Psychiatry

Introduction and Heritage

Major Depressive Disorder (MDD) is a significant Public Health Concern

  • MDD is one of the most common mental health disorders, over 300 million people are estimated to suffer from depression, equivalent to 4.4% of the world’s population and resulting in more than 800,000 annual suicides.1
  • Prevalence rates vary by age, peaking in older adulthood (above 7.5% among females aged 55-74 years, and above 5.5% among males).1
  • The total estimated number of people living with depression increased by 18.4% between 2005 and 2015; this reflects the overall growth of the global population, as well as a proportionate increase in the age groups at which depression is more prevalent.1
  • Depressive disorders led to a global total of over 50 million Years Lived with Disability (YLD) in 2015. More than 80% of this non-fatal disease burden occurred in low- and middle-income countries.1
  • WHO expects depression to be the worldwide leading cause of burden of disease (DALYs) by 2030.2
  • Self-reported survey responses from 1,441 respondents during COVID-19 and 5,065 before the pandemic showed a 3-fold increase in depressive symptoms in the USA.3
  • Depression is associated with functional impairment that is comparable to that of other major chronic illnesses.4,5
    • Distress or impairment in social, occupational, or other important areas of functioning represent a defining characteristic of MDD.6
    • On average, individuals with very severe MDD (as defined by SDS score) experience up to 26.4% of the year out of role.7

Numerous Barriers Exist to Recovery From MDD:

  • Untreated
    1. More than 50% are untreated.8
  • Nonadherence
    1. Overall nonadherence up to 70%9
    2. Early nonadherence may worsen long-term outcomes
      1. 44% of patients stop antidepressant therapy before 3 months10
      2. 28% of primary care patients stop antidepressant therapy after 1 month10
  • Treatment failures
    1. 40%–60%11
  • Recurrence/Relapse
    1. Response and remission rates in MDD are low despite proven pharmacological (antidepressants) and nonpharmacological treatments
      1. Up to 80% recur or relapse11
      2. Residual symptoms are associated with increased risk of relapse and recurrence12,13

The goal of depression treatment is remission, defined as minimal or no symptoms and a return to normal functioning in all life domain.14

Failure to achieve remission is associated with many negative outcomes.14

Achievement of response rather than remission is associated with a substantially greater risk of relapse/recurrence.14-16

Patients who do not achieve remission have been shown to experience:

  • More chronic depressive episodes14
  • Shorter durations between episodes14

Non-remitters continue to suffer from impaired psychosocial functioning (e.g., work and relationships).17

Sustained depression may increase all-cause mortality18 and morbidity/mortality with stroke,19 diabetes,20,21 MI,22 CVD,23 CHF,24 HIV,25 etc.

Results from a 16-year prospective longitudinal study showed that the risk of all-cause mortality was 1.5 times higher in patients with depression (with or without concomitant anxiety).18

Major depression has been shown to increase 6-month mortality after myocardial infarction.22 A subsequent study demonstrated that the presence of major or minor depression increased the risk of cardiac mortality, even among subjects without preexisting cardiac disease.23

Prevalence of Anxiety

  • The total estimated number of people living with anxiety disorders in the world is 264 million.1
  • The proportion of the global population with anxiety disorders in 2015 is estimated to be 3.6%. As with depression, anxiety disorders are more common among females than males (4.6% compared to 2.6% at the global level).1
  • Anxiety disorders are the sixth-leading cause of disability (defined by years of life lived with disability), with greater rates of disability occurring in females and in people aged 15 to 34 years26,27
  • The optimal goal is full remission of symptoms and return to premorbid level of functioning28

Numerous Barriers Exist to Recovery from Anxiety:

  • Diagnosis
    • Anxiety disorders are often misdiagnosed because the patient presents with somatic complaints29
  • Untreated
    • 87% of patients with GAD show primary symptoms that are not considered “anxiety” to be treated with current options as antidepressants/anxiolytic 29
      • In a primary care setting, 55% anxiety disorders are properly diagnosed versus 45% failure to recognize as anxiety disorder29
      • In patients with depression, a coexisting anxiety disorder is often missed29
  • Burden of disease30
    • For many patients, anxiety disorders are a significant cause of disability
      • Work productivity impairment:34%
      • Social impairment:40%

Anxiety disorders led to a global total of 24.6 million YLD in 2015.

