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Treatment for Depression After Unsatisfactory Response to SSRIs in Adults and Adolescents

Treatment for Depression After Unsatisfactory Response to SSRIs in Adults and Adolescents. Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov. Background: Depression. Depressions is a complex mental illness that is associated with: Disability

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Treatment for Depression After Unsatisfactory Response to SSRIs in Adults and Adolescents

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  1. Treatment for Depression After Unsatisfactory Responseto SSRIs in Adults and Adolescents Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov

  2. Background: Depression • Depressions is a complex mental illness that is associated with: • Disability • Reduced quality of life for the person with depression • Substantial societal burden • It is common among adults and adolescents. • It is characterized by chronic, recurrent episodes that significantly impact disability and mortality. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  3. Background: Depressive Disorders • Major depressive disorder (MDD): characterized by the occurrence of one or more major depressive episodes. • Dysthymic disorder: characterized by the presence of depression symptoms more often than not for at least 2 years. However, symptoms are insufficient to meet MDD criteria. • Subsyndromal depression: subthreshold depression, defined by some professional groups as having at least two depressive symptoms from those listed in the DSM-IV-TR but insufficient symptoms to meet MDD criteria. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. 1994. Cuijpers P, Smit F. Acta Psychiatr Scand. 2004;109(5):325-31. PMID: 15049768. Gartlehner G, Thaler K, Hill S, et al. Curr Psychiatry Rep. 2012;14(4):360-9. PMID: 22648236. Judd LL, Akiskal HS, Paulus MP. J Affect Disord. 1997;45(1-2):5-17. PMID: 9268771. Lavretsky H, Kumar A. Am J Geriatr Psychiatry. 2002;10(3):239-55. PMID: 11994211. Olfson M, Broadhead WE, Weissman MM, et al. Arch Gen Psychiatry. 1996;53(10):880-6. PMID: 8857864. Rapaport MH, Judd LL, Schettler PJ, et al. Am J Psychiatry. 2002;159(4):637-43. PMID: 11925303. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  4. Background: Prevalence of Depressive Disorders • Depression among adults in the United States has an estimated lifetime prevalence of 16 percent and an estimated annual prevalence of 7 percent. • The prevalence of major depressive disorder in adolescents, 12 to 16 years of age, varies from 4 to 8 percent but has been reported to be as high as 20 percent. • Risk of depression increases following puberty, especially in girls relative to boys (2:1 ratio). • Reports of dysthymia prevalence vary from 1.6 to 8 percent. • Adolescents with depression have high rates of comorbid psychiatric conditions (reports vary from 40% to 90%). Beck CA, Patten SB. Compr Psychiatry. 2004;45(4):268-74. PMID: 15224269. Birmaher B, Brent D, Bernet W, et al. J Am Acad Child Adolesc Psychiatry. 2007;46(11):1503-26. PMID: 18049300. Birmaher B, Ryan ND, Williamson DE, et al. J Am Acad Child Adolesc Psychiatry. 1996;35(12):1575-83. PMID: 8973063. Brugha T, Jenkins R, Bebbington P, et al. Soc Psychiatry Psychiatr Epidemiol. 2004;39(12):939-46. PMID: 15583900. Kessler RC, Berglund P, Demler O, et al. JAMA. 2003;289(23):3095-105. PMID: 12813115. Kessler RC, Demler O, Frank RG, et al. N Engl J Med. 2005;352(24):2515-23. PMID: 15958807. US Preventive Services Task Force. J Am Acad Pediatr. 2009;123(4):1223-8. PMID: 19336383.

  5. Background: Disease Burden Associated With Major Depressive Disorder • Major depressive disorder is a leading cause of disability throughout the world. • The economic burden of depression is estimated to be $83.1 billion per year. • Depressive disorders negatively affect quality of life: • Negative effect on children and family dynamics • Negative impact on occupational/school functioning • Negative impact on physical health • Reduced treatment adherence and preventative activities • Increased risk factors (e.g., obesity, smoking, sedentary lifestyle) • Increase in chronic disease incidence • Increased mortality rates and suicide Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  6. Background: Clinical Assessment • Depression is frequently underdiagnosed in primary practice. • Only an estimated 42 percent of adult patients with major depression were diagnosed by primary care physicians. • Primary care physicians encounter a broad spectrum of depressive symptoms. • A comparative study found no major differences in benefits between several instruments used for monitoring depressive symptoms. • Patients in primary care may not be receptive to suggested treatment for a condition that was not the reason for the visit to the physician. Rush AJ, Trivedi MH, Wisniewski SR, et al. N Engl J Med. 2006;354(12):1231-42. PMID: 16554525. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm. Williams JW, Pignone M, Ramirez G, et al. Gen Hosp Psychiatry. 2002;24(4):225-37. PMID:12100833.

