Guideline Watch: Practice Guideline for the Treatment of  
Patients With Major Depressive Disorder, 2nd Edition

Laura Fochtmann; Alan Gelenberg

APA Practice Guidelines >

< Previous

Next >

Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition

Laura J. Fochtmann; Alan J. Gelenberg

DOI: 10.1176/appi.books.9780890423363.148217

Content

References

text A A A

SECTION QUICK LINKS

Introduction
Antidepressants and Other Somatic Treatments
Psychotherapy and Other Psychosocial Treatments

Continuation and Maintenance Treatment
Treatment of Depression in Older Adults
References

Introduction

Since the publication in 2000 of the APA's Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition (1), two important safety concerns have emerged (hepatotoxicity with nefazodone and suicide risk with antidepressants), and two new antidepressants have been approved for use (escitalopram and duloxetine). This watch describes these developments as well as evidence that has accrued since 2000 in other areas related to the treatment of major depressive disorder.

The American Psychiatric Association (APA) practice guidelines are developed by expert work groups using an explicit methodology that includes rigorous review of available evidence, broad peer review of iterative drafts, and formal approval by the APA Assembly and Board of Trustees. APA practice guidelines are intended to assist psychiatrists in clinical decision making. They are not intended to be a standard of care. The ultimate judgment regarding a particular clinical procedure or treatment plan must be made by the psychiatrist in light of the clinical data presented by the patient and the diagnostic and treatment options available. Guideline watches summarize significant developments in practice that have occurred since publication of an APA practice guideline. Watches may be authored and reviewed by experts associated with the original guideline development effort and are approved for publication by APA's Executive Committee on Practice Guidelines. Thus, watches represent the opinion of the authors and approval of the Executive Committee but not policy of the APA. This guideline watch was published in September 2005. Copyright © 2005 American Psychiatric Association. All rights reserved. Suggested citation: Fochtmann LJ, Gelenberg AJ: Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition. Arlington, VA: American Psychiatric Association, 2005. Available online at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm.

Antidepressants and Other Somatic Treatments

Hepatotoxicity with nefazodone

The guideline recommends the serotonin modulator nefazodone as an effective medication for the treatment of depression. However, before initiating or continuing treatment with nefazodone, consideration should be given to the recent reports of life-threatening hepatic failure in patients treated with nefazodone (2–8). These reports have led the Food and Drug Administration (FDA) to change the drug's labeling, adding a black box warning of possible liver failure leading to death and/or a need for transplant and contraindicating the drug in patients who were withdrawn from it because of evidence of liver injury. According to the warning, the reported rate of liver failure resulting in death or transplant in the United States is about 1 case per 250,000–300,000 patient-years of nefazodone treatment. This represents a rate of about three to four times the estimated background rate of liver failure and is probably an underestimate. There are no known predictors of the development of liver toxicity and failure with nefazodone; toxicity and failure have been reported in individuals early in the course of treatment as well as in persons receiving stable dosages for many months. The FDA warns that patients with preexisting liver disease should not be treated with nefazodone and that patients should be advised to immediately report symptoms that may indicate liver dysfunction, such as jaundice, anorexia, gastrointestinal complaints, and malaise. The warning is available at http://www.fda.gov/medwatch/SAFETY/2002/serzone_deardoc.pdf.

Suicide risk and antidepressants

Because patients with major depressive disorder are at greater risk of suicide, the guideline indicates that they should be assessed for suicide risk initially and over the course of treatment. The guideline also notes that "the risk of suicide in some patients recovering from major depressive disorder increases transiently as they develop the energy and capacity to act on self-destructive plans made earlier in the course of their illness" (1). The guideline describes factors associated with an increased risk of suicide in patients with major depressive disorder but notes that "the ability to predict suicide attempts and completed suicide is poor, with both many false positives (i.e., patients who appear more likely to make attempts or complete suicide but who do not) and false negatives (i.e., patients who appear less likely to make attempts or complete suicide but who do)" (1). With respect to children and adolescents, the guideline recommends caution when basing treatment decisions on adult data. All of these general principles remain true.

Recent research has raised concern about the safety of antidepressant use for children and adolescents and has led the FDA to add additional warnings, including a black box warning, to the labeling of all antidepressant medications (9). Although the APA practice guideline focused on treatment of adults, not children and adolescents, discussion of this research is appropriate in this watch. In 23 short-term (4- to 16-week) trials involving more than 4,400 patients receiving nine antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and others), suicidal thinking or behavior was observed in 78 individuals. The average risk of suicidal thinking or behaviors was 3.8% for participants receiving a drug compared with 2.1% for those given placebo, suggesting an approximately twofold increase in risk (10). Consequently, in the new labeling, the FDA notes that pooled analyses of placebo-controlled antidepressant trials (available at http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1.htm) have shown an increased risk of suicidal thinking or behavior in children and adolescents with major depressive disorder, obsessive-compulsive disorder, and other psychiatric disorders. However, it is important to note that no suicides occurred in any of these trials. Furthermore, according to the Centers for Disease Prevention and Control, suicidal thinking and suicide attempts are common among adolescents, occurring respectively in about 17% and 8.5% of adolescents each year. As a result of such attempts, only 0.002% of girls and 0.012% of boys ultimately die (11), highlighting the fact that suicidality (i.e., suicidal thoughts and behaviors) and suicide are not equivalent.

