Differences

Last edited on April 30, 2020

This shows you the differences between two versions of the page.

--- mood:1-depression:home [on April 26, 2020]
+++ mood:1-depression:home [on February 27, 2024] (current)
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 ===== Primer =====
-**Major Depressive Disorder (MDD)** is a mental disorder characterized by persistent, often daily, low mood and/or decreased interest (anhedonia). There also associated neurovegetative symptoms, such as a change in sleep, appetite, cognition, and energy levels. Suicidal ideation may also occur.
+**Major Depressive Disorder (MDD)** is a mental disorder characterized by persistent, often daily, low mood and/or decreased interest (anhedonia). There are also associated neurovegetative symptoms, such as a change in sleep, appetite, cognition, and energy levels. [[teaching:suicide|Suicidal ideation or attempts]] may also occur during depressive episodes.
 == Epidemiology ==
-The one month prevalence is 1.3%, one year is 4.0%, and lifetime is 10.8%.[([[http://www.canmat.org/canmatpub.html|Lam RW, Kennedy SH, Parikh SV, MacQueen GM, Milev RV, Ravindran AV; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder]])] Women have a two times higher risk of developing MDD versus men. The reasons for the difference are hypothesized to involve hormonal differences, the effects of childbirth, differing psychosocial stressors for women and for men, and behavioural models of learned helplessness. The average age of onset is about 40 years old.
+  * In Canada, the annual prevalence of a depressive episode is 4.7%, and a lifetime prevalence is 11.3%.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994787/|Lam, R. W., Kennedy, S. H., Parikh, S. V., MacQueen, G. M., Milev, R. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Introduction and Methods. Canadian journal of psychiatry.]])]
+  * In the United States, the annual prevalence is 7%, with 18 to 29-year-olds having a three times higher prevalence than individuals 60 and older.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994787/|Lam, R. W., Kennedy, S. H., Parikh, S. V., MacQueen, G. M., Milev, R. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Introduction and Methods. Canadian journal of psychiatry.]])]
+  * Females have a 2 to 3 times higher rate of being diagnosed with depression than males.
+    * The reasons for the difference are hypothesized to involve hormonal differences, the effects of childbirth, differing psychosocial stressors for women and for men, increased seeking of clinical care, and behavioural models of learned helplessness.
+== Prognosis ==
+  * MDD can appear at any age, but the chance increases with the onset of puberty. The age of onset peaks in the mid-20s.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+  * The course of MDD can vary significantly between individuals, such that some individuals have a chronic illness course, while others can have years with few or no symptoms between depressive episodes. 50% of depressive episodes are brief and resolve within three months.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994789/|Lam, R. W., McIntosh, D., Wang, J., Enns, M. W., Kolivakis, T., Michalak, E. E., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry, 61(9), 510-523.]])]
+  * Those with underlying personality, anxiety, and substance use disorders are most likely to have a chronic course of symptoms and lower likelihood of full symptom remission.
+    * Other factors for chronic symptoms or recurrence include early age of onset, greater number of episodes, severity of the initial episode, disruption of the sleep-wake cycle, presence of comorbid psychopathology (particularly [[mood:persistent-depressive-disorder-dysthymia|dysthymia]]), a family history of psychiatric illness, presence of negative cognitions, high neuroticism, poor social support, and stressful life events.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994789/|Lam, R. W., McIntosh, D., Wang, J., Enns, M. W., Kolivakis, T., Michalak, E. E., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry, 61(9), 510-523.]])]
+  * The longer the period of full remission, the lower the chance of recurrence.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+    * This means that the persistence of even mild depressive symptoms during a period of remission is a significant predictor for a future recurrence.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+  * Negative prognostic factors include having psychotic features, comorbid anxiety, personality disorders, and greater symptom severity.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+  * Many individuals with [[bipolar:home|bipolar disorders]] are initially misdiagnosed with a major depressive disorder, but over the course of the illness, will later be correctly diagnosed with bipolar disorder.
+    * This is especially true for individuals who present with mixed features (i.e. - some symptoms of bipolar, but not full hypomanic or manic episodes).[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+  * The impairment from MDD can range from being mild to severe, depending on the individual, and depend on the symptom profile.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+== Comorbidity ==
+  * MDD is associated with chronic medical conditions including heart disease, arthritis, back pain, chronic pulmonary disease, asthma, hypertension, and migraine.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994789/|Lam, R. W., McIntosh, D., Wang, J., Enns, M. W., Kolivakis, T., Michalak, E. E., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry, 61(9), 510-523.]])]
+    * Associated lifestyle risk factors include a more sedentary lifestyle, obesity, and cigarette smoking.
+  * Other comorbid psychiatric disorders include [[anxiety:panic|panic disorder]], [[addictions:home|substance use disorders]], [[ocd:1-ocd|obsessive compulsive disorder]], [[eating-disorders:anorexia|anorexia nervosa]], [[eating-disorders:bulimia|bulimia nervosa]], and [[personality:borderline|borderline personality disorder]].[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
 == Risk Factors ==
-MDD occurs most often in persons without close interpersonal relationships or in those who are divorced or separated. There is no correlation between socioeconomic status. It is more slightly more common in rural areas than in urban areas.[([[https://www.ncbi.nlm.nih.gov/pubmed/24857610|Breslau, J., Marshall, G. N., Pincus, H. A., & Brown, R. A. (2014). Are mental disorders more common in urban than rural areas of the United States?. Journal of psychiatric research, 56, 50-55.]])]
+  * MDD occurs most often in persons without close interpersonal relationships or in those who are divorced or separated. There is no correlation between socioeconomic status. It is slightly more common in rural areas than in urban areas.[([[https://www.ncbi.nlm.nih.gov/pubmed/24857610|Breslau, J., Marshall, G. N., Pincus, H. A., & Brown, R. A. (2014). Are mental disorders more common in urban than rural areas of the United States?. Journal of psychiatric research, 56, 50-55.]])]
+  * High neuroticism, adverse childhood events are risk factors for depression.
+  * First-degree family members of an individual with MDD have a 2 to 4 times higher risk for depression.
+  * The heritability of MDD is estimated to be 40%.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
+  * Medical conditions such as diabetes, obesity, and cardiovascular disease also increase the risk for depression.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
-{{page>ad}}
+===== DSM-5 Diagnostic Criteria =====
+== Criterion A ==
+  * At least **''5''** out of 9 symptoms present in the same **''2-week''** period and represent a change from previous functioning, **//AND//**
+  * At least **''1''** of the 5 symptoms is either (1) depressed mood or (2) loss of interest or pleasure (anhedonia).
-===== Diagnostic Criteria =====
 <WRAP group>
 <WRAP half column>
-== Criterion A ==
-At least **''5''** out of 9 symptoms present in the same **''2-week''** period and represent a change from previous functioning. At least **''1''** of the 5 symptoms is either (1) depressed mood or (2) loss of interest or pleasure (anhedonia).
   - **Mood** is depressed most of the day, nearly every day, as indicated by either subjective report (e.g. - feels sad, empty, hopeless) or observation made by others (e.g. - appears tearful) <callout type="info" icon="fa fa-child">In children and adolescents, there can be irritable mood.</callout>
   - **Sleep changes**: insomnia or hypersomnia nearly every day
@@ Line 27: / Line 51: @@
   - **Psychomotor agitation or retardation** nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
   - **Suicide**, recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
-<callout icon="true" type="danger">Do not include symptoms that are clearly attributable to another medical condition.</callout>
-== Criterion B ==
-The symptoms cause clinically significant distress or impairment in social, occupational, or other
-important areas of functioning.
 </WRAP>
 <WRAP half column>
+<callout icon="true" type="danger">
+If there are symptoms that are clearly attributable to another medical condition (e.g. - insomnia from chemotherapy treatment), then they do not count as part of meeting the criterion for diagnosis!
+</callout>
 <callout icon="fa fa-lightbulb-o" type="success" title="Mnemonic">
 The mnemonic ''**MSIGECAPS**'' can be used to remember the criteria for major depressive disorder.[([[http://www.mdedge.com/currentpsychiatry/article/63313/mnemonics-mnutshell-32-aids-psychiatric-diagnosis|Mnemonics in a mnutshell: 32 aids to psychiatric diagnosis. Current Psychiatry. 2008 October;7(10):27-33]])]
-<HTML><br><br></HTML>
+\\
   * ''**M**'' - **Mood**
   * ''**S**'' - **Sleep**
@@ Line 51: / Line 70: @@
   * ''**S**'' - **Suicide**
 </callout>
+</WRAP>
+</WRAP>
+== Criterion B ==
+The symptoms cause clinically significant distress or impairment in social, occupational, or other
+important areas of functioning.
 == Criterion C ==
@@ Line 56: / Line 81: @@
 condition.
-<callout>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 contest of loss.</callout>
+<callout title="Bereavement and Loss">
+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 contest of loss.** See the [[mood:1-depression:home#griefloss|Differential Diagnosis]] section below for more details on differentiating between the two.
+</callout>
 == Criterion D ==
@@ Line 64: / Line 91: @@
 == Criterion E ==
-There has never been a manic episode or a hypomanic episode. (i.e. - a bipolar diagnosis trumps a depression diagnosis)
+There has never been a [[bipolar:bipolar-i#diagnostic-criteria|manic]] episode or a [[bipolar:bipolar-ii#hypomanic-episode-criteria|hypomanic]] episode. (i.e. - a bipolar diagnosis trumps a major depressive disorder diagnosis)
-</WRAP>
-</WRAP>
 ==== Specifiers ====
@@ Line 105: / Line 131: @@
 </panel>
 <panel icon="fa fa-plus-circle fa-fw" size="xs" title="With mixed features">
-  * **A**. At least ''3'' of the following manic/hypomanic symptoms are present nearly every day during the majority of days of a major depressive episode:
+  * **A**. At least ''3'' of the following manic/hypomanic symptoms are present during the majority of days of a major depressive episode:
     * (1) Elevated, expansive mood
     * (2) Inflated self-esteem or grandiosity
@@ Line 114: / Line 140: @@
     * (7) Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
   * **B**. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
-  * **C**. For individuals whose symptoms meet full criteria for either mania or hypomania, the diagnosis should be [[mood:bipolar-i|bipolar I]] or [[mood:bipolar-ii|bipolar II disorder]].
