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    Depression (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention

    continued...

    Antidepressant medication selection

    The choice of antidepressant depends on a patient's medical history and concomitant medical problems, the symptoms referable to depression, previous responses to antidepressant medications, and the side effects associated with the agents available.

    The types of medications used to treat depression in patients with cancer include the SSRIs, tricyclic antidepressants (TCAs), and analeptic or CNS stimulant agents (i.e., amphetamines). Table 2 outlines the commonly used antidepressants and highlights starting dosages used in cancer patients. The Side Effects/Comments column identifies drug-specific side effects that may be clinically advantageous or problematic depending on the clinical situation when selecting antidepressant medications and monitoring patients receiving these drugs. Generally, there is a long latency period (3-6 weeks) from initiation of antidepressant medications until the onset of a therapeutic response. In many cases, antidepressant treatment begins at low doses followed by a period of gradual dose titration to achieve an optimum individualized response. Initial low doses may help to avoid initial side effects, but dose escalation may be required in order to see therapeutic effects. For some agents, there is a therapeutic window during which plasma concentrations correlate with a patient's antidepressant response (e.g., nortriptyline). For patients receiving these agents, serial drug concentration monitoring guides therapy and facilitates providing an adequate therapeutic trial, because plasma concentrations less than and greater than the defined therapeutic ranges are associated with treatment failure, suboptimal responses, and in the case of high drug concentrations, unnecessary toxicity.

