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Controversies in bipolar disorder: Trust evidence or experience?

Today’s buzzword in health care is evidence-based medicine. Most clinicians would agree that evidence from clinical research should guide decisions about treating bipolar disorder. In theory, randomized controlled trials should tell us how to manage bipolar patients and achieve therapeutic success. page 40.)

We rarely have encountered a patient with postpartum depression or psychosis who does not have a history of (often undiagnosed and untreated) recurrent mood episodes. For most of these patients, a mood stabilizer may be a better choice than an antidepressant.

The role of thyroid hormones

Adding a thyroid hormone—usually liothyronine—to an antidepressant has been demonstrated to accelerate, page 47.)

Atypical depression and the bipolar spectrum

Depressive episodes are considered either “typical” (a category that includes melancholic depression—in DSM-IV-TR, major depression with melancholic features) or “atypical” (in DSM-IV-TR, major depression with atypical features). Atypical features were originally associated with response to monoamine oxidase inhibitor antidepressants, whereas non atypical depression was thought more likely to respond to tricyclic antidepressants.34 The depression of bipolar disorder is usually atypical ( Box 4 ), especially in patients with softer variants of the illness.35

 

We believe that depressed patients with atypical symptoms aggregate into groups according to the presence, severity, and character of interdepressive manic or hypomanic episodes. Some patients experience recurrent depressive episodes with intervening euthymia (recurrent major depression), whereas others experience depressive episodes punctuated by brief subthreshold hypomanic episodes. Patients in these groups occasionally tolerate or even benefit from cautiously managed antidepressant monotherapy. Patients with atypical depressive episodes alternating with frank hypomanic, manic, mixed, or manic-psychotic episodes usually require a mood stabilizer and may benefit from cotreatment with an atypical antipsychotic.

Akiskol and Benazzi35 suggest that atypical depression may be a subtype of the bipolar spectrum. Our experience suggests that the bipolar spectrum is a continuum of degrees of risk for mood instability in persons with recurrent atypical depression.

Box 4

 

Atypical depression: Who sees ‘leaden paralysis’?

DSM-IV-TR defines atypical depression as depression characterized by mood reactivity and at least 2 of these 4 features:

 

  • hypersomnia
  • increased appetite or weight gain
  • leaden paralysis
  • sensitivity to interpersonal rejection.

The term ‘hypersomnia’ is misleading. Many of these patients do not sleep excessively because work or school attendance prevents oversleeping. Instead, they experience an increased sleep requirement manifested by difficulty getting up in the morning and increased daytime sleepiness.

Increased appetite and weight gain (hyperphagia) often are present, but almost as often our patients report no change in appetite or weight or even anorexia and weight loss.

We rarely see a condition one would term ‘leaden paralysis.’ We also find that ‘sensitivity to interpersonal rejection’ is too narrow a construct. Our patients with atypical depression experience increased sensitivity to every stressor in their lives—work, school, family, and social stressors—not just interpersonal rejection.

Related resources

 

  • Lieber AL. Bipolar spectrum disorder: an overview of the soft bipolar spectrum. www.psycom.net/depression.central.lieber.html.
  • Phelps J. Why am I still depressed? Recognizing and managing the ups and downs of bipolar II and soft bipolar disorder. www.psycheducation.org.
  • Maier T. Evidence-based psychiatry: understanding the limitations of a method. J Eval Clin Pract. 2006;12(3):325.

Drug brand names

 

  • Liothyronine • Cytomel
  • Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

References

 

1. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 1: First-line treatments. J Clin Psychiatry. 2007;68:1982-1983.

2. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 2: Complex presentations and clinical context. J Clin Psychiatry. 2008;69:495-496.

3. Levine R, Fink M. Why evidence-based medicine cannot be applied to psychiatry. Psychiatric Times. 2008;25(4):10.

4. Akiskol HS, Benazzi F. The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum. J Affect Disord. 2006;92:45-54.

5. Goodwin FK, Jamison KR. Manic-depressive illness: bipolar disorders and recurrent depression. 2nd ed. New York, NY: Oxford University Press; 2007:3–27.

6. Hirschfeld RMA, Lewis L, Vornik L. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161-167.

7. Blanco C, Laje G, Olfson M, et al. Trends in the treatment of bipolar disorder by outpatient psychiatrists. Am J Psychiatry. 2002;159:1005-1010.

8. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001;62:565-569.

9. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61:804-808.

10. Gijsman HF, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2005;161:1537-1547.

11. Ghaemi SN, Sachs GS, Chiou AM, et al. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord. 1999;52:134-144.

12. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711-1722.

