- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
A wide range of effective treatments is available for major depressive disorder. Brief psychotherapy (eg, cognitive behavioral therapy, interpersonal therapy) has been shown in clinical trials to be an effective treatment option, either alone or in combination with medication. Medication alone also can relieve symptoms. However, the combined approach generally provides the patient with the quickest and most sustained response.
- Initial pharmacotherapy: All antidepressants on the market are potentially effective. Usually, 2-6 weeks at a therapeutic dose level are needed to observe a clinical response. The choice of medication should be guided by anticipated safety and tolerability, which aid in compliance; physician familiarity, which aids in patient education and anticipation of adverse effects; and history of prior treatments. Treatment failures often are caused not by clinical resistance, but by medication noncompliance, inadequate duration of therapy, or inadequate dosing.
- SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). This group has the advantage of ease of dosing and low toxicity in overdose. Common adverse effects include GI upset, sexual dysfunction, and changes in energy level (ie, fatigue, restlessness).
- Selective serotonin/norepinephrine reuptake inhibitors (SNRIs) include venlafaxine (Effexor) and duloxetine (Cymbalta). Safety, tolerability, and side effect profiles are similar to that of the SSRIs, with the exception that the SNRIs have been associated (rarely) with a sustained rise in blood pressure. SNRIs can be used as first-line agents, particularly in patients with significant fatigue or pain syndromes associated with the episode of depression. The SNRIs also have an important role as second-line agents in patients who have not responded to SSRIs. Venlafaxine and duloxetine are discussed in more detail in the Medication section.
- St. John's wort (Hypericum perforatum)
- While St. John's wort is considered a first-line antidepressant in many European countries, it has gained popularity in the United States only recently. Uses include treatment of mild-to-moderate depressive symptoms.
- Research indicates that it acts as an SSRI and not as a monoamine oxidase inhibitor (MAOI) as previously believed.
- The dosage is 300 mg 3 times a day with meals to prevent GI upset. If no clinical response occurs after 3-6 months, encouraging the use of another medication is essential.
- Atypical antidepressants include bupropion (Wellbutrin), nefazodone (Serzone), mirtazapine (Remeron), and trazodone (Desyrel). This group also shows low toxicity in overdose and may have an advantage over the SSRIs by causing less sexual dysfunction and GI distress.
- Bupropion is associated with a risk of seizure at higher doses, especially in patients with a history of seizure or EDs.
- Mirtazapine is a potent antagonist at 5-HT2, 5-HT3, alpha2-, and histamine (H1) receptors and, thus, can be very sedating. Adverse effects such as drowsiness and weight gain may tend to improve over time and with higher doses.
- Trazodone is very sedating and usually is used as a sleep aid rather than as an antidepressant.
- A 2007 research review by the Agency for Healthcare Research and Quality (AHRQ) compared 12 second-generation antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine. The AHRQ review found that overall, 38% of patients did not respond during 6-12 weeks of treatment with these agents, and 54% did not achieve remission.5
The AHRQ noted that there is no reliable way to predict whether an individual patient will respond. The average effectiveness of the antidepressants appeared similar, but the studies reviewed were not designed to test variation among patients’ responses to individual drugs. However, the AHRQ did find moderately strong evidence of differences among individual second-generation antidepressants with respect to onset of action and some measures (eg, sexual functioning) that could affect health-related quality of life. - Tricyclic antidepressants (TCAs) include amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin), clomipramine (Anafranil), doxepin (Sinequan), protriptyline (Vivactil), trimipramine (Surmontil), and imipramine (Tofranil).
- This group has a long record of efficacy in the treatment of depression and has the advantage of lower cost. They are used less commonly now because of the need to titrate the dose to a therapeutic level and because of their considerable toxicity in overdose.
- Adverse effects largely are due to their anticholinergic and antihistaminic properties and include sedation, confusion, dry mouth, orthostasis, constipation, urinary retention, sexual dysfunction, and weight gain. Caution should be used in patients with cardiac conduction abnormalities.
- MAOIs include phenelzine (Nardil) and tranylcypromine (Parnate).
- MAOIs are widely effective in a broad range of affective and anxiety disorders.
- Because of the risk of hypertensive crisis, patients on these medications must follow a low-tyramine diet. Other adverse effects can include insomnia, anxiety, orthostasis, weight gain, and sexual dysfunction.
- Nonpharmacologic treatments
- Electroconvulsive therapy (ECT) is a highly effective treatment for depression and may have a more rapid onset of action than drug treatments. Advances in brief anesthesia and neuromuscular paralysis have improved the safety and tolerability of this modality. Risks include those associated with brief anesthesia, postictal confusion, and, more rarely, short-term memory difficulties. ECT is used when a rapid antidepressant response is needed, when drug therapies have failed, when there is a history of good response to ECT, or when there is patient preference. ECT is particularly effective in the treatment of delusional depression.
- Light therapy: Broad-spectrum light exposure has long been in use for the treatment of SAD. Some evidence now exists that it may have some efficacy in nonseasonal depression or as an augmenting agent with antidepressant medication.
- Transcranial magnetic stimulation: This modality is in investigational stages for the treatment of major depressive disorder. Initial results suggest that it may be an effective intervention without the risks and adverse effects of ECT.
- Vagus nerve stimulation also is in investigational stages and has shown some efficacy in treatment-resistant depression.
Consultations
Consultation can be important at many stages of the treatment process. Certainly, consultation should be sought if treating physicians exhaust the options with which they feel comfortable.
- A psychiatrist must be involved in the care of patients in whom more severe symptoms develop and for whom a more intensive level of care will be needed (eg, suicidal ideation, psychosis, mania, severe decline in physical health). Expertise in pharmacotherapy, other somatic therapies, and psychotherapy should be readily available. Collaboration of psychiatrists and family practitioners/internists is of particular importance in patients with acute and chronic medical issues. A psychologist can be involved if psychological testing or more intensive specialized psychotherapy (eg, interpersonal therapy, cognitive behavior therapy) is needed.
- With the patient's consent, communication with the patient's therapist can be invaluable in guiding medical treatment of major depressive disorder. The therapist can provide information regarding clinical progress, symptoms, and adverse effects. This can facilitate timely and appropriate medical interventions.
Diet
Dietary restrictions are necessary only when prescribing MAOIs. Foods high in tyramine, which can produce a hypertensive crisis in the presence of MAOIs, should be avoided. These foods include soy sauce, sauerkraut, aged chicken or beef liver, aged cheese, fava beans, air-dried sausage and similar meats, pickled or cured meat or fish, overripe fruit, canned figs, raisins, avocados, yogurt, sour cream, meat tenderizer, yeast extracts, caviar, and shrimp paste. Beer and wine also should be avoided.
Activity
Physical activity and exercise contribute to recovery from major depressive disorder. Patients should be counseled regarding stress reduction.
Medication
The following are examples from various classes of antidepressants and augmenting agents that are used with TCAs or SSRIs to augment therapeutic effect in resistant depression. Available medications from each class are listed in Treatment.
SSRIs are greatly preferred over the other classes of antidepressants. Because the adverse effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.
Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Antidepressants
Have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of NE and serotonin. SSRIs are metabolized via the cytochrome P-450 system and may have drug interactions on that basis. The degree of enzyme inhibition varies among SSRIs. Effects on blood levels and bioavailability of coadministered drugs account for most clinically significant SSRI-drug interactions.
Desipramine (Norpramin)
Commonly used TCA. Fairly specific NE reuptake inhibitor. May have effects in the desensitization of adenyl cyclase and down-regulation of beta-adrenergic or serotonin receptors. Tends to have fewer anticholinergic and antihistaminic adverse effects than other TCAs.
Adult
25 mg PO qhs, increase gradually prn to 150-250 mg/d PO in divided doses, not to exceed 300 mg/d
Used with an SSRI (25-75 mg/d)
Pediatric
<6 years: Not established
6-12 years: 1-5 mg/kg/d PO in equally divided doses; not to exceed 5 mg/kg/d
>12 years: 25-50 mg/d PO, gradually increase prn to 100 mg/d PO in single or divided doses; not to exceed 150 mg/d
Decreases antihypertensive effects of clonidine, but increases effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin, carbamazepine, and barbiturates; marked increases in blood level of desipramine when used with P-450 2d6 inhibitors such as fluoxetine and paroxetine
Documented hypersensitivity; narrow-angle glaucoma; recent postmyocardial infarction; cardiac conduction abnormalities; receiving MAOI or fluoxetine currently or within past 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
All TCAs are toxic in overdose; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, patients receiving thyroid replacement, and elderly individuals
Fluoxetine (Prozac)
Commonly used SSRI, first of the SSRIs to become available in the United States. Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in reuptake of NE or DA.
Adult
20 mg PO qam, and increase after several wk by 20 mg/d; not to exceed 80 mg/d
Pediatric
<18 years: Not established; initial doses of 5-10 mg/d PO in children aged 5-18 y have been used; usual maximum dose is 20 mg/d
>18 years: Administer as in adults
Increases toxicity of diazepam and trazodone by decreasing clearance; raises blood levels of TCAs, warfarin, neuroleptics, carbamazepine, phenytoin, and benzodiazepines; reduces conversion of codeine to active metabolite, thereby reducing analgesic effects; increases toxicity of highly protein-bound drugs
Serotonin syndrome may occur when used with other serotonergic agents such as buspirone, meperidine, tramadol, dextromethorphan, triptans, mirtazapine, nefazodone, and other SSRIs, but especially with MAOIs
Documented hypersensitivity; currently taking MAOI or within past 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic impairment and history of seizures; MAOI should be discontinued at least 14 d before initiating fluoxetine therapy
Venlafaxine (Effexor)
Mixed serotonin and NE reuptake inhibitor. In addition, causes beta-receptor down-regulation. In lower doses (75 mg/d) acts much like an SSRI. SSRI-like adverse effects such as GI upset often improve at higher doses (150- 300 mg/d).
Adult
Immediate release: 75 mg/d PO divided bid/tid with food, and increase in 75 mg/d increments q4d to 225-375 mg/d
Extended release: 75 mg PO qd with food, and increase in 75 mg/d increments q4d to 225 mg/d; for some new patients may be desirable to start at 37.5 mg/d for 4-7 d before increasing to 75 mg qd
Pediatric
Not established
Cimetidine, MAOI, sertraline, fluoxetine class 1-C antiarrhythmics, TCAs, and phenothiazines may increase effects of venlafaxine
Documented hypersensitivity; current MAOI or within past 2 wk; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid abruptly stopping venlafaxine because withdrawal symptoms (dizziness, malaise) can be prominent; adjust dose in hepatic or renal failure; may experience hypertension; caution in patients with cardiovascular disorders
Desvenlafaxine (Pristiq)
Selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for treatment of major depressive disorder (MDD).
Adult
50 mg PO qd (swallow whole, do not divide, crush, chew, or dissolve)
Moderate renal impairment: 50 mg PO qd
Severe renal impairment: 50 mg PO qod
Pediatric
Not established
Hypertensive crisis may occur when coadministered with MAOIs (see Contraindications); coadministration with other drugs known to affect serotonergic neurotransmitter systems (eg, SSRIs, triptans) increases risk of serotonin syndrome (ie, agitation, hallucinations, coma, tachycardia, labile blood pressure, hyperthermia, hyperreflexia, incoordination, nausea, vomiting, diarrhea); may increase bleeding risk when coadministered with NSAIDs, aspirin, or warfarin; caution when coadministered with other drugs that affect CNS (eg, alcohol); coadministration with CYP3A4 inhibitors (eg, ketoconazole) may result in higher desvenlafaxine serum levels; may inhibit CYP2D6 and decrease clearance of CYP2D6 substrates (eg, desipramine)
Documented hypersensitivity; coadministration with or within 14 d of stopping an MAOI; allow 7 d after stopping desvenlafaxine before starting an MAOI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for clinical worsening and suicide risk; may increase risk of suicidal ideation and behavior in children, adolescents, and young adults when taken for MDD or other psychiatric disorders; may cause or exacerbate serotonin syndrome, hypertension, narrow-angle glaucoma, cardiovascular disease, hypercholesterolemia, hypertriglyceridemia, hyponatremia, interstitial lung disease and eosinophilic pneumonia, and seizures; when discontinuing, gradually taper downward to avoid discontinuation symptoms; may exacerbate or activate mania associated with bipolar disorder; caution with renal impairment (decrease dose)
Duloxetine (Cymbalta)
Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS.
Adult
20 mg PO bid; may increase to 60 mg/d administered qd or divided as 30 mg bid
Pediatric
Not established
Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase blood levels and toxicity; moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, tricyclic antidepressants, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAOIs may cause serious, sometimes fatal, reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes, including extreme agitation, delirium, and coma (see Contraindications)
Documented hypersensitivity; uncontrolled narrow-angle glaucoma; do not administer within 14 d after stopping MAOIs; do not initiate MAOIs within 5 d of stopping duloxetine
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing, do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and increased sweating
Lithium carbonate (Eskalith, Lithane, Lithobid)
Can be used as an effective augmenting agent in combination with an antidepressant in cases of treatment-resistant depression. Influences reuptake of serotonin and/or NE at cell membrane.
Serum levels should be monitored weekly to biweekly until levels are stabilized, at which point, levels can be checked every 3-4 months. Serum levels can be tested after 5 days at a given dose, usually just prior to the am dose. As with most medications, the lowest effective dose should be used to avoid adverse effects and toxicity
Adult
600-1800 mg/d PO in divided doses; maximum usual maintenance dose is 2.4 g/d or 450-900 mg bid of sustained release form
Target blood levels may be lower than those needed in bipolar disorder, but should be above 0.4 mEq/L (reference range: 0.4-0.8 mEq/L)
Pediatric
<6 years: Not established
6-12 years: 15-60 mg/kg/d PO divided tid/qid; not to exceed usual adult dose
>12 years: Administer as in adults
Drug levels may be reduced by urinary alkalinizing agents (eg, acetazolamide); lithium increases toxicity of thiazide diuretics, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, ACE inhibitors, NSAIDs, metronidazole, and calcium channel blockers
Documented hypersensitivity; severe cardiovascular disease; renal failure; pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Prior to beginning lithium therapy, obtain baseline BUN, creatinine, TSH, CBC, and electrolytes; pregnancy should be excluded; obtain baseline ECG for individuals >40 y or with heart disease
Advise patients of possible adverse effects (eg, GI distress, polydipsia/polyuria, acne, weight gain, mild cognitive changes, fine hand tremor); reduce GI symptoms and tremor by using divided doses; manage acne with interventions (eg, benzoyl peroxide)
Hypothyroidism can occur, and TSH should be monitored q6mo; diabetes insipidus has occurred and responds to discontinuation of the drug, little evidence that lithium causes renal damage over time; benign leukocytosis often appears, and requires no intervention unless there is evidence of another underlying problem
ECG showing T-wave flattening or inversion requires no intervention unless there is suspicion of a separate cardiac condition
Counsel patients to maintain adequate water intake because dehydration or restricted sodium intake can enhance lithium reabsorption by the kidney and lead to toxicity; reduce doses if creatinine clearance is decreased and in elderly persons
Prolongs effects of neuromuscular blockers; lithium toxicity is related closely to serum levels and can occur at therapeutic doses; serum lithium determinations are required to monitor therapy
Buspirone (BuSpar)
Marketed as an antianxiety medication; however, may have antidepressant effect at doses above 45 mg/d. Effects may increase when used in combination with SSRIs and TCAs. Buspirone is a partial 5-HT agonist with serotonergic and some dopaminergic effects in CNS. Has anxiolytic effect but may take up to 2-3 wk for full efficacy.
Adult
15 mg/d PO divided tid and increase by 5 mg/d q2-4d; not to exceed 60 mg/d
Pediatric
Not established
Toxicity is increased with MAOIs, phenothiazines, and CNS depressants; increases toxicity of digoxin and haloperidol
Documented hypersensitivity; current MAOIs or within past 2 wk
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic impairment
Mirtazapine (Remeron, Remeron SolTab)
Exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, has been shown superior to other SSRI drugs.
Adult
15 mg (range 15-45 mg) PO hs; dose increases should not be made more frequently than q1-2wk
Pediatric
Not established
May increase effect of CNS depressants; concurrent administration with MAOI may trigger hypertensive crisis
Documented hypersensitivity; MAOI within 14 d
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause drowsiness; discontinue use if patient develops sore throat, fever, or other signs of infection; suicide ideation is inherent in depression and may persist until significant remission occurs; severe neutropenia reported in clinical trials
Escitalopram (Lexapro)
SSRI and the S-enantiomer of citalopram. Used to treat depression and appropriate as first-line agent. Mechanism of action is thought to be potentiation of serotonergic activity in CNS resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief may be obtained after 1-2 wk, which is sooner than other antidepressants.
Adult
10 mg PO qd initially; if needed, may increase to 20 mg/d after 1 wk
Pediatric
Not established
Primarily metabolized by CYP-450 3A4 and 2C19 though no evidence of competitive inhibition; coadministration with alcohol or other centrally acting drugs increases CNS depression; do not use concurrently or within 14 d of administering MAOIs; cimetidine increases AUC and maximum serum concentration; coadministration with sumatriptan and SSRIs has caused weakness and hyperreflexia
Documented hypersensitivity; do not use concurrently or within 14 d of administering MAOIs
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with history of seizures, mania, suicide; common adverse effects include insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating, fatigue, and somnolence
Tranylcypromine (Parnate)
Treats major depression. Binds irreversibly to MAO, thereby reducing monoamine breakdown and enhancing synaptic availability.
Adult
10 mg PO bid; titrate as tolerated with 10-mg increments; usual dose is 30-60 mg/d PO in divided doses
Pediatric
Not established
Increases effect or toxicity (serotonin syndrome, hypertensive crisis, CNS depression, cardiac arrhythmias, anticholinergic effects) of appetite suppressants, antidepressants, sympathomimetics (including decongestants), SSRIs, dopaminergic agents, caffeine, chocolate, tryptophan, tyrosine, tyramine, carbamazepine, and St. John's wort
Documented hypersensitivity; uncontrolled hypertension; cardiac disease; cerebrovascular disease; pheochromocytoma; concurrent use with meperidine has been associated with coma, death, excitation, respiratory distress, sweating, and cardiovascular collapse
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include orthostatic hypotension, sexual dysfunction, weight gain, and headache; patients should follow a low-tyramine diet and be aware of restrictions regarding potential OTC and prescription drug interactions
Selegiline transdermal patch (Emsam)
Irreversible MAOI. Has greater affinity for MAO-B compared with MAO-A; however, at antidepressant doses, inhibits both isoenzymes. MAO-A and MAO-B catabolize neurotransmitter amines in CNS (eg, norepinephrine, dopamine, serotonin). Indicated for treating MDD. At lowest strength (ie, 6 mg delivered over 24 h), may be used without the dietary restrictions required for oral MAOIs used to treat depression.
Adult
Starting dose: 6 mg/24 h patch; apply topically once q24h; remove previous day's patch when applying new patch
Dosage range: 6-12 mg/24 h patch; if dose increase is warranted, increase by 3 mg/24 h at >2-wk intervals; not to exceed 12 mg/24 h
Apply to dry, intact, nonoily, nonhairy skin on upper torso (ie, below neck, above waist), upper thigh, or outer surface of upper arm; avoid reapplication to same site on consecutive days
Pediatric
Not established
Do not coadminister with other drugs that cause or increase risk of serotonin syndrome (eg, SSRIs [fluoxetine, sertraline, paroxetine], SNRIs [venlafaxine, duloxetine], TCAs [imipramine, amitriptyline], MAOIs [isocarboxazid, phenelzine, tranylcypromine], mirtazapine, bupropion, meperidine, tramadol, methadone, propoxyphene, pentazocine, dextromethorphan, cyclobenzaprine, oral selegiline, St John's wort)
Do not ingest tyramine-containing foods and beverages (eg, aged cheese, wine, beer, dried or fermented meats [sausage], fava beans, soybean products, yeast extract, sauerkraut) with patches that release > 6 mg/24 h or for 2 wk following discontinuation of patch;
Sympathomimetic amines (eg, cold products or appetite depressants containing pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine) increase risk of hypertensive crisis
General or local anesthesia containing sympathomimetics or cocaine increases risk of hypertensive crisis (avoid elective surgery during treatment and for at least 10 d after discontinuing patch
If surgery is required immediately, benzodiazepines, mivacurium, rapacuronium, fentanyl, morphine, and codeine may used cautiously)
Carbamazepine and oxcarbazepine may increase plasma levels
Alcohol may increase mental and motor skills impairment
Documented hypersensitivity; SSRIs; dual SNRIs; TCAs; bupropion; mirtazapine; meperidine and other analgesics; carbamazepine; oxcarbazepine; sympathomimetic amines
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause mild redness on skin at application site; may cause lightheadedness or postural hypotension secondary to decreased blood pressure; applying direct heat to patch may increase amount of drug absorbed from patch so avoid direct heat exposure (eg, heating pads, electric blankets, sauna, hot tubs, prolonged sunlight); as with all antidepressants, labeling includes a warning for risk of increased suicidality in children and adolescents; all patients with depression should be monitored closely for suicidality; rule out risk of bipolar disorder before initiating antidepressant therapy (treatment with antidepressants alone may precipitate a mixed/manic episode); may impair judgment, thinking, or motor skills
CNS stimulants
Used in patients with resistant depression.
Dextroamphetamine (Dexedrine)
Augmenting agent in resistant depression, most studied in treating patients who are medically ill and depressed. Available as a sustained-release preparation.
Adult
5-60 mg/d PO in divided doses
Pediatric
Not established
Coadministration with MAOIs may precipitate hypertensive crisis and, with anesthetics, may precipitate arrhythmias; dextroamphetamine may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and NE
Documented hypersensitivity; psychosis; agitation; hyperthyroidism; uncontrolled hypertension; cardiac disease; glaucoma; current MAOI or within past 2 wk; substance abuse
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in angina, glaucoma, cardiovascular disease, and psychopathic personalities
Methylphenidate (Ritalin)
Most studied in treating patients who are medically ill and depressed. Available as a sustained-release preparation.
Adult
2.5 mg PO qam; may increase dose q2-3d by 2.5-5 mg to maximum 60 mg/d; if unable to sleep because of taking medication late in day, take last dose before noon or 6 pm
Pediatric
Not established
Reduces effects of guanethidine and bretylium; toxicity of phenytoin, TCAs, warfarin, primidone, and phenobarbital may increase when administered concurrently with methylphenidate; MAOIs increase toxicity of methylphenidate
Documented hypersensitivity; psychosis; agitation; hyperthyroidism; uncontrolled hypertension; cardiac disease; glaucoma; current MAOI or within past 2 wk; substance abuse
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in dementia, seizures, and hypertension
Thyroid hormones
May modulate the effect of antidepressants.
Liothyronine (T3, Cytomel)
Synthetic salt of endogenous thyroid hormone, may convert nonresponders (to antidepressants) to responders by increasing receptor sensitivity and enhancing effects of TCAs.
Adult
5 mcg PO qd; titrate prn to 25-50 mcg PO qd
Pediatric
Not established
Increased effect/toxicity of sympathomimetics and vasopressors; decreases beta-blocker effect; increases/decreases effects of antidiabetic agents and corticosteroids; effect decreased by barbiturates, carbamazepine, phenytoin, and rifampin
Documented hypersensitivity; hyperthyroidism; cardiac disease; osteoporosis; adrenal insufficiency; use as weight loss therapy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Symptoms of hyperthyroidism; increased risk of cardiac dysfunction; monitor glucose levels of patients with diabetes
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Further Reading
Keywords
clinical depression, major depression, depression treatment, anxiety depression, major depressive disorder, MDD, unipolar depression, unipolar affective disorder, serotonin, norepinephrine, dopamine, selective serotonin reuptake inhibitors, SSRIs, tricyclic antidepressants, TCAs, norepinephrine, NE, dopamine, DA, suicide, suicidality, dysthymia, electroconvulsive therapy, ECT, electroshock therapy, shock therapy, light therapy
seasonal affective disorder, SAD, antidepressants, lithium, psychotherapy, cognitive behavioral therapy, CBT, neurasthenia, insomnia, hypersomnia, psychomotor agitation, psychomotor retardation, feelings of worthlessness, anhedonia, irritability, dementia of depression, pseudodementia, Parkinson disease, Huntington disease, multiple sclerosis, stroke, seizure disorders, systemiclupuserythematosus, SLE, autoimmune cerebritis, obstructive sleep apnea, syphilis, Lyme disease, HIV encephalopathy, Addison disease, Cushing disease, hyperthyroidism, hypothyroidism, prolactinomas
hyperparathyroidism, alcohol abuse, cocaine abuse, amphetamines abuse, marijuana abuse, narcotics abuse, inhalant abuse, bright light therapy, anxiety disorders, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, phobia, eating disorders, bulimia, anorexia nervosa, psychosis, organic brain syndrome, hopelessness, psychosocial stress, chronic pain