Although the studies reviewed by the FDA showed some variations among antidepressants, it was not clear whether the increase in suicidal thinking or behavior was specific to particular antidepressants, extended to adults, or occurred with longer-term antidepressant use (i.e., beyond several months). Thus, the FDA labeling change recommends that "all pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases" (9). To facilitate this, the FDA suggests an increased frequency of face-to-face contacts (i.e., weekly for the first 4 weeks, biweekly for the next 8 weeks), with prescriptions written for "the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose." The FDA also recommends that patients be screened for bipolar disorder before antidepressant therapy is initiated. Medication guides that will accompany prescriptions of antidepressant medications are intended to alert families and caregivers of pediatric and adult patients to the need to monitor patients for the emergence of agitation, irritability, hostility (aggressiveness), impulsivity, anxiety, panic attacks, insomnia, akathisia, hypomania, mania, or unusual changes in behavior so that such symptoms can be reported immediately to health care professionals.

When signs or symptoms are observed that suggest an increased suicide risk, recommendations are available for assessing and managing suicidal behaviors in children and adolescents from the American Academy of Child and Adolescent Psychiatry (12) and in adults from the APA (13).

As with all decisions about treatment for individuals with psychiatric illnesses, the choice to initiate antidepressant therapy must balance the potential risks of treatment against the potential therapeutic benefit and the risks of untreated illness (14–16). The risks of untreated depression, including suicide and other suicidal behaviors, are high and have been clearly delineated in youths and in adults (1, 12, 13, 17). In adults, the evidence for antidepressant efficacy is also clear, as reviewed in the APA guideline.

In children and adolescents, the issue has been confounded by a smaller number of clinical trials as well as by negative trials. Positive evidence includes the studies of fluoxetine that led to its receiving an FDA indication for treatment of depression in children and adolescents and the recent Treatment for Adolescents With Depression Study (TADS) sponsored by the National Institute of Mental Health. This large, yearlong community effectiveness trial (18) of youths with moderate to severe major depressive disorder found that by 12 weeks of treatment, rates of response to fluoxetine alone (60.9%) were greater than those with either placebo (35%) or cognitive behavior therapy (CBT) alone (43.2%). In combination with CBT, fluoxetine was associated with an even greater response rate (71%)twice that seen with placebo. Furthermore, clinically significant suicidal thinking, which was observed in 29% of study subjects prior to treatment, improved in all groups.

In addition to this direct evidence of antidepressant efficacy from clinical trials, the national decreases in youth suicide and overall suicide rates, during a period when the prescribing of antidepressants has increased, might provide indirect evidence for an overall preventive effect of antidepressant treatment on suicide (14, 19, 20).

Because additional information on the issue of antidepressants and suicide risk is likely to emerge, readers are urged to seek updates on the Web sites of the FDA (http://www.fda.gov), the American Academy of Child and Adolescent Psychiatry (http://www.aacap.org), and the APA (http://www.psych.org).

Availability of new antidepressants

Two new antidepressants, escitalopram and duloxetine, have been approved by the FDA since publication of the guideline. Escitalopram, the active S-enantiomer of citalopram, is an SSRI antidepressant that has FDA approval for acute and maintenance treatment of major depressive disorder. Evidence from randomized, clinical trials suggests that escitalopram is superior to placebo in the short-term treatment of depression (21), with efficacy and tolerability comparable to that of other antidepressants, including venlafaxine (22, 23) and citalopram (21, 24).

Duloxetine, a dual serotonin-norepinephrine reuptake inhibitor, has also been approved for the treatment of depression. Randomized, clinical trials show duloxetine to be more efficacious than placebo (25–28) and comparable in efficacy to SSRI antidepressants (27, 28). The drug is generally well tolerated, with reported adverse effects of treatment (e.g., nausea, dry mouth, dizziness, somnolence, insomnia, constipation, and asthenia) varying across studies but typically being infrequent at total oral daily doses of 40–120 mg. In addition to ameliorating core symptoms of depression, duloxetine exhibits efficacy relative to placebo in treating painful physical symptoms (26, 28–31) and anxiety in depressed individuals (32). It also appears to ameliorate pain in the absence of depression (31), and it is FDA indicated for the management of pain associated with diabetic peripheral neuropathy.

Since publication of the guideline, the combination of fluoxetine and olanzapine has received FDA approval on the basis of a randomized, clinical trial supporting its use (33). Although the combination product (brand name Symbyax) is indicated for the treatment of episodes of bipolar depression, combined treatment with fluoxetine and olanzapine has also been found useful in treating episodes of major depression with psychotic features (34) and in treatment-resistant depression (35, 36).

Reboxetine, a selective norepinephrine reuptake inhibitor that was noted in the guideline to be possibly close to receiving approval, is not currently approved for use. Atomoxetine, another selective norepinephrine reuptake inhibitor, has recently become available but is approved for the treatment of attention deficit hyperactivity disorder. Although the possibility of using atomoxetine, either alone or in combination with an SSRI, for the treatment of depression has prompted interest among clinicians, the drug does not have an FDA indication for this use, and data on its use in the treatment of depression are limited (37–39). In addition, the FDA has just added a bolded warning to atomoxetine's labeling noting that the medication should be discontinued in patients who develop jaundice or laboratory evidence of liver injury (http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01335.html).

The evidence cited here on new medications is based on premarketing research. Clinicians are cautioned that real-world experiences after a drug is approved often bring unexpected findings, including less efficacy in some circumstances and unanticipated adverse events.

