Depression


SIG EM CAPS
S Sleep: increase during day or decreased sleep at night
I Interest (loss): of interest in activities that used to interest them
G Guilt (worthless): depressed elderly tend to devalue themselves
E Energy (lack): common presenting symptom (fatigue)
M Mood: Depressed
C Cognition/C oncentration: reduced cognition &/or difficulty concentrating
A Appetite (wt. loss); usually declined, occasionally increased
P Psychomotor: agitation (anxiety) or retardations (lethargic)
S Suicide/death preocp.


 
Depression  VS Normal Grief
Depression Normal Grief
> 1yr, sooner if symptoms sever Normal up to 1 year
Crying, libido, weight loss, insomnia Crying, libido, weight loss, insomnia
Abnormal over-identification, personality change Longing, wish to see loved one, may think they hear or see loved one in a crowd
Loss of self Loss of others
Suicidal ideation common Suicidal ideation RARE
Symptoms do not stop (may persist for years) Self-limited, usually < 6 Mo
Antidepressants helpful Antidepressants NOT helpful

 

Screening

  • In 2009, the USPSTF updated the guideline by specifically stipulating that staff-assisted depression care supports (such as case management or mental health specialist involvement) needed to be in place to assure accurate diagnosis, effective treatment, and follow-up (USPSTF B recommendation).
    • In addition, it recommended against routinely screening for depression when staff-assisted supports are not in place (USPSTF C recommendation).
    • The USPSTF found insufficient evidence to recommend a specific screening interval (USPSTF I recommendation)
       
  • A “yes” response to the following 2 questions may be as effective as using longer screening tools. (USPSTF, 2002)
    1. Over the past 2 weeks, have you ever felt down, depressed, or hopeless?
    2. Have you felt little interest or pleasure in doing things?
       
  • USPSTF found evidence is insufficient to recommend for or against routine screening of children (7-11 years old) for depression
  • USPSTF recommends screening adolescents (12-18 years old) and adults for depression in clinical practices with systems in place for diagnosis, treatment, follow-up First postpartum evaluation should include screening for depression



 

Diagnosis of Major Depression

  1. Depressed mood
  2. Loss of enjoyment (anhedonia)
  3. Weight or appetite change
  4. Sleep changes
  5. Psychomotor changes (restlessness or slowing)
  6. Poor energy
  7. Feelings of guilt
  8. Poor concentration
  9. Thoughts of death

    (NOTE: #1 or #2 must be present)

Major depressive disorder with atypical features :

  • A subtype of major depression.
  • Criteria for the diagnosis:
    • Presence of marked mood reactivity (i.e., improvement in mood in response to actual or potential positive events) and two or more of the following:
      • Significant weight gain or increase in appetite,
      • Hypersomnia
      • Leaden paralysis (a heavy, leaden feeling in the arms or legs), and
      • A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment (SOR C).
  • Treatment:
    • MAO inhibitors have greater efficacy than tricyclic antidepressants.
    • Other options include SSRIs, Bupropion, cognitive-behavioral therapy, and electroconvulsive therapy.

Dysthymia

  • Requires depressed mood for at least two years with no symptom-free period lasting longer than two months
  • Along with 2 or more of the following:
    – Appetite or sleep changes
    – Decreased energy or concentration
    – Thoughts of guilt or death
    – Psychomotor changes (restlessness or slowing)
    – Hopelessness


Affective spectrum disorder

Affective spectrum disorder Treatment
Major depressive disorder These disorders likely share a common set of causal factors, and all respond to multiple classes of antidepressant medications that have a primary effect on the monoamine neurotransmitter system
attention deficit/hyperactivity disorder
bulimia nervosa
dysthymic disorder
fibromyalgia
generalized anxiety disorder
irritable bowel syndrome
migraine
obsessive-compulsive disorder
panic disorder
posttraumatic stress disorder
premenstrual dysphoric disorder
social phobia

Suicide Risk Factors

Risk factors related to suicidal acts in patients with major depressive episodes include the following:

  • A previous history of a suicide attempt
  • The patient’s subjective assessment of the severity of depression
  • Hopelessness
  • The number of perceived reasons for living
  • The presence of comorbid substance use disorders, including cigarette smoking
  • The presence of a cluster personality disorder
  • Impulsivity
  • Aggression

Etiologies

Drugs

  • Narcotics
  • Antineoplastic agents
  • Sedative hypnotics
  • Centrally-acting antihypertensives
  • Steroids
  • Anxiolytics (long-term use)
  • Alcohol

Medical Conditions:

  • Hypothyroidism
  • MI
  • Stroke
  • Chronic pain syndrom
  • HIV
  • Parkinson's Disease
  • It is unclear if DM increases the risk of depression.

