Medical Pharmacology: Drugs Used to Manage Depression

Differential Diagnosis in Depression I

Certain clinical presentations make definitive diagnosis of depression more difficult.²⁶

Chronic pain and depression may be associated. Patients with persistent pain as the only clinical complaint may suggest depression at any age, if the pain presents as an unremitting daily tension headache and the clinical examination is otherwise normal.
- Sometimes if the source of pain cannot be elucidated, the pain might be described as "psychogenic"; however, in some patients pain may be reduced by antidepressant medications.
- In other circumstances, if the pain has been present for less than a year with an onset coincident with depressive symptoms, antidepressant medication response may be favorable.
- Depression may also be a component in those individuals who have experienced several surgical procedures, possibly with dependency on analgesic drugs.
  - Examples of individuals in this category include those who have become disabled following multiple surgeries for ruptured intervertebral discs or arthritic hips as well as patients with atypical facial pain.²⁶
Depression and alcoholism are routinely associated, although it may be difficult to determine which condition is primary and which is secondary.²⁶
- Depression made evolve initially from a background of alcoholism.
  - In the 1970s based on a large series of alcoholic patients, secondary depression occurred in about 50% of females and in about 33% of males. The development of alcoholism against a background of primary depressive disorder is less frequently noted.^26,31
- Analysis from the National Comorbidity Survey suggested that lifetime prevalence of major depression was about 25% among alcohol-dependent males and about 50% among alcohol-dependent females.³²
  - These frequencies were higher than noted in individuals without alcohol use disorders. Lifetime rates of co-occurrence are estimated between 50% and 70%.³²
- The basis for association between alcohol use disorder and depression has been investigated.
  - However, no single definitive cause or shared etiological risk factor has been determined to underlie both conditions.³³
    - A recent meta-analysis (2009) considered 74 studies. 58 studies obtain data from clinical settings, 10 were community-based, and six studies combined both clinical and community-based data.
    - Participants had a mean age of about 38 years; 70% were men and 82% were white.
      - About 80% of the sample had completed high school with about 50% employed and about 40% married.
    - This meta-analysis found the positive association of depression with concurrent alcohol use and impairment.³⁴
      - Using standard criteria, the association size was small and, based on Binomial Effect Size Display (BESD)³⁵, 60.5% of individuals with above-average levels of depressive symptoms exhibited above-average levels of current alcohol use and impairment; this result may be compared to 39.5% of individuals with below-average levels of depressive symptoms.³⁴

Childhood and adolescent depression²⁶

Depressive states have been documented in children and may be misdiagnosed.
- Typical manifestations include chronic headache, withdrawal from social activities, resistance to going to school, vomiting, anorexia and weight loss, and poor scholastic performance.
- A time of onset is puberty; however, depressive disease may manifest in late childhood and be commonly noted in both high school and college students.
- Because of the risk of suicide, emergence of depressive disorder during this extended timeframe must be taken seriously.

In order to identify which children may be at risk for depression and suicidal ideation, a recent study considered whether young children with ADHD (attention-deficit/hyperactivity disorder) might be at increased risk for depression and suicidal ideation and attempts during adolescence.²⁶

This concern follows from the finding that about 16% to 37% of clinically referred adults with ADHD have comorbid major depressive disorder and/or dysthymia.

A group of 125 children meeting DSM-IV criteria for ADHD at 4 to 6 years of age were compared with 123 demographically matched children without ADHD. These children were followed up in seven structured diagnostic assessments of depression and suicidal behavior in year 6 through 14, corresponding to an age range of 9 through 18.³⁶

The principal finding was that children with ADHD at 4 to 6 years of age were at greatly increased risk for meeting DSM-IV criteria for either dysthymia or major depression and for attempting suicide through the age of 18, relative to comparison children.³⁶

**Childhood Symptoms and Ultimately Meeting Criteria for Depression³⁶**

"Association between the total number of depression, anxiety, oppositional defiant disorder, and conduct disorder symptoms in assessment year 1 and their meeting diagnostic criteria for depression at least once during assessment years 6 through 14 among the 125 children who met criteria for attention-deficit/hyperactivity disorder in year 1. MDD indicates major depressive disorder."³⁶ (Figure 4 from reference 36)

Risk variation was reported with respect to these outcomes among children with ADHD.
However, within the ADHD group, children with each ADHD subtype exhibited risk albeit for different adverse outcomes.³⁶
- Girls exhibited greater risk for depression and suicide attempts.
  - Female sex, maternal depression, and concurrent at 4-6 years of age appear to identify those with ADHD at greatest risk for adverse outcomes.
  - Identification of these relatively higher-risk children with ADHD suggests the value of early prevention trials with the aim of reducing risk for later depression and suicidal behaviors.³⁶

Depression in the geriatric setting

Depression, delirium and dementia in elderly patients

**"2021 Neuroscience Symposium: The 3 D's: Dementia, Delirium and Depression"**

Attribution: Hart RN 2021 Neuroscience Symposium: The 3 D's: Dementia, Delirium and Depression https://www.youtube.com/watch?v=uGO7cTkhBOU (11/2021) Norton Healthcare YouTube Channel: https://www.youtube.com/channel/UCDDlENhQJEyOQS3ZVH65kzg

**"The Clinical Differences Between Depression, Delirium and Dementia"**

Attribution: Weiss T The Clinical Differences Between Depression, Delirium, and Dementia https://www.youtube.com/watch?v=TWUyUhHXT7w (11/2018) mmlearn.org YouTube Channel: https://www.youtube.com/channel/UCDy97u6dcHQPgvLnZDZjFeg

Etiology of depression:
- Although the exact cause of major depressive disorder remains to be elucidated, a number of factors have been suggested.²
  - These potential contributors include genetic, psychodynamic, socioenvironmental and biochemical factors.²
- Genetics:
  - Despite the recognition that depression is inheritable, identification of specific genes responsible remains a challenge.
    - Some genes that exhibit variance which may be associated with predisposition to depression have been identified and some genes may be associated with pathogenesis mechanisms, at least proposed mechanisms.
      - These genes include:
        
        type 1 receptor for corticotrophin-releasing factor (CRHR1).
        
        Another candidate gene is the glucocorticoid receptor gene (GR)
        
        The gene coding for chaperone protein for the glucocorticoid receptor is another candidate; this gene is the FKBP5.
        
        The serotonin transporter gene (SLA6A4) is another possibility.
        
        Both the catechol-O-methyl transferase gene (COMT) and the brain-derived neurotrophic factor gene (BDNF) represent additional possibilities.³⁷

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