St. John's wort

Since publication of the guideline, results from additional meta-analyses and well-designed trials of St. John's wort have become available. Although some additional randomized, controlled trials have shown St. John's wort to be superior to placebo (40–42) or to comparator antidepressants (43, 44) in treating mild to moderate depression, other large trials have shown it to be no better than placebo (45–47) or comparator antidepressants in efficacy (42, 46–50). Several factors continue to confound interpretation of the literature, including trial length, adequacy of comparison treatment, and the reliability, stability, and comparability of Hypericum preparations. The most recent meta-analysis noted a trend for decreasing effect sizes in trials of St. John's wort over time, suggesting that it may be less effective in treating depression than previously thought (51). Although St. John's wort is generally well tolerated in clinical trials, increasing attention has been given to its tendency to compromise the effectiveness of other medications (e.g., cyclosporine, HIV protease inhibitors, oral contraceptives, digoxin, warfarin, and theophylline) by interactions mediated through cytochrome P450 enzymes (e.g., CYP3A4, CYP2C9, CYP1A2, CYP2C19) and transport protein P-glycoproteins (52–56).

Other somatic treatments

Evidence for the efficacy of electroconvulsive therapy (ECT) in treating major depressive episodes, already compelling at the time the guideline was published, has been strengthened by additional findings. Recent meta-analyses have highlighted the superior efficacy of ECT relative to sham treatment and also relative to pharmacotherapies for depression (57, 58). In depressed patients who received an acute course of ECT, data from the Consortium for Research in ECT have shown that thrice-weekly bilateral ECT is associated with rapid initial response and high rates of sustained response and remission (59). In comparison with bilateral ECT, right unilateral ECT has been associated with fewer cognitive effects (60, 61), particularly in autobiographical memory (62). However, as with bilateral ECT, cognitive effects vary with the extent to which the electrical stimulus exceeds the seizure threshold (60). In addition, the overall efficacy of unilateral ECT appears to be less than that with bilateral ECT (57). Several additional studies highlight the diminished efficacy of barely suprathreshold electrical stimulation with right unilateral electrode placement (60, 61, 63) and a corresponding need to administer right unilateral ECT at stimulus intensities that are at least six times the initial seizure threshold (64). Additional details on the clinical use of ECT in the treatment of major depression can be found in the 2001 revision of the APA's The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging (64).

Although other somatic treatments, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, and vagal nerve stimulation, have also been studied over the past 5 years, evidence is not yet sufficient to recommend their use in routine clinical practice.

Psychotherapy and Other Psychosocial Treatments

Recent studies have provided additional support for the efficacy of a number of psychosocial treatment approaches, including problem-solving treatment (65, 66), group psychoeducation (65), and the cognitive behavioral analysis system of psychotherapy (67). Additional meta-analyses have suggested that among psychotherapeutic approaches, other bona fide psychotherapies have efficacy comparable with CBT for treating depression (68, 69), although more research with CBT has been done. Given the evidence for the benefits of exercise in older depressed adults (70, 71), exercise may also be of value in other subgroups of patients with major depression.

Psychotherapy combined with pharmacotherapy

As noted in the guideline, studies examining combination treatment with psychotherapy and pharmacotherapy have shown mixed results. Although this has continued to be true in subsequently published studies (66, 67, 72, 73), a recent meta-analysis suggested that a combination of psychotherapy and pharmacotherapy is more effective than pharmacotherapy alone (74). Combination therapy may be particularly useful in improving treatment adherence (73, 74) and might be of some use in targeting particular symptoms or patient subgroups (75–77).

Continuation and Maintenance Treatment

At the time the guideline was published, much data suggested the importance of continuation and maintenance treatment in individuals at high risk of recurrent depression, although the majority of studies on this practice examined the use of tricyclic antidepressants. Several more recent studies have confirmed the benefits of continuation and maintenance treatment with antidepressants in other classes (e.g., sertraline, venlafaxine, and mirtazapine) in decreasing the likelihood of recurrence (78–82).

Supplementing the earlier data on continuation and maintenance psychotherapy, most (83–87) but not all (88) additional studies of CBT support its use either alone or in addition to pharmacotherapy in decreasing depressive recurrence.

Inadequate response to treatment

Given the clinical importance of treatment nonresponse, it is not surprising that a number of studies and meta-analyses have examined strategies for augmenting antidepressant therapy. Although no consistently effective approach has emerged (89), pharmacotherapeutic approaches with some recent positive results include augmentation with thyroid hormone (particularly in women) (90), lithium (91, 92), buspirone (93), and lamotrigine (94). Addition of a benzodiazepine may also be helpful in some individuals after a careful weighing of potential advantages and disadvantages (95). Some studies have suggested that adjunctive treatment with omega-3 fatty acids is efficacious (96–98), although a single study using omega-3 fatty acid monotherapy showed no benefit (99). Evidence on the use of estradiol augmentation in perimenopausal or postmenopausal women is mixed (100, 101), and other potentially negative health effects of estrogen treatment are emerging. The possible adjunctive use of mifepristone in treating psychotic depression has also generated interest recently, although data are sparse (102, 103).

Modafinil has been used increasingly in depressed patients, either as an augmenting agent or to counteract symptoms of fatigue resulting from depression or sedation from other agents. Evidence for the efficacy of modafinil is limited and comes primarily from small or uncontrolled trials (104–107). A single randomized trial showed a brief period of improvement in fatigue after initiating adjunctive treatment with modafinil but no augmenting effect on depressive symptoms relative to placebo (108).

Some additional evidence suggests that response may be enhanced by increasing the dosage of antidepressant medication, although an increase in side effects may also be observed (109–111).

In terms of the choice of antidepressant medication, some studies (111–114) and meta-analyses (115–118) suggest that greater efficacy is seen with medications that act on more than one neurotransmitter system (e.g., venlafaxine and mirtazapine), although this is not invariably the case (119, 120). Despite the fact that tricyclic antidepressants are no longer typically used as first-line agents because of problems with tolerability and toxicity, they are efficacious (120–125) and may still be indicated in individuals whose illness has not responded to other treatments.

Gender may also play a role in response to and tolerability with specific antidepressants, but findings across studies are inconsistent (126–132).