Lab/Work-up

  • • History & Physical
    – (Especially the neurological exam)
  • CBC
  • CMP
  • Thyroid panel, TSH
  • RPR

Treatment

  • Patient education (the diagnosis, treatment options, duration of treatment and costs, side effects, goals of the treatment, recurrence and relapse, etc.)
  • Reassurance (such as, “depression is a medical illness, not a character defect or weakness; recovery is the rule, not the exception; treatments are effective; an effective treatment can be found for nearly all patients,” etc.)
  • Regular monitoring for symptoms and adverse effects
  • Adjustments or changes in the treatment plan if response is lacking or suboptima

Alternative to medications:

  • Several systematic reviews reported a significant reduction of depression symptoms with:
    • Exercise, particularly high-energy aerobic or resistance training.
    • A smaller number of trials suggest that yoga may be an effective intervention as well.
       
  • Tai chi, qigong, and meditation have not been found to be effective as alternative treatments for the management of depression

Choice of Antidepressant

  • All modern antidepressants are equally effective
  • Patient preference
  • Cost
  • History of prior response to specific medication
  • Response of first-degree relative to specific medication
  • Use one antidepressant

Treatment of Depression

  • Usually begin with selective serotonin reuptake inhibitors (SSRIs)
  • Once-a-day dosing
  • No titration 80% of the time
  • Few side effects (GI, sexual)
  • Safe in overdose

Drugs

Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine (Prozac) 20mg More activating
Sertraline (Zoloft) 50mg  
Paroxetine (Paxil) 20mg
Escitalopram (Lexapro) 10mg
Citalopram (Celexa) 20mg
Fluvoxamine (Luvox) 100mg More relaxing

 
Other Antidepressants
Medicine Comments
Bupropion (Wellbutrin) 150-450 mg No sexual side effects, not with seizures
Venlafaxine (Effexor XR) 75-225 mg Mixed nor-epi & serotonin
Nefazodone (Serzone) 50-100 mg No sexual side effects, sedating
Mirtazapine (Remeron) 15-45 mg At low doses, sedating, appetite increased
Duloxetine (Cymbalta) 40-60 mg May be useful if chronic pain is present
Vilazodone (Viibryd) 20-40 mg Serotonin agonist and reuptake blocker
Vortioxetine (Brintellix) 10-20 mg Serotonin agonist and reuptake blocker
Levomilnacipran (Fetzima) 20-40 mg SNRI

 
If no response to any newer agents, or if chronic pain is a large issue in the depression, consider a tricyclic antidepressant
 
TCA
Medicine Comments
Desipramine (Norpramin) 50-150 mg – Less sedation
– Maximum dosage up to 300 mg/day
Nortriptyline (Pamelor) 50-100 mg – More sedation
– Maximum dosage up to 125 mg/day

 
Depression PLUS Rx Options
Smoker Wellbutrin, Nortriptyline
Too Tired Wellbutrin, Prozac, Celexa, Lexapro.
Sexual Dysf. Wellbutrin.
Weight Concern Wellbutrin  (can help w/ weight loss)
Anxiety Paxil, Zoloft.
Insomnia Paxil, Zoloft, Trazodone, Mirtazapine.
Chronic Pain Amitriptyline, Cymbalta, Effexor.
Pregnant Zoloft (sertaline), Prozac (Fluoxetine) and Celexa (citalopram)
AVOID PAXIL
Anorexia Mirtazapine
PTSD Paxil, Amitriptyline
Depression in Hospice pt Ritalin (amphetamine)
No Insurance Celexa, Paxil, Zoloft, Prozac.