13. Altshuler L, Suppes T, Black D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry. 2003;160:1252-1262.

14. Akiskol HS. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J Am Acad Child Adolesc Psychiatry. 1995;34(6):754-763.

15. Geller B, Zimmerman B, Williams M, et al. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry. 2001;158:125-127.

16. Food and Drug Administration: Center for Drug Evaluation and Research. Revisions to product labeling. Available at: http://www.FDA.gov/cder/drug/antidepressants/default.htm. Accessed January 12, 2009.

17. McElroy S, Strakowski S, West S, et al. Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder. Am J Psychiatry. 1997;154:44-49.

18. Olfson M, Marcus SC. A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. J Clin Psychiatry. 2008;69:425-432.

19. Keck PE, Jr, McElroy SL, Havens JR, et al. Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness. Compr Psychiatry. 2003;44:263-269.

20. Jones I, Craddock N. Familiarity of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry. 2001;158:913-917.

21. Chaudron LH, Pies RW. The relationship between postpartum psychosis and bipolar disorder: a review. J Clin Psychiatry. 2003;64:1284-1292.

22. Wisner KL, Peindl KS, Hanusa BH. Psychiatric episodes in women and young children. J Affect Disord. 1995;34:1-11.

23. Sharma V. A cautionary note on the use of antidepressants in postpartum depression. Bipolar Disord. 2006;8:411-414.

24. O’Malley S. “Are you there alone?” The unspeakable crime of Andrea Yates. New York, NY: Simon and Schuster; 2004.

25. Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158:1617-1622.

26. Joffe RT. The use of thyroid supplements to augment antidepressant medication. J Clin Psychiatry. 2008;59:26-29.

27. Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2007;64:679-688.

28. Gold MS, Pottash AL, Extein I. Hypothyroidism and depression: evidence from complete thyroid function evaluation. JAMA. 1981;245:28-31.

29. Kupka RW, Nolen WA, Post RM, et al. High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry. 2002;51:305-311.

30. Szuba MP, Amsterdam JD. Rapid antidepressant response after nocturnal TRH administration in patients with bipolar I and bipolar type II major depression. J Clin Psychopharmacol. 2005;25:325-330.

31. Extein I, Pottash AL, Gold MS. Does subclinical hypothyroidism predispose to tricyclic-induced rapid mood cycles? J Clin Psychiatry. 1982;43:32-33.

32. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Prac. 2002;8:457-469.

33. El-Mallakh RS, Karippott A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder. J Affect Disord. 2005;84:267-272.

34. Henkl V, Mergl R, Antje-Kathrin A, et al. Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res. 2006;141(1):89-101.

35. Perugi G, Akiskal HS, Lattanzi D, et al. The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry. 1998;39(2):63-71.

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Clinical professor of psychiatry, University of Texas Health Science Center, Houston, TX
Richard L. Noel, MD
Assistant clinical professor of psychiatry, University of Texas Health Science Center, Houston, TX

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Clinical professor of psychiatry, University of Texas Health Science Center, Houston, TX
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Assistant clinical professor of psychiatry, University of Texas Health Science Center, Houston, TX

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Hear Dr. Miller discuss this article
 

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Assistant clinical professor of psychiatry, University of Texas Health Science Center, Houston, TX

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Hear Dr. Miller discuss this article
 

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Today’s buzzword in health care is evidence-based medicine. Most clinicians would agree that evidence from clinical research should guide decisions about treating bipolar disorder. In theory, randomized controlled trials should tell us how to manage bipolar patients and achieve therapeutic success. page 40.)

We rarely have encountered a patient with postpartum depression or psychosis who does not have a history of (often undiagnosed and untreated) recurrent mood episodes. For most of these patients, a mood stabilizer may be a better choice than an antidepressant.

The role of thyroid hormones

Adding a thyroid hormone—usually liothyronine—to an antidepressant has been demonstrated to accelerate, page 47.)

Atypical depression and the bipolar spectrum

Depressive episodes are considered either “typical” (a category that includes melancholic depression—in DSM-IV-TR, major depression with melancholic features) or “atypical” (in DSM-IV-TR, major depression with atypical features). Atypical features were originally associated with response to monoamine oxidase inhibitor antidepressants, whereas non atypical depression was thought more likely to respond to tricyclic antidepressants.34 The depression of bipolar disorder is usually atypical ( Box 4 ), especially in patients with softer variants of the illness.35

 

We believe that depressed patients with atypical symptoms aggregate into groups according to the presence, severity, and character of interdepressive manic or hypomanic episodes. Some patients experience recurrent depressive episodes with intervening euthymia (recurrent major depression), whereas others experience depressive episodes punctuated by brief subthreshold hypomanic episodes. Patients in these groups occasionally tolerate or even benefit from cautiously managed antidepressant monotherapy. Patients with atypical depressive episodes alternating with frank hypomanic, manic, mixed, or manic-psychotic episodes usually require a mood stabilizer and may benefit from cotreatment with an atypical antipsychotic.