    Table 2. Antidepressant Medications for Ambulatory Adult Patients

    Drug Class/Generic Name (Proprietary Name)/Dosagesa Side Effects/Comments
    ALT = alanine aminotransferase; BP = blood pressure; EKG = electrocardiogram; MAOIs = monoamine oxidase inhibitors; SSRIs = selective serotonin reuptake inhibitors; TCAs = tricyclic antidepressants.
    a Consult complete prescribing information for appropriate administration schedules.
    b TCAs prolong cardiac conduction through His-Purkinje system similar to Type IA antiarrhythmic agents (e.g., quinidine). They are specifically contraindicated in patients with bundle-branch disease and second- or third-degree heart block. Their effects on conduction correlate with dosage and serum concentrations and for those agents with positive chronotropic and adrenergic-stimulating properties, TCAs can cause reentry arrhythmias. Persons at greatest risk are those with preexisting cardiac conduction defects and those who have taken an overdose.
    c Plasma concentrations are most useful for guiding treatment in elderly patients who are (1) experiencing signs and symptoms of toxicity, (2) unresponsive to treatment, (3) suspected of being noncompliant with planned treatment, or (4) receiving other medications that may interact or otherwise alter antidepressant medication pharmacokinetics.
    d TCAs and other antidepressants may cause sexual dysfunction characterized as decreased libido, penile erectile dysfunction, and decreased sensation during orgasm and ejaculation. Management consists of waiting for spontaneous resolution with continued therapy, decreasing the antidepressant dose, selecting an alternative antidepressant, or concomitant treatment with medications that treat the dysfunction (e.g., bethanechol for antidepressants with prominent anticholinergic effects).
    e Common antimuscarinic or anticholinergic effects include dry mouth, blurred vision, constipation, and urinary retention. Although patients may eventually develop tolerance to these effects with repeated medication use, symptoms may not completely resolve until the drug is discontinued.
    TCAs Can cause cardiac arrhythmias.
    EKG at baseline to evaluate for preexisting cardiac conduction abnormalities. Therapeutic drug concentration ranges in plasma have been identified for all agents, but dosage adjustments should be based on a patient's clinical response and not solely on plasma concentrations.b
    In responding patients, decrease daily dosages to the lowest effective amount needed to sustain a response.c Can cause sexual dysfunction.
    May be associated with weight gain.d
    amitriptyline (Elavil) Marked sedation, dizziness, headache, weight gain, anticholinergic effects,e orthostatic BP changes (postural hypotension); may produce sexual dysfunction. Therapeutic plasma concentrations (parent drug + active metabolite) = 110-250 ng/mL.
    initial: 10-25 mg as a single daily dose, preferably at bedtime
    maintenance: 150-300 mg/d
    clomipramine (Anafranil) Anticholinergic effects, dizziness, drowsiness, headache, weight gain, orthostatic hypotension.
    initial: 25 mg/d and gradually increase to 100 mg/d the first 2 weeks; may be given at bedtime
    maintenance: 100-250 mg/d maximum
    desipramine (Norpramin) Mild sedation, increased appetite, nausea, minimal anticholinergic effects,e orthostatic BP changes. Therapeutic plasma concentrations = 125-300 ng/mL.
    initial: 25-50 mg/d as a single daily dose, preferably at bedtime
    maintenance: 100-300 mg/d as a single daily dose; In elderly patients, daily doses >150 mg are not recommended
    doxepin (Sinequan) Moderate to heavy sedation, dizziness, headache, weight gain, moderate anticholinergic effects,e postural hypotension. Optimal antidepressant effect is characteristically delayed by 2-3 weeks, but onset of antianxiety effect is comparatively rapid. Therapeutic plasma concentrations (parent drug + active metabolite) = 100-200 ng/mL.
    initial: 10-25 mg/d as a single daily dose, preferably at bedtime
    maintenance: 75-300 mg/d as a single daily dose, preferably at bedtime
    imipramine (Tofranil) Moderate to heavy sedation, dizziness, headache, weight gain, moderate anticholinergic effects,e moderate to marked orthostatic BP changes; may produce sexual dysfunction (both genders). Therapeutic plasma concentrations (parent drug + active metabolite) = 200-350 ng/mL.
    initial: 25-50 mg/d as a single daily dose, preferably at bedtime
    maintenance: 75-200 mg/d as a single daily dose, preferably at bedtime
    nortriptyline (Pamelor, Aventyl) Mild to moderate sedation, constipation, nausea, increased appetite, mild to moderate anticholinergic effects.e Is the TCA least likely to produce postural hypotension. Therapeutic plasma concentrations = 50-150 ng/mL.
    initial: 10-25 mg, 3-4 times daily
    maintenance: 30-50 mg, 3 times daily, daily doses >150 mg are not recommended
    SSRIs Have few anticholinergic and cardiovascular adverse effects. Life-threatening and fatal reactions have occurred in patients who receive within 2 weeks of using MAOIs. Sexual dysfunction has been reported to be associated with use. There is limited experience with long-term use.
    citalopram (Celexa) Ejaculation disorder and other sexual dysfunctions, insomnia, dry mouth, nausea, somnolence.In vitro studies indicated that CYP3A4 and CYP2C19 are the primary enzymes involved in citalopram metabolism.[18]Is a relatively weak inhibitor of CYP2D6.
    initial: 10 mg/d
    maintenance: 10-40 mg/d
