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To the Editor The review by Dr Simon and colleagues, "Management of Depression in Adults: A Review," 1 provides many treatment options for depressive illnesses. However, we were surprised and disappointed that monoamine oxidase inhibitors (MAOIs), a well-established treatment, were not included among the third-line treatment options for nonresponding depression. There are more than 6 decades of data confirming MAOIs' efficacy in controlled trials and metaanalyses. In addition, MAOIs are included in national and international treatment guidelines and expert reviews for refractory mood disorders. [2][3][4] In the earlier days of MAOI use, fear of adverse events and the believed complexity of dietary restrictions as well as drugdrug interactions diminished use of MAOIs and education about their use in psychiatry residency programs. In fact, in the oftenreferenced STAR*D study of nonresponding depression, tranylcypromine, an MAOI, performed poorly. However, it was inadequately dosed, likely reflecting the researchers' limited experience with MAOIs. 5 Several recent publications have demonstrated both their relative ease of use and effectiveness when other, often newer, antidepressant treatments have failed for these patients. 4 With current improved safety standards in the commercial food industry limiting potential tyramine content in foods, the dietary limitations required for MAOIs are neither extensive nor complicated. 4 Since the review was geared toward primary care clinicians, it is important for them (as well as, of course, psychiatric professionals) to be aware of the clinical appropriateness and evidence-based use of MAOIs as another third-line treatment option. In contrast with the authors' inclusion of treat-ments such as intravenous ketamine for nonresponders, which presently lacks long-term efficacy and safety data, MAOIs have such data for both acute and long-term maintenance treatment. 4 Clinical experience, including that of this writer, has found MAOIs successful even when multiple treatments, including ECT or ketamine, have not been successful. 4 We recommend that all clinicians familiarize, or refamiliarize, themselves with this potentially lifesaving option.
To the Editor The review by Dr Simon and colleagues, "Management of Depression in Adults: A Review," 1 provides many treatment options for depressive illnesses. However, we were surprised and disappointed that monoamine oxidase inhibitors (MAOIs), a well-established treatment, were not included among the third-line treatment options for nonresponding depression. There are more than 6 decades of data confirming MAOIs' efficacy in controlled trials and metaanalyses. In addition, MAOIs are included in national and international treatment guidelines and expert reviews for refractory mood disorders. [2][3][4] In the earlier days of MAOI use, fear of adverse events and the believed complexity of dietary restrictions as well as drugdrug interactions diminished use of MAOIs and education about their use in psychiatry residency programs. In fact, in the oftenreferenced STAR*D study of nonresponding depression, tranylcypromine, an MAOI, performed poorly. However, it was inadequately dosed, likely reflecting the researchers' limited experience with MAOIs. 5 Several recent publications have demonstrated both their relative ease of use and effectiveness when other, often newer, antidepressant treatments have failed for these patients. 4 With current improved safety standards in the commercial food industry limiting potential tyramine content in foods, the dietary limitations required for MAOIs are neither extensive nor complicated. 4 Since the review was geared toward primary care clinicians, it is important for them (as well as, of course, psychiatric professionals) to be aware of the clinical appropriateness and evidence-based use of MAOIs as another third-line treatment option. In contrast with the authors' inclusion of treat-ments such as intravenous ketamine for nonresponders, which presently lacks long-term efficacy and safety data, MAOIs have such data for both acute and long-term maintenance treatment. 4 Clinical experience, including that of this writer, has found MAOIs successful even when multiple treatments, including ECT or ketamine, have not been successful. 4 We recommend that all clinicians familiarize, or refamiliarize, themselves with this potentially lifesaving option.
To the Editor I read the review on management of depression in adults by Dr Simon and colleagues 1 with great interest. I would like to provide some supplementary information with regard to one of their references, and would also like to add a cautionary note on their use of the term "mild depression."With regard to the dose-response relationships of selective serotonin reuptake inhibitors, the authors contrasted our dose-response meta-analysis, which reported that higher doses did not increase the likelihood of response, 2 with that of a former systematic review, which found modest evidence for greater improvement at the upper end of recommended dosing ranges. 3 In the latter study, however, the majority of the included studies were flexible-dose studies in which clinicians could up-or down-titrate within a predesignated dose range and the maximum of the flexible dose range was used as the dose representing the treatment groups, whereas our meta-analysis was limited to studies with fixed-dose arms.Additionally, in their Figure, Simon and colleagues used the term "mild depression" when the Patient Health Questionnaire-9 (PHQ-9) score was less than 10. Upon careful review, I remain unsure whether the authors meant "mild major depression" or "subthreshold depression" with this term. If the former, it must be pointed out that the likelihood ratio for PHQ-9 scores between 5 and 9 to detect major depression is much smaller than 1.0, 4 meaning that someone with a pretest probability of major depression of 10%, for example, would have a posttest probability of actually having major depression of approximately 5%, or even less. If the authors meant to refer to "subthreshold depression" by using the term "mild depression," then it could be confusing to readers because "mild major depression" in this scheme would be termed "moderate depression." This may only be a matter of words or definitions, but I believe words would serve their purposes better if they were more clearly defined and in line with the standard diagnostic schemes.
To the Editor We read with great interest the review "Management of Depression in Adults" by Drs Simon and colleagues. 1 We appreciated the comprehensive view of the patient, the attention paid to nonpharmacological treatment, and the thinking process guiding the choice of the antidepressants. However, we could not find trazodone among the antidepressants. Possibly, the search criteria accounted for this gap. Nevertheless, trazodone is a US Food and Drug Administration (FDA)-approved antidepressant and, at low doses (50-150 mg daily), is also used to treat sleep disorders and anxiety as well as behavioral and psychological symptoms of dementia. 2 Treatment effects occur through a complex central mechanism of action: trazodone increases noradrenaline release and turnover through a 2-presynaptic receptor and is a 5-hydroxytryptamine 2 antagonist and serotonin reuptake inhibitor, with moderate histamine-1 receptor antagonism properties. 3 Trazodone is primarily an antidepressant at dosages up to 300 mg daily. Trazodone has no anticholinergic effects, neither causes nor worsens parkinsonism, and does not affect the libido. However, hypotension and dizziness are not uncommon adverse effects. 4 Trazodone serum levels may vary depending upon genetic P-glycoprotein polymorphisms, but trazodone does not affect liver cytochromes and thus does not have many drug interactions. 5 The lack of drug interactions and the high prevalence of sleep problems and anxiety in elderly patients make trazodone a potentially useful antidepressant in geriatric medicine. 4 Thus, we think that a review on the treatment of depression should include trazodone to provide the readers of JAMA with complete information on the available pharmacological choices.
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