+  * **C**. For individuals whose symptoms meet full criteria for either mania or hypomania, the diagnosis should be [[bipolar:bipolar-i|bipolar I]] or [[bipolar:bipolar-ii|bipolar II disorder]].
   * **D**. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, other treatment)
@@ Line 169: / Line 195: @@
 This specifier applies to recurrent major depressive disorder.
   * **A**. There has been a regular temporal relationship between the onset of major depressive episodes in major depressive disorder and a particular time of the year (e.g. - in the fall or winter). Do not include cases in which there is an obvious effect of seasonally related psychosocial stressors (e.g. - regularly being unemployed every winter).
-  * **B**. Full remissions (or a change from major depression to mania or hypomania) also occur at a characteristic time of the year (e.g. - depression disappears in the spring)
+  * **B**. Full remissions also occur at a characteristic time of the year (e.g. - depression disappears in the spring)
   * **C**. In the last ''2'' years, ''2'' major depressive episodes have occurred that demonstrate the temporal seasonal relationships defined above and no nonseasonal major depressive episodes have occurred during that same period.
   * **D**. Seasonal major depressive episodes (as described above) substantially outnumber the nonseasonal major depressive episodes that may have occurred over the individual’s lifetime.
@@ Line 177: / Line 203: @@
 </WRAP>
+==== Signs and Symptoms ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[teaching:1-psych-interview|]]**
+</alert>
+  * When inquiring about a history of depressive symptoms, it can be helpful to ask an individual when was the last time they had at least ''2'' months where they were //entirely// free of depressive symptoms.
+  * Hypersomnia and hyperphagia are more likely in younger individuals, while melancholic symptoms (psychomotor disturbances, weight loss) are more common in geriatric depression.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
 ===== Subtypes =====
-Various subtypes of depression have been identified. Clinically, it is important to ask the right questions to target the correct treatments to these subtypes.
+<alert type="info" icon="fa fa-book fa-lg fa-fw">
+**See also:**
+  * **[[https://pubmed.ncbi.nlm.nih.gov/31995137/|Kendler, K. S. (2020). The Origin of Our Modern Concept of Depression—The History of Melancholia From 1780-1880: A Review. JAMA psychiatry.]]**
+  * **[[https://pubmed.ncbi.nlm.nih.gov/10910777/|Parker, G. (2000). Classifying depression: should paradigms lost be regained?. American journal of psychiatry, 157(8), 1195-1203.]]**
+</alert>
-==== Seasonal Affective ====
+  * Various subtypes of depression have been identified. Clinically, it is important to ask the right questions to target the correct treatments to these subtypes.
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[mood:1-depression:seasonal-affective-disorder|]]**</alert>
+  * The history of depression and melancholia has gone through various periods splitting and subtyping, followed by unifying theories of depression, and back again. Having an understanding of the history behind diagnostic classification of depression can be helpful (see above links).
-**Seasonal Affective Disorder (SAD)** is a subtype of depression with a usual annual onset between September-November with spontaneous remission in April-May. There is generally an increased prevalence in countries the father it is from the equator (interestingly, Iceland has low rates of SAD[([[https://www.ncbi.nlm.nih.gov/pubmed/10671392|Magnusson, A., Axelsson, J., Karlsson, M. M., & Oskarsson, H. (2000). Lack of seasonal mood change in the Icelandic population: results of a cross-sectional study. American Journal of Psychiatry, 157(2), 234-238.]])]). The development of SAD is thought to be due to dark/grey conditions in the winter season, and lack of light availability. Fluctuations in circadian rhythms and melatonin release also plays a role.[([[https://www.ncbi.nlm.nih.gov/pubmed/3462335|Rosenthal, N. E., Sack, D. A., Jacobsen, F. M., James, S. P., Parry, B. L., Arendt, J., ... & Wehr, T. A. (1986). Melatonin in seasonal affective disorder and phototherapy. Journal of neural transmission. Supplementum, 21, 257-267.]])] SAD can be considered as an evolutionary phenomenon and many individuals have non-clinical symptoms of SAD. Clinically symptomatic SAD can occur in up to 2.6% of the Canadian population, with premenopausal women most affected.
-Individuals with certain serotonin transporter genotypes may be more predisposed to SAD.[([[https://www.ncbi.nlm.nih.gov/pubmed/29163018|Nørgaard, M., Ganz, M., Svarer, C., Fisher, P. M., Churchill, N. W., Beliveau, V., ... & Knudsen, G. M. (2017). Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter. Frontiers in Neuroscience, 11.]])] [[meds:antidepressants:ndri:bupropion|Bupropion]] has been shown to be effective in the prevention of SAD by starting treatment prior to the winter season.[([[https://www.ncbi.nlm.nih.gov/pubmed/16271314|Modell, J. G., Rosenthal, N. E., Harriett, A. E., Krishen, A., Asgharian, A., Foster, V. J., ... & Wightman, D. S. (2005). Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biological psychiatry, 58(8), 658-667.]])]
 ==== Atypical ====
@@ Line 190: / Line 224: @@
 <WRAP half column>
 **Atypical Depression** is a depression characterized by mood reactivity (moods that are strongly reactive to environmental circumstances, and feeling extremely sensitive - this is a must have feature), hypersomnia, carbohydrate craving/increased appetite, leaden paralysis (profound fatigue), and chronic rejection sensitivity. Atypical depression results in more disability than melancholic depression, because individuals often have more interpersonal difficulties. Atypical depression patients lack classic melancholic depression features such as insomnia, weight loss, loss of reactivity of mood.
-Atypical depression is also associated with conduct disorder, social phobia, interpersonal dependency, low self-esteem, and parental substance abuse.[([[https://www.ncbi.nlm.nih.gov/pubmed/9766772/|Sullivan, P. F., Kessler, R. C., & Kendler, K. S. (1998). Latent class analysis of lifetime depressive symptoms in the national comorbidity survey. American Journal of Psychiatry, 155(10), 1398-1406.]])]
-Atypical depression has a poor response to TCAs and ECT, but excellent response to MAOis, due to suspected elevated MAO activity.[([[https://www.ncbi.nlm.nih.gov/pubmed/3276282|Liebowitz, M. R., Quitkin, F. M., Stewart, J. W., McGrath, P. J., Harrison, W. M., Markowitz, J. S., ... & Klein, D. F. (1988). Antidepressant specificity in atypical depression. Archives of General Psychiatry, 45(2), 129-137.]])][([[https://www.nature.com/articles/npp2013297|Chiuccariello, L., Houle, S., Miler, L., Cooke, R. G., Rusjan, P. M., Rajkowska, G., ... & Wilson, A. A. (2014). Elevated monoamine oxidase a binding during major depressive episodes is associated with greater severity and reversed neurovegetative symptoms. Neuropsychopharmacology, 39(4), 973-980.]])] Atypical depression is also associated with higher rates of early childhood trauma, whereas melancholic depression is not.[([[https://www.ncbi.nlm.nih.gov/pubmed/9842786|Levitan, R. D., Parikh, S. V., Lesage, A. D., Hegadoren, K. M., Adams, M., Kennedy, S. H., & Goering, P. N. (1998). Major depression in individuals with a history of childhood physical or sexual abuse: relationship to neurovegetative features, mania, and gender. American Journal of Psychiatry, 155(12), 1746-1752.]])] This again suggests a difference in the etiology and pathophysiology of different depression subtypes.[([[https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.160.6.1188#|Levitan, R. D., & Parikh, S. V. (2003). Childhood trauma and depression. American Journal of Psychiatry, 160(6), 1188-1188.]])]
 </WRAP>
 <WRAP half column>
 <callout type="question" title="Are atypical depression, borderline personality disorder, bipolar II disorder, and cyclothymic disorder overlapping conditions?" icon="true">The common feature in all these diagnoses are emotional dysregulation and mood reactivity. The research hints that these disorders may all exist on a continuum.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048510/|Perugi, G., Fornaro, M., & Akiskal, H. S. (2011). Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?. World Psychiatry, 10(1), 45-51.]])][([[https://www.ncbi.nlm.nih.gov/pubmed/12507741|Perugi, G., Toni, C., Travierso, M. C., & Akiskal, H. S. (2003). The role of cyclothymia in atypical depression: toward a data-based reconceptualization of the borderline–bipolar II connection. Journal of affective disorders, 73(1), 87-98.]])][([[https://www.ncbi.nlm.nih.gov/pubmed/15840417/|Chopra, K. K., Bagby, R. M., Dickens, S., Kennedy, S. H., Ravindran, A., & Levitan, R. D. (2005). A dimensional approach to personality in atypical depression. Psychiatry research, 134(2), 161-167.]])] Clinically, it can be challenging to distinguish between these disorders.</callout>
 </WRAP></WRAP>
+==== Childhood and Adolescent ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[mood:1-depression:pediatric-child-adolescent]]**
+</alert>
+**Childhood and Adolescent Depression** is a subtype of [[mood:1-depression:home|depression]] characterized by low mood, anxiety, and irritability in children and youth.