Akiskol and Benazzi35 suggest that atypical depression may be a subtype of the bipolar spectrum. Our experience suggests that the bipolar spectrum is a continuum of degrees of risk for mood instability in persons with recurrent atypical depression.

Box 4

 

Atypical depression: Who sees ‘leaden paralysis’?

DSM-IV-TR defines atypical depression as depression characterized by mood reactivity and at least 2 of these 4 features:

 

  • hypersomnia
  • increased appetite or weight gain
  • leaden paralysis
  • sensitivity to interpersonal rejection.

The term ‘hypersomnia’ is misleading. Many of these patients do not sleep excessively because work or school attendance prevents oversleeping. Instead, they experience an increased sleep requirement manifested by difficulty getting up in the morning and increased daytime sleepiness.

Increased appetite and weight gain (hyperphagia) often are present, but almost as often our patients report no change in appetite or weight or even anorexia and weight loss.

We rarely see a condition one would term ‘leaden paralysis.’ We also find that ‘sensitivity to interpersonal rejection’ is too narrow a construct. Our patients with atypical depression experience increased sensitivity to every stressor in their lives—work, school, family, and social stressors—not just interpersonal rejection.

Related resources

 

  • Lieber AL. Bipolar spectrum disorder: an overview of the soft bipolar spectrum. www.psycom.net/depression.central.lieber.html.
  • Phelps J. Why am I still depressed? Recognizing and managing the ups and downs of bipolar II and soft bipolar disorder. www.psycheducation.org.
  • Maier T. Evidence-based psychiatry: understanding the limitations of a method. J Eval Clin Pract. 2006;12(3):325.

Drug brand names

 

  • Liothyronine • Cytomel
  • Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Today’s buzzword in health care is evidence-based medicine. Most clinicians would agree that evidence from clinical research should guide decisions about treating bipolar disorder. In theory, randomized controlled trials should tell us how to manage bipolar patients and achieve therapeutic success. page 40.)

We rarely have encountered a patient with postpartum depression or psychosis who does not have a history of (often undiagnosed and untreated) recurrent mood episodes. For most of these patients, a mood stabilizer may be a better choice than an antidepressant.

The role of thyroid hormones

Adding a thyroid hormone—usually liothyronine—to an antidepressant has been demonstrated to accelerate, page 47.)

Atypical depression and the bipolar spectrum

Depressive episodes are considered either “typical” (a category that includes melancholic depression—in DSM-IV-TR, major depression with melancholic features) or “atypical” (in DSM-IV-TR, major depression with atypical features). Atypical features were originally associated with response to monoamine oxidase inhibitor antidepressants, whereas non atypical depression was thought more likely to respond to tricyclic antidepressants.34 The depression of bipolar disorder is usually atypical ( Box 4 ), especially in patients with softer variants of the illness.35

 

We believe that depressed patients with atypical symptoms aggregate into groups according to the presence, severity, and character of interdepressive manic or hypomanic episodes. Some patients experience recurrent depressive episodes with intervening euthymia (recurrent major depression), whereas others experience depressive episodes punctuated by brief subthreshold hypomanic episodes. Patients in these groups occasionally tolerate or even benefit from cautiously managed antidepressant monotherapy. Patients with atypical depressive episodes alternating with frank hypomanic, manic, mixed, or manic-psychotic episodes usually require a mood stabilizer and may benefit from cotreatment with an atypical antipsychotic.

Akiskol and Benazzi35 suggest that atypical depression may be a subtype of the bipolar spectrum. Our experience suggests that the bipolar spectrum is a continuum of degrees of risk for mood instability in persons with recurrent atypical depression.

Box 4

 

Atypical depression: Who sees ‘leaden paralysis’?

DSM-IV-TR defines atypical depression as depression characterized by mood reactivity and at least 2 of these 4 features:

 

  • hypersomnia
  • increased appetite or weight gain
  • leaden paralysis
  • sensitivity to interpersonal rejection.

The term ‘hypersomnia’ is misleading. Many of these patients do not sleep excessively because work or school attendance prevents oversleeping. Instead, they experience an increased sleep requirement manifested by difficulty getting up in the morning and increased daytime sleepiness.