    fluoxetine (Prozac) Anxiety, nervousness, insomnia, anorexia, mild bradycardia, sinoatrial node slowing, weight loss, solar photosensitivity, hyponatremia, sexual dysfunction; may alter glycemic control in diabetic patients. Substantially inhibits CYP2D6 and may inhibit the clearance of other drugs metabolized by cytochrome P450 CYP2D6 isozymes.[18]Probably inhibits CYP2C9/10, moderately inhibits CYP2C19, and mildly inhibits CYP3A4.[18]Fluoxetine metabolism is impaired in elderly patients.
    initial: 10-20 mg/d
    maintenance: 20-80 mg/d
    escitalopram (Lexapro) Nausea, vomiting, diarrhea, constipation, upset stomach, loss of appetite, dizziness, drowsiness, trouble sleeping, back pain, dry mouth.
    initial: 10 mg/d
    maintenance: 10-20 mg/d
    fluvoxamine (Luvox) Nausea, sexual dysfunction, headache, nervousness, insomnia, drowsiness.
    initial: 50 mg at bedtime, adjust in 50 mg increments at 4- to 7-day intervals
    maintenance: 100-300 mg/d
    paroxetine (Paxil) Anxiety, nervousness, insomnia, mild weight loss, headache, solar photosensitivity, hyponatremia, sexual dysfunction. Substantially inhibits and may interact with other drugs metabolized by cytochrome P450 CYP2D6 isozyme.[18]Paroxetine metabolism is impaired in elderly patients.
    initial: 10-20 mg/d
    maintenance: 20-50 mg/d
    sertraline (Zoloft) Anxiety, nervousness, insomnia, mild weight loss, headache, solar photosensitivity, hyponatremia, sexual dysfunction. Produces mild inhibition of and may interact with drugs metabolized by cytochrome P450 CYP2D6 isozymes with little, if any, effect on CYP1A2, CYP2C9/10, CYP2C19, or CYP3A3/4.[18]
    initial: 25-50 mg/d
    maintenance: 50-200 mg/d
    MAOIs
    tranylcypromine (Parnate) Orthostatic hypotension, drowsiness, hyperexcitability, headache. Low-tyramine diet required.
    initial: 10 mg twice daily, increase by 10-mg increments at 1- to 3-week intervals
    maintenance: 10-40 mg/d
    phenelzine (Nardil) Orthostatic hypotension, drowsiness, hyperexcitability, headache. Low-tyramine diet required.
    initial: 15 mg 3 times a day
    maintenance: 15-90 mg/d
    selegiline (EMSAM) Application site reaction, orthostatic hypotension, diarrhea, headache, insomnia, dry mouth. Any dosages higher than 6 mg/24 h require low-tyramine diet.
    initial: 6-mg patch/24 h (20-mg patch topically every 24 h)
    maintenance: 6-mg patch/24 h (20-mg patch topically every 24 h). May increase at increments of 3 mg/24 h at 2-week intervals up to 12 mg/24 h.
    ATYPICAL ANTIDEPRESSANTS In general, serum drug concentrations do not correlate with antidepressant response.
    bupropion (Wellbutrin, also approved for the treatment of smoking cessation as Zyban) Initially activating dose-related seizure-inducing potential; contraindicated in patients with CNS involvement, a history of seizure, and concomitant conditions predisposing to seizure and in patients taking other drugs that lower seizure threshold. Mild to moderate sedation, mild to moderate anticholinergic effects,e mild orthostatic BP changes, agitation, insomnia, headache, confusion, dizziness, seizures, weight loss.
    initial: 75 mg/d
    maintenance: 200-450 mg/d not to exceed 150 mg/dose
    trazodone (Desyrel) Mild to moderate sedation; negligible anticholinergic effects; mild to moderate orthostatic BP changes, particularly in elderly patients; dizziness; headache; confusion; muscle tremors; may produce priapism. Taking with food can decrease gastrointestinal upset. Therapeutic plasma concentrations = 800-1,600 ng/mL.
    initial: 50 mg/d
    maintenance: 150-600 mg/d
    mirtazapine (Remeron) A tetracyclic antidepressant. Elimination is decreased in elderly persons. Somnolence, dizziness, increased appetite and weight gain, constipation, hypertension, edema, confusion, increased nonfasting triglycerides and cholesterol, significantly increased hepatic ALT, orthostatic hypotension. When used concomitantly with drugs that reduce seizure threshold (e.g., phenothiazines), may increase risk of seizure.
    initial: 7.5-15 mg/d
    maintenance: 15-45 mg/d
    venlafaxine (Effexor) Dose-related sustained hypertension, headache, dizziness, insomnia, nausea, constipation, abnormal ejaculation. Life-threatening and fatal reactions have occurred in patients who receive within 2 weeks of using MAOIs.
    initial: 75 mg/d
    maintenance: 150-375 mg/d
    duloxetine (Cymbalta) Nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, increased sweating, decreased sexual drive or ability, urinary hesitation.
    initial: 30 mg/d
    maintenance: 30-60 mg/d
    PSYCHOSTIMULANTS Restlessness, agitation, insomnia, nightmares, psychosis, anorexia; may exacerbate preexisting cardiac disease. Should be administered early in a patient's daily waking cycle. Sometimes used adjuvantly to antagonize opioid analgesics' sedative effects.
    dextroamphetamine (Dexedrine) Drug tolerance, abuse, and dependence liability. Arrhythmia, nervousness, restlessness, insomnia. Contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, and glaucoma.
    initial: 2.5-5 mg/d
    maintenance: 10-30 mg/d
    methylphenidate (Ritalin, Methylin) Drug tolerance, abuse, and dependence liability. Hypertension, tachycardia, nervousness, insomnia, anorexia, drowsiness, dizziness. May decrease convulsive threshold in patients with history of seizure disorders.
    initial: 2.5-10 mg/d
    maintenance: 20-60 mg/d
    dexmethylphenidate (Focalin) Dry mouth, tremor or muscle spasms, nervousness, trouble sleeping, headache, drowsiness, nausea, insomnia, increased sweating, dizziness, lightheadedness, changes in sexual function.
    initial: 10 mg/d
    maintenance: 10-20 mg/d
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