 ==== Melancholic ====
 <alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[mood:1-depression:melancholic|]]**</alert>
-**Melancholic Depression** (sometimes known as "endogenous depression") as a subtype of depression characterized by a profound sense of sadness, lack of mood reactivity (i.e. - absolutely nothing can brighten one's mood), and anhedonia. It is considered to be a biologically-based depression. Individuals often have hypercortisolemia and there is a strong genetic and familial association in melancholic depression. Theories on the pathophysiology of melancholic depression include disruption of the HPA axis.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149795/|Levitan, R. D., Vaccarino, F. J., Brown, G. M., & Kennedy, S. H. (2002). Low-dose dexamethasone challenge in women with atypical major depression: pilot study. Journal of Psychiatry and Neuroscience, 27(1), 47.]])][([[http://www.psychiatrictimes.com/electroconvulsive-therapy/endocrine-psychiatry-dexamethasone-suppression-test-and-electroconvulsive-therapy|Kellner, C. H. (2011). Endocrine psychiatry: the dexamethasone suppression test and electroconvulsive therapy. Psychiatric Times, 28(3), 57-57.]])] Melancholic depression often progresses into psychotic depression (where delusions are usually nihilistic in nature). Females are less affected in melancholic depression, and there is typically an older age of onset. Melancholic depression is shorter in duration and more episodic. It also features diurnal variation (early-morning worsening of mood, with an afternoon slump or evening worsening).[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181887/|Wirz-Justice A. Diurnal variation of depressive symptoms. Dialogues in Clinical Neuroscience. 2008;10(3):337-343.]])] There is concern from older clinicians that the proper diagnosis and treatment of melancholic depression has been overshadowed by the introduction of mass-marketed SSRIs.[([[http://www.nejm.org/doi/full/10.1056/NEJMbkrev57417|Taylor, M. A., & Fink, M. (2006). Melancholia: the diagnosis, pathophysiology and treatment of depressive illness. Cambridge University Press.]])] There is evidence to suggest that melancholic depression responds better to TCAs and ECT.[([[http://www.psychiatrictimes.com/cme/update-melancholia/page/0/5|Psychiatric Times: An Update on Melancholia]])][([[https://www.ncbi.nlm.nih.gov/pubmed/8835647|Perry, P. J. (1996). Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. Journal of affective disorders, 39(1), 1-6.]])]
+**Melancholic Depression** (also known as **Major Depressive Disorder with melancholic features** in the DSM-5, and previously as "endogenous depression") is a subtype of [[mood:1-depression:home|depression]] characterized by a severe loss of pleasure and prominent physical symptoms. Classic melancholic depression features include insomnia, weight loss, and psychomotor changes.
 ==== Geriatric ====
 <alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[mood:1-depression:geriatric|]]**</alert>
 **Geriatric Depression** is one of the major geriatric giants (dementia, delirium, and depression). As a treatment population, special considerations need to be taken into account.
-==== Postpartum ====
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[mood:1-depression:postpartum-peripartum]]**</alert>
+==== Post-Stroke ====
-==== Menopause ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
-In women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Since estrogen and serotonin may modulate hypothalamic thermoregulatory function, abrupt changes in neuromodulatory function and reproductive-hormone levels during menopause are thought to contribute to mood and vasomotor symptoms seen in menopause.[([[https://jamanetwork.com/journals/jamapsychiatry/fullarticle/209471|Cohen, L. S., Soares, C. N., Vitonis, A. F., Otto, M. W., & Harlow, B. L. (2006). Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Archives of general psychiatry, 63(4), 385-390.]])] There is scant evidence to suggest that hormone replacement therapy should be used to prevent depressive symptoms during the menopause transition.[([[https://www.ncbi.nlm.nih.gov/pubmed/29322164|Gordon, J. L., Rubinow, D. R., Eisenlohr-Moul, T. A., Xia, K., Schmidt, P. J., & Girdler, S. S. (2018). Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial. JAMA psychiatry.]])] Additionally, the U.S. Preventive Services Task Force recently found “no net benefit” of hormone therapy for primary prevention of most chronic disorders related to menopause, but they did find “convincing evidence” of risks like breast cancer, thromboembolism, and cardiovascular disease.[([[https://jamanetwork.com/journals/jama/fullarticle/2665782|Grossman, D. C., Curry, S. J., Owens, D. K., Barry, M. J., Davidson, K. W., Doubeni, C. A., ... & Landefeld, C. S. (2017). Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement. Jama, 318(22), 2224-2233.]])]
+See main article: **[[mood:1-depression:post-stroke|]]**
+</alert>
+**Post-Stroke Depression (PSD)** can develop acutely after a stroke, and associated with poorer functional outcomes.
+==== Peripartum and Postpartum ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[mood:1-depression:postpartum-peripartum]]**
+</alert>
+**Postpartum Depression (PPD)** (also known as **Peripartum Depression**, or **Major Depressive Disorder with peripartum onset** in the DSM-5) is a subtype of [[mood:1-depression:home|depression]] that occurs during pregnancy or in the first ''4'' weeks after delivery. However, women remain at risk for developing depression up to several months following delivery. PPD is the most common psychiatric complication related to child-bearing.
+==== Psychotic ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[mood:1-depression:psychotic|]]**
+</alert>
+**Psychotic Depression** (also known as **Major Depressive Disorder with psychotic features** in the DSM-5) is a subtype of [[mood:1-depression:home|depression]] characterized by psychosis (delusions, hallucinations) in addition to mood changes. It requires the treatment of the underlying mood disorder first to resolve the psychosis.
+==== Perimenopause ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[mood:1-depression:perimenopausal|]]**
+</alert>
+**Perimenopausal Depression** (also known as **Major Depressive Disorder with peripartum onset** in the DSM-5) is a subtype of [[mood:1-depression:home|depression]] experienced by women during the perimenopausal period, defined as the interval when a women’s menstrual cycles become irregular, usually between ages of 45 and 49.
+==== Seasonal Affective ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[mood:1-depression:seasonal-affective-disorder|]]**</alert>
+**Seasonal Affective Disorder (SAD)** is a subtype of depression with a usual annual onset between September-November with spontaneous remission in April-May. There is generally an increased prevalence in countries the father it is from the equator (interestingly, Iceland has low rates of SAD[([[https://www.ncbi.nlm.nih.gov/pubmed/10671392|Magnusson, A., Axelsson, J., Karlsson, M. M., & Oskarsson, H. (2000). Lack of seasonal mood change in the Icelandic population: results of a cross-sectional study. American Journal of Psychiatry, 157(2), 234-238.]])]). The development of SAD is thought to be due to dark/grey conditions in the winter season, and lack of light availability. Fluctuations in circadian rhythms and melatonin release also plays a role.[([[https://www.ncbi.nlm.nih.gov/pubmed/3462335|Rosenthal, N. E., Sack, D. A., Jacobsen, F. M., James, S. P., Parry, B. L., Arendt, J., ... & Wehr, T. A. (1986). Melatonin in seasonal affective disorder and phototherapy. Journal of neural transmission. Supplementum, 21, 257-267.]])] SAD can be considered as an evolutionary phenomenon and many individuals have non-clinical symptoms of SAD. Clinically symptomatic SAD can occur in up to 2.6% of the Canadian population, with premenopausal women most affected. Individuals with certain serotonin transporter genotypes may be more predisposed to SAD.[([[https://www.ncbi.nlm.nih.gov/pubmed/29163018|Nørgaard, M., Ganz, M., Svarer, C., Fisher, P. M., Churchill, N. W., Beliveau, V., ... & Knudsen, G. M. (2017). Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter. Frontiers in Neuroscience, 11.]])] [[meds:antidepressants:ndri:bupropion|Bupropion]] has been shown to be effective in the prevention of SAD by starting treatment prior to the winter season.[([[https://www.ncbi.nlm.nih.gov/pubmed/16271314|Modell, J. G., Rosenthal, N. E., Harriett, A. E., Krishen, A., Asgharian, A., Foster, V. J., ... & Wightman, D. S. (2005). Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biological psychiatry, 58(8), 658-667.]])]
+==== Situational ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[mood:1-depression:situational-reactive-exogenous|]]**
+</alert>
+**Situational Depression** (also known as **Reactive Depression**, **Exogenous Depression**, and **[[trauma-and-stressors:adjustment|Adjustment Disorder]]**) are depressive symptoms that occur when an individual is unable to adjust to or cope with a particular stress or a major life event. This was a previously historical diagnosis that has fallen out of clinical use. Its close counterpart is now called [[trauma-and-stressors:adjustment|adjustment disorder]], which reflects much of the same symptoms.
+===== Suicide =====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[teaching:suicide|]]**
+</alert>
+Suicide is the most serious consequence of a major depressive episode. Suicidal ideation, planning, and attempts are highly prevalent in depression. The risk for suicidal behaviour is present at all times during a depressive episode. Thus, a [[teaching:suicide-risk-assessment-sra|suicide risk assessment]] should be done as part of routine clinical care. Certain risk factors place an individual for higher risk of suicide, with a past history of suicide attempts or behaviours being the highest risk factor.
+<panel type="info" title="Risk Factors for Suicide During a Depressive Episode" subtitle="Lam, Raymond W., et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry 61.9 (2016): 510-523." no-body="true" footer="">
+^ Non-modifiable Risk Factors                                                                                                                                      ^ Modifiable Risk Factors                                                                                                                                                                                                 ^ Modifiable Risk Factors                                                                                                                                                                                                                                                                           ^
+| • Older men\\ • Past suicide attempt\\ • History of self-harm behaviour\\ • Being a sexual minority\\ • Family history of suicide\\ • History of legal problems  | **Symptoms and life events**\\ • Active suicidal ideation\\ • Hopelessness\\ • Psychotic symptoms\\ • Anxiety\\ • Impulsivity\\ • Stressful life events such as financial stress (e.g. - bankruptcy) and victimization  | **Comorbid conditions**\\ • Substance use disorders (especially alcohol use disorder)\\ • Posttraumatic stress disorder\\ • Comorbid personality disorders (especially cluster B personality disorders)\\ • Chronic painful medical conditions (e.g. - migraine headaches, arthritis)\\ • Cancer  |
+</panel>
 ===== Screening and Rating Scales =====
 Various scales can be used to measure depression severity in an individual. Below are the most common ones, with an indication for each. [[meds:measurement-based-care|Measurement based care]] with scales has been shown to lead to better recovery in depression.[([[https://www.ncbi.nlm.nih.gov/pubmed/26315978|Guo, T., Xiang, Y. T., Xiao, L., Hu, C. Q., Chiu, H. F., Ungvari, G. S., ... & Feng, Y. (2015). Measurement-based care versus standard care for major depression: a randomized controlled trial with blind raters. American Journal of Psychiatry, 172(10), 1004-1013.]])]