As noted in the guideline, there is some evidence that addition of cognitive-behavior psychotherapy may be beneficial for patients who have had only a partial response to pharmacotherapy. However, more recent findings have been mixed, with some (87, 133) but not all (88) studies showing adjunctive psychotherapy to be beneficial. One study suggests that in women, outcomes with combined treatment may not be as good as outcomes using sequential treatment with initial interpersonal psychotherapy followed by pharmacotherapy in nonresponders (134). Although the full implications of this finding are unclear, the sequential treatment approach merits further study and may be of particular relevance to women in the childbearing years.

Treatment of Depression in Older Adults

A number of recent randomized, controlled trials have examined the treatment of depression in older adults. Comparisons of several SSRIs with the tricyclic antidepressant nortriptyline show better tolerability with SSRIs in this group of patients (135–137). Although the efficacies of nortriptyline and SSRIs generally appear to be comparable (135, 136), some data suggest that nortriptyline may be more effective in severely depressed individuals (137). An additional randomized, controlled outpatient trial showed comparable efficacy for two SSRIs, sertraline and fluoxetine, in the acute treatment of major depression (138).

Maintenance antidepressant therapy is associated with a lesser likelihood of relapse in older adults (139, 140). These data extend the findings of Reynolds et al. (141), discussed in the guideline, which showed antidepressant medication (nortriptyline) or interpersonal therapy to be effective maintenance therapy for elderly patients with recurrent major depressive disorder.

In the PROSPECT study (142), in which elderly patients were treated in primary care practices with facilitation by case managers, interventions included treatment with an antidepressant (typically citalopram) and interpersonal psychotherapy (for patients who declined antidepressant). Compared with treatment as usual, intervention was associated with more rapid and more prominent reductions in suicidal ideation and depressive symptoms, and the beneficial impact on depression extended throughout the 12-month study period. Although not all patients in the intervention group continued to receive treatment for depression throughout the study period, a greater proportion of intervention patients received ongoing treatment compared with the treatment-as-usual group, strengthening the observation that maintenance treatment is beneficial in depressed older adults.

Several studies have compared antidepressant treatment, nonpharmacological treatments, or combined treatments in older adults. Blumenthal et al. (143) found comparable rates of response in older depressed patients randomly assigned to treatment with sertraline, aerobic exercise, or combination treatment. After 10 months, greater sustained benefit was seen in the exercise-alone group, whereas response rates in the sertraline-alone and sertraline-plus-exercise groups were comparable (71). Thompson et al. (144) showed combination treatment with desipramine and CBT to be better than desipramine alone, comparable to CBT alone, and of particular benefit in elderly outpatients who were severely depressed. These findings supplement those of Reynolds et al. (141), who showed a trend for superior acute response with combined nortriptyline and interpersonal therapy. With maintenance treatment, either therapy was effective in rapid responders to treatment, but combined treatment was superior in patients who had a mixed or delayed response to initial therapy (139). In addition, combination therapy was more effective in maintaining social adjustment than either therapy alone (145).

References

1. American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157:1–45

2. Aranda-Michel J, Koehler A, Bejarano PA, Poulos JE, Luxon BA, Khan CM, Ee LC, Balistreri WF, Weber FL Jr: Nefazodone-induced liver failure: report of three cases. Ann Intern Med 1999; 130:285–288
[PubMed]

3. Choi S: Nefazodone (Serzone) withdrawn because of hepatotoxicity. CMAJ 2003; 169:1187
[PubMed]

4. Conway CR, McGuire JM, Baram VY: Nefazodone-induced liver failure. J Clin Psychopharmacol 2004; 24:353–354
[PubMed]

5. Eloubeidi MA, Gaede JT, Swaim MW: Reversible nefazodone-induced liver failure. Dig Dis Sci 2000; 45:1036–1038
[PubMed]

6. Lucena MI, Andrade RJ, Gomez-Outes A, Rubio M, Cabello MR: Acute liver failure after treatment with nefazodone. Dig Dis Sci 1999; 44:2577–2579
[PubMed]

7. Schirren CA, Baretton G: Nefazodone-induced acute liver failure. Am J Gastroenterol 2000; 95:1596–1597
[PubMed]

8. Tzimas GN, Dion B, Deschenes M: Early onset, nefazodone-induced fulminant hepatic failure. Am J Gastroenterol 2003; 98:1663–1664
[PubMed]

9. Food and Drug Administration: Labeling Change Request Letter for Antidepressant Medications. Rockville, Md, October 28, 2004. Available at: http://www.fda.gov/cder/drug/antidepressants/SSRIlabelChange.htm

10. Newman TB: A black-box warning for antidepressants in children? N Engl J Med 2004; 351:1595–1598
[PubMed]

11. National Center for Injury Prevention and Control: Web-based Injury Statistics Query and Reporting System (WISQARS). Atlanta, Ga, Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/ncipc/wisqars

12. American Academy of Child and Adolescent Psychiatry: Practice parameter for the assessment and treatment of children and adolescents with suicidal behavior. J Am Acad Child Adolesc Psychiatry 2001; 40:24S–51S

13. American Psychiatric Association: Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry 2003; 160(suppl 11):1–60

14. Brent DA: Antidepressants and pediatric depression: the risk of doing nothing. N Engl J Med 2004; 351:1598–1601
[PubMed]

15. American Academy of Child and Adolescent Psychiatry: Message to Members and Supplementary Talking Points for Child and Adolescent Psychiatrists Regarding the FDA Black Box Warning on the Use of Antidepressants for Pediatric Patients Washington, DC, 2004. Available at: http://www.aacap.org/press_releases/2004/SSRIemail10_29_041.pdf

