In standard

treatment of depression, MAOIs are not recommended except for the treatment of

atypical depression where this class appears to have a small efficacy advantage over

other classes.

5,10 Data comparing TCAs with SSRIs for atypical depression suggest

that the two classes are comparable in efficacy and both are superior to placebo and

so SSRIs should still be tried first due to safety concerns.

10,206

The “cheese reaction,” which can manifest as a hypertensive crisis, is so named

because it occurred in patients who were taking nonselective MAOIs and ingested

foods high in tyramine, a by-product of tyrosine metabolism that is found in certain

foods and beverages, such as aged cheese or Chianti wine (Table 86-12). When

tyramine is ingested in the absence of an MAOI, it is rapidly metabolized by the

MAO enzyme in the GI tract before systemic absorption. In the presence of an MAOI,

more tyramine is absorbed and relatively high concentrations of tyramine may be

achieved in circulation, resulting in the displacement of NE (and other

catecholamines) from presynaptic storage granules. NE surges into the synapse, and

as metabolic degradation is inhibited by the MAOI, a profound pressor response is

triggered.

207 A slightly safer version of the MAOI class is the once-daily selegiline

transdermal. By avoiding the GI tract, selegiline has less effect on the MAO that

reduces tyramine from entering the bloodstream via food. Despite the improved

safety of selegiline transdermal to oral MAOIs, there still remains a risk of food–

drug interactions resulting in hypertensive reactions, particularly at higher doses, and

so the FDA has recommended diet restrictions for doses over 6 mg/24 hours.

Additionally, there are application site reactions that occur in approximately 35% of

patients.

5,208,209 This agent is available in 6, 9, and 12 mg strengths. Selegiline

transdermal as well as oral MAOIs are reserved for refractory cases and should be

used only by skilled clinicians.

5,209

Table 86-12

Foods Containing Tyramine

High Amounts of Tyramine

a

Smoked, aged, or pickled meat or fish

Sauerkraut

Aged cheeses (e.g., Stilton, blue cheese)

Yeast extracts (e.g., marmite)

Fava beans

Moderate Amounts of Tyramine

b

Beer (microbrewed > commercial)

Avocados

Meat extracts

Red wines such as Chianti

Low Amounts of Tyramine

c

Caffeine-containing beverages

Distilled spirits

Chocolate

Soy sauce

Cottage and cream cheese

Yogurt and sour cream

aMay not consume.

bMay consume in moderation.

cMay consume.

Adapted with permission from Shulman KI et al. Dietary restriction, tyramine, and the use of monoamine oxidase

inhibitors. J Clin Psychopharmacol. 1989;9:397.

ADVERSE EFFECTS

Orthostatic hypotension, weight gain, edema, and sexual dysfunction are common

during MAOI therapy.

191 As is the case with the TCAs, the nonselective MAOIs can

cause clinically significant postural decreases in BP. However, with the MAOIs, the

mechanism is believed to be a direct sympatholytic effect because both the lying and

the standing systolic BP readings are decreased.

210,211 Phenelzine seems to cause

orthostatic hypotension more commonly than does tranylcypromine.

212 Because the

orthostatic hypotension appears to be dose-related, a reduction in dosage may be

helpful.

213 Sexual dysfunction occurs in up to 20% of patients taking MAOIs but may

diminish and disappear spontaneously over time.

214,215 A switch into mania has been

reported in up to 10% of patients with a history of bipolar disorder. Therefore,

MAOIs should be avoided in this population.

191 Although MAOIs are not known as

antimuscarinic medications, some patients complain of anticholinergic-like side

effects, including blurred near vision and urinary retention. Dosage reduction may be

helpful, but these effects may also diminish over time. The nonselective MAOIs are

not associated with proarrhythmic, antiarrhythmic, or contractility effects when used

in therapeutic dosages. Like other MAOIs, selegiline can be quite activating, and

insomnia is frequently reported.

Several potentially fatal drug–drug interactions occur with nonselective MAOI

antidepressants. Like the reaction with tyramine, indirect sympathomimetics such as

phenylpropanolamine and pseudoephedrine (common ingredients in over-the-counter

cold preparations and diet pills) can cause a precipitous rise in BP that can result in

stroke.

The potential for serotonin syndrome with the combined use of SSRIs and MAOI

antidepressants or other medications with MAOI effect is well documented. A

washout period of at least 14 days should separate the use of an SSRI and an MAOI.

Because fluoxetine (and its primary active metabolite norfluoxetine) has a much

longer half-life, the recommended washout period is at least 5 weeks after

discontinuing this particular SSRI. Caution is advised when any other proserotonergic mediations are prescribed such as triptans and tramadol.