 <panel title="Psychometric Scales for Depression" no-body="true">
-!^ Name                                               ^ Rater      ^ Description                                                                                                                                                                                   ^ Download  ^
+<mobiletable 1>
-^ Beck Depression Inventory (BDI)                    | Patient    | A 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. Designed for individuals aged 13 and over.      | {{:mood:bdi.pdf|BDI Download}}         |
+^ Name                                                    ^ Rater      ^ Description                                                                                                                                                                                   ^ Download                                ^
-^ Patient Health Questionnaire (PHQ-9)                | Patient    | A 9-question instrument given to patients in a primary care setting to screen for the presence and severity of depression.                                                                    | {{:mood:phq-9.pdf|PHQ-9 Download}}          |
+^ Beck Depression Inventory (BDI)                         | Patient    | A 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. Designed for individuals aged 13 and over.      | Not Available                           |
-^ Hamilton Rating Scale for Depression (HAM-D/HDRS)  | Clinician  | Rates patient between 17 to 29 dimensions (depending on version) with a score on a 3 or 5 point scale. Max Hamilton maintained that his scale should not be used as a diagnostic instrument.  | {{:mood:ham-d.pdf|HAM-D Download}}          |
+^ Patient Health Questionnaire (PHQ-9)                    | Patient    | A 9-question instrument given to patients in a primary care setting to screen for the presence and severity of depression.                                                                    | {{:mood:phq-9.pdf|PHQ-9 Download}}      |
-^ Montgomery–Åsberg Depression Rating Scale (MADRS)  | Clinican   | 10-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.                                                      | {{:mood:madrs.pdf|MADRS Download}}          |
+^ Hamilton Rating Scale for Depression (HAM-D/HDRS)       | Clinician  | Rates patient between 17 to 29 dimensions (depending on version) with a score on a 3 or 5 point scale. Max Hamilton maintained that his scale should not be used as a diagnostic instrument.  | {{:mood:ham-d.pdf|HAM-D Download}}      |
-^ Quick Inventory of Depressive Symptomatology (QIDS-C)  | Clinican   | A 16-item clinician rating of the patient's depressive symptoms                             | {{:mood:qids-c.pdf|QIDS-C Download}}          |
+^ Montgomery–Åsberg Depression Rating Scale (MADRS)       | Clinican   | 10-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.                                                      | {{:mood:madrs.pdf|MADRS Download}}      |
-^ Quick Inventory of Depressive Symptomatology (QIDS-SR)  | Patient   | A 16-item patient's self-report of depressive symptoms                                                      | {{:mood:qids-sr.pdf|QIDS-SR Download}}        |
+^ Quick Inventory of Depressive Symptomatology (QIDS-C)   | Clinican   | A 16-item clinician rating of the patient's depressive symptoms                                                                                                                               | {{:mood:qids-c.pdf|QIDS-C Download}}    |
+^ Quick Inventory of Depressive Symptomatology (QIDS-SR)  | Patient    | A 16-item patient's self-report of depressive symptoms                                                                                                                                        | {{:mood:qids-sr.pdf|QIDS-SR Download}}  |
+</mobiletable>
 </panel>
 ===== Pathophysiology =====
-<callout type="danger" icon="true" title="Never, Ever, Forget This">
+<alert type="info" icon="fa fa-book fa-lg fa-fw">
-"Major depressive disorder is a clinically heterogeneous group of conditions that respond variably to a diverse group of interventions."[([[https://www.ncbi.nlm.nih.gov/pubmed/26813206|Thase, M. E. (2016). Recommendations for screening for depression in adults. Jama, 315(4), 349-350.]])]
+See also: **[[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330161/|Hidaka, B. H. (2012). Depression as a disease of modernity: explanations for increasing prevalence. Journal of affective disorders, 140(3), 205-214.]]**
-</callout>
+</alert>
-The etiology of depression is heterogeneous and multifactorial. Often, [[mood:1-depression:home#subtypes|subtyping]] the depression can be helpful in determing its etiology. Refer to the subtypes section for more information. More recently, diffusion tensor imaging (DTI) imaging has shown that the cingulum bundle microstructure is altered in people at risk for depression. The uncinate fasciculus and medial forebrain bundle microstructures are also altered during acute depression in adults.[([[https://www.ncbi.nlm.nih.gov/pubmed/26318270|Bracht, T., Linden, D., & Keedwell, P. (2015). A review of white matter microstructure alterations of pathways of the reward circuit in depression. Journal of affective disorders, 187, 45-53.]])]
+  * The etiology of depression is heterogeneous and multifactorial, and also can be due to medical etiologies ("organic").
+    * As such, there cannot be a "single cause" or etiology for depression.
+    * This similarly means there is no "single cure" for depression.
+  * Sometimes, [[mood:1-depression:home#subtypes|subtyping]] the depression can be helpful in determining its etiology.
+==== Neuroimaging ====
+  * Amygdala hyperactivity and volumetric changes are a well-replicated finding in major depressive disorder.[([[https://pubmed.ncbi.nlm.nih.gov/19545982/|Peluso, M. A., Glahn, D. C., Matsuo, K., Monkul, E. S., Najt, P., Zamarripa, F., ... & Soares, J. C. (2009). Amygdala hyperactivation in untreated depressed individuals. Psychiatry Research: Neuroimaging, 173(2), 158-161.]])][([[https://pubmed.ncbi.nlm.nih.gov/19605536/|Sibille, E., Wang, Y., Joeyen-Waldorf, J., Gaiteri, C., Surget, A., Oh, S., ... & Lewis, D. A. (2009). A molecular signature of depression in the amygdala. American Journal of Psychiatry, 166(9), 1011-1024.]])][([[https://pubmed.ncbi.nlm.nih.gov/18504424/|Hamilton, J. P., Siemer, M., & Gotlib, I. H. (2008). Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Molecular psychiatry, 13(11), 993-1000.]])]
+  * Neuroimaging studies with diffusion tensor imaging (DTI) imaging have shown that the cingulum bundle microstructure is altered in people at risk for depression.
+    * The uncinate fasciculus and medial forebrain bundle microstructures are also altered during acute depression in adults.[([[https://www.ncbi.nlm.nih.gov/pubmed/26318270|Bracht, T., Linden, D., & Keedwell, P. (2015). A review of white matter microstructure alterations of pathways of the reward circuit in depression. Journal of affective disorders, 187, 45-53.]])]
+  * Functional magnetic resonance imaging (fMRI) studies also suggest functional abnormalities in specific neural networks involved in emotion processing, reward seeking, and emotion regulation.[(American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.)]
 ===== Differential Diagnosis =====
-See also: [[https://www.karger.com/Article/FullText/367913|Cosci, F., Fava, G. A., & Sonino, N. (2015). Mood and anxiety disorders as early manifestations of medical illness: a systematic review. Psychotherapy and psychosomatics, 84(1), 22-29.]]
+<callout type="danger" title="Do Not Forget Medical Illness Etiologies of Depression!" icon="true">
-  * [[trauma-and-stressors:adjustment|Adjustment disorder]]
+  * **[[https://www.karger.com/Article/FullText/367913|Cosci, F. et al. (2015). Mood and anxiety disorders as early manifestations of medical illness: a systematic review. Psychotherapy and psychosomatics, 84(1), 22-29.]]**
-  * [[sleep:breathing:1-osa|Sleep apnea]]
+  * **[[https://www.mdedge.com/psychiatry/article/63655/medical-illness-causing-your-patients-depression|Carroll, V. K., & Rado, J. T. (2009). Is a medical illness causing your patient's depression? Endocrine, neurologic, infectious, or malignant processes could cause mood symptoms. Current psychiatry, 8(8), 43-50.]]**
-  * [[addictions:stimulants|Stimulant withdrawal]]
+</callout>
-  * Hypothyroidism
-  * Vitamin B12 deficiency
+<WRAP group>
-  * Multiple Sclerosis
+<WRAP half column>
-  * [[mood:bipolar-i]] or [[mood:bipolar-ii]]
+  * **[[bipolar:bipolar-i|Manic episodes with irritable mood or mixed episodes]] (i.e. - bipolar disorder)**
+    * Major depressive episodes with prominent irritable mood can be difficult to distinguish from manic episodes with irritable mood or from mixed episodes as seen in bipolar disorder.
+  * **[[trauma-and-stressors:adjustment|Adjustment disorder]] with depressed mood**
+    * If the full criteria for a major depressive episode are not met, then an individual may meet criteria for an adjustment disorder.
+  * **[[mood:z-depressive-medical|Depressive disorder due to another medical condition]]**
+    * A diagnosis of major depressive episode is only appropriate if the mood disturbance is not judged, based on individual history, physical examination, and laboratory findings, to be the direct pathophysiological consequence of a specific medical condition (e.g. - [[geri:parkinsons|Parkinson's disease]], [[cl:vitamin-b12-cyanocobalamin-deficiency|vitamin B12 deficiency]], [[cl:huntingtons-disease|Huntington's disease]], [[cl:multiple-sclerosis|multiple sclerosis]], stroke, [[cl:thyroid-disorders:hypothyroidism|hypothyroidism]]).
+    * There are many medical conditions that can masquerade as MDD, and it is important for the clinician to have a broad differential diagnosis at all times.
+  * **[[sleep:breathing:1-osa|Obstructive sleep apnea]]**
+    * Sleep apnea is often missed and not diagnosed. Adequately treated sleep apnea reduces depressive symptoms significantly in the absence of antidepressant treatment.[([[https://pubmed.ncbi.nlm.nih.gov/31312807/|Zheng, D., Xu, Y., You, S., Hackett, M. L., Woodman, R. J., Li, Q., ... & Lorenzi-Filho, G. (2019). Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis. EClinicalMedicine, 11, 89-96.]])] Do not miss this!
+</WRAP>
+<WRAP half column>
+  * **[[mood:substance-medication|Substance/medication-induced depressive]] or [[bipolar:substance-medication|bipolar disorder]]**
+    * This is distinguished from MDD by the fact that a substance (e.g. - a drug of abuse, a medication, a toxin) appears to be etiologically and temporally related to the mood disturbance. For example, a depressed mood that occurs only in the context of withdrawal from alcohol would be diagnosed as alcohol-induced depressive disorder.