16. American Psychiatric Association: News Release: APA Statement on the FDA's Hearing on Antidepressant Use in Pediatric Patients. Arlington, Va, September 16, 2004. Available at: http://www.psych.org/news_room/press_releases/antidepressantuse09202004.pdf

17. American Academy of Child and Adolescent Psychiatry: Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 1998; 37:63S–83S

18. March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J: Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA 2004; 292:807–820
[PubMed]

19. Grunebaum MF, Ellis SP, Li S, Oquendo MA, Mann JJ: Antidepressants and suicide risk in the United States, 1985–1999. J Clin Psychiatry 2004; 65:1456–1462
[PubMed]

20. Olfson M, Shaffer D, Marcus SC, Greenberg T: Relationship between antidepressant medication treatment and suicide in adolescents. Arch Gen Psychiatry 2003; 60:978–982
[PubMed]

21. Burke WJ, Gergel I, Bose A: Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002; 63:331–336
[PubMed]

22. Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry 2004; 65:1190–1196
[PubMed]

23. Montgomery SA, Huusom AK, Bothmer J: A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology 2004; 50:57–64
[PubMed]

24. Lepola U, Wade A, Andersen HF: Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder. Int Clin Psychopharmacol 2004; 19:149–155
[PubMed]

25. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA: Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res 2002; 36:383–390
[PubMed]

26. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA: Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002; 63:308–315
[PubMed]

27. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA: Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 2002; 63:225–231
[PubMed]

28. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA: Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol 2004; 24:389–399
[PubMed]

29. Goldstein DJ, Lu Y, Detke MJ, Hudson J, Iyengar S, Demitrack MA: Effects of duloxetine on painful physical symptoms associated with depression. Psychosomatics 2004; 45:17–28
[PubMed]

30. Fava M, Mallinckrodt CH, Detke MJ, Watkin JG, Wohlreich MM: The effect of duloxetine on painful physical symptoms in depressed patients: do improvements in these symptoms result in higher remission rates? J Clin Psychiatry 2004; 65:521–530
[PubMed]

31. Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, Goldstein DJ: A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004; 50:2974–2984
[PubMed]

32. Dunner DL, Goldstein DJ, Mallinckrodt C, Lu Y, Detke MJ: Duloxetine in treatment of anxiety symptoms associated with depression. Depress Anxiety 2003; 18:53–61
[PubMed]

33. Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, Mitchell PB, Centorrino F, Risser R, Baker RW, Evans AR, Beymer K, Dube S, Tollefson GD, Breier A: Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60:1079–1088
[PubMed]

34. Rothschild AJ, Williamson DJ, Tohen MF, Schatzberg A, Andersen SW, Van Campen LE, Sanger TM, Tollefson GD: A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features. J Clin Psychopharmacol 2004; 24:365–373
[PubMed]

35. Corya SA, Andersen SW, Detke HC, Kelly LS, Van Campen LE, Sanger TM, Williamson DJ, Dube S: Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study. J Clin Psychiatry 2003; 64:1349–1356
[PubMed]

36. Shelton RC, Tollefson GD, Tohen M, Stahl S, Gannon KS, Jacobs TG, Buras WR, Bymaster FP, Zhang W, Spencer KA, Feldman PD, Meltzer HY: A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001; 158:131–134
[PubMed]

37. Berigan TR: Atomoxetine used adjunctively with selective serotonin reuptake inhibitors to treat depression. Prim Care Companion J Clin Psychiatry 2004; 6:93–94
[PubMed]

38. Chouinard G, Annable L, Bradwejn J: An early phase II clinical trial of tomoxetine (LY139603) in the treatment of newly admitted depressed patients. Psychopharmacology (Berl) 1984; 83:126–128
[PubMed]

39. Chouinard G, Annable L, Bradwejn J, Labonte A, Jones B, Mercier P, Belanger MC: An early phase II clinical trial with followup of tomoxetine (LY139603) in the treatment of newly admitted depressed patients. Psychopharmacol Bull 1985; 21:73–76
[PubMed]

40. Kalb R, Trautmann-Sponsel RD, Kieser M: Efficacy and tolerability of Hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients: a randomized double-blind multicenter clinical trial. Pharmacopsychiatry 2001; 34:96–103
[PubMed]

41. Lecrubier Y, Clerc G, Didi R, Kieser M: Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002; 159:1361–1366
[PubMed]

42. Philipp M, Kohnen R, Hiller KO: Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ 1999; 319:1534–1538
[PubMed]

43. Friede M, Henneicke von Zepelin HH, Freudenstein J: Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort. Pharmacopsychiatry 2001; 34(suppl 1):S38–S41

44. Schrader E: Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild–moderate depression. Int Clin Psychopharmacol 2000; 15:61–68
[PubMed]

45. Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U: Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 2001; 285:1978–1986
[PubMed]

46. Hypericum Depression Trial Study Group: Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002; 287:1807–1814

47. Bjerkenstedt L, Edman GV, Alken RG, Mannel M: Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients. Eur Arch Psychiatry Clin Neurosci 2004 (epub 12 Nov)

48. van Gurp G, Meterissian GB, Haiek LN, McCusker J, Bellavance F: St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002; 48:905–912

49. Behnke K, Jensen GS, Graubaum HJ, Gruenwald J: Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther 2002; 19:43–52
[PubMed]

50. Harrer G, Schmidt U, Kuhn U, Biller A: Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung 1999; 49:289–296
[PubMed]

51. Werneke U, Horn O, Taylor DM: How effective is St John's wort? The evidence revisited. J Clin Psychiatry 2004; 65:611–617
[PubMed]

52. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P: St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54:349–356
[PubMed]

53. Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HH: St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004; 75:191–197
[PubMed]

54. Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, Mulcahy F, Feely J: St John's wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002; 53:75–82
[PubMed]

55. Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD: Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290:1500–1504
[PubMed]

56. Obach RS: Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 2000; 294:88–95
[PubMed]

57. UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361:799–808

58. Kho KH, van Vreeswijk MF, Simpson S, Zwinderman AH: A meta-analysis of electroconvulsive therapy efficacy in depression. J ECT 2003; 19:139–147
[PubMed]

59. Husain MM, Rush AJ, Fink M, Knapp R, Petrides G, Rummans T, Biggs MM, O'Connor K, Rasmussen K, Litle M, Zhao W, Bernstein HJ, Smith G, Mueller M, McClintock SM, Bailine SH, Kellner CH: Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a Consortium for Research in ECT (CORE) report. J Clin Psychiatry 2004; 65:485–491
[PubMed]

60. McCall WV, Reboussin DM, Weiner RD, Sackeim HA: Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects. Arch Gen Psychiatry 2000; 57:438–444
[PubMed]

61. Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, Fitzsimons L, Moody BJ, Clark J: A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 2000; 57:425–434
[PubMed]

62. Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA: The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry 2000; 57:581–590
[PubMed]

63. McCall WV, Dunn A, Rosenquist PB, Hughes D: Markedly suprathreshold right unilateral ECT versus minimally suprathreshold bilateral ECT: antidepressant and memory effects. J ECT 2002; 18:126–129
[PubMed]

64. American Psychiatric Association: The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. A Task Force Report of the American Psychiatric Association, 2nd Edition. Washington, DC, American Psychiatric Press, 2001

65. Dowrick C, Dunn G, Ayuso-Mateos JL, Dalgard OS, Page H, Lehtinen V, Casey P, Wilkinson C, Vazquez-Barquero JL, Wilkinson G: Problem solving treatment and group psychoeducation for depression: multicentre randomised controlled trial. Outcomes of Depression International Network (ODIN) Group. BMJ 2000; 321:1450–1454
[PubMed]

66. Mynors-Wallis LM, Gath DH, Day A, Baker F: Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ 2000; 320:26–30
[PubMed]

67. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, Markowitz JC, Nemeroff CB, Russell JM, Thase ME, Trivedi MH, Zajecka J: A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000; 342:1462–1470
[PubMed]

68. Leichsenring F: Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach. Clin Psychol Rev 2001; 21:401–419
[PubMed]

69. Wampold BE, Minami T, Baskin TW, Callen TS: A meta-(re)analysis of the effects of cognitive therapy versus "other therapies" for depression. J Affect Disord 2002; 68:159–165
[PubMed]

70. Mather AS, Rodriguez C, Guthrie MF, McHarg AM, Reid IC, McMurdo ME: Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomised controlled trial. Br J Psychiatry 2002; 180:411–415
[PubMed]

71. Babyak M, Blumenthal JA, Herman S, Khatri P, Doraiswamy M, Moore K, Craighead WE, Baldewicz TT, Krishnan KR: Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med 2000; 62:633–638
[PubMed]

72. de Jonghe F, Hendricksen M, van Aalst G, Kool S, Peen V, Van R, van den EE, Dekker J: Psychotherapy alone and combined with pharmacotherapy in the treatment of depression. Br J Psychiatry 2004; 185:37–45

73. de Jonghe F, Kool S, van Aalst G, Dekker J, Peen J: Combining psychotherapy and antidepressants in the treatment of depression. J Affect Disord 2001; 64:217–229

74. Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C: Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry 2004; 61:714–719
[PubMed]

75. Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT, McCullough JP Jr, Weiss PM, Dunner DL, Rothbaum BO, Kornstein S, Keitner G, Keller MB: Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci USA 2003; 100:14293–14296
[PubMed]

76. Thase ME, Rush AJ, Manber R, Kornstein SG, Klein DN, Markowitz JC, Ninan PT, Friedman ES, Dunner DL, Schatzberg AF, Borian FE, Trivedi MH, Keller MB: Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression. J Clin Psychiatry 2002; 63:493–500
[PubMed]

77. Kool S, Dekker J, Duijsens IJ, de Jonghe F, Puite B: Efficacy of combined therapy and pharmacotherapy for depressed patients with or without personality disorders. Harv Rev Psychiatry 2003; 11:133–141
[PubMed]

78. Kocsis JH, Schatzberg A, Rush AJ, Klein DN, Howland R, Gniwesch L, Davis SM, Harrison W: Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo. Arch Gen Psychiatry 2002; 59:723–728
[PubMed]

79. Koran LM, Gelenberg AJ, Kornstein SG, Howland RH, Friedman RA, DeBattista C, Klein D, Kocsis JH, Schatzberg AF, Thase ME, Rush AJ, Hirschfeld RM, LaVange LM, Keller MB: Sertraline versus imipramine to prevent relapse in chronic depression. J Affect Disord 2001; 65:27–36
[PubMed]

80. Lepine JP, Caillard V, Bisserbe JC, Troy S, Hotton JM, Boyer P: A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder. Am J Psychiatry 2004; 161:836–842
[PubMed]

81. Simon JS, Aguiar LM, Kunz NR, Lei D: Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. J Psychiatr Res 2004; 38:249–257
[PubMed]

82. Thase ME, Nierenberg AA, Keller MB, Panagides J: Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients. J Clin Psychiatry 2001; 62:782–788
[PubMed]

83. Petersen T, Harley R, Papakostas GI, Montoya HD, Fava M, Alpert JE: Continuation cognitive-behavioural therapy maintains attributional style improvement in depressed patients responding acutely to fluoxetine. Psychol Med 2004; 34:555–561
[PubMed]

