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Depression

Definition
  • Depressive disorders are characterised by:
    • Persistent low mood
    • Loss of interest and enjoyment
    • Neurovegetative disturbance
    • Reduced energy
  • Causes varying levels of social and occupational dysfunction.
  • Depressive symptoms include:
    • depressed mood
    • anhedonia
    • weight changes
    • libido changes
    • sleep disturbance
    • psychomotor problems
    • low energy
    • excessive guilt
    • poor concentration
    • suicidal ideation
  • Minor depression is characterised by the presence of 2 to 4 depressive symptoms, including depressed mood or anhedonia, of greater than 2 weeks in duration. 
  • Dysthymic disorder is characterised by at least 2 years of 3 or 4 dysthymic symptoms for more days than not.
    • Dysthymic symptoms are depressed mood, appetite change, sleep disturbance, low energy, low self-esteem, poor concentration, and hopelessness. 
  • Major depressive disorder is characterised by the presence of at least 5 symptoms and exists along a spectrum of mild to severe.
    • The greater the number of symptoms, the more severe the depression. [1] 
    • Severe episodes may include psychotic symptoms such as paranoia or hallucinations
Risk Factors
  • Strong
    • age >65 years
    • postnatal status
    • personal or family history of depressive disorder or suicide
    • corticosteroids
    • interferon
    • propranolol
    • oral contraceptives
    • co-existing medical conditions (diabetes, MI, cancer, stroke, obesity)
  • Weak
    • isotretinoin
    • co-morbid substance use
    • personality disorders
Differential diagnosis
  • Situational adjustment reaction with depressed mood
    • This is a subsyndromal depression with a clearly identified precipitating event
    • It usually does not require medicine and resolves with resolution of the acute stressor.
  • Bipolar disorder 
    • In this condition, major depressive disorder is accompanied by or interspersed with one or more manic or mixed episodes.
  • Pre-menstrual dysphoric disorder (PMDD) 
    • PMDD is characterised by depressed mood, anxiety, and irritability during the week before menses and resolving with menses. PMDD also has prominent pain symptoms. 
  • Grief reaction 
    • The syndrome of major depression may be transiently present in normal grief
    • The duration and expression of normal grief varies among racial/ethnic groups. [33] 
    • Patients with unremitting symptoms after 4 to 6 months should be assessed for depression. 
  • Dementia 
    • Dementia is characterised by cognitive (memory) changes, psychiatric symptoms, personality changes, problem behaviours, and changes in day-to-day functioning. 
    • A mini-mental state examination (MMSE) [34] or neuropsychiatric testing should be conducted if the diagnosis is uncertain. 
    • Focused laboratory testing (i.e., TSH level, vitamin B12 level) should be considered for reversible causes of dementia. 
  • Anxiety disorders 
    • Anxiety disorders frequently occur along with depression.
    • Generalised anxiety disorder is characterised by excessive worry, muscular tension, fatigue, autonomic hyperactivity, and increased vigilance.
    • Specific anxiety disorders (i.e., panic disorder, social phobia, OCD, PTSD) should also be considered. 
  • Alcohol abuse 
    • Patients often may complain of insomnia, nightmares, poor memory, and nervousness. 
    • Consider use of the CAGE questionnaire
  • Anorexia nervosa 
    • Eating disorders such as anorexia nervosa are more common in women and characterised by disturbance in the perception of body weight, size, or shape, and refusal to maintain healthy body weight. 
  • Hypothyroidism 
    • Associated signs and symptoms include weight gain, constipation, and fatigue. 
    • An elevated serum TSH level suggests hypothyroidism. 
  • Medicine adverse effects 
    • Patient should be asked about use of glucocorticoids, interferon, levodopa, propranolol, and oral contraceptives.
    • The data regarding isotretinoin remain unclear. [36] 
  • Cushing's disease 
    • This disease is associated with progressive obesity, dermatological manifestations, signs of adrenal androgen excess, and proximal muscle wasting. 
    • Check elevated 24-hour urinary free cortisol level. 
  • Vitamin B12 deficiency 
    • This deficiency is associated with macrocytic anaemia, paraesthesia, numbness, and impaired memory. 
    • Reduced serum vitamin B12 level.
Epidemiology
  • Depressive disorders are very common and are the fourth highest cause of disability worldwide. [9] [10] 
  • In people aged 18 to 44 years, depression is the leading cause of disability and premature death.
  • Depression is predicted to be the second leading cause of disability in people of all ages by the year 2020. [11] 
  • The prevalence of major depression is between 5% and 10% of people seen in primary care settings. [12]