  7. Background: Three Phases of Treatment for Major Depressive Disorder • Acute phase • Elimination of symptoms of depression and the restoration of psychosocial functioning with a target goal of remission • Continuation phase • Prolongation of treatment from 4 to 9 months to completely resolve a depressive episode • Maintenance phase • Prevention of recurrence of new episodes of major depressive disorder Kupfer DJ. J Clin Psychiatry. 1991;52 Suppl:28-34. PMID: 1903134. McIntyre RS, Fallu A, Konarski JZ, et al. Clin Ther. 2006;28(11):1882-91. PMID: 17213009. Paykel ES, Ramana R, Cooper Z, et al. Psychol Med. 1995;25(6):1171-80. PMID: 8637947.

  8. Background: Pharmacological Treatment for Major Depressive Disorder • Pharmacological agents are one of several treatment modalities used for depression. • Selective serotonin-reuptake inhibitors (SSRIs) are frequently used to treat depression. • A 50-percent decrease in symptom severity constitutes a response to SSRIs. • Remission is defined as free or nearly free of symptoms for the current episode. Carvalho AF, Cavalcante JL, Castelo MS, et al. J Clin Pharm Ther. 2007;32(5):415-28. PMID: 17875106. McIntyre RS, Fallu A, Konarski JZ. Clin Ther. 2006;28(11):1882-91. PMID: 17213009. Souery D, Papakostas GI, Trivedi MH. J Clin Psychiatry. 2006;67(Suppl 6):16-22. PMID: 16848672.

  9. Background: Inadequate Response to Selective Serotonin-Reuptake Inhibitors • Although patients with major depressive disorder have a 63-percent response rate during 6 to 12 weeks of treatment with second-generation antidepressants, 53 percent did not achieve remission. • Additionally, up to two-thirds of patients may not achieve remission with a selective serotonin-reuptake inhibitor (SSRI), a commonly used class of second-generation antidepressants. • In a review on the efficacy of treatment for adolescents, those failing to respond to an initial trial of SSRIs varied from 31 to 64 percent. • Up to 60 percent of adolescents on combined treatment for depression respond positively to these interventions. Brent D, Emslie G, Clarke G, et al. JAMA. 2008;299(8):901-13. PMID: 18314433. Gartlehner G, Hansen R, Morgan LC, et al. Ann Intern Med. 2011;155:772-85. PMID: 22147715. Perahia DG, Quail D, Desaiah D. J Psychiatr Res. 2009;43(5):512-8. PMID: 18707693. Souery D, Papakostas GI, Trivedi MH. J Clin Psychiatry. 2006;67(Suppl 6):16-22. 3. PMID: 16848672. Trivedi MH, Greer TL, Grannemann BD, et al. J Psychiatr Pract. 2006;12(4):205-13. PMID: 16883145. Williams AL, Girard C, Jui D, et al. Clin Invest Med. 2005;28(3):132-9. PMID: 16021987.

  10. Background: Treatment-Resistant Depression • Some patients who have an inadequate response may go on to have their depression defined as treatment resistant if they do not respond to subsequent treatments. • Treatment resistance usually describes depression that has not responded to at least two trials of medication that have been of adequate dose and duration. • Nonadherence may account for up to 20 percent of patients classified as having treatment-resistant depression. • Heterogeneity exists across studies that evaluate the efficacy of selective serotonin-reuptake inhibitors within this patient population. Berlim MT, Fleck MP, Turecki G. Ann Med. 2008;40(2):149-59. PMID: 18293145. Souery D, Amsterdam J, de Montigny C, et al. Eur Neuropsychopharmacol. 1999;9(1-2):83-91. PMID: 10082232.

