Definitions and Diagnosis

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Definitions and Diagnosis

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Definitions and Diagnosis (MDD)
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Definitions
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Depression I
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References

This slide shows core definitions for depression based on World Health Organization’s ICD-10 classification system or the American Psychiatric Association’s DSM-IV and DSM-5 system

  1. NICE CG90. Depression in adults: recognition and management. 2009. Update April 2016 Available at: https://www.nice.org.uk/guidance/cg90 Accessed April 2016
  2. WHO. ICD-10 Classification .1993. Available from: http://www.who.int/classifications/icd/en/GRNBOOK.pdf. Accessed April 2016
  3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition:  American Psychiatric Association. 1994:866
  4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition:  American Psychiatric Association. 2013
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Depression II
References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition:  American Psychiatric Association. 2013

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Depression is a clinically heterogeneous disorder
References
  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Health Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013
  2. Marazziti D et al. Eur J Pharmacol 2010;626(1):83–86
  3. Hammar A, Ardal G. Front Hum Neurosci 2009;3:26. doi: 10.3389/neuro.09.026.2009
  4. Fehnel SE et al. CNS Spectr 2013;21:43–52. 
  5. Jaeger J et al. Psychiatry Res 2006;145:39–48
  6. World Health Organization Depression Fact Sheet N369. http://www.who.int/mediacentre/factsheets/fs369/en/#. Accessed August 2015
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Cognitive symptoms of depression have a negative impact on many aspects of the patient’s life
References
  1. McIntyre RS et al. Depress Anxiety 2013;30(6):515–527
  2. Hammar A, Ardal G. Front Hum Neurosci 2009;3:26. doi: 10.3389/neuro.09.026.2009

 

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MDD symptoms – American Psychiatric Association
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References

The American Psychiatric Association (APA) describes nine depressive symptoms for diagnostic purposes.1

Depressed mood

• Patients may describe their mood as depressed, sad, hopeless, discouraged, or ‘down in the dumps’.1 Alternatively, the patient may describe having no feelings at all, or feeling anxious.1

• The lowered mood varies little from day to day, and is unresponsive to circumstances.1,2

• Many individuals will report or show increased irritability, e.g., persistent annoyance, hostility, or a tendency to respond to events with outwardly expressed anger, ranging from argumentativeness to rage.1,3

• At least one of ‘depressed mood’ or ‘loss of interest or pleasure’ is required for a diagnosis of MDD, according to APA criteria (see section on Diagnosis of MDD).1

Loss of interest or pleasure

• Loss of interest or pleasure (known as ‘anhedonia’) in all, or almost all, activities, is nearly always present.1,2

• Individuals may report feeling less interest in hobbies, ‘not caring anymore’, or not finding enjoyment in activities that were previously considered pleasurable.1

• Family members, rather than the patient, may be the ones who notice social withdrawal or neglect of pleasurable activities.1

• Some patients may experience a significant reduction in levels of sexual interest or desire (i.e., decreased libido).1,2

• At least one of ‘depressed mood’ or ‘loss of interest or pleasure’ is required for a diagnosis of MDD, according to APA criteria (see section on Diagnosis of MDD).1

Psychomotor agitation/retardation

• ‘Psychomotor agitation’ describes the inability to sit still; pacing or hand-wringing; or pulling/rubbing of skin, clothing, or other objects.1,2

• ‘Psychomotor retardation’ describes slowed speech, thinking, and body movements; increased pauses before answering; or speech that is decreased in volume, inflection, amount, or variety of content, or muteness.1,2

Worthlessness/guilt

• Self-esteem and self-confidence are almost always reduced; feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) may be present.1,2

• The sense of worthlessness or guilt may include unrealistic negative evaluations of one’s worth, or guilty preoccupations or ruminations over minor past failings.1

• Individuals often misinterpret neutral or trivial day-to-day events as evidence of personal defects.1

Cognitive dysfunction

• Many individuals report an impaired ability to think, concentrate, remember things, or make even minor decisions.1,2

• Patients engaged in cognitively-demanding pursuits are often unable to function.1

Fatigue

• Decreased energy, tiredness, and fatigue are common.1,2

• Even the smallest tasks seem to require substantial effort, and result in marked tiredness.1,2

• Patients may complain that, for example, washing and dressing in the morning are exhausting and take twice as long as usual.1

Thoughts of death/suicide

• Recurrent thoughts of death, suicidal ideation, or suicide attempts, are common.1

• The severity of suicidal thoughts ranges from a passive wish to not awaken in the morning or a belief that others would be better off if the individual were dead, to transient but recurrent thoughts of committing suicide, to a specific suicide plan.1

Weight/appetite change

• Patients may experience either a reduction or an increase in appetite, which can present as significant weight loss (without dieting) or weight gain.1

• Some patients report that they have to force themselves to eat; others report a craving for specific foods (e.g., sweets or other carbohydrates).1

Sleep disturbance

• Sleep is usually disturbed, and may take the form of either difficulty sleeping (insomnia), or sleeping excessively (hypersomnia).1,2

• ‘Initial insomnia’ is having difficulty falling asleep, ‘middle insomnia’ is waking up during the night and then having difficulty returning to sleep, and ‘terminal insomnia’ is waking too early and being unable to return to sleep.1

• Hypersomnia may take the form of prolonged sleep at night, or increased daytime sleep.1

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.
2. World Health Organization (WHO). International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) Version for 2010. http://apps.who.int/classifications/icd10/browse/2010/en. Accessed 12th March 2014. 
3. Judd LL, Schettler PJ, Coryell W, et al. Overt irritability/anger in unipolar major depressive episodes: past and current characteristics and implications for long-term course. JAMA Psychiatry 2013; 70 (11): 1171–1180.