84. Kocsis JH, Rush AJ, Markowitz JC, Borian FE, Dunner DL, Koran LM, Klein DN, Trivedi MH, Arnow B, Keitner G, Kornstein SG, Keller MB: Continuation treatment of chronic depression: a comparison of nefazodone, cognitive behavioral analysis system of psychotherapy, and their combination. Psychopharmacol Bull 2003; 37:73–87
[PubMed]

85. Scott J, Palmer S, Paykel E, Teasdale J, Hayhurst H: Use of cognitive therapy for relapse prevention in chronic depression: cost-effectiveness study. Br J Psychiatry 2003; 182:221–227
[PubMed]

86. Klein DN, Santiago NJ, Vivian D, Blalock JA, Kocsis JH, Markowitz JC, McCullough JP Jr, Rush AJ, Trivedi MH, Arnow BA, Dunner DL, Manber R, Rothbaum B, Thase ME, Keitner GI, Miller IW, Keller MB: Cognitive-behavioral analysis system of psychotherapy as a maintenance treatment for chronic depression. J Consult Clin Psychol 2004; 72:681–688
[PubMed]

87. Paykel ES, Scott J, Teasdale JD, Johnson AL, Garland A, Moore R, Jenaway A, Cornwall PL, Hayhurst H, Abbott R, Pope M: Prevention of relapse in residual depression by cognitive therapy: a controlled trial. Arch Gen Psychiatry 1999; 56:829–835
[PubMed]

88. Perlis RH, Nierenberg AA, Alpert JE, Pava J, Matthews JD, Buchin J, Sickinger AH, Fava M: Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder. J Clin Psychopharmacol 2002; 22:474–480
[PubMed]

89. Stimpson N, Agrawal N, Lewis G: Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression: systematic review. Br J Psychiatry 2002; 181:284–294
[PubMed]

90. Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP, Leight KL, Whybrow PC: Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001; 158:1617–1622
[PubMed]

91. Bauer M, Dopfmer S: Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 1999; 19:427–434
[PubMed]

92. Januel D, Poirier MF, D'alche-Biree F, Dib M, Olie JP: Multicenter double-blind randomized parallel-group clinical trial of efficacy of the combination clomipramine (150 mg/day) plus lithium carbonate (750 mg/day) versus clomipramine (150 mg/day) plus placebo in the treatment of unipolar major depression. J Affect Disord 2003; 76:191–200
[PubMed]

93. Appelberg BG, Syvalahti EK, Koskinen TE, Mehtonen OP, Muhonen TT, Naukkarinen HH: Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry 2001; 62:448–452
[PubMed]

94. Normann C, Hummel B, Scharer LO, Horn M, Grunze H, Walden J: Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry 2002; 63:337–344
[PubMed]

95. Furukawa TA, Streiner DL, Young LT: Is antidepressant-benzodiazepine combination therapy clinically more useful? A meta-analytic study. J Affect Disord 2001; 65:173–177
[PubMed]

96. Nemets B, Stahl Z, Belmaker RH: Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 2002; 159:477–479
[PubMed]

97. Su KP, Huang SY, Chiu CC, Shen WW: Omega-3 fatty acids in major depressive disorder: a preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003; 13:267–271
[PubMed]

98. Peet M, Horrobin DF: A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59:913–919
[PubMed]

99. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ: A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003; 160:996–998
[PubMed]

100. Soares CN, Almeida OP, Joffe H, Cohen LS: Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001; 58:529–534
[PubMed]

101. Morrison MF, Kallan MJ, Ten Have T, Katz I, Tweedy K, Battistini M: Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial. Biol Psychiatry 2004; 55:406–412
[PubMed]

102. Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF: An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 2002; 52:386–392
[PubMed]

103. Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF: Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol 2001; 21:516–521
[PubMed]

104. Menza MA, Kaufman KR, Castellanos A: Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry 2000; 61:378–381
[PubMed]

105. Schwartz TL, Azhar N, Cole K, Hopkins G, Nihalani N, Simionescu M, Husain J, Jones N: An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy. J Clin Psychiatry 2004; 65:1223–1227
[PubMed]

106. Ninan PT, Hassman HA, Glass SJ, McManus FC: Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue. J Clin Psychiatry 2004; 65:414–420
[PubMed]

107. DeBattista C, Lembke A, Solvason HB, Ghebremichael R, Poirier J: A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol 2004; 24:87–90
[PubMed]

108. DeBattista C, Doghramji K, Menza MA, Rosenthal MH, Fieve RR: Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003; 64:1057–1064
[PubMed]

109. Schmidt ME, Fava M, Zhang S, Gonzales J, Raute NJ, Judge R: Treatment approaches to major depressive disorder relapse, part 1: dose increase. Psychother Psychosom 2002; 71:190–194
[PubMed]

110. Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C: Effectiveness of antidepressants: meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 1999; 174:297–303
[PubMed]

111. Mehtonen OP, Sogaard J, Roponen P, Behnke K: Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry 2000; 61:95–100
[PubMed]

112. Rudolph RL, Feiger AD: A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord 1999; 56:171–181
[PubMed]

113. Schatzberg AF, Kremer C, Rodrigues HE, Murphy GM Jr: Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry 2002; 10:541–550
[PubMed]

114. Tzanakaki M, Guazzelli M, Nimatoudis I, Zissis NP, Smeraldi E, Rizzo F: Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol 2000; 15:29–34
[PubMed]

115. Entsuah AR, Huang H, Thase ME: Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry 2001; 62:869–877
[PubMed]

116. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I: Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 2002; 180:396–404
[PubMed]