Increased appetite and weight gain (hyperphagia) often are present, but almost as often our patients report no change in appetite or weight or even anorexia and weight loss.

We rarely see a condition one would term ‘leaden paralysis.’ We also find that ‘sensitivity to interpersonal rejection’ is too narrow a construct. Our patients with atypical depression experience increased sensitivity to every stressor in their lives—work, school, family, and social stressors—not just interpersonal rejection.

Related resources

 

  • Lieber AL. Bipolar spectrum disorder: an overview of the soft bipolar spectrum. www.psycom.net/depression.central.lieber.html.
  • Phelps J. Why am I still depressed? Recognizing and managing the ups and downs of bipolar II and soft bipolar disorder. www.psycheducation.org.
  • Maier T. Evidence-based psychiatry: understanding the limitations of a method. J Eval Clin Pract. 2006;12(3):325.

Drug brand names

 

  • Liothyronine • Cytomel
  • Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

References

 

1. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 1: First-line treatments. J Clin Psychiatry. 2007;68:1982-1983.

2. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 2: Complex presentations and clinical context. J Clin Psychiatry. 2008;69:495-496.

3. Levine R, Fink M. Why evidence-based medicine cannot be applied to psychiatry. Psychiatric Times. 2008;25(4):10.

4. Akiskol HS, Benazzi F. The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum. J Affect Disord. 2006;92:45-54.

5. Goodwin FK, Jamison KR. Manic-depressive illness: bipolar disorders and recurrent depression. 2nd ed. New York, NY: Oxford University Press; 2007:3–27.

6. Hirschfeld RMA, Lewis L, Vornik L. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161-167.

7. Blanco C, Laje G, Olfson M, et al. Trends in the treatment of bipolar disorder by outpatient psychiatrists. Am J Psychiatry. 2002;159:1005-1010.

8. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001;62:565-569.

9. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61:804-808.

10. Gijsman HF, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2005;161:1537-1547.

11. Ghaemi SN, Sachs GS, Chiou AM, et al. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord. 1999;52:134-144.

12. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711-1722.

13. Altshuler L, Suppes T, Black D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry. 2003;160:1252-1262.

14. Akiskol HS. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J Am Acad Child Adolesc Psychiatry. 1995;34(6):754-763.

15. Geller B, Zimmerman B, Williams M, et al. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry. 2001;158:125-127.

16. Food and Drug Administration: Center for Drug Evaluation and Research. Revisions to product labeling. Available at: http://www.FDA.gov/cder/drug/antidepressants/default.htm. Accessed January 12, 2009.

17. McElroy S, Strakowski S, West S, et al. Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder. Am J Psychiatry. 1997;154:44-49.

18. Olfson M, Marcus SC. A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. J Clin Psychiatry. 2008;69:425-432.

19. Keck PE, Jr, McElroy SL, Havens JR, et al. Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness. Compr Psychiatry. 2003;44:263-269.

20. Jones I, Craddock N. Familiarity of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry. 2001;158:913-917.

21. Chaudron LH, Pies RW. The relationship between postpartum psychosis and bipolar disorder: a review. J Clin Psychiatry. 2003;64:1284-1292.

22. Wisner KL, Peindl KS, Hanusa BH. Psychiatric episodes in women and young children. J Affect Disord. 1995;34:1-11.

23. Sharma V. A cautionary note on the use of antidepressants in postpartum depression. Bipolar Disord. 2006;8:411-414.

24. O’Malley S. “Are you there alone?” The unspeakable crime of Andrea Yates. New York, NY: Simon and Schuster; 2004.

25. Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158:1617-1622.

26. Joffe RT. The use of thyroid supplements to augment antidepressant medication. J Clin Psychiatry. 2008;59:26-29.

27. Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2007;64:679-688.

28. Gold MS, Pottash AL, Extein I. Hypothyroidism and depression: evidence from complete thyroid function evaluation. JAMA. 1981;245:28-31.

29. Kupka RW, Nolen WA, Post RM, et al. High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry. 2002;51:305-311.

30. Szuba MP, Amsterdam JD. Rapid antidepressant response after nocturnal TRH administration in patients with bipolar I and bipolar type II major depression. J Clin Psychopharmacol. 2005;25:325-330.

31. Extein I, Pottash AL, Gold MS. Does subclinical hypothyroidism predispose to tricyclic-induced rapid mood cycles? J Clin Psychiatry. 1982;43:32-33.

32. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Prac. 2002;8:457-469.

33. El-Mallakh RS, Karippott A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder. J Affect Disord. 2005;84:267-272.

34. Henkl V, Mergl R, Antje-Kathrin A, et al. Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res. 2006;141(1):89-101.