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MDD symptoms – The Montgomery–Åsberg Depression Rating Scale
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References

The Montgomery–Åsberg Depression Rating Scale (MADRS), which was designed to be sensitive to the effects of antidepressants, includes ten depressive symptoms, six of which are described as ‘core symptoms’.1,2

MADRS item 1. Apparent sadness
Representing despondency, gloom and despair (more than just ordinary transient low spirits), reflected in speech, facial expression, and posture.1
This item is a core symptom of the MADRS.2
 
MADRS item 2. Reported sadness
Representing reports of depressed mood, regardless of whether it is reflected in appearance or not.1 Includes low spirits, despondency or the feeling of being beyond help and without hope.1
This item is a core symptom of the MADRS.2

MADRS item 3. Inner tension
Representing feelings of ill-defined discomfort, edginess, inner turmoil, mental tension mounting to either panic, dread or anguish.1
This item is a core symptom of the MADRS.2
 
MADRS item 4. Reduced sleep
Representing the experience of reduced duration or depth of sleep compared to the subject’s own normal pattern when well.1
 
MADRS item 5. Reduced appetite
Representing the feeling of a loss of appetite compared with when well.1
 
MADRS item 6. Concentration difficulties
Representing difficulties in collecting one’s thoughts mounting to incapacitating lack of concentration.1
 
MADRS item 7. Lassitude
Representing a difficulty getting started or slowness initiating and performing everyday activities.1
Some elements also correspond to psychomotor retardation in the APA system.3
This item is a core symptom of the MADRS.2
 
MADRS item 8. Inability to feel
Representing the subjective experience of reduced interest in the surroundings, or activities that normally give pleasure.1 The ability to react with adequate emotion to circumstances or people is reduced.1
This item is a core symptom of the MADRS.2
 
MADRS item 9. Pessimistic thoughts
Representing thoughts of guilt, inferiority, self-reproach, sinfulness, remorse and ruin.1
This item is a core symptom of the MADRS.2
 
MADRS item 10. Suicidal thoughts
Representing the feeling that life is not worth living, that a natural death would be welcome, suicidal thoughts, and preparations for suicide.1

1. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–389.
2. Bech P, Tanghøj P, Andersen HF, Overø K. Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology (Berl) 2002; 163 (1): 20–25.
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

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The course of MDD
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References

This slide illustrates the typical course of illness for patients with depression. Discontinuing antidepressant treatment in the acute phase before full symptomatic remission drastically increases the likelihood of relapse of the original episode, and discontinuing treatment during the continuation phase after symptomatic remission likewise increases the risk of relapse. Discontinuing treatment during the maintenance phase, which begins after full recovery, increases the risk of developing a new depressive episode (ie, recurrence).

The optimal outcome for a patient with major depressive disorder (MDD) is a full recovery from the major depressive episode and to never become depressed again.1 Treatment of MDD is divided into three phases, corresponding to different stages of the illness.2 Each of these phases has a different treatment goal.2

Acute phase
‘Acute phase treatment’ of MDD occurs during a major depressive episode; it runs from the initiation of treatment until remission is achieved.3,4 The goals of acute phase treatment are to achieve remission (removal of symptoms, such that the criteria for a major depressive episode are no longer met), and an improvement in functioning and quality of life.3,5 Remission is a clinically-meaningful endpoint: patients who achieve remission are less likely to relapse than those who do not achieve remission.6,7 Response, i.e., a 50% improvement from baseline in a depression rating scale score, is an intermediate treatment goal; it is used to evaluate whether or not a treatment is benefiting the patient.3

Continuation phase
‘Continuation phase treatment’ of MDD follows on from acute phase treatment, i.e., it starts when remission is achieved.3,4 The goals of continuation phase treatment are to prevent a relapse (a return of symptoms sufficient to meet the criteria for a major depressive episode) in the vulnerable period immediately following remission, to eliminate any unresolved symptoms, and to restore the patient’s level of psychosocial and occupational functioning – at least to levels seen prior to the current episode and, if possible, to levels seen prior to the onset of MDD.3,5 Continuation phase treatment continues until recovery is achieved (the end of a major depressive episode).3 The moment of recovery is difficult to identify in clinical practice.3

Maintenance phase
‘Maintenance phase treatment’ of MDD follows on from continuation phase treatment, provided the patient did not experience a relapse.3,4 The goals of maintenance phase treatment are to prevent a new episode of depression (recurrence), to prevent suicide, and to enable full and lasting functional recovery.3 Typically, maintenance treatment is indicated in patients with chronic/recurrent MDD (i.e., those susceptible to recurrence).5

 