  11. Background: Different Treatment Options After an Inadequate Response to Selective Serotonin-Reuptake Inhibitors • Monotherapy options • Using an optimization strategy • Switching to another selective serotonin-reuptake inhibitor (SSRI) • Switching to another class of antidepressants • Switching to a nonpharmacological intervention • Combination or add-on therapy options: • Adding medications (e.g., augmenting agents, a different SSRI, or other antidepressants) • Switching to another agent (e.g., a different SSRI) and adding another medication • Adding a nonpharmacological treatment • Combinations of these treatments • Fava M. Biol Psychiatry. 2003;53(8):649-59. PMID: 12706951. • Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  12. Scope and Purpose of the Comparative Effectiveness Review on Treatments for Depression After Unsatisfactory Response to a Selective Serotonin-Reuptake Inhibitor • A variety of treatment strategies aimed at helping individuals who have inadequate responses to selective serotonin-reuptake inhibitors (SSRIs) have been studied in patients with depression. • Primary goals of the comparative effectiveness review (CER) include: • Examining the evidence guiding clinical treatment decisions • Aiding clinicians in their care of patients when SSRI therapy does not result in an adequate treatment response • This CME activity will summarize these results from the CER: • The range of recommended clinical actions following failure of an adequate course of an SSRI based on clinical practice guidelines • Benefits/adverse effects of monotherapy and combination therapies for adults whose depression failed to improve on an SSRI • How the therapies compare in different populations Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  13. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development • Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, the public, and others. • A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment. • The results of these reviews are summarized into Clinician Research Summaries and Consumer Research Summaries for use in decisionmaking and in discussions with patients. The research reviews and the full report, with references for included and excluded studies, are available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  14. Rating the Strength of Evidence From the Comparative Effectiveness Review • The strength of evidence was classified into four broad categories: AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Available at http://www.effectivehealthcare.ahrq.gov/methodsguide.cfm. Brozek J, Oxman A, Schünemann H. GRADEpro [computer program]. Version 3.2 for Windows. Available at http://www.cc-ims.net/revman/other-resources/gradepro/gradepro. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  15. SSRI* Interventions Eligible for Inclusion in the Comparative Effectiveness Review • Citalopram (Celexa®) • Escitalopram (Lexapro®) • Fluoxetine (Prozac®, Prozac Weekly®, Sarafem®, and Symbyax®) • Fluvoxamine (Luvox® and Luvox CR®) • Paroxetine (Paxil®, Paxil CR®, and Pexeva®) • Sertraline (Zoloft®) *Concomitant use of selective serotonin-reuptake inhibitors (SSRIs) in patients taking monoamine oxidase inhibitors (MAOIs; e.g., phenelzine [Nardil®], selegiline transdermal system [EMSAM®], tranylcypromine [Parnate®]) is contraindicated, as cases of serious and sometimes fatal reactions have been reported. These reactions have also been reported in patients who have recently discontinued an SSRI or other drugs that interfere with serotonin metabolism and have been started on an MAOI. For additional information, see the U.S. Food and Drug Administration safety announcements at www.fda.gov. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  16. Non-SSRI Antidepressants Eligible for Inclusion in the Comparative Effectiveness Review (1 of 2) • Amitriptyline and its combination with other drugs (Amitid®, Amitril®, Elavil®, Endep®, Etrafon 2-10, Etrafon 2-25, Etrafon-a, Etrafon-Forte, Limbitrol®, Limbitrol DS®, Perphenazine®, Triavil 2-10, Triavil 2-25, and Triavil 4-10) • Bupropion (Aplenzin®, Wellbutrin®, Wellbutrin SR®, Wellbutrin XL®, and Zyban®) • Clomipramine (Anafranil®) • Desipramine (Norpramin® and Pertofrane®) • Desvenlafaxine (Pristiq®) • Doxepin (Sinequan® and Zonalon®) • Duloxetine (Cymbalta®) • Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  17. Non-SSRI Antidepressants Eligible for Inclusion in the Comparative Effectiveness Review (2 of 2) • Imipramine (Janimine®, Presamine®, Tofranil®, Tofranil-PM®) • Maprotiline (Ludiomil®) • Mirtazapine (Remeron® and Remeron SolTab®) • Phenelzine (Nardil®) • Protriptyline (Vivactil®) • Selegiline transdermal system (EMSAM®) • Tranylcypromine (Parnate®) • Trazodone (Desyrel® and Trialodine®) • Trimipramine (Surmontil®) • Venlafaxine (Effexor® and Effexor XR®) • Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  18. Nonantidepressant and Nonpharmacological Interventions Eligible for Inclusion in the CER • Nonantidepressant agents • Anticonvulsants • Antiprogestational agents • Dopamine agonists • Psychostimulants • Sex hormones • Thyroid medications • Other drugs such as buspirone (Buspar®), lithium, pindolol, and tryptophan • Atypical antipsychotics* • Aripiprazole (Abilify®) • Olanzapine (Zyprexa®) • Quetiapine (Seroquel®) • Risperidone (Risperdal®) • Ziprasidone (Geodon®) • Nonpharmacological therapies • Cognitive behavioral therapy • Exercise • Interpersonal therapy • Other psychotherapies • Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  19. Outcomes of Importance • A number of outcomes are used within primary care and psychiatry to assess and monitor response to treatment. • Outcomes may be assessed with self-report instruments or scales that are completed by the clinician. • Outcome assessment is usually conducted with validated interviewer-rated scales such as the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Scale. • Response is typically defined as a greater than 50-percent reduction in scores on these scales. • Remission is defined as a score within the normal range on these scales. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  20. CER Results for Available Treatment Options for Adults and Adolescents With MDD Who Have an Inadequate Response to SSRIs • Analysis of Clinical Practice Guidelines • Monotherapy options • Optimizing the current selective serotonin-reuptake inhibitor (SSRI) • Switching monotherapy agents • Monotherapy versus combination therapy • Adding medications to the existing SSRI • Adding medications to a new antidepressant • Adding nonpharmacological treatment to the existing SSRI • Combination therapies CER = comparative effectiveness review; MDD = major depressive disorder Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  21. Analysis of Clinical Practice Guidelines (1 of 2) • Variations among clinical practice guidelines (CPGs) reflect the high amount of uncertainty that exists in the current evidence base. • Of the 27 CPGs reviewed (guidelines from January 2004 to April 2011), most do not specify definitions of “inadequate response.” • All 27 CPGs provide recommendations for patients with major depressive disorder, but 7 do not provide any recommendations for patients with previous inadequate responses to therapy. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  22. Analysis of Clinical Practice Guidelines (2 of 2) • When an increase in dose or duration is recommended for adults, the change in dose or duration is not specified. • When switching to a different monotherapy agent is recommended, most CPGs do not mention a specific antidepressant. • When combination therapy is recommended, there is a greater tendency to specify the drug to be added to the antidepressants, but there is great variability in the augmenting agents recommended. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  23. Analysis of Clinical Practice Guidelines: Treating Adolescents With Depression • For adolescents, nonpharmacological interventions are the preferred first-line therapy for depression. • Some clinical practice guidelines cited research done in adult populations as the basis for treatment strategies in children and adolescents. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  24. Clinical Bottom Line for Adults With MDD: Optimizing the Current SSRI or Switching Monotherapy Agents • Evidence is insufficient to determine if differences exist in response and remission rates if treatment with the current selective serotonin-reuptake inhibitor (SSRI) for major depressive disorder (MDD) is maintained versus: • Dose escalation of the current SSRI • Switching to a different SSRI • Switching to a non-SSRI antidepressant • Switching to a psychological intervention (e.g., cognitive behavioral therapy) Strength of Evidence = Insufficient Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  25. Clinical Bottom Line for Adults With MDD: Monotherapy Versus Combination Therapy—Adding Medications to the Existing SSRI • Adding risperidone or olanzapine to ongoing treatment with a selective serotonin-reuptake inhibitor (SSRI) for major depressive disorder (MDD) may slightly improve response and remission rates versus continuing SSRI treatment alone. • Strength of Evidence = Low • Evidence is insufficient to determine if there are differences in response and remission rates for continuing monotherapy with an SSRI versus: • Adding buspirone • Adding other augmenting agents (e.g., lithium or mianserin) • Adding a non-SSRI antidepressant: clomipramine, bupropion, or desipramine • Strength of Evidence = Insufficient Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  26. Clinical Bottom Line for Adults With MDD: Monotherapy Versus Combination Therapy—Adding Medications to a New Antidepressant • For adults with major depressive disorder (MDD), comparable results were achieved in response and remission rates for switching to a new antidepressant versus: • Combining the new monotherapy with another treatment (e.g., a new selective serotonin-reuptake inhibitor [SSRI], a non-SSRI, or nonpharmacological treatment) • Combining the new antidepressant with buspirone Strength of Evidence = Low Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  27. Clinical Bottom Line for Adults With MDD: Monotherapy Versus Combination Therapy—Adding Nonpharmacological Treatment • Evidence is insufficient to determine if there are differences in response and remission rates for continuing therapy for major depressive disorder (MDD) with a selective serotonin-reuptake inhibitor (SSRI) versus combining that SSRI with: • Cognitive behavioral therapy • Dialectical behavioral therapy • Exercise Strength of Evidence = Insufficient Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  28. Clinical Bottom Line for Adults With Major Depressive Disorder: Combination Therapy • Evidence is insufficient to determine if there are differences in response and remission rates when a selective serotonin-reuptake inhibitor (SSRI) is given in combination with another SSRI, another antidepressant, an augmenting agent, or cognitive behavioral therapy. Strength of Evidence = Insufficient Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  29. Clinical Bottom Line for Adults With Major Depressive Disorder: Adverse Effects • In general, most reported adverse effects were consistent with those typically associated with antidepressant use and were likely mild to moderate in nature. • Common adverse events included headaches, dry mouth, dizziness, weight gain, sexual dysfunction, and fatigue. • In adults with major depressive disorder, serious and severe adverse events (e.g., suicidality) were not measured or not reported in most studies, so there is insufficient evidence to compare the adverse effects of various treatment approaches. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  30. Clinical Bottom Line for Adolescents With Major Depressive Disorder • For adolescents with major depressive disorder (MDD) who have an inadequate response to selective serotonin-reuptake inhibitors (SSRIs), adding cognitive behavioral therapy (CBT) may be superior to an SSRI alone. • Strength of Evidence = Low • In one study of adolescents, there were no significant differences in adverse effects for patients on an SSRI or venlafaxine with or without CBT, except for an increase in skin rashes and cardiovascular events in patients on venlafaxine. • The U.S. Food and Drug Administration has issued a warning about suicidality and antidepressant drugs. There is an increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  31. Additional Information • For adults with dysthymia or subsyndromal symptoms who have an inadequate response to selective serotonin-reuptake inhibitors, there is insufficient evidence to evaluate treatment approaches. • Some evidence suggests that people with concurrent anxiety symptoms have a lesser likelihood of achieving remission. • Some evidence suggests that milder depression, less family conflict, and the absence of suicidal behavior are associated with a greater likelihood of a positive treatment response in adolescents. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  32. Conclusions (1 of 2) • Evidence remains limited to support clinical decisionmaking about the available approaches for treating patients with major depressive disorder (MDD) who have an inadequate response to selective serotonin-reuptake inhibitors. • With only a few exceptions, evidence for adults with MDD is insufficient to guide decisionmaking for: • Comparisons among monotherapies • Monotherapies versus combination therapies • Comparisons among combination therapies • Evidence is insufficient to evaluate interventions for adults with dysthymia or subsyndromal symptoms. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  33. Conclusions (2 of 2) • Adding the atypical antipsychotics risperidone or olanzapine to ongoing treatment with a selective serotonin-reuptake inhibitor (SSRI) may slightly improve response and remission rates when compared with continuing SSRI treatment alone. • Low-level evidence suggests that comparable response and remission rates are obtained from switching to a new antidepressant versus combining the new antidepressant with pharmacological or nonpharmacological treatment. • For adults, most reported adverse effects were consistent with those associated with antidepressant use; however, comparative evidence is insufficient to guide decisionmaking about adverse effects in adults. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  34. Conclusions:Adolescents With Major Depressive Disorder • For adolescents with major depressive disorder, low-level evidence suggests that combining an antidepressant and cognitive behavioral therapy may be superior to medication alone. • Comparative evidence is insufficient for decisionmaking about adverse effects in adolescents. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  35. Gaps in Knowledge • Overall, few studies have evaluated the impact of different depressive diagnoses, disease severity, previous comorbidities, age, sex, and race on treatment outcomes. • There is inconsistency between studies in the definition of “inadequate response” and in the distinction between response and remission. • More studies are needed on the response and remission rates in children and adolescents to treatments subsequent to an inadequate response to a selective serotonin-reuptake inhibitor (SSRI). • Evidence is very limited on response and remission rates for patients with subsyndromal depression or dysthymia who have inadequate responses to an SSRI. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  36. What To Discuss With Your Patients • The health consequences of depression • The rate of treatment response following treatment with selective serotonin-reuptake inhibitors (SSRIs) and the possibility of treatment-resistant depression • The various interventions for treating depression after an unsatisfactory response to SSRIs • Patient preferences regarding cost, nonpharmacological treatment, medication type, and potential side effects • What is known about nonpharmacological interventions for treating depression • Potential drug interactions with medications • The risk of antidepressants and other medications for pregnant or nursing women • The possibility of severe adverse effects such as suicidality and that additional resources are available from the National Suicide Prevention Lifeline at www.suicidepreventionlifeline.org or 1-800-273-8255. Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

  37. Resource for Patients • Treatment Options When Your SSRI Antidepressant Is Not Working Well is a free companion to this continuing medical education activity. It covers: • Background information about depression and unsatisfactory response to selective serotonin reuptake inhibitors • Descriptions of the types of treatments, how they work, and their potential side effects • Questions to guide a discussion with their health care provider about treatment options • Santaguida P, MacQueen G, Keshavarz H, et al. AHRQ Comparative Effectiveness Review No. 62. Available at http://www.effectivehealthcare.ahrq.gov/ssri-depression.cfm.

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