World Health Organization 2017.1

COVID-19 has resulted in increased prevalence of anxiety, depression, or both, >3 fold higher vs prepandemic period.31

Prevalence of Schizophrenia

  • The worldwide prevalence of schizophrenia is 0.32% affecting approximately 24 million people.32 About 1/3 of the schizophrenic patients are so called treatment resistant33 and majority of them are treatment resistant from illness onset34 (it means they not responding to or intolerant of classic antipsychotics).
    • TRS has severe clinical and economic impacts on patients (e.g., worse disease course; poorer scores on measures of psychopathology, psychosocial functioning, and cognitive performance), families (many hours spent care-giving; reduced productivity; strain on relationships), and society as a whole (higher rates of unemployment, homelessness, aggressive behavior and substance abuse; longer/more frequent hospitalizations; higher healthcare resource utilization; absenteeism)35-38
    • Early identification and treatment of TRS could reduce this burden of disease on the patient and family as well as its societal and economic impact
  • Up to 60% of schizophrenia patients have co-morbid depression. In routine clinical setting these symptoms are always treated with antidepressants/anxiolytic.39

Viatris offers a comprehensive armamentarium for different mental disorders:

ZOLOFT® (sertraline hydrochloride) is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD), obsessive compulsive disorder (OCD), panic disorder (PD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD).40

EFFEXOR® XR (venlafaxine hydrochloride) is indicated for the treatment of major depressive disorder (MDD), general anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD).41

  • EFFEXOR® XR: Over 20 years of clinical experience with venlafaxine41
  • In 2014, EFFEXOR® XR received the American Chemical Society’s Heroes of Chemistry award for innovation in research & development for first SNRI42

ZELDOX® (ziprasidone hydrochloride monohydrate)  

Schizophrenia 

ZELDOX® is indicated for the treatment of schizophrenia, related psychoses, prevention of relapse and for maintenance of clinical improvement during continuation therapy.43 

Bipolar Mania 

ZELDOX® is indicated as monotherapy for the short term treatment of acute manic or mixed episodes associated with bipolar I disorder.43 

ZELDOX IM® (ziprasidone mesilate) 

ZELDOX IM® is indicated for the acute treatment and short term management of agitation and disturbed behaviour in patients with schizophrenia and related psychoses when oral therapy is not appropriate.44

Clozaril®  (clozapine)

Clozaril® is indicated for treatment-resistant schizophrenia.45

Before prescribing refer to Product Information at https://www.ebs.tga.gov.au/

AU-NON-2024-00017. Date of preparation: July 2024.

References:

  1. World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates. Geneva, Switzerland: World Health Organization; 2017. https://www.who.int/publications/i/item/depression-global-health-estimates.
  2. World Health Organization. The global burden of disease: 2004 update. https://www.who.int/publications/i/item/9789241563710. Published 2008
  3. Ettman CK, Abdalla SM, Cohen GH, Sampson L, Vivier PM, Galea S. Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic. JAMA Netw Open.2020;3(9):e2019686.
  4. McKnight PE, Kashdan TB. The importance of functional impairment to mental health outcomes: a case for reassessing our goals in depression treatment research. Clin Psychol Rev. 2009;29(3):243-259.
  5. Hays RD, Wells KB, Sherbourne CD, Rogers W, Spritzer K. Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Arch Gen Psychiatry. 1995;52(1):11-19.
  6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.5th ed. Arlington, VA: American Psychiatric Association; 2013.
  7. Kessler RC, Berglund P, Demler O, et al. The Epidemiology of Major Depressive Disorder: Results From the National Comorbidity Survey Replication (NCS-R). 2003;289(23):3095-3105.
  8. Lecrubier Y. Widespread underrecognition and undertreatment of anxiety and mood disorders: results from 3 European studies. J Clin Psychiatry. 2007;68 Suppl 2:36-41.
  9. Cassano P, Fava M. Tolerability issues during long-term treatment with antidepressants. Ann Clin Psychiatry. 2004;16(1):15-25.
  10. Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care. 1995;33(1):67-74.
  11. Masand PS. Tolerability and adherence issues in antidepressant therapy. Clin Ther. 2003;25(8):2289-2304.
  12. McIntyre RS, O'Donovan C. The human cost of not achieving full remission in depression. Can J Psychiatry. 2004;49(3 Suppl 1):10S-16S.
  13. Zajecka J, Kornstein SG, Blier P. Residual symptoms in major depressive disorder: prevalence, effects, and management [published correction appears in J Clin Psychiatry. 2013 May;74(5):519]. J Clin Psychiatry. 2013;74(4):407-414.
  14. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2010;157(4 Suppl):1-45.
  15. Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995;25(6):1171-1180.
  16. Thase ME, Simons AD, McGeary J, et al. Relapse after cognitive behavior therapy of depression: potential implications for longer courses of treatment. Am J Psychiatry. 1992;149(8):1046-1052.
  17. Miller IW, Keitner GI, Schatzberg AF, et al. The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine. J Clin Psychiatry. 1998;59(11):608-619.
  18. Murphy JM, Monson RR, Olivier DC, Sobol AM, Leighton AH. Affective Disorders and Mortality: A General Population Study. Arch Gen Psychiatry. 1987;44(5):473-480.
  19. Everson SA, Roberts RE, Goldberg DE, Kaplan GA. Depressive symptoms and increased risk of stroke mortality over a 29-year period. Arch Intern Med.1998;158(10):1133-1138.
  20. Lustman PJ, Clouse RE, Nix BD, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63(5):521-529.
  21. de Groot M, Kushnick M, Doyle T, et al. Depression Among Adults With Diabetes: Prevalence, Impact, and Treatment Options. Diabetes Spectr. 2010;23(1):15-18.
  22. Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival [published correction appears in JAMA 1994 Apr 13;271(14):1082]. JAMA. 1993;270(15):1819-1825.
  23. Penninx BW, Beekman AT, Honig A, et al. Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry. 2001;58(3):221-227.
  24. Vaccarino V, Kasl SV, Abramson J, Krumholz HM. Depressive symptoms and risk of functional decline and death in patients with heart failure. J Am Coll Cardiol. 2001;38(1):199-205.
  25. Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA. 2001;285(11):1466-1474.
  26. Baxter AJ, Vos T, Scott KM, Ferrari AJ, Whiteford HA. The global burden of anxiety disorders in 2010. Psychol Med. 2014;44(11):2363-2374.
  27. Hendriks SM, Spijker J, Licht CM, et al. Disability in anxiety disorders. J Affect Disord. 2014; 166:227–233
  28. Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1(Suppl 1):S1.
  29. Bandelow B, Boerner J R, Kasper S, Linden M, Wittchen HU, Möller HJ. The diagnosis and treatment of generalized anxiety disorder. Dtsch Arztebl Int. 2013;110(17):300-310.
  30. Sheehan DV, Kamijima K. An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. Int Clin Psychopharmacol. 2009;24(2):43-60.
  31. Twenge JM, Joiner TE. U.S. Census Bureau-assessed prevalence of anxiety and depressive symptoms in 2019 and during the 2020 COVID-19 pandemic. Depress Anxiety. 2020;37(10):954-956.
  32. http://www.tdrdata.com
  33. Lally J, Ajnakina O, Di Forti M, et al. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses. Psychol Med. 2016;46(15):3231-3240.
  34. Demjaha A, Lappin JM, Stahl D, et al. Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors. Psychol Med. 2017;47(11):1981-1989
  35. Lasevoli F, Giordano S, Balletta R, et al. Treatment resistant schizophrenia is associated with the worst community functioning among severely-ill highly-disabling psychiatric conditions and is the most relevant predictor of poorer achievements in functional milestones. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:34-48.
  36. Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29(2):63-76.
  37. Flyckt L, Löthman A, Jörgensen L, Rylander A, Koernig T. Burden of informal care giving to patients with psychoses: a descriptive and methodological study. Int J Soc Psychiatry. 2013;59(2):137-146. doi:10.1177/0020764011427239
  38. Jones SG, Castle D. Management of treatment resistant schizophrenia. S Afr Psychiatry Rev. 2006;9:17–23.
  39. Upthegrove R, Marwaha S, Birchwood M. Depression and Schizophrenia: Cause, Consequence, or Trans-diagnostic Issue?. Schizophr Bull. 2017;43(2):240-244
  40. ZOLOFT® Product Information.
  41. EFFEXOR® XR Product Information.
  42. American Chemical Society. Heroes of Chemistry Recipients.
  43. ZELDOX Product Information.
  44. ZELDOX IM® Product Information.
  45. CLOZARIL Product Information.

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