+  * **[[child:adhd|Attention-deficit/hyperactivity disorder (ADHD)]]**
+    * Distractibility and poor frustration tolerance can occur in both ADHD and MDD. Thus, if the criteria are met for both, both can be diagnosed. However, the clinician must be cautious not to //overdiagnose// depression in children with ADHD whose disturbance in mood is characterized by irritability rather than by sadness or loss of interest.
+  * **Normal sadness!**
+    * Sadness is an inherent part of the human condition and should not be medicalized. Thus, a major depressive episode should only be diagnosed if there is significant severity (i.e. - five out of nine symptoms), an appropriate duration (i.e. - most of the day, nearly every day for at least ''2'' weeks), and also clinically significant distress or impairment.
+  * **[[teaching:dsm-v-icd-z-codes|Other Conditions That May Be a Focus of Clinical Attention]]**
+    * These are situations or conditions that may be causing some "symptoms" but are not diagnosable mental disorders.
+</WRAP>
+</WRAP>
+==== Grief/Loss ====
+<panel type="info" title="Grief/Loss vs. Depression" subtitle="Adapted from: American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA." no-body="true" footer="* = If self derogatory ideation is present in grief, it usually involves feelings with respect to the deceased (e.g. - not visiting frequently enough, not telling the deceased how much they were loved)">
+<mobiletable 1>
+^ Presentation                      ^ Grief                                                                              ^ Major Depressive Episode                                                                 ^
+^ Predominant affect                | Emptiness, loss                                                                    | Persistent low mood, inability to feel happiness or pleasure                             |
+^ Course                            | Decreases in intensity over days to weeks, and occurs in waves ("pangs of grief")  | Persistent and not tied to specific thoughts                                             |
+^ Thought Content                   | Mostly preoccupied with thoughts and memories of the deceased                      | Self-critical, pessimistic ruminations                                                   |
+^ Self-esteem                       | Preserved*                                                                         | Worthlessness, self-loathing is common                                                   |
+^ Death thoughts/suicidal ideation  | Thoughts involve wanting to "join" the deceased                                    | Idea of ending one's life associated with feelings of worthlessness, pain of depression  |
+</mobiletable>
+</panel>
 ===== Investigations =====
-  * When clinically indicated, a laboratory assessment should be performed, including liver function tests and a metabolic workup
+  * When clinically indicated, bloodwork includes: complete blood count (BC), iron studies, liver function tests, [[cl:thyroid-disorders|TSH]], [[cl:vitamin-b12-cyanocobalamin-deficiency|vitamin B12]], 25-OH Vitamin D, serum zinc, calcium, magnesium, phosphate
-  * TSH
+  * The hypothalamic-pituitary-adrenal axis is associated with melancholia, psychotic features, and suicidality.
+    * The [[teaching:biomarkers#depression|dexamethasone suppression test]] has previously been used to identify the melancholic subtype of depression, but has fallen out of use.
+  * [[neurology:polysomnography|Polysomnography]] and [[neurology:eeg|EEG]]
+    * Individuals with depression have decreased sleep efficiency, decreased slow-wave sleep (meaning decreased stage 3 and stage 4 sleep time), shorter/decreased REM latency (i.e. - shorter time between sleep onset and first REM period),[([[https://pubmed.ncbi.nlm.nih.gov/4115821/|Kupfer, D., & Foster, F. G. (1972). Interval between onset of sleep and rapid-eye-movement sleep as an indicator of depression. The Lancet, 300(7779), 684-686.]])] and increased REM intensity.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181772/|Thase M. E. (2006). Depression and sleep: pathophysiology and treatment. Dialogues in clinical neuroscience, 8(2), 217–226.]])]
 ===== Treatment =====
-The following treatment recommendations
+<callout type="danger" icon="true" title="Never, Ever, Forget This">
- are based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder.[([[http://journals.sagepub.com/toc/cpab/61/9|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & McInerney, S. J. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder. The Canadian Journal of Psychiatry, 61(9), 540-560.]])] See also: [[https://jamanetwork.com/journals/jama/fullarticle/2735004|Köhler-Forsberg, O., Cusin, C., & Nierenberg, A. A. Evolving Issues in the Treatment of Depression. JAMA.]]
+"Major depressive disorder is a clinically heterogeneous group of conditions that respond variably to a diverse group of interventions."[([[https://www.ncbi.nlm.nih.gov/pubmed/26813206|Thase, M. E. (2016). Recommendations for screening for depression in adults. Jama, 315(4), 349-350.]])]
+</callout>
-<callout type="question" title="Treatment with Medication or Psychotherapy?" icon="true">
+<WRAP group>
-Whenever possible, psychotherapy should be offered to a patient first. Recovery rates from depression when treated with medication //monotherapy// is around 30%. Both [[psychotherapy:cbt|]] and [[psychotherapy:ipt|]] provides stronger protection from relapse following treatment discontinuation compared to medications.[([[https://www.ncbi.nlm.nih.gov/pubmed/29792234|Lemmens, L. H., van Bronswijk, S. C., Peeters, F., Arntz, A., Hollon, S. D., & Huibers, M. J. (2019). Long-term outcomes of acute treatment with cognitive therapy v. interpersonal psychotherapy for adult depression: follow-up of a randomized controlled trial. Psychological medicine, 49(3), 465-473.]])] Most patients also have a significantly higher preference for psychotherapy over medications.[([[https://www.ncbi.nlm.nih.gov/pubmed/23842011|McHugh, R. K., Whitton, S. W., Peckham, A. D., Welge, J. A., & Otto, M. W. (2013). Patient preference for psychological vs. pharmacological treatment of psychiatric disorders: a meta-analytic review. The Journal of clinical psychiatry, 74(6), 595.]])] CBT provides also provides stronger protection from relapse following treatment discontinuation compared to medications.[([[https://www.ncbi.nlm.nih.gov/pubmed/29792234|Lemmens, L. H., van Bronswijk, S. C., Peeters, F., Arntz, A., Hollon, S. D., & Huibers, M. J. (2019). Long-term outcomes of acute treatment with cognitive therapy v. interpersonal psychotherapy for adult depression: follow-up of a randomized controlled trial. Psychological medicine, 49(3), 465-473.]])] Unfortunately, psychological therapies can be very limited in availability, and sometimes medications are the only option.
+<WRAP half column>
+  * It is important to remember that there is no one-size-fits-all treatment for individuals with depression.
+  * Pharmacological, psychological, complementary and alternative medicine, neurostimulation, and exercise treatments can all play a role in the treatment of depression, and prevention of recurrence.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994789/|Lam, R. W., McIntosh, D., Wang, J., Enns, M. W., Kolivakis, T., Michalak, E. E., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 1. Disease burden and principles of care. The Canadian Journal of Psychiatry, 61(9), 510-523.]])]
+  * Depression is a highly placebo-sensitive condition.[([[https://pubmed.ncbi.nlm.nih.gov/24962638/|Cipriani, A., & Geddes, J. R. (2014). Placebo for depression: we need to improve the quality of scientific information but also reject too simplistic approaches or ideological nihilism. BMC medicine, 12(1), 1-3.]])][([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/|Kirsch, I. (2015). Antidepressants and the placebo effect. Zeitschrift für Psychologie.]])]
+    * Placebo response rates can be anywhere up to 30-40%.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181672/|Sonawalla, S. B., & Rosenbaum, J. F. (2002). Placebo response in depression. Dialogues in clinical neuroscience, 4(1), 105.]])]
+    * In individuals with mild-moderate depression, symptoms may remit without treatment as part of the //natural history// of the course of the disorder. Up to 50% may have full remission within 12 months.[([[https://pubmed.ncbi.nlm.nih.gov/22883473/|Whiteford, H. A., Harris, M. G., McKeon, G., Baxter, A., Pennell, C., Barendregt, J. J., & Wang, J. (2013). Estimating remission from untreated major depression: a systematic review and meta-analysis. Psychological medicine, 43(8), 1569-1585.]])][([[https://pubmed.ncbi.nlm.nih.gov/6406462/|Lehmann, H. E. (1983). Clinical evaluation and natural course of depression. The Journal of clinical psychiatry.]])]
+  * The following treatment recommendations are mostly based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder, but there are various international treatment guidelines that are equally applicable (see guidelines section).[([[http://journals.sagepub.com/toc/cpab/61/9|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & McInerney, S. J. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder. The Canadian Journal of Psychiatry, 61(9), 540-560.]])]
+</WRAP>
+<WRAP half column>
+<callout type="question" title="Treatment with Medication or Psychotherapy? Both?" icon="true">
+  * Whenever possible, psychotherapy should be offered to a patient first. Recovery rates from depression when treated with medication //monotherapy// is around 30%. Both [[psychotherapy:cbt|cognitive behavioural therapy]] and [[psychotherapy:ipt|interpersonal therapy]] provides stronger protection from relapse following treatment discontinuation compared to medications.[([[https://www.ncbi.nlm.nih.gov/pubmed/29792234|Lemmens, L. H., van Bronswijk, S. C., Peeters, F., Arntz, A., Hollon, S. D., & Huibers, M. J. (2019). Long-term outcomes of acute treatment with cognitive therapy v. interpersonal psychotherapy for adult depression: follow-up of a randomized controlled trial. Psychological medicine, 49(3), 465-473.]])]
+    * Most patients also have a significantly higher preference for psychotherapy over medications.[([[https://www.ncbi.nlm.nih.gov/pubmed/23842011|McHugh, R. K., Whitton, S. W., Peckham, A. D., Welge, J. A., & Otto, M. W. (2013). Patient preference for psychological vs. pharmacological treatment of psychiatric disorders: a meta-analytic review. The Journal of clinical psychiatry, 74(6), 595.]])]
+    * Unfortunately, psychological therapies can be very limited in availability, and sometimes medications are the only option.