1. Nierenberg AA, DeCecco LM. Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression. J Clin Psychiatry 2001; 62 (Suppl 16): 5–9.
2. Sadock BJ, Sadock VA, Ruiz P (eds). Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th Edition. Vol 1–2. © Lippincott Williams & Wilkins, 2009.
3. Bauer M, Pfennig A, Severus E, et al.; World Federation of Societies of Biological Psychiatry (WFSBP) Task Force on Unipolar Depressive Disorders. WFSBP guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry 2013; 14 (5): 334–385.
4. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991; 52 (Suppl 5): 28–34.
5. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd Edition. © American Psychiatric Association, 2010. http://psychiatryonline.org/guidelines.aspx. Accessed November 2017.
6. Nelson JC, Pikalov A, Berman RM. Augmentation treatment in major depressive disorder: focus on aripiprazole. Neuropsychiatr Dis Treat 2008; 4 (5): 937–948.
7. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163 (11): 1905–1917.

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MDD is a complex, often recurrent and remitting disorder
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Previous slide illustrates the typical course of illness for patients with depression; either receiving only acute-phase treatment or receiving longer-term treatment designed to prevent relapse. It also highlights that long-term treatment of depression with antidepressants benefits many patients by1 reducing the likelihood of relapse or recurrence and2 increasing the amount of time spent asymptomatic between episodes. 

Discontinuing antidepressant treatment in the acute phase before full symptomatic remission drastically increases the likelihood of relapse of the original episode, and discontinuing treatment during the continuation phase after symptomatic remission likewise increases the risk of relapse. 

Discontinuing treatment during the maintenance phase, which begins after full recovery, increases the risk of developing a new depressive episode (i.e., recurrence).

  1. Kupfer DJ. J Clin Psychiatry 1991;52(suppl):28–34.
  2. Eaton WW et al. Arch Gen Psychiatry 2008;65:513–520
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Depression – signs and symptoms
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References

The slide aims at giving a simple definition for the terms signs and symptoms. It also highlights that the criteria used in the diagnostic manuals cover all major signs and symptoms of depression.

1. Shivani, et al. Alcohol Research & Health. 2002;26:90-8

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Definitions of epidemiological terms
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The slide explains the difference between prevelance and incidence as key epidemiological terms. While prevalence is the number of persons with disease, in a given population, at a designated time, the incidence looks into the number of new persons with disease over a specified period of time, in a given population.

Last JM. A dictionary of epidemiology. New York: Oxford University Press, 2000.

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Definitions of burden of disease and key epidemiological terms
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This slide gives definitions for key epidemiological terms used in studies to quantify the burden of a disease. Term defined are the Burden of disease (BoD), Quality adjusted life years (QALYs), Years of life lost (YLLs), Years lived with disability (YLDs), Disability adjusted life years (DALYs), and Healthy life expectancy, or health-adjusted life expectancy (HALE).

  1. Last JM. A dictionary of epidemiology. New York: Oxford University Press, 2000; 
  2. http://www.healthdata.org/sites/default/files/files/policy_report/2013/G... Accessed April 2014.
     
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Definitions of Clinical Course and Treatment Outcomes I
References
  1. Nierenberg et al. J Clin Psychiatry 2003; 64 (suppl 15): 13–17; page 13 (‘Remission, relapse, recurrence’ section)
  2. Riso et al. J Affect Disord 1997; 43 (2): 131–142
  3. Nierenberg & DeCecco. J Clin Psychiatry 2001; 62 (suppl 16): 5–9; page 8
  4. Frank et al. Arch Gen Psychiatry 1991; 48 (9): 851–855; page 853.
  5. Keller MB. Long-term treatment of recurrent and chronic depression. J Clin Psychiatry 2001; 62 Suppl 24: 3–5.
  6. Lavori PW, Keller MB, Mueller TI, et al. Recurrence after recovery in unipolar MDD: an observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatr Res 1994; 4 (4): 211–229.
     
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Definitions of Clinical Course and Treatment Outcomes II
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MDD is a chronic disorder, most frequently characterised by relapses and recurrences.(Nierenberg et al., 2003) Relapse can be defined as an episode of MDD that occurs within 6 months of response or remission;(Nierenberg et al., 2003; Riso et al., 1997) theoretically, relapse signifies the return of a major depressive episode, rather than a new episode.(Nierenberg & DeCecco, 2001; Frank et al., 1991) Recurrence can be defined as a depressive episode that occurs after 6 months following response or remission;(Nierenberg et al., 2003; Riso et al., 1997) theoretically, recurrence signifies the start of a new major depressive episode.(Nierenberg & DeCecco, 2001; Frank et al., 1991) Naturalistic studies have found that most patients will eventually experience either relapse or recurrence if followed for a long enough period without sustained treatment.(Nierenberg et al., 2003; Lavori et al., 1994) Following an acute depressive episode, almost 90% of patients could be expected to become depressed again in the next 15 years.(Nierenberg et al., 2003; Keller, 2001)