35. Perugi G, Akiskal HS, Lattanzi D, et al. The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry. 1998;39(2):63-71.

References

 

1. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 1: First-line treatments. J Clin Psychiatry. 2007;68:1982-1983.

2. Goldberg JF. What constitutes evidence-based pharmacotherapy for bipolar disorder? Part 2: Complex presentations and clinical context. J Clin Psychiatry. 2008;69:495-496.

3. Levine R, Fink M. Why evidence-based medicine cannot be applied to psychiatry. Psychiatric Times. 2008;25(4):10.

4. Akiskol HS, Benazzi F. The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum. J Affect Disord. 2006;92:45-54.

5. Goodwin FK, Jamison KR. Manic-depressive illness: bipolar disorders and recurrent depression. 2nd ed. New York, NY: Oxford University Press; 2007:3–27.

6. Hirschfeld RMA, Lewis L, Vornik L. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161-167.

7. Blanco C, Laje G, Olfson M, et al. Trends in the treatment of bipolar disorder by outpatient psychiatrists. Am J Psychiatry. 2002;159:1005-1010.

8. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001;62:565-569.

9. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61:804-808.

10. Gijsman HF, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2005;161:1537-1547.

11. Ghaemi SN, Sachs GS, Chiou AM, et al. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord. 1999;52:134-144.

12. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711-1722.

13. Altshuler L, Suppes T, Black D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry. 2003;160:1252-1262.

14. Akiskol HS. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J Am Acad Child Adolesc Psychiatry. 1995;34(6):754-763.

15. Geller B, Zimmerman B, Williams M, et al. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry. 2001;158:125-127.

16. Food and Drug Administration: Center for Drug Evaluation and Research. Revisions to product labeling. Available at: http://www.FDA.gov/cder/drug/antidepressants/default.htm. Accessed January 12, 2009.

17. McElroy S, Strakowski S, West S, et al. Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder. Am J Psychiatry. 1997;154:44-49.

18. Olfson M, Marcus SC. A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. J Clin Psychiatry. 2008;69:425-432.

19. Keck PE, Jr, McElroy SL, Havens JR, et al. Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness. Compr Psychiatry. 2003;44:263-269.

20. Jones I, Craddock N. Familiarity of the puerperal trigger in bipolar disorder: results of a family study. Am J Psychiatry. 2001;158:913-917.

21. Chaudron LH, Pies RW. The relationship between postpartum psychosis and bipolar disorder: a review. J Clin Psychiatry. 2003;64:1284-1292.

22. Wisner KL, Peindl KS, Hanusa BH. Psychiatric episodes in women and young children. J Affect Disord. 1995;34:1-11.

23. Sharma V. A cautionary note on the use of antidepressants in postpartum depression. Bipolar Disord. 2006;8:411-414.

24. O’Malley S. “Are you there alone?” The unspeakable crime of Andrea Yates. New York, NY: Simon and Schuster; 2004.

25. Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158:1617-1622.

26. Joffe RT. The use of thyroid supplements to augment antidepressant medication. J Clin Psychiatry. 2008;59:26-29.

27. Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2007;64:679-688.

28. Gold MS, Pottash AL, Extein I. Hypothyroidism and depression: evidence from complete thyroid function evaluation. JAMA. 1981;245:28-31.

29. Kupka RW, Nolen WA, Post RM, et al. High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry. 2002;51:305-311.

30. Szuba MP, Amsterdam JD. Rapid antidepressant response after nocturnal TRH administration in patients with bipolar I and bipolar type II major depression. J Clin Psychopharmacol. 2005;25:325-330.

31. Extein I, Pottash AL, Gold MS. Does subclinical hypothyroidism predispose to tricyclic-induced rapid mood cycles? J Clin Psychiatry. 1982;43:32-33.

32. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Prac. 2002;8:457-469.

33. El-Mallakh RS, Karippott A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder. J Affect Disord. 2005;84:267-272.

34. Henkl V, Mergl R, Antje-Kathrin A, et al. Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res. 2006;141(1):89-101.

35. Perugi G, Akiskal HS, Lattanzi D, et al. The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry. 1998;39(2):63-71.

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Controversies in bipolar disorder: Trust evidence or experience?
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bipolar disorder; evidence-based medicine; bipolar spectrum; subthreshold hypomania; manic switches; antidepressant monotherapy; Gary E Miller; Richard L noel
Legacy Keywords
bipolar disorder; evidence-based medicine; bipolar spectrum; subthreshold hypomania; manic switches; antidepressant monotherapy; Gary E Miller; Richard L noel
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