140

CASE 86-2, QUESTION 3: M.G. still had some residual symptoms despite a therapeutic trial of duloxetine

60 mg QAM. An increase to 90 mg resulted in intolerable insomnia. She has had a partial response

(approximately 40% reduction in symptoms) but is still impaired by her depression. What are possible next

steps?

Antidepressant Augmentation with NonAntidepressants

Treatment refractory depression (TRD) is considered to be a failure to reach

remission with 2 or more antidepressant monotherapy trials that were given at a

therapeutic dose and given

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for an appropriately therapeutic period. Generally, a therapeutic dose is for 4 to 8

weeks. This would not include the time it takes to titrate to a therapeutic dose.

216,217 A

common strategy for TRD includes combining antidepressants such as an SSRI with

bupropion or mirtazapine, as mentioned previously. Other strategies are augmenting

an antidepressant with a medication from another class, or somatic treatments,

particularly ECT.

5,10,26,216,217

There are many options to augment an SSRI/SNRI if the patient has not achieved a

full response. Some atypical antipsychotics, lithium and triiodothyronine, all have

studies showing efficacy. Buspirone has less robust data but is still

recommended.

5,216,217 The use of atypical antipsychotics for the management of

treatment-resistant depression has become relatively common among mental health

providers due to well-designed and replicated studies. Four atypical antipsychotics

(olanzapine in combination with fluoxetine, aripiprazole, brexpiprazole, and

quetiapine) have received FDA approval as adjunctive agents with SSRIs or SNRIs

for depression that has poorly responded to monotherapy, and others have been

reported to be effective as well.

5,216,217 Generally, lower doses of second-generation

antipsychotics have been successfully used in trials for depression (vs.

schizophrenia), and relatively rapid improvement was evident. Given the significant

risk of metabolic side effects that have been reported, clinicians must carefully weigh

the risks and benefits of recommending this augmentation strategy prior to maximizing

antidepressant monotherapy trials and antidepressant combinatioms.

5,10

It is

recommended that nonbehavioral health specialists use caution when using the

atypical antipsychotics for poorly responding patients.

182

One instance where the use of an atypical antipsychotic adjunct is given during the

acute phase is with psychotic depression. Patients with psychosis during the

depressed episode, as with multiple previous episodes and depression severity, are

at greater risk of chronicity and suicidality.

10 Multiple studies have shown benefit of

antipsychotic and antidepressant combination better than either monotherapy. Despite

the fact that monotherapy may be appropriate for the maintenance phase, it is

recommended to start an antipsychotic with the antidepressant during the acute phase

and slowly taper off after the persons depression and psychosis remits.

5,10,218 The

least preferred antidepressant is bupropion. Its prodopaminergic effect could worsen

the psychosis.

10 ECT is also a recommended treatment.

5,10,218

Lithium’s antidepressant properties as an augmenting agent have primarily been

conducted with TCAs.

217 Seven of nine antidepressant augmentation trials with

lithium have reported positive therapeutic effects, usually within 1 week of achieving

steady state dynamics (i.e., 3–7 days of daily dosing).

219 Effective lithium blood

levels are generally within the range used to treat bipolar disorder (0.5–1.2 mEq/L).

Lithium has a very narrow therapeutic index along with multiple significant drug

interactions and should only be used by a clinician skilled in its use.

5

Triiodothyronine (T3

) also has a long history of use in psychiatric circles for

patients exhibiting partial or suboptimal responses to antidepressant monotherapy.

Five of six RCTs support the use of T3 supplementation for antidepressant

augmentation, with an average effect size of 0.58 reported.

220 Triiodothyronine, at a

dosage of 25 mg/day, can accelerate as well as augment antidepressant response, and

superior effects have been reported in female patients, in particular. The response to

the thyroid supplementation should be noticeable within 1 to 2 weeks, much like that

found when lithium is used to augment therapy. Thyroxine (T4

) may also be effective

with typical daily doses of 75 to 100 mcg daily often used. In the STAR*D trials, T3

was compared to lithium for antidepressant augmentation with citalopram in patients

with two previous treatment failures.

221 Remission rates were modest for both agents

in this challenging population (24.7% with T3 vs. 15.9% with lithium), and there was

no significant difference between these two therapies.

In the STAR*D trial, augmentation with bupropion was compared to buspirone and

both adjunctive treatments showed 30% remission rates.

221 Buspirone may be of

benefit to patients with residual symptoms of anxiety, in particular, and titration up to

daily doses of 30 to 60 mg daily is often required.