  1. Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991; 48 (9): 851–855.
  2. Keller MB. Long-term treatment of recurrent and chronic depression. J Clin Psychiatry 2001; 62 Suppl 24: 3–5.
  3. Lavori PW, Keller MB, Mueller TI, et al. Recurrence after recovery in unipolar MDD: an observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatr Res 1994; 4 (4): 211–229.
  4. Nierenberg AA, DeCecco LM. Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression. J Clin Psychiatry 2001; 62 Suppl 16: 5–9.
  5. Nierenberg AA, Petersen TJ, Alpert JE. Prevention of relapse and recurrence in depression: the role of long-term pharmacotherapy and psychotherapy. J Clin Psychiatry 2003; 64 Suppl 15: 13–17.
  6. Riso LP, Thase ME, Howland RH, et al. A prospective test of criteria for response, remission, relapse, recovery, and recurrence in depressed patients treated with cognitive behavior therapy. J Affect Disord 1997; 43 (2): 131–142
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Diagnosis, Signs and Symptoms
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Signs and Symptoms of depression – Diagnostic criteria
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References

This slide gives the signs and symptoms listed in the major diagnostic manuals, DSM-IV, DSM-5 and ICD10 used to describe the diagnostic critera. The silde highlights the high level of agreement between the manuals. Low self-esteem or self-confidence is listed as a seperate criteria in the ICD-10, which is not the case in the DSM-IV or -5. However, low self-esteem is often taken together with feelings of worthlessness and inappropriate guilt and represents as such not necessarely a criteria in itself, which would not be recognised using DSMIV or-5 manuals. 

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition:  American Psychiatric Association. 1994:866
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition:  American Psychiatric Association. 2013
  3. WHO. ICD-10 Classification .1993. Available from: http://www.who.int/classifications/icd/en/GRNBOOK.pdf. Accessed April 2016
     
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Depression is a clinically heterogeneous disorder
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References

This slide expands the signs and symptoms used to define diagnostic criteria, to highlight the heterogeneity of the disease. It also highlights that the disease affects all aspects of every day life. Real life functional impairments affect social, occupational, family and daily activities, of which the listed signs and symptoms are part of. Signs and symptoms are grouped by emotional, cognitive and physical categories. 

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: APA; 2013.
  2. World Federation for Mental Health. Depression: a global crisis. 10 October 2012. Available at http://www.who.int
  3. Fehnel et al. CNS spectrums 2013 (1-10)
  4. Hammar et al. Front in Hum Neurosci 3 (2009)
  5. Bair M. Archives of internal medicine 163.20 (2003): 2433-2445
  6. Clayton A. Effects of Psychiatric Illness and Medication on Sexual Function http://www.medscape.org/viewarticle/482059_3; accessed 29 September 2014
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Depression – Levels of Severity
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Various levels of depression exist including mild, moderate and severe. The table shows the DSM-IV definitions of depression. A comprehensive assessment of depression should not rely simply on a symptom count, but should take into account the degree of functional impairment and/or disability. 

Note: NICE defines the depression severities based on  DSM-IV. ICD-10 is similar but the threshold for mild depression is lower at 4 symptoms. 

  1. NICE CG90. Depression in adults: recognition and management. 2009. Update April 2016 Available at: https://www.nice.org.uk/guidance/cg90 Accessed April 2016; 
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5 2013.
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Depression in Diagnostic Manuals
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References

Major manuals used for the diagnosis of depression.

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition:  American Psychiatric Association. 1994:866; 
  2. WHO. ICD-10 Classification .1993. Available from: http://www.who.int/classifications/icd/en/GRNBOOK.pdf. Accessed April 2016; 
  3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition:  American Psychiatric Association. 2013
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Depression – DSM-5: Updates from DSM-IV
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Highlights of Changes from DSM-IV-TR to DSM-5. American Psychiatric Association 2013. Available from: http://www.psychiatry.org/dsm5  Accessed April 2016

While bereavement may precipitate major depression in people who are especially vulnerable (i.e. they have already suffered a significant loss or have other mental disorders), when grief and depression coexist, the grief is more severe and prolonged than grief without major depression. Despite some overlap between grief and MDD, they are different in important ways, and therefore they should be distinguished separately to enable people to benefit from the most appropriate treatment.1

A more chronic form of depression, persistent depressive disorder (dysthymia), can be diagnosed when the mood disturbance continues for at least 2 years in adults or 1 year in children. This diagnosis, new in DSM-5, includes both the DSM-IV diagnostic categories of chronic major depression and dysthymia.2

In DSM-IV, a diagnosis of mixed episode required an individual to simultaneously meet all criteria for an episode of major depression and an episode of mania. During its review of the latest research, the DSM-5 Mood Disorders Work Group recognized that individuals rarely meet full criteria for both episode types at the same time. In order to be diagnosed with the new specifier in the case of major depression, the new DSM-5 specifier will require the presence of at least three manic/hypomanic symptoms that don’t overlap with symptoms of major depression. In the case of mania or hypomania, the specifier will require the presence of at least three symptoms of depression in concert with the episode of mania/hypomania.3

 
 

  1. American Psychiatric Association_DSM-5-Depression-Bereavement-Exclusion: https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/APA..., last assessed April 2016
  2. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders 5th edition:  APA. 2013
  3. Source: American Psychiatric Association_DSM-5-Mixed-Features-Specifier, Changes in the new edition: Mixed features. Available: https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/APA..., last assessed April 2016
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Depression – the Diagnostic and Statistical Manual (DSM-IV) criteria for major depression
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The Diagnostic and Statistical Manual (DSM) of Mental Disorders is published by the American Psychiatric Association and provides standard criteria for the classification of mental disorders. It is now in its fifth edition, DSM-5, which was published in 2013.  