+  * However, there is also evidence that combination treatment with both medications and psychotherapy offers more benefit than psychological treatment alone or medication treatment alone.[([[https://pubmed.ncbi.nlm.nih.gov/27486150/|Parikh, S. V., Quilty, L. C., Ravitz, P., Rosenbluth, M., Pavlova, B., Grigoriadis, S., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. The Canadian Journal of Psychiatry, 61(9), 524-539.]])]
 </callout>
+</WRAP>
+</WRAP>
 ==== Psychotherapy ===
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[:psychotherapy|]]**</alert>
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
-First-line psychotherapy treatments include [[psychotherapy:cbt|]], [[psychotherapy:ipt|]], and behavioural activation.[([[https://www.ncbi.nlm.nih.gov/pubmed/2684085|Elkin, I., Shea, M. T., Watkins, J. T., Imber, S. D., Sotsky, S. M., Collins, J. F., ... & Fiester, S. J. (1989). National Institute of Mental Health treatment of depression collaborative research program: General effectiveness of treatments. Archives of general psychiatry, 46(11), 971-982.]])] Psychotherapy is effective for mild, moderate, and severe depression. For individuals with sub-threshold depression symptoms or mild depression, computerized CBT or guided self-help is recommended.[([[https://www.ncbi.nlm.nih.gov/pubmed/30994877|Cuijpers, P., Noma, H., Karyotaki, E., Cipriani, A., & Furukawa, T. A. (2019). Effectiveness and acceptability of cognitive behavior therapy delivery formats in adults with depression: a network meta-analysis. JAMA psychiatry.]])]
+See main article: **[[:psychotherapy|]]**
+</alert>
+<WRAP group>
+<WRAP half column>
+  * Psychotherapy is appropriate for both men and women, individuals of all ages, all levels of education, and all cultural and ethnic backgrounds.[([[https://pubmed.ncbi.nlm.nih.gov/27486150/|Parikh, S. V., Quilty, L. C., Ravitz, P., Rosenbluth, M., Pavlova, B., Grigoriadis, S., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. The Canadian Journal of Psychiatry, 61(9), 524-539.]])]
+  * Psychotherapy is effective for mild, moderate, and severe depression.
+    * Importantly, [[psychotherapy:cbt|cognitive behavioural therapy]] can be as effective in severe depression as medications.[([[https://pubmed.ncbi.nlm.nih.gov/27486150/|Parikh, S. V., Quilty, L. C., Ravitz, P., Rosenbluth, M., Pavlova, B., Grigoriadis, S., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. The Canadian Journal of Psychiatry, 61(9), 524-539.]])]
+  * First-line psychotherapy treatments for acute depression include [[psychotherapy:cbt|cognitive behavioural therapy]], [[psychotherapy:ipt|interpersonal therapy]], and behavioural activation.[([[https://www.ncbi.nlm.nih.gov/pubmed/2684085|Elkin, I., Shea, M. T., Watkins, J. T., Imber, S. D., Sotsky, S. M., Collins, J. F., ... & Fiester, S. J. (1989). National Institute of Mental Health treatment of depression collaborative research program: General effectiveness of treatments. Archives of general psychiatry, 46(11), 971-982.]])]
+  * For individuals with sub-threshold depression symptoms or mild depression, computerized CBT or guided self-help is recommended.[([[https://www.ncbi.nlm.nih.gov/pubmed/30994877|Cuijpers, P., Noma, H., Karyotaki, E., Cipriani, A., & Furukawa, T. A. (2019). Effectiveness and acceptability of cognitive behavior therapy delivery formats in adults with depression: a network meta-analysis. JAMA psychiatry.]])]
+</WRAP>
+<WRAP half column>
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-==== Medications ====
+<panel type="info" title="Psychological Treatments" subtitle="Adapted from: Parikh, S. V. et al (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. The Canadian Journal of Psychiatry, 61(9), 524-539." no-body="true" footer="">
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[meds:antidepressants:home|]]**</alert>
+^           ^ Acute Episode                                                                                                                                                                                                                                                               ^ Maintenance                                                                                                                       ^
-Depression is a highly placebo-sensitive condition. Placebo response rates can be anywhere up to 30-40%.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181672/|Sonawalla, S. B., & Rosenbaum, J. F. (2002). Placebo response in depression. Dialogues in clinical neuroscience, 4(1), 105.]])] If there is a poor response to the initial antidepressant, consider switching to another antidepressant when: it is the first antidepressant trial, if there are poorly tolerated side effects to the initial antidepressant, if there is no response (<25% improvement) to the initial antidepressant, there is more time to wait for a response (less severe, less functional impairment), or patient prefers to switch to another antidepressant.
+^ 1st line  | • [[psychotherapy:cbt|Cognitive behavioural therapy (CBT)]] \\ • [[psychotherapy:ipt|Interpersonal therapy (IPT)]] \\ • Behavioural activation (BA)                                                                                                                                                                      | •[[psychotherapy:cbt|Cognitive behavioural therapy (CBT)]] \\ • [[psychotherapy:mindfulness|Mindfulness-based cognitive therapy (MBCT)]]                                             |
+^ 2nd line  | • [[psychotherapy:mindfulness|Mindfulness-based cognitive therapy (MBCT)]] \\ • Cognitive-behavioural analysis system of psychotherapy (CBASP)\\ • Problem-solving therapy (PST)\\ • [[psychotherapy:brief-short-psychodynamic|Short-term psychodynamic therapy (STPP)]] \\ • Telephone-delivered CBT and IPT\\ • Internet + computer-assisted therapy  | • [[psychotherapy:ipt|Interpersonal therapy (IPT)]] \\ • Behavioural activation (BA)\\ • Cognitive-behavioural analysis system of psychotherapy (CBASP)  |
+^ 3rd line  | • [[psychotherapy:psychodynamic:home|Long-term psychodynamic psychotherapy (PDT)]] \\ • Videoconferenced psychotherapy\\ • [[psychotherapy:mi|Motivational interviewing]]                                                                                                                                                              | • Long-term psychodynamic psychotherapy (PDT)                                                                                     |
+</panel>
+==== Pharmacotherapy ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[meds:antidepressants:home|]]**
+</alert>
+  * For individuals who do not improve at the 2 to 4 week mark, the dose should be optimized during this time (instead of switching antidepressants).
+  * If there is a poor response to the initial antidepressant past the 4 week point, then consider switching to another antidepressant when:[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994790/|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560.]])]
+      * It is the first antidepressant trial
+      * If there are poorly tolerated side effects to the initial antidepressant
+      * If there is no response (<25% improvement) to the initial antidepressant
+      * There is more time to wait for a response (less severe, less functional impairment), or
+      * If the patient prefers to switch to another antidepressant
-Consider a adding an adjunctive medication when there have been 2 or more antidepressant trials, the initial antidepressant is well tolerated, there is partial response (>25% improvement) to the initial antidepressant, there are specific residual symptoms or side effects to the initial antidepressant that can be targeted, there is less time to wait for a response (more severe, more
+<callout type="question" title="Which First-Line Antidepressant Do I Choose?" icon="true">
-functional impairment), or the patient prefers to add on another medication.
+Based on the latest meta-analyses, several antidepressants have been found to be more efficacious and better tolerated, including: [[meds:antidepressants:ssri:escitalopram|escitalopram]], [[meds:antidepressants:snri:venlafaxine|venlafaxine]], [[meds:antidepressants:nassa:mirtazapine|mirtazapine]], [[meds:melatonin-agonist:agomelatine|agomelatine]] + [[meds:antidepressants:tca:amitriptyline|amitriptyline]] (combination), [[meds:antidepressants:ssri:paroxetine|paroxetine]], and [[meds:antidepressants:serotonin-modulator:vortioxetine|vortioxetine]].[([[https://pubmed.ncbi.nlm.nih.gov/29477251/|Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., & Ogawa, Y. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet [Internet]. 2018; 391 (10128): 1357–66.]])] Some clinical guidelines also recommend picking based on the specifier diagnosis and symptom profile, though this approach has not necessarily borne out in evidence.
+</callout>
+<panel type="info" title="Pharmacotherapy for major depressive disorder" subtitle="Kennedy, S. H. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560." no-body="true">
+^ 1st line  | [[meds:melatonin-agonist:agomelatine|Agomelatine]], [[meds:antidepressants:ndri:bupropion|bupropion]], [[meds:antidepressants:ssri:citalopram|citalopram]], [[meds:antidepressants:snri:v-desvenlafaxine|desvenlafaxine]], [[meds:antidepressants:snri:duloxetine|duloxetine]], [[meds:antidepressants:ssri:escitalopram|escitalopram]], [[meds:antidepressants:ssri:fluoxetine|fluoxetine]], [[meds:antidepressants:ssri:fluvoxamine|fluvoxamine]], mianserin, milnacipran, [[meds:antidepressants:nassa:mirtazapine|mirtazapine]], [[meds:antidepressants:ssri:paroxetine|paroxetine]], [[meds:antidepressants:ssri:sertraline|sertraline]], [[meds:antidepressants:snri:venlafaxine|venlafaxine]], [[meds:antidepressants:serotonin-modulator:vortioxetine|vortioxetine]]  |
+^ 2nd line  | [[meds:antidepressants:tca:amitriptyline|Amitriptyline]], [[meds:antidepressants:tca:clomipramine|clomipramine]], [[meds:antidepressants:tca:home|other tricyclics]], [[meds:antidepressants:snri:levomilnacipran|levomilnacipran]], [[meds:antidepressants:maoi:moclobemide|moclobemide]], [[meds:antipsychotics:second-gen-atypical:6-quetiapine|quetiapine]], [[meds:antidepressants:maoi:selegiline|selegiline]] (transdermal), [[meds:antidepressants:sari:trazodone|trazodone]], [[meds:antidepressants:spari:vilazodone|vilazodone]]                                                                                                                                                                                                                                   |
+^ 3rd line  | [[meds:antidepressants:maoi:phenelzine|Phenelzine]], [[meds:antidepressants:maoi:tranylcypromine-parnate|tranylcypromine]], reboxetine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |
+</panel>
+==== Length of Pharmacotherapy ====
+  * Depression treatment guidelines recommend that patients remain on an antidepressant for another 6 to 9 months after they have achieved remission of symptoms.