 

Side Effects

 
Medicine SE
Tricyclics: Anticholinergic effects, narrow-angle glaucoma, caution in bundle branch blocks, weight gain
SSRIs Sexual dysfunction; hyponatremia, Osteioporosis
 - Citalopram In August 2011, the FDA issued a drug safety communication warning health care professionals that the antidepressant citalopram should no longer be used at dosages above 40 mg daily.
Citalopram has been found to be associated with dose-dependent QT interval prolongation, and the FDA concluded based on post-marketing reports that dosages greater than 40 mg daily can lead to abnormal heart rhythms, including torsades de pointes
SNRIs Mild anticholinergic, narrow-angle glaucoma, hepatic dysfunction
Bupropion Seizure induction (0.4%)
MAOI - Dietary restrictions
- Can cause hypertensive crisis

 

Duration of Treatment

  • For 1st episodes of depression, treat for 9-12 months.
  • For recurrent depression, treat for at least 2 years.
  • If patient relapses after successful treatment, > 90% will respond to the same antidepressant.

Augmentation of Antidepressants

  • Lithium carbonate 300-600 mg daily (MOST EFFECTIVE)
    • Response usually rapid, 7-9 days
       
  • (LOW-DOSE) Cytomel (T-3) 25-50 mcg qam
     
  • Bupropion (STAR*D study)

Resistant to Drugs

  • If no response to multiple antidepressants, consider a trial of electroconvulsive therapy (ECT)
  • ECT: most effective treatment in patients with severe resistance or psychotic depression
    Safe; memory loss is short-term, reversible
  • Transcranial Magnetic Stimulation (TMS) is an emerging outpatient treatment that can be effective in treatment resistant cases

Geriatric Depression

Facts:

  • Depression is not a part of normal aging
  • Less common in the elderly than in younger patients.
  • Physicians are often less likely to diagnose and treat depression appropriately in the elderly because they assume that all elderly patients are somewhat depressed.
  • A patient who develops major depressive disorder for the first time in later life actually has a much higher risk of recurrence or chronicity, probably because of both social support deficiencies and neurochemical abnormalities.

Risk Factor:

  • Death of Spouse = Strogest risk factor for depression in elderly
  • In community-residing elderly patients
  • Increased age
  • Personal history of depression
  • Health-related factors, and
  • Comorbid organic brain disorders or anxiety syndromes

Treatment:

  • Usually begin with selective serotonin reuptake inhibitors (SSRIs)
    • Once-a-day dosing
    • No titration 80% of the time
    • Few side effects (GI, sexual)
    • Safe in overdose
    • Patient must have an adequate trial of medication
    • Ranges from 4-12(!) weeks, but if no response at all by 4 weeks, it is unlikely response will develop later
    • If partial response at 4 weeks, maximize dose and continue
    • If partial response to SSRI, change to another SSRI
    • If no response to SSRI, try switching to another category
Other Antidepressants Tolerated Well by the Elderly
Bupropion (Wellbutrin) 50-100 mg
Venlafaxine (Effexor) 37.5 mg
Desvenlafaxine (Pristiq) 50 mg
Nefazodone 25-50 mg
Mirtazapine (Remeron) 7.5-15 mg
Duloxetine (Cymbalta) 20-40 mg

Pediatrics

  • Fluoxetine and escitalopram only ones FDA-approved (7-17 years)

Pregnant Patient

  • Relapse risk 5x higher if antidepressant is stopped
  • SSRIs are first-line
    – Risk of PPHN with SSRI use in late pregnancy
    Paroxetine: changed to pregnancy category D
    TCAs also considered safe and effective
    – SSRIs appear to have a more favorable side-effect profile than TCAs
    – One small study supports the use of venlafaxine
  • Informed consent is key

Lactation

  • Antidepressants are NOT contraindicated!
  • In most cases, infant blood concentrations of TCAs and SSRIs have been below the detection limit of commercial labs & well tolerated
  • Fluoxetine: can check infant blood levels at 6 weeks

 

[Also see Postpartum Depression/Blues]


 