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition:  American Psychiatric Association. 1994:866
     
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Depression – the Diagnostic and Statistical Manual (DSM-IV) criteria for major depression
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References

D - A diagnosis cannot be reached if the patient has a substance abuse disorder.

The Diagnostic and Statistical Manual (DSM) of Mental Disorders is published by the American Psychiatric Association and provides standard criteria for the classification of mental disorders. It is now in its fifth edition, DSM-V, which was published in 2013. The next three slides summarize the changes.

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition: American Psychiatric Association. 1994:866
     
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Depression – the Diagnostic and Statistical Manual (DSM-5) criteria for major depression
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References

The Diagnostic and Statistical Manual (DSM) of Mental Disorders is published by the American Psychiatric Association and provides standard criteria for the classification of mental disorders. It is now in its fifth edition, DSM-5, which was published in 2013.  

Slide represent diagnostic criteria for a major depressive episode according to the DSM-5. Note that Criteria A-C represent a major depressive episode

Criteria A Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
Note: Do not include symptoms that are clearly attributable to another medical condition.

Criteria B: (next slide) 

Criteria C: (next slide) 

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.

Criteria D. The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

Criteria E. There has never been a manic episode or a hypomanie episode. Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical
condition.

 

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition: American Psychiatric Association. 2013
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Depression – the Diagnostic and Statistical Manual (DSM-5) criteria for major depression
Slide information
References

The Diagnostic and Statistical Manual (DSM) of Mental Disorders is published by the American Psychiatric Association and provides standard criteria for the classification of mental disorders. It is now in its fifth edition, DSM-5, which was published in 2013.  

Slide represent diagnostic criteria for a major depressive episode according to the DSM-5. Note that Criteria A-C represent a major depressive episode

Criteria A (previous slide) 

Criteria B: The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Criteria C: The episode is not attributable to the physiological effects of a substance or to another medical condition.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.

Criteria D. The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

Criteria E. There has never been a manic episode or a hypomanie episode. Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical condition.
 

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition: American Psychiatric Association. 2013
     
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Depression – the Diagnostic and Statistical Manual (DSM-IV & DSM-5) Criteria for Major Depression
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The Diagnostic and Statistical Manual (DSM) of Mental Disorders is published by the American Psychiatric Association and provides standard criteria for the classification of mental disorders. This slide represents the diagnostic criteria for major depression in accordance with DSM-IV, as well as DSM-5.

Generally, for diagnosing MDD five (or more) of the A symptoms have been present during the same 2-week period and represent a change from previous functioning: at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Further, The symptoms  have to cause clinically significant distress or impairment in social, occupational or other important areas of functioning (symptom C in DSM-IV and symptom B in DSM-5) and, the episode is not attributable to the physiological effects of a substance or to another medical condition (symptom D in DSM-IV and symptom C in DSM-5).

The DSM-5 excluded further criteria, which were present in DSM-IV, namely:

  • The bereavement exclusion has been removed. DSM-5 edition characterizes bereavement as a severe psychological stressor that can incite a major depressive episode
  • The coexistence within a major depressive episode of at least three manic symptoms (insufficient to satisfy criteria for a manic episode) is now acknowledged by the specifier “with mixed features”. The presence of mixed features in an episode of major depressive disorder increases the likelihood that the illness exists in a bipolar spectrum; however, if the individual has never met criteria for a manic or hypomanic episode, the diagnosis of major depressive disorder is retained

Another major difference, not present on this slide, is that “dysthymia” is now under the category of ‘persistent depressive disorder’, which includes both chronic major depressive disorder and the previous dysthymic disorder. An inability to find scientifically meaningful differences between these two conditions led to their combination.

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edition:  American Psychiatric Association. 1994:866
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th edition:  American Psychiatric Association. 2013
     
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Depression – the WHO ICD-10 classification of mental and behavioral disorders
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Slide represent a depressive episode according to the WHO ICD10 Classification

Step 1: In typical depressive episodes of all three varieties described (mild (F32.0), moderate (F32.1), and severe (F32.2 and F32.3)), the individual usually suffers from depressed mood, loss of interest and enjoyment, and reduced energy leading to increased fatigability and diminished activity. Marked tiredness after only slight effort is common. 

Step 2: Other common symptoms are listed in Step 2 (a-g):

(a) reduced concentration and attention;
(b) reduced self-esteem and self-confidence;
(c) ideas of guilt and unworthiness (even in a mild type of episode);
(d) bleak and pessimistic views of the future;
(e) ideas or acts of self-harm or suicide;
(f) disturbed sleep
(g) diminished appetite.