+  * For individuals with risk factors for recurrence, the CANMAT 2016 Depression guidelines recommend that treatment be extended to 2 years or more after achieving remission of symptoms.
+    * These factors include: frequent and/or recurrent episodes, severe episodes (psychosis, severe impairment, suicidality), cronic episodes, presence of comorbid psychiatric or other medical conditions, presence of residual symptoms, and difficult-to-treat episodes.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994790/|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560.]])]
+  * There is recent evidence to suggest that antidepressants can be successfully discontinued when concurrent preventive cognitive therapy (PCT) or [[psychotherapy:mindfulness|mindfulness-based cognitive therapy]] (MBCT) is offered.[([[https://pubmed.ncbi.nlm.nih.gov/34009273/|Breedvelt, J. J., Warren, F. C., Segal, Z., Kuyken, W., & Bockting, C. L. (2021). Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis. JAMA psychiatry.]])]
+==== Switching or Adjunctive Pharmacotherapy ====
+<alert type="info" icon="fa fa-book fa-lg fa-fw">
+See also the ongoing debate about switching and increasing antidepressants:
+  * **[[https://pubmed.ncbi.nlm.nih.gov/34009273/|Breedvelt, J. J. et al. (2021). Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis. JAMA psychiatry.]]**
+  * **[[https://pubmed.ncbi.nlm.nih.gov/27929611/|Bschor, T. et al. (2016). Switching the antidepressant after nonresponse in adults with major depression: a systematic literature search and meta-analysis. The Journal of clinical psychiatry, 77(1), 0-0.]]**
+  * **[[https://pubmed.ncbi.nlm.nih.gov/29873954/|Rink, L. et al. (2018). Dose increase versus unchanged continuation of antidepressants after initial antidepressant treatment failure in patients with major depressive disorder: a systematic review and meta-analysis of randomized, double-blind trials. The Journal of clinical psychiatry, 79(3), 0-0.]]**
+</alert>
+  * The decision to switch antidepressants or to add an adjunctive medication depends on patient preferences and factors. Increasingly, some meta-analyses have shown that dose increases and switching do not confer any additional benefits.[([[https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/optimal-dose-of-aripiprazole-for-augmentation-therapy-of-antidepressantrefractory-depression-preliminary-findings-based-on-a-systematic-review-and-doseeffect-metaanalysis/CEB3BE0764C4ADCFF2700C1E93F3195D#.YdHdq5fcVfg.twitter|Cipriani, A., & Ostinelli, E. (2021). Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis. British Journal of Psychiatry.]])][([[https://pubmed.ncbi.nlm.nih.gov/34965534/|Rink, L., Adams, A., Braun, C., Bschor, T., Kuhr, K., & Baethge, C. (2021). Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials. Psychotherapy and Psychosomatics, 1-10.]])]
+  * The other issue to consider with antipsychotic augmentation is that although short-term studies have shown efficacy in improving depressive //symptoms//, clinically meaningful improvement (i.e., actual remission remains limited. Additionally, there are concerns about the side effects of antipsychotic medications including including weight gain, [[meds:antipsychotics:metabolic-syndrome|metabolic dysfunction]] and [[meds:antipsychotics:eps|extrapyramidal symptoms]] with long-term use.[([[https://pubmed.ncbi.nlm.nih.gov/36855876/|Jha, M. K., & Mathew, S. J. (2023). Pharmacotherapies for treatment-resistant depression: how antipsychotics fit in the rapidly evolving therapeutic landscape. American Journal of Psychiatry, 180(3), 190-199.]])]
 <WRAP group>
 <WRAP half column>
-<panel type="info" title="Pharmacotherapy for major depressive disorder" no-body="true">
+  * Consider **switching completely to another medication** when:[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994790/|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560.]])]
-^ 1st line            | Agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mianserin, milnacipran, mirtazapine, paroxetine, sertraline, venlafaxine, vortioxetine   |
+    * It is the first antidepressant trial
-^ 2nd line            | Amitriptyline, clomipramine, other tricyclics, levomilnacipran, moclobemide, quetiapine, selegiline (transdermal), trazodone, vilazodone  |
+    * There are poorly tolerated side effects to the initial antidepressant
-^ 3rd line            | Phenelzine, tranylcypromine, reboxetine   |
+    * There is no response (<25% improvement) to the initial antidepressant
-</panel>
+    * There is more time to wait for a response (less severe, less functional impairment)
+    * Patient prefers to switch to another antidepressant
 </WRAP>
 <WRAP half column>
-<panel type="info" title="Adjunctive pharmacotherapy for major depressive disorder" no-body="true">
+  * Consider **adding an adjunctive medication** when:[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994790/|Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560.]])]
-^ Adjunctive therapy (1st line)  | Aripiprazole, quetiapine, risperidone  |
+    * There have been 2 or more antidepressant trials, with poor response
-^ Adjunctive therapy (2nd line)  | Brexpiprazole, bupropion, lithium, mirtazapine, mianserin, modafinil, olanzapine, triiodothyronine  |
+    * If the initial antidepressant is well tolerated
-^ Adjunctive therapy (3rd line)  | Other antidepressants, other stimulants (methylphenidate, lisdexamfetamine), tricyclic antidepressants, ziprasidone |
+    * If there is partial response (>25% improvement) to the initial antidepressant
-^ Not recommended     | Pindolol  |
+    * If there are specific residual symptoms or side effects to the initial antidepressant that can be targeted
+    * If there is less time to wait for a response (more severe, more functional impairment)
+    * Or if the patient prefers to add on another medication.
+</WRAP>
+</WRAP>
+<panel type="info" title="Adjunctive pharmacotherapy for major depressive disorder" subtitle="Kennedy, S. H. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560." no-body="true">
+^ 1st line         | **Adjunctive therapy**: [[meds:antipsychotics:second-gen-atypical:3-aripiprazole|aripiprazole]][([[https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/optimal-dose-of-aripiprazole-for-augmentation-therapy-of-antidepressantrefractory-depression-preliminary-findings-based-on-a-systematic-review-and-doseeffect-metaanalysis/CEB3BE0764C4ADCFF2700C1E93F3195D#.YdHdq5fcVfg.twitter|Cipriani, A., & Ostinelli, E. (2021). Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis. British Journal of Psychiatry.]])], [[meds:antipsychotics:second-gen-atypical:6-quetiapine|quetiapine]], [[meds:antipsychotics:second-gen-atypical:1-risperidone|risperidone]]                                                                                                                                                                                                 |
+^ 2nd line         | **Adjunctive therapy**: [[meds:antipsychotics:second-gen-atypical:3-brexpiprazole|brexpiprazole]], [[meds:antidepressants:ndri:bupropion|bupropion]], [[meds:mood-stabilizers-anticonvulsants:1-lithium|lithium]], [[meds:antidepressants:nassa:mirtazapine|mirtazapine]], mianserin, [[meds:stimulants:modafinil|modafinil]], [[meds:antipsychotics:second-gen-atypical:3-olanzapine|olanzapine]], [[meds:thyroid:triiodothyronine-t3|triiodothyronine]]  |
+^ 3rd line         | **Adjunctive therapy**: other antidepressants, other stimulants ([[meds:stimulants:2-methylphenidate:home|methylphenidate]], [[meds:stimulants:amphetamine:lisdexamfetamine|lisdexamfetamine]]), [[meds:antidepressants:tca:home|tricyclic antidepressants]], [[meds:antipsychotics:second-gen-atypical:4-ziprasidone|ziprasidone]]                                                                                                         |
+^ Not recommended  | Pindolol                                                                                                                                                                                                                                                                                                                                                                                                                                    |
 </panel>
-</WRAP></WRAP>
-==== Phototherapy ====
+<panel type="info" title="Selecting Antidepressants Based on Clinical Specifiers and Dimension of Depression" subtitle="From: Kennedy, S. H. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. The Canadian Journal of Psychiatry, 61(9), 540-560." no-body="true" footer="">
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[teaching:phototherapy]]**</alert>
+<mobiletable 1>
-Phototherapy is indicated for treatment of depression with seasonal affective subtype.