  • During their lifetime, about 20% of adults will be affected by a mood disorder needing treatment, and specifically 8% will have a major depressive episode. [11] 
  • Additionally, women are affected twice as often as men.
  • In patients with an affected first-degree relative, the lifetime risk of depression increases to 1.5 to 3.0 times average.
  • First onset occurs most frequently in patients aged 12 to 24 years (1.4% to 9.1%) and in those older than 65 years (1.3% to 1.8%). [11]
Aetiology
  • The aetiology of depression remains poorly understood.
  • Integrative models, taking into account biological and social variables, most effectively reflect the complex aetiology.
  • Susceptibility to a depressive disorder is 2 to 4 times greater among the first-degree relatives of patients with a mood disorder than among other people.
  • It is unclear whether a gene X environment interaction can help explain susceptibility to depression or predict response to treatment.
  • A meta-analysis proposed by the National Institute of Mental Health in 2009 supported the previous finding that stressful life events have a potent relationship with the risk of depression.
    • The addition of the serotonin transporter genotype (5-HTTLPR) did not improve prediction of risk for depression. [13] 
  • However, other studies suggest a role for genetic polymorphisms in predicting medication adverse effects. [14]
Clinical features
  • Presence of risk factors
    • older age
    • recent childbirth
    • stress, or trauma
    • co-existing medical conditions (diabetes, cancer, stroke, MI, and obesity)
    • personal or family hx of depression
    • certain medications (e.g., corticosteroids)
    • female gender
  • Depressed mood
    • Depressed mood most of the day, nearly every day, for a period of 2 weeks along with 4 other symptoms of depression. [2]
  • Anhedonia
    • Diminished interest or pleasure in all or almost all activities most of the day, nearly every day, for a period of 2 weeks along with 4 other symptoms of depression. [2] 
  • Weight change
    • Significant weight loss when not dieting, weight gain, or decrease or increase in appetite nearly every day. [2] 
  • Libido changes
    • May show reduced libido
  • Sleep disturbance
    • Insomnia or hypersomnia nearly every day. [2] 
  • Psychomotor problems
    • Psychomotor agitation or retardation nearly every day. [2] 
  • Low energy
    • Fatigue or loss of energy nearly every day. [2] 
  • Excessive guilt
    • Feelings of worthlessness or excessive or inappropriate guilt nearly every day. [2]
  • Poor concentration
    • Diminished ability to think or concentrate nearly every day. [2] 
  • Suicidal ideation
    • Recurrent thoughts of death, recurrent suicidal ideation without a specific plan. [2] 
  • No mixed symptoms of depression and mania
    • There should be no evidence of mixed symptoms suggesting a mixed episode. [2] 
  • Functional impairment
    • Symptoms cause impairment in, for example, social or occupational functions. [2]
  • Grief reaction ruled out
    • The depressive symptoms should not be related to a grief reaction. [2] 
  • Substance abuse disorder ruled out
    • The depressive symptoms should not be related to substance abuse. [2]
Pathophysiology
  • Possible contributory factors:
    • Abnormal concentrations of neurotransmitters
    • Dysregulation of the hypothalamic-pituitary-adrenal axis
    • Elevated levels of corticotrophin-releasing factor
    • Abnormalities of second messenger systems
  • Stressful life events, personality, and sex may also play a role
  • There is growing evidence concerning the role of specific neurotransmitters and clinical manifestations of depression:
    • While much work still needs to be done, some evidence suggests that in depression, abnormalities in dopamine may be related to impaired motivation and concentration [15]
    • Low levels of noradrenaline (norepinephrine) and dopamine may play a role in the fatigue and hypersomnia [16]
    • Impaired noradrenaline and serotonergic regulation may contribute to physical symptoms. [17] 
  • Genetic traits may help identify patients at risk for suicide on pharmacotherapy.
Investigations
  • Clinical diagnosis
    • DSM-IV-TR diagnostic criteria depending on the depressive subcategory
  • Public Health Questionnaire-2 (PHQ-2)
    • Positive result screens for depression in primary care 
  • PHQ-9
    • Positive result screens for depression in primary care 
  • Edinburgh Postnatal Depression Scale
    • Positive result screens for depression in postnatal period 
  • Geriatric Depression Scale
    • >5 suggests depression; >10 strongly suggests depression 
  • Cornell Scale for Depression in Dementia
    • >10 suggests probable depression; >18 indicates definite depression 
  • FBC
    • Normal 
  • TFTs
    • Normal 
  • 24-hour free cortisol
    • Normal 
  • Vitamin B12
    • Normal 
  • Folic acid
    • Normal
Management

a) conservative


b) medical


c) surgical


Prognosis

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