Step 3: The ICD10 differentiates diagnosis on the grades of severity, mild (F32.0), moderate (F32.1) and severe (F32.2 and F32.3) depressive episodes. These should be used only for a single (first) depressive episode. Further depressive episodes should be classified under one of the subdivisions of recurrent depressive disorder (F33.-). These grades of severity are specified to cover a wide range of clinical states that are encountered in different types of psychiatric practice. Individuals with mild depressive episodes are common in primary care and general medical settings, whereas psychiatric inpatient units deal largely with patients suffering from the severe grades.
 

  1. WHO. ICD-10 Classification .1993. Available from: http://www.who.int/classifications/icd/en/GRNBOOK.pdf. Accessed April 2016
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Depression can be evaluated from different perspectives
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References

This slide highlights the differences in assessing the depression status depending on the perspective. For example in treatment studies of depression, remission is typically defined narrowly, based on scores on symptom severity scales. Patients treated in clinical practice, however, define the concept of remission more broadly and consider functional status, coping ability, and life satisfaction as important indicators of remission status.  

 

  1. Danner M, et al. Int J Technol Assess Health Care. 2011, Integrating patients’ views into health technology assessment: Analytic hierarchy process (AHP) as a method to elicit patient preferences:27(4):369–75
  2. Zimmerman M, et al. Why do some depressed outpatients who are in remission according to the Hamilton Depression Rating Scale not consider themselves to be in remission? J Clin Psychiatry. 2012;73:790–95
  3. Zimmerman M, et al. Symptom differences between depressed outpatients who are in remission according to the Hamilton Depression Rating Scale who do and don’t consider themselves to be in remission: J Affect Disord. 2012;142:77–81.
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Common Screening Instruments for MDD
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References

A 2002 literature review found that median sensitivity across 16 instruments, including the BDI, CES-D, SDS, and GDS, for major depression was 85%, ranging from 50-97%, while median specificity was 74%, ranging from 51-98%.6 The more common screening tools will be reviewed in this topic, including the following:

  1. Hamilton M. J Neurol Neurosurg Psychiatry. 1960,23:56-62
  2. Montgomery & Åsberg Brit J Psychiatry 1979; 134: 382-389
  3. Poznanski et al. Pediatrics 1979; 164: 442-450
  4. Beck et al Arch Gen Psychiatry. 1961 Jun. 4:561-71
  5. Yesavage et al. J Psychiatr Res 1983; 17: 37-49
  6. Radloff LS. Appl Psych Meas 1977; 1: 385–401; (7) Williams et al. Gen Hosp Psychiatry. 2002 Jul-Aug. 24(4):225-37; (8) Youngstrom  et al. Jof Child & Adoles Psychopharm 2013; 23: 72-79. 
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Hamilton Depression Rating Scale (HAMD)
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References

The Hamilton Depression Rating Scale is the most widely used interview scale, developed in 1960 to measure severity of depression in an inpatient population. Since then, many versions have been adapted, including structured interview guides, self-report forms, and computerized versions. Widely used modified versions include:

Hamilton Depression Rating Scale and Beck-Rafaelson Melancholia Scale (HAM-DMES), 23 items measuring severity of depressive symptoms including melancholic symptoms3
Hamilton Depression Rating Scale (HAM-D24), 24 items measuring severity of depressive symptoms including helplessness, hopelessness and worthlessness4 

In the original clinician-administered scale, the first 17 items are tallied for the total score, while items 18-21 are used to further qualify the depression. The scale takes 20-30 minutes to administer. Scores of 0-7 are considered normal, and scores greater than or equal to 20 indicate moderately severe depression. Each item either is scored on a 5-point scale, representing absent, mild, moderate, or severe symptoms, or on a 3-point scale, representing absent, slight or doubtful, and clearly present symptoms. The HDRS contains a relatively large number of somatic symptoms and relatively few cognitive or affective symptoms (Williams et al 2001, Hamilton 1960). The 21 items it assesses are as follows:

  • Depressed mood
  • Feelings of guilt
  • Thoughts of suicide
  • Insomnia
  • Work and activities
  • Psychomotor retardation
  • Psychomotor agitation
  • Psychic anxiety
  • Somatic anxiety
  • Gastrointestinal symptoms
  • General somatic symptoms
  • Genital symptoms
  • Hypochondriasis
  • Loss of insight
  • Loss of weight
  • Diurnal variation
  • Depersonalization and derealization
  • Paranoid symptoms
  • Obsessional and compulsive symptoms
  1. Williams JW. Eur Arch Psychiatry Clin Neurosci. 2001. 251 (suppl 2):116
  2. Hamilton M. J Neurol Neurosurg Psychiatry. 1960,23:56-62
  3. Bech et al. Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM-III syndromes Act Psych Scand, 1986. 73 (suppl 326):22-28
  4. Miller et al. The modified Hamilton rating scale for depression: reliability and validity. Psych Res 1984,14:131-142
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Montgomery and Åsberg Depression Rating Scale (MADRS)
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References

The MADRS is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. An experienced clinician can use the MADRS after a training session. It takes approximately 15 to 20 minutes to administer and rate the MADRS.
 

  1. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Brit J Psychiatry 1979; 134: 382-389
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Children Depression Rating Scale - Revised (CDRS-R)
References
  1. Poznanski EO, Cook SC, Carroll BJ. A depression rating scale for children. Pediatrics 1979; 164: 442-450. 
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Beck Depression Inventory (BDI-II)
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References

The Beck Depression Inventory (BDI) is the most widely used self-rating scale, developed in 1961 by Aaron Beck based on symptoms he observed to be common among depressed patients.