5,182 Stimulants and modafinil have

generally shown no benefit on depressive symptoms overall.

182,222 However, they may

provide temporary relief from excessive fatigue and somnolence while waiting for

the full antidepressant effect of the primary treatments.

5,217

Because M.G. had a failure to two monotherapies and some response to

duloxetine, the option of adding a medication to the SNRI is the next step.

Combinations of duloxetine with another antidepressant (mirtazapine or bupropion)

or with an atypical antipsychotic are both recommended. Mirtazapine, quetiapine,

and olanzapine would help if there is any insomnia and would protect against this

side effect if duloxetine were to be increased in the future. Bupropion would

possibly worsen the insomnia. Aripiprazole, brexpiprazole, mirtazapine, quetiapine,

and olanzapine (least to most) all could cause weight gain worsen cholesterol.

Discussing the risks of each option is critical and letting M.G. help decide which

choice fits her lifestyle will ensure better adherence. M.G. decided to start

aripiprazole 2 mg QAM and will increase her exercising to mitigate the possible

weight gain and cholesterol increase.

Pediatric Depression

CASE 86-3

QUESTION 1: A.A. is a 15 year old male who has had a mood and behavior change over the last 6 months.

A.A. is a sophomore in high school who averages B’s in his classes. He was a member of the varsity lacrosse

team, with many friends. Over the last 6 months he has been less involved with his friends to the point that he

now doesn’t want to go out. After lacrosse season was over he normally would participate in off season

lacrosse camps. This year he didn’t want to. His grades have dropped as he can’t concentrate as well on his

school work. He has missed some days of school lately because he doesn’t want to get out of bed. Important

rule outs are illicit drug use and recent trauma. Both have been ruled out. His medical history is unremarkable

except for a 10 pound weight loss since last year, likely due to a poor appetite. His parents are very supportive.

What are the recommendations for the treatment of pediatric depression?

Rates of pediatric depression are less than in adults. As a person ages, the risk of

depression increases with rates of 0.5% in 3- to 5-year-olds increasing to 3.5% in

12- to 17-year-olds.

10,223 Diagnosing pediatric depression uses the same criteria from

the DSM 5 as for adults; however, the interview questions may be slightly different.

For example, poor concentration may be mislabeled as procrastination or anhedonia

might be described as “being bored.”

9 Treatment guidelines do differ compared to

adults. One reason for this is that placebo rates are much higher in pediatric studies

resulting in the medication not having as dramatic a difference when compared to the

difference between placebo and drug in adult studies. Thus, there are many studies

where SSRIs had strong response rates but placebo also did and the medication was

not considered to be statistically different.

224–226 Due to this high response rate from

placebo and the support given by being a subject in a research study, the expert

guidelines recommend supportive care and formal talking therapy be the first option

for mild-to-moderate depression.

227,228 Medications can be used if symptoms are

moderate to severe. Pharmacotherapy options are limited, though, compared to

adults. Fluoxetine is FDA-approved down to age 8, escitalopram to age 12.

Clomipramine (10 and

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older), fluvoxamine (8 and older), and sertraline (6 and older) are FDA-approved

for obsessive compulsive disorder but not depression. The SNRI duloxetine is

approved for 7 years old and above for generalized anxiety disorder, and imipramine

is approved for 6 and older for enuresis. To summarize, only two antidepressants are

FDA-approved for depression in children although some other antidepressants do

have nondepression indications in children.

CASE 86-3, QUESTION 2: The child psychiatrist’s initial recommendation is to have A.A. meet with a

psychologist. After 4 months of talking therapy A.A. is improved in general but is still having bouts of sadness

that prevent him from going to school a couple days a month. It is decided to continue talk therapy but to add a

medication. Which medication is the preferred agent?

Unlike adults where all antidepressants are similarly effective, pediatric

depression guidelines have recommended that SSRIs particularly fluoxetine and

escitalopram be the treatments of choice.

227,228 Fluoxetine’s starting dose is 10 mg

QAM with a target dose of 20 to 40 mg a day. Escitalopram’s starting dose is 5 to 10

mg QAM with a target dose of 10 to 20 mg a day. Interestingly, the separation from

placebo increases as the child ages for many of the SSRIs. For example,

escitalopram did not statistically differ from placebo in the under 12 year old age

group but did so in the adolescent age group.

224,229 Paroxetine is not recommended for

depression due to overall lack of efficacy in any age group when studies are

combined and a high dropout rate in the younger patient.

224,226 Bupropion,

mirtazapine, venlafaxine and duloxetine have recommendations as treatment options

but after failures to the SSRIs.