Co-morbidities

Depressing and CAD

Depression Post-MI
  • Depression causes abnormalities in autonomic tone that may increase susceptibility to ventricular arrhythmias
  • Pt with CAD has 17-27% risk of developing depression.
  • An independent predictor of mortality following MI.
    • Depressed pt is at 2-3 fold increased risk of developing CAD independent of baseline cardiac function.
  • Depression is a common consequence of ST-elevation myocardial infarction (STEMI), with major depression occurring in 15%–20% of patients.
  • Presence of major depressive disorder at the time of hospital discharge after myocardial infarction or unstable coronary syndrome is one of the most powerful predictors of short-term mortality
  • Although there is strong evidence that both psychosocial interventions and SSRIs improve depression in MI survivors, it has not been proven that appropriate treatment of depression decreases mortality or cardiac events
  • Associated with poor compliance with risk-reducing treatment recommendations

Mechanism by which depression causes CAD:

  • Increased platelet activation.
  • Increased Systemic and localized inflammation
  • Alteration in cardiac autonomic tone
    • Nervous system activation characterized by decreased vagal and increased sympathetic tone, which may predispose to arrythmias
    • Reduced heart rate variability
  • Increase catecholamine level
  • Decrease Omega-3 fatty acid levels.
  • Underlying stress that leads to the development of both of these disorders

Treatment

  • Cardiac rehabilitation programs, social support, cognitive-behavioral therapy, and SSRIs are useful in the management of depression occurring in the year following MI.
  • DO NOT USE:
    • TCA are not favored because they can cause
      •   resting HR
      • Orthostatic hypotension
      • Alter intracardiac conduction = susceptibility to ventricular arrhythmias.
    • TCA have a quinidine-like effect on cardiac rate and conduction, and they should be avoided in patients with ventricular arrhythmias and ischemic heart disease.
 

Depression in Pregnancy

Decision to Treat during Pregnancy

  • The decision to use an antidepressant in a pregnant woman is based primarily upon:
    • Severity of her depression
    • Her desire to treat her depression with medication, and
    • An assessment of the potential harm to the newborn if a severely depressed mother is not effectively treated to remission.
      • If there is strong benefit from treatment, stopping the antidepressant before delivery is not appropriate because the withdrawal syndrome is mild and transient.
  • Maternal use of SSRIs in late pregnancy has been linked to the possible development of persistent pulmonary hypertension of the newborn

Withdrawal syndrome

  • Happens with SSRI use during 3rd trimester.
  • Occurs roughly two to three times as often in newborns of mothers treated with antidepressants compared to infants of mothers not taking antidepressants.
  • The absolute incidence is small, however, perhaps 5%–10%.
  • The behavioral syndrome consists of
    • Irritability
    • Jitteriness
    • Poor feeding,
    • Abnormal crying, and
    • Poor muscle tone
  • Is usually mild and transient, with no long-term ill effects.

 

 

 

Depression and BPH

  • Benign prostatic hyperplasia (BPH) and other potential causes of bladder outlet obstruction are relative contraindications to the use of antidepressant medications with antimuscarinic properties.

Treatment:

  • OK to use:
    • Serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine), SSRIs, and bupropion do not possess antimuscarinic activity and would be less likely to cause urinary retention.
       
  • DO NOT use:
    • Trazodone
    • Tertiary amine tricyclic antidepressants such as amitriptyline
    • MAO inhibitors

 

Depression and Parkinson's Dz

  • The presence of Parkinson’s disease is an important risk factor for major depression.
  • Major depressive disorder may be present to some degree in up to 40%–50% of patients.

Treatment:

  • OK to use:
    • Although all antidepressants appear equally effective for patients with Parkinson’s disease, SNRIs such as venlafaxine, duloxetine, or desvenlafaxine, as well as noradrenergic agents such as desipramine, are preferred (SOR C).
       
  • DO NOT use:
    • Amoxapine, a tetracyclic antidepressant, has dopamine-receptor blocking properties and the potential for causing a worsening of Parkinson’s symptoms.
    • Serotonin-enhancing agents such as SSRIs are associated with a higher risk for exacerbating symptoms, including increases in “off” time and worsening of the tremor.
    • Although the agonistic action of bupropion on the dopaminergic system might be expected to improve the symptoms of Parkinson’s disease, this potential benefit is offset by a tendency to induce psychotic symptoms in some patients.

Depression: Terms

  • Response: at least a 50% reduction in symptoms of depression as assessed by rating scale
  • Remission: resolution of essentially all symptoms
  • Recovery: remission lasting for 6 to 12 months
  • Relapse: worsening before achieving recovery
  • Recurrence: new depressive episode within a few months of recovery