The BDI consists of 21 items of emotional, behavioral, and somatic symptoms that takes 5-10 minutes to administer. The items are scored from 0 to 3 and measure mood, pessimism, sense of failure, lack of satisfaction, guilty feelings, sense of punishment, self-hate, self-accusations, self-punitive wishes, crying spells, irritability, social withdrawal, indecisiveness, body image, work inhibition, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation, and loss of libido.

Scores of 10-18 indicate mild depression, 19-29 indicate moderate depression, and greater than 30 indicate severe depression (Beck et al 1961). Other versions have been developed, including the Beck Depression Inventory II (BDI-II), a revision of the BDI in 1996 in response to the fourth edition of the DSM, and the Beck Depression Inventory for Primary Care (BDI-PC). The BDI-II is scored in the same manner as the BDI, but the cut-offs differ slightly. The BDI-PC is a screening 7-item scale for primary care outpatients, with a cut-off of 4 points for major depression. One study found a 97% sensitivity and 99% specificity rate for identifying patients with major depression (Steer et al 1999) (The BDI is copyright protected).

  1. Beck et al An inventory for measuring depression.Arch Gen Psychiatry. 1961 Jun. 4:561-71
  2. Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999 Mar-Apr. 21(2):106-11.
  3. Beck A, Steer R, Brown G. Manual for the Beck Depression Inventory-II. San Antonio, Tex: Psychological Corporation; 1996. 
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Geriatric Depression Scale (GDS)
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References

The Geriatric Depression Scale (GDS) was specifically developed for use in geriatric populations, originally as a 30-item scale. It was modified a 15-item scale, which has been widely used. The GDS was later reduced to 5 items, so as to be better received by elderly patients. The questions elicit only “yes” or “no” responses, making comprehension easier compared with multiple-choice answers.

The 5-item scale has a sensitivity of 94%, specificity of 81%, and demonstrated a significant agreement in the clinical diagnosis of depression with the 15-item scale. The 5-item scale is scored by 1 point for a “no” answer on the first question or a “yes” answer for the remaining questions. A score of greater than or equal to 2 is a positive screen for depression (Rinaldi et al 2003, Yesavage et al 1983)

  1. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1983; 17: 37-49.
  2. Rinaldi P, Mecocci P, Benedetti C, Ercolani S, Bregnocchi M, Menculini G. Validation of the five-item geriatric depression scale in elderly subjects in three different settings. J Am Geriatr Soc. 2003 May. 51(5):694-8.
     
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Center for Epidemiologic Studies Depression Scale (CES-D)
References
  1. Radloff LS. Appl Psych Meas 1977; 1: 385–401
  2. Van Dam & Earleywine. Psychiatry Res. 2011. 186(1):128-32
     
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Patient Health Questionnaire (PHQ2 or PHQ9)
References
  1. Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov. 41(11):1284-92.
  2. Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression
  3. Williams JW Jr, Pignone M, Ramirez G, Perez Stellato C. Identifying depression in primary care: a literature synthesis of case-finding instruments. Gen Hosp Psychiatry. 2002 Jul-Aug. 24(4):225-37.sion in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med. 2007 Nov. 22(11):1596-602
     
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General Behavior Inventory 10-Item Depression Scale (GBI-10D)
References
  1. Youngstrom EA, Zhao J, Mankoski R., Forbes RA, Marcus RM, Carson W, et al. Clinical significance of treatment effects with aripiprazole versus placebo in a study of manic or mixed episodes associated with pediatric bipolar I disorder Journal of Child & Adolescent Psychopharmacology 2013; 23: 72-79.
     
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Depression rating scales measure symptom reduction in clinical trials, but are rarely used in clinical practice
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References

This slide highlights that rating scales used for mood or specifically depression, are widely used in clinical trials. These scales are validated, meet general clinical and research purpose and have a proven reliability. However, there practical value, interpretability and feasibility in clinical practice is a matter of debate and has been questioned. 

  1. Furukawa TA. J Psychosom Res. 2010;68(6);581-589
  2. Snaith P. Br J Psychiatry. 1993;163:293-298
  3. Demyttenaere K, De Fruyt. Pscyhother Psychosom. 2003;72(2):61-70
  4. Montgomery SA, et al. Br J Psychiatry. 1979;134:382-389
  5. Hamilton M. J Neurol Neurosurg Psychiatry. 1960;23:56-62
  6. Poznanski et al. Pediatrics 1979; 164: 442-450. 
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There are multiple ways to measure clinical outcomes in depression
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References

This slide describes the difference in the outcome evaluation based on the perspective of either physicians or patients. In describing treatment outcome for depression, a distinction is made between response and remission. Treatment response is commonly defined as a 50% or greater improvement in scores on symptom measures such as the Hamilton Depression Rating Scale (HDRS), whereas remission is usually defined as a score below a predetermined cut-off score on the scale. Through the years, many cut-off scores have been used on the HDRS to define remission; however, since the publication of the recommendations of Frank and colleagues, a general consensus emerged to define remission on the 17-item HDRS as a score of 7 or less. Recognizing remission among patients who have responded to treatment is clinically important, because the presence of residual symptoms in treatment responders predicts an increased likelihood of relapse and greater psychosocial morbidity. In consideration of the clinical significance of residual symptoms, experts in the treatment of depression have suggested that achieving remission of symptoms should be viewed as the primary goal. Some patients who meet symptom-based definitions of remission nonetheless experience low levels of symptoms or functional impairment or deficits in coping ability, thereby warranting a modification in treatment. These findings raise caution in relying exclusively on symptom-based definitions of remission to guide treatment decision-making in clinical practice. (Zimmermann et al 2012)

The AHP study included two AHP workshops, one with twelve patients and one with seven healthcare professionals. In these workshops, both patients and professionals rated their preferences with respect to the importance of different endpoints of antidepressant treatment by a pairwise comparison of individual endpoints. These comparisons were performed and evaluated by the AHP method and relative weights were generated for each endpoint. “Response” was rated the most important endpoint by the group of patients, followed by the endpoint “improvement of cognitive function.” The endpoint “remission” received the highest weighting within the group of professionals, followed by “avoidance of relapse.” The professionals rated “sexual dysfunction” lowest, as did the patients. In both workshop groups, there was good consistency in the results (CR<0.1). The set of the six most important patient-relevant outcome measures was the same for both groups. Three of these are related to efficacy: response, remission, and no relapse. Three are related to different aspects of quality of life: improvement of social functioning, improvement of cognitive function and reduction of anxiety.

Thus patients considered a return to normal level of functioning, coping with the daily stressors of life, and the presence of features of positive mental well-being such as self-confidence and optimism as equal if not more important indicators of remission as a resolution of depression symptoms.

  1. Sanderson WC. Behav Modif. 2003;27(3):290-299
  2. Barlow DH, et al. Behav Res Ther. 1999;37(Suppl 1):S147-S162
  3. Herbert JD, Gaudiano BA. J Clin Psychol. 2005;61(7):893-908
  4. Danner M, et al. Int J Technol Assess Health Care. 2011:27(4):369–75
  5. Zimmerman M, et al. J Clin Psychiatry. 2012;73:790–95
  6. Zimmerman M, et al. J Affect Disord. 2012;142:77–81
     
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Functional impairment in MDD
References
  1. Sheehan DV. Importance of Restoring Function in Patients With Major Depressive Disorder. J Clin Psychiatry. 2016 Jul;77(7):e908.3.
     
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Patient-reported psychopathology is significant among those meeting clinical criteria for remission
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References

This slide shows data demonstrating that patients who met the clinical criteria for remission and patients who did not consider themselves to be in remission had significantly greater severity of symptoms and levels of anxiety than those who did, demonstrating that the HAM-D17 definition of remission may not align with the patients’ view of well-being.

Remission: equivalent to ≤7 on the 17-item Hamilton Rating Scale for Depression [HAM-D17]

Study Background:

  • 274 psychiatric outpatients diagnosed with DSM-IV major depressive disorder, who were in ongoing treatment, were interviewed 
  • Patients were rated by the authors on the HAM-D17 and DSM-IV Global Assessment of Functioning (GAF) scale
  • Patient were assessed for depressive and anxious symptoms, psychosocial functioning, and quality of life
  • Patients completed seven self-report scales: 
  • A demographic form, including a question regarding the patient's perception of whether they were currently in remission from depression
  • The Clinically Useful Depression Outcome Scale (CUDOS), a brief measure of depression severity that assesses the DSM-IV symptoms of major depressive disorder 
  • The Quick Inventory of Depressive Symptomatology (QIDS), a reliable and valid measure of the DSM-IV symptom criteria of major depressive disorder 
  • The Clinically Useful Anxiety Outcome Scale (CUXOS), general measure of psychic and somatic anxiety rather than a disorder-specific scale 
  • The Patient Global Index of Severity of Depression (PGI) 
  • The psychosocial functioning and quality of life subscales of the Diagnostic Inventory for Depression (DID), a self-report scale designed to assess the DSM-IV symptom inclusion criteria for a major depressive episode, assess psychosocial impairment due to depression, and evaluate subjective quality of life
  • The Remission from Depression Questionnaire (RDQ), consists of 41 items assessing multiple components of remission, such as positive mental health, symptom levels, and coping ability
  1. Zimmerman M et al. Symptom differences between depressed outpatients who are in remission according to the Hamilton Depression Rating Scale who do and don’t consider themselves to be in remission J Clin Psychiatry 2012;73:790–795
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The definition of treatment success in depression has evolved
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References

This slide illustrates that the definition of treatment success has evolved since the 1970s, when a reduction in symptom severity was the top treatment priority. It is now accepted that treatment success requires more than symptomatic improvement, with full functional recovery the ultimate aim – a change that reflects the increasing importance of considering the patient perspective in treatment decisions.

  1. Nierenberg AA & DeCecco LM. J Clin Psychiatry 2001;62(suppl 16):5–9
  2. Hawley CJ et al. J Affect Disord 2002;72(2):177–184
  3. Saltiel PF & Silvershein DI. Depress Anxiety 2012;29(7):638–645
     
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