+^                             ^ Recommendations                                                                                                                                                   ^ Notes                                                                                                                                                        ^
+^ With anxious distress       | • Use an antidepressant with efficacy in generalized anxiety disorder (Level 4)                                                                                   | • No differences in efficacy between SSRIs, SNRIs, and bupropion (Level 2)                                                                                   |
+^ With catatonic features     | • Benzodiazepines (Level 3)                                                                                                                                       | • No antidepressants have been studied                                                                                                                       |
+^ With melancholic features   | • No specific antidepressants have demonstrated superiority (Level 2)                                                                                             | • TCAs and SNRIs have been studied                                                                                                                           |
+^ With atypical features      | • No specific antidepressants have demonstrated superiority (Level 2)                                                                                             | • Older studies found MAO inhibitors superior to TCAs                                                                                                        |
+^ With psychotic features     | • Use antipsychotic and antidepressant cotreatment (Level 1)                                                                                                      | • Few studies involved atypical antipsychotics                                                                                                               |
+^ With mixed features         | • Lurasidone (Level 2)\\ • Ziprasidone (Level 3)                                                                                                                  | • No comparative studies                                                                                                                                     |
+^ With seasonal pattern       | • No specific antidepressants have demonstrated superiority (Level 2 and 3)                                                                                       | • SSRIs, agomelatine, bupropion, and moclobemide have been studied                                                                                           |
+^ With cognitive dysfunction  | • Vortioxetine (Level 1)\\ • Bupropion (Level 2)\\ • Duloxetine (Level 2)\\ • SSRIs (Level 2)\\ • Moclobemide (Level 3)                                           | • Limited data available on cognitive effects of other antidepressants and on comparative differences in efficacy                                            |
+^ With sleep disturbances     | • Agomelatine (Level 1)\\ • Mirtazapine (Level 2)\\ • Quetiapine (Level 2)\\ • Trazodone (Level 2)                                                                | • Beneficial effects on sleep must be balanced against potential for side effects (e.g., daytime sedation)                                                   |
+^ With somatic symptoms       | • Duloxetine (pain) (Level 1)\\ • Other SNRIs (pain) (Level 2)\\ • Bupropion (fatigue) (Level 1)\\ • SSRIs (fatigue) (Level 2)\\ • Duloxetine (energy) (Level 2)  | • Few antidepressants have been studied for somatic symptoms other than pain\\ • Few comparative antidepressant studies for pain and other somatic symptoms  |
+</mobiletable>
+</panel>
+==== Natural Health Products ====
+<panel type="info" title="Natural Health Products in Major Depressive Disorder" subtitle="Ravindran, A. V. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 5. Complementary and alternative medicine treatments. The Canadian Journal of Psychiatry, 61(9), 576-587." no-body="true" footer="">
+<mobiletable 1>
+^ Product                                             ^ Indication                                              ^ Recommendation                      ^ Monotherapy or Adjunctive Therapy                ^
+^ [[meds:supplements:st-johns-wort|St. John’s wort]]  | **• Mild to moderate MDD**\\ • Moderate to severe MDD   | **• First line**\\ • Second line    | **• Monotherapy** \\ • Adjunctive                |
+^ [[meds:supplements:omega-3|Omega-3]]                | **• Mild to moderate MDD** \\ • Moderate to severe MDD  | **• Second line** \\ • Second line  | **• Monotherapy or adjunctive** \\ • Adjunctive  |
+^ S-adenosyl-L-methionine (SAM-e)                     | • Mild to moderate \\ • MDD Moderate to severe MDD      | • Second line \\ • Second line      | • Adjunctive\\ • Adjunctive                      |
+^ Acetyl-L-carnitine                                  | • Mild to moderate MDD                                  | • Third line                        | • Monotherapy                                    |
+^ Crocus sativus (saffron)                            | • Mild to moderate MDD                                  | • Third line                        | • Monotherapy or adjunctive                      |
+^ Dehydroepiandrosterone (DHEA)                       | • Mild to moderate MDD                                  | • Third line                        | • Monotherapy                                    |
+^ Folate                                              | • Mild to moderate MDD                                  | • Third line                        | • Adjunctive                                     |
+^ Lavandula (lavender)                                | • Mild to moderate MDD                                  | • Third line                        | • Adjunctive                                     |
+^ Inositol                                            | Not recommended                                         | Not recommended                     | Not recommended                                  |
+^ Tryptophan                                          | Not recommended                                         | Not recommended                     | Not recommended                                  |
+^ Rhodiola rosea (roseroot)                           | Not recommended                                         | Not recommended                     | Not recommended                                  |
+</mobiletable>
+</panel>
 ==== ECT ====
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[brain-stimulation:ect|]]**</alert>
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[brain-stimulation:ect|]]**
+</alert>
+  * In cases of severe, treatment-refractory depression, or in cases where there are significant safety concerns, electroconvulsive therapy (ECT) can be a safe and rapid treatment.
+==== Light Therapy ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[teaching:phototherapy]]**
+</alert>
+  * Light therapy is indicated for treatment of depression with seasonal affective subtype and can also be used in the treatment of mild to moderate depression.
+<panel type="info" title="Summary of Recommendations for Physical and Meditative Treatments" subtitle="Ravindran, A. V. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 5. Complementary and alternative medicine treatments. The Canadian Journal of Psychiatry, 61(9), 576-587." no-body="true" footer="">
+<mobiletable 1>
+^ Intervention                                 ^ Indication                                                    ^ Recommendation                ^ Evidence               ^ Monotherapy or Adjunctive Therapy              ^
+^ [[teaching:exercise-prescription|Exercise]]  | • Mild to moderate MDD \\ • Moderate to severe MDD            | • First line\\ • Second line  | • Level 1\\ • Level 1  | • Monotherapy \\ • Adjunctive                  |
+^ [[teaching:phototherapy|Light therapy]]      | • Seasonal (winter) MDD\\ • Mild to moderate nonseasonal MDD  | • First line\\ • Second line  | • Level 1\\ • Level 2  | • Monotherapy \\ • Monotherapy and adjunctive  |
+^ Yoga                                         | • Mild to moderate MDD                                        | • Second line                 | • Level 2              | • Adjunctive                                   |
+^ Acupuncture                                  | • Mild to moderate MDD                                        | • Third line                  | • Level 2              | • Adjunctive                                   |
+^ Sleep deprivation                            | • Moderate to severe MDD                                      | • Third line                  | • Level 2              | • Adjunctive                                   |
+</mobiletable>
+</panel>
 ==== Exercise ====
-<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[teaching:exercise-prescription]]**</alert>
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[teaching:exercise-prescription]]**
+</alert>
-Antidepressants and/or psychotherapy may not adequately treat all patients with depression. Combining these treatments with lifestyle changes through exercise is supported by well-designed studies.[([[http://www.mdedge.com/currentpsychiatry/article/63598/exercise-prescription-practical-effective-therapy-depression|Sidhu, Kanwaldeep S., Pankhuree Vandana, and Richard Balon. "Exercise prescription: A practical, effective therapy for depression." Current Psychiatry 8.6 (2009): 38. APA]])]
+  * Exercise has evidence as a treatment for mild to moderate depression and is recommended for all individuals.[([[https://www.bmj.com/content/384/bmj.q320|Bellón, J. Á. (2024). Exercise for the treatment of depression. bmj, 384.]])]
+  * Antidepressants and/or psychotherapy may not adequately treat all patients with depression. Combining these treatments with lifestyle changes through exercise is supported by well-designed studies.[([[http://www.mdedge.com/currentpsychiatry/article/63598/exercise-prescription-practical-effective-therapy-depression|Sidhu, Kanwaldeep S., Pankhuree Vandana, and Richard Balon. "Exercise prescription: A practical, effective therapy for depression." Current Psychiatry 8.6 (2009): 38. APA]])]
-==== Nutrition ====
+ ==== Nutrition ====
-Adhering to a healthy diet, especially a traditional Mediterranean diet or avoiding a pro-inflammatory diet, offers protection against depression in observational studies.[([[https://www.ncbi.nlm.nih.gov/pubmed/30254236|Lassale, C., Batty, G. D., Baghdadli, A., Jacka, F., Sánchez-Villegas, A., Kivimäki, M., & Akbaraly, T. (2018). Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Molecular psychiatry, 1.]])] There is evidence to suggest that dietary changes can help elevate serotonin levels as well. Studies have shown that tryptophan can have anxiolytic effects.[([[https://www.ncbi.nlm.nih.gov/pubmed/18066139|Hudson C, Hudson S, MacKenzie J. Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study. Can J Physiol Pharmacol. 2007 Sep;85(9):928-32.]])][([[https://www.ncbi.nlm.nih.gov/pubmed/3783150|Schweiger U, Laessle R, Kittl S, Dickhaut B, Schweiger M, Pirke KM. Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets. J Neural Transm. 1986;67(1-2):77-86.]])][([[http://ajcn.nutrition.org/content/77/1/128.full.pdf+html|Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ. Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. Am J Clin Nutr. 2003 Jan;77(1):128-32.]])][([[http://nutritionfacts.org/video/the-best-way-to-boost-serotonin/|Nutrition Facts: The Best Way to Boost Serotonin]])]
+  * Adhering to a healthy diet, especially a traditional Mediterranean diet or avoiding a pro-inflammatory diet, offers protection against depression in observational studies.[([[https://www.ncbi.nlm.nih.gov/pubmed/30254236|Lassale, C., Batty, G. D., Baghdadli, A., Jacka, F., Sánchez-Villegas, A., Kivimäki, M., & Akbaraly, T. (2018). Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Molecular psychiatry, 1.]])]
+  * Randomized controlled trials (RCTs) of dietary interventions suggest that a less sugar-sweetened drinks, reduced processed foods and meats, and higher vegetable, fruit and legume intake is associated with lower depressive symptoms.[([[https://www.cmaj.ca/content/195/21/E739|Korczak, D. J., Westwell-Roper, C., & Sassi, R. (2023). Diagnosis and management of depression in adolescents. CMAJ, 195(21), E739-E746.]])]
+===== Guidelines =====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See also: **[[teaching:clinical-practice-guidelines-cpg|]]**
+</alert>
+{{page>teaching:clinical-practice-guidelines-cpg#depression&nouser&noheader&nodate&nofooter}}
 ===== Resources =====
@@ Line 312: / Line 582: @@
 <WRAP quarter column>
 == For Patients ==
-  * [[https://headsupguys.org/|HeadsUpGuys: Mental Health for Men]]
   * [[http://sad.psychiatry.ubc.ca/frequently-asked-questions-about-sad-and-light-therapy/|UBC: FAQ on SAD and Light Therapy]]
 </WRAP>
@@ Line 318: / Line 587: @@
 <WRAP quarter column>
 == For Providers ==
+  * **[[https://www.nature.com/articles/nrdp201665|Otte, C. et al. (2016). Major depressive disorder. Nature Reviews Disease Primers, 2(1), 1-20.]]**
 </WRAP>
 <WRAP quarter column>
 == Articles ==
   * [[https://www.nytimes.com/2016/12/14/opinion/should-i-tell-my-students-i-have-depression.html|NYT: Should I Tell My Students I Have Depression?]]
 </WRAP>
 <WRAP quarter column>
 == Research ==
 </WRAP>
 </WRAP>
-<callout type="default">//“It’s so difficult to describe depression to someone who’s never been there, because it’s not sadness. I know sadness. Sadness is to cry and to feel. But it’s that cold absence of feeling — that really hollowed-out feeling.”//
-<TEXT align="right">— J.K. Rowling[(http://themighty.com/2015/08/5-times-j-k-rowling-got-real-about-depression/#ixzz3nZW2EGd2)]</TEXT></callout>
+<callout type="default">
+//“It’s so difficult to describe depression to someone who’s never been there, because it’s not sadness. I know sadness. Sadness is to cry and to feel. But it’s that cold absence of feeling — that really hollowed-out feeling.”//
+\\ \\
+-- J.K. Rowling
+</callout>