robinson RG, Shultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, Curdue K, Petracca G, Starkstein S: Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry2000; 157:351–359
 
Danish University Antidepressant Group: Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disorder  1990; 18:289–299
[CrossRef]
 
Danish University Antidepressant Group: Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study. Psychopharmacology  1986; 90:131–138
[PubMed]
 
Ferrier IN: Treatment of major depression: is improvement enough? J Clin Psychiatry 1999; 60(suppl 6):10–14
 
de Abajo FJ, Rodriguez LA, Montero D: Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. Br Med J 1999; 319:1106–  1109
 
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