117. Stahl SM, Entsuah R, Rudolph RL: Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry 2002; 52:1166–1174
[PubMed]

118. Thase ME, Entsuah AR, Rudolph RL: Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178:234–241
[PubMed]

119. Freemantle N, Anderson IM, Young P: Predictive value of pharmacological activity for the relative efficacy of antidepressant drugs: meta-regression analysis. Br J Psychiatry 2000; 177:292–302
[PubMed]

120. Anderson IM: Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000; 58:19–36
[PubMed]

121. Joyce PR, Mulder RT, Luty SE, McKenzie JM, Rae AM: A differential response to nortriptyline and fluoxetine in melancholic depression: the importance of age and gender. Acta Psychiatr Scand 2003; 108:20–23
[PubMed]

122. Montgomery SA: A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression. Int Clin Psychopharmacol 2001; 16:169–178
[PubMed]

123. Nelson JC, Mazure CM, Jatlow PI, Bowers MB Jr, Price LH: Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 2004; 55:296–300
[PubMed]

124. Robinson RG, Schultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, Curdue K, Petracca G, Starkstein SE: Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry 2000; 157:351–359
[PubMed]

125. Guaiana G, Barbui C, Hotopf M: Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev 2003, CD004186

126. Baca E, Garcia-Garcia M, Porras-Chavarino A: Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28:57–65
[PubMed]

127. Joyce PR, Mulder RT, Luty SE, Sullivan PF, McKenzie JM, Abbott RM, Stevens IF: Patterns and predictors of remission, response, and recovery in major depression treated with fluoxetine or nortriptyline. Aust N Z J Psychiatry 2002; 36:384–391
[PubMed]

128. Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Davis SM, Harrison WM, Keller MB: Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 2000; 157:1445–1452
[PubMed]

129. Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E, Chen Y, Ma G, Klein DF: Are there differences between women's and men's antidepressant responses? Am J Psychiatry 2002; 159:1848–1854
[PubMed]

130. Scheibe S, Preuschhof C, Cristi C, Bagby RM: Are there gender differences in major depression and its response to antidepressants? J Affect Disord 2003; 75:223–235
[PubMed]

131. Parker G, Parker K, Austin MP, Mitchell P, Brotchie H: Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med 2003; 33:1473–1477
[PubMed]

132. Wohlfarth T, Storosum JG, Elferink AJ, van Zwieten BJ, Fouwels A, van den BW: Response to tricyclic antidepressants: independent of gender? Am J Psychiatry 2004; 161:370–372
[PubMed]

133. Kennedy SH, Segal ZV, Cohen NL, Levitan RD, Gemar M, Bagby RM: Lithium carbonate versus cognitive therapy as sequential combination treatment strategies in partial responders to antidepressant medication: an exploratory trial. J Clin Psychiatry 2003; 64:439–444
[PubMed]

134. Frank E, Grochocinski VJ, Spanier CA, Buysse DJ, Cherry CR, Houck PR, Stapf DM, Kupfer DJ: Interpersonal psychotherapy and antidepressant medication: evaluation of a sequential treatment strategy in women with recurrent major depression. J Clin Psychiatry 2000; 61:51–57
[PubMed]

135. Mulsant BH, Pollock BG, Nebes R, Miller MD, Sweet RA, Stack J, Houck PR, Bensasi S, Mazumdar S, Reynolds CF III: A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients. Am J Geriatr Psychiatry 2001; 9:406–414
[PubMed]

136. Bondareff W, Alpert M, Friedhoff AJ, Richter EM, Clary CM, Batzar E: Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life. Am J Psychiatry 2000; 157:729–736
[PubMed]

137. Navarro V, Gasto C, Torres X, Marcos T, Pintor L: Citalopram versus nortriptyline in late-life depression: a 12-week randomized single-blind study. Acta Psychiatr Scand 2001; 103:435–440
[PubMed]

138. Newhouse PA, Krishnan KR, Doraiswamy PM, Richter EM, Batzar ED, Clary CM: A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. J Clin Psychiatry 2000; 61:559–568
[PubMed]

139. Dew MA, Reynolds CF III, Mulsant B, Frank E, Houck PR, Mazumdar S, Begley A, Kupfer DJ: Initial recovery patterns may predict which maintenance therapies for depression will keep older adults well. J Affect Disord 2001; 65:155–166
[PubMed]

140. Klysner R, Bent-Hansen J, Hansen HL, Lunde M, Pleidrup E, Poulsen DL, Andersen M, Petersen HE: Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy. Br J Psychiatry 2002; 181:29–35
[PubMed]

141. Reynolds CF III, Frank E, Perel JM, Imber SD, Cornes C, Miller MD, Mazumdar S, Houck PR, Dew MA, Stack JA, Pollock BG, Kupfer DJ: Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years. JAMA 1999; 281:39–45
[PubMed]

142. Bruce ML, Ten Have TR, Reynolds CF III, Katz II, Schulberg HC, Mulsant BH, Brown GK, McAvay GJ, Pearson JL, Alexopoulos GS: Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA 2004; 291:1081–1091
[PubMed]

143. Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR: Effects of exercise training on older patients with major depression. Arch Intern Med 1999; 159:2349–2356
[PubMed]

144. Thompson LW, Coon DW, Gallagher-Thompson D, Sommer BR, Koin D: Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mild-to-moderate depression. Am J Geriatr Psychiatry 2001; 9:225–240
[PubMed]

145. Lenze EJ, Dew MA, Mazumdar S, Begley AE, Cornes C, Miller MD, Imber SD, Frank E, Kupfer DJ, Reynolds CF III: Combined pharmacotherapy and psychotherapy as maintenance treatment for late-life depression: effects on social adjustment. Am J Psychiatry 2002; 159:466–468
[PubMed]