227 TCAs are not recommended primarily due to a high

risk of harm being much greater than the small benefit on symptoms.

227,230

CASE 86-3, QUESTION 3: A.A. is started on fluoxetine 10 mg QAM. What safety monitoring is required

when starting a young adult or pediatric patient on an antidepressant?

Generally, the SSRIs are well tolerated in children. One black box warning is for

suicidal thinking. As with adults, the clinician needs to monitor for suicidality, but in

children there is a doubling of suicidal thoughts, not suicide attempts or completions,

from 2% in the placebo arms to 4% in medication arms. It is important to note that

actual suicides are much higher in untreated depressed youth compared to those

taking antidepressants.

94,231–233 This risk diminishes as age groups increase. For

patients over age 24, it is not required to be so vigilant regarding suicidal thinking

although many guidelines recommend continuing to monitor throughout the age ranges

due to the possibility of disease-related risk. In pediatrics and young adults, the

experts recommend the use of antidepressants with the FDA-sanctioned monitoring

for suicidal thinking of every week for the first week, every other week for the next 4

weeks, then monthly or as decided by the patient and clinician.

227,234 Talking therapy

may have some protection against the side effect of increased suicidal thoughts.

235

Geriatric Depression

Depression in late life is typically more difficult to recognize than depression in

younger adults. Clinicians and patients may inappropriately attribute depressive

symptoms to the “aging process” and minimize their significance. In addition,

functional expectations are often lowered after retirement, making the degree of

impairment difficult to evaluate. Because medical comorbidities are also more

common in the elderly, depressive symptoms may be overlooked or misinterpreted in

the workup as well.

116,236

In general, the elderly present with the same depressive

target symptoms as younger adults, which is reflected in the fact that DSM-5

diagnosis for major depression in adults is not specific for age. However,

qualitatively, the presentation of depression among the elderly may be quite different.

For instance, older patients are more likely to present with psychomotor retardation

and are less likely to acknowledge “depression” per se, preferring instead to dwell

on somatic concerns (e.g., poor sleep, low energy, changes in bowel function, bodily

aches and pains).

10 They are also much less likely to share or admit suicidal thoughts,

and because elderly men have the highest suicide completion rate, an accurate

assessment of depression and attendant risks is critical.

10,116,237

In assessing

nonspecific behavioral and cognitive symptoms in the elderly, a careful differential

diagnosis between medical and other psychiatric disorders is essential because

numerous medical illnesses can mimic depressive symptoms. Anemia, malignancies,

congestive heart failure (CHF), and endocrine abnormalities may all present in a

manner similar to that in depressive illness.

Aging does result in decreased monoamine depletion as well as increased

monoamine oxidase activity.

116 One of the more difficult differential diagnoses in this

setting involves the distinction of depression from dementias.

238,239 Like depression,

patients with dementia may present with apathy, poor memory or concentration,

reduced facial expression, and lack of spontaneous interaction. The illnesses are

often comorbid, as 30% to 70% of patients with dementia also suffer from major

depression.

239 Some experts have suggested, in fact, that new-onset depression in

elderly patients may actually be part of a prodrome toward the manifestation of

Alzheimer dementia.

239,240 A longitudinal cohort study found that among elderly

patients suffering from an acute episode of major depression, 57% were ultimately

diagnosed with Alzheimer dementia within the next 3 years.

238 Diagnostically, there

are three notable differences between dementia and depression: (a) the symptoms

(slow and subtle changes with dementia, rapid with depression), (b) orientation

(markedly impaired with dementia, intact with depression), and (c) principal CNS

impairment (short-term memory with dementia, concentration with depression).

Drug Selection in the Elderly

A therapeutic trial of an antidepressant in a depressed individual with cognitive

impairment may reverse the symptoms of the affective illness and restore functional

capacity. Depression-related cognitive dysfunction will also improve to some

degree. Moreover, because primary degenerative dementia is largely a diagnosis of

exclusion, a successful trial of an antidepressant may help clarify the underlying

pathologic condition and is strongly recommended in patients with a positive

personal or family history of mood disorders.

241 The overall efficacy of

antidepressants in elderly patients is believed to be comparable to that observed in

younger subjects, although the response to treatment is somewhat slower (i.e., 6-

week therapeutic trial usually warranted).

5 Psychotherapy may be somewhat more

effective in the elderly particularly due to the emotional impact of medical

comorbidities and neurodegeneration effects as long as there is no dementia

hindering talking therapy’s effect.

5 Similarly, the comparative therapeutic effects of

individual antidepressants do not appear to differ qualitatively between elderly

patients and the general population. The selection of antidepressants for geriatric

depression is the same as the process for younger patients. The elderly are much

more sensitive to side effects compared to the younger patient, and the presence of

medical comorbidities and concurrent medications will have a greater influence on

antidepressant selection. For example, the anticholinergic effects of TCAs preclude

their use in elderly patients particularly if they are suffering from narrow

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p. 1832

angle glaucoma, chronic constipation, or urinary hesitancy. Anticholinergic impact on

memory and the cardiac-related effects such as arrhythmias, orthostasis, and

tachycardia are other critical reasons not to use the TCAs in the elderly. As noted

previously, the risk of falls from TCAs due to antihistaminic, anticholinergic, and α

receptor antagonistic properties is another reason not to use them in the elderly

population.

SSRIs are recommended as first line but among this list paroxetine is considered

the worst option due to its anticholinergic effects (albeit mild) compared to no effect

from the others. SNRIs also have data showing efficacy.

5,10,26 There does seem to be

more dropouts with venlafaxine compared to the SSRIs.

5 Although sedating

antidepressants such as mirtazapine may serve to promote sleep in depressed patients

suffering from insomnia, other geriatric clients may be candidates for more activating

medications that can increase energy or enhance alertness (e.g., bupropion).

All antidepressants have a risk of causing the syndrome of antidiuretic hormone

secretion (SIADH) with SSRIs being the group with the highest reported cases.

Elderly patients, compared to younger patients, are at a much greater risk of this

event with some reviews reporting hyponatremia up to 32%.

10,242 As with other

medications used in the elderly, the antidepressants should be started at lower initial

doses compared to adults.

5,10,116 Titration to a known therapeutic target dose has the

best evidence even if the geriatric seems to be responding to a subtherapeutic dose.

5

Therapeutic Blood Level Monitoring

Attempts to demonstrate an association between plasma concentrations and

therapeutic response for SSRIs and SNRIs have been largely unsuccessful. In

contrast, the serum concentration of some TCAs correlates well with clinical

response. Nortriptyline exhibits a curvilinear effect, whereas imipramine

demonstrates a sigmoidal relationship between serum levels and clinical

response.

243,244 Maximum benefit of imipramine is usually associated with serum

levels of imipramine plus its demethylated metabolite, desipramine, in excess of 250

ng/mL. The relationship between plasma concentration of desipramine and clinical

response is less clear, but a linear relationship is likely.

245 The most controversy

surrounds amitriptyline; studies have shown a linear relationship, a curvilinear

relationship, and no relationship between serum concentration and outcome.

246–248

The APA Task Force on the Use of Laboratory Tests in Psychiatry recommends

plasma concentration monitoring of TCAs when patients are elderly, not responding

to therapy, nonadherent, experiencing adverse effects, or on multiple medications that

may result in a possible drug interaction.

249 Plasma concentrations of imipramine,

nortriptyline, and desipramine should be obtained after at least 1 week of a constant

dosage when steady state has been achieved. Samples should be drawn 12 hours after

the last dose has been administered. Routine therapeutic blood monitoring of other

antidepressants is not recommended because information concerning their usefulness

is limited; however, serum levels may be useful for evaluating adherence in some

patients or ruling out serious toxicities.

250

Antidepressants and Chronic Pain

CASE 86-4

QUESTION 1: D.C. is a 42-year-old woman with a history of chronic lower back and left leg pain who has

noted increased crying spells and a decreased interest in social activities during the course of the last 4 months.

She attributes this downturn to the stress she is experiencing as she cares for her disabled mother who recently

moved in with her. When asked, she also notes significant decreases in energy and concentration, and

difficulties in falling and staying asleep.

In the past, D.C. recalls one previous episode of depression 8 years ago, when she was treated initially with

venlafaxine (discontinued due to nausea) and ultimately responded to a course of psychotherapy. Her past

medical history is significant for chronic pain from a car accident 7 years ago which continues to bother her on

a daily basis (she rates pain at 5 of 10 currently), hypertension and hyperlipidemia. Her current medications

include lisinopril 10 mg QAM and atorvastatin 10 mg QHS. In addition, she started amitriptyline 50 mg at

bedtime 2 months ago for her insomnia but noticed a 12-pound weight gain and recently discontinued. In the

meantime, she has continued to see her therapist on a weekly basis during this time frame.

What considerations may influence treatment selection in this patient with chronic pain? What treatment

should be recommended?

There is a strong and complex association between chronic pain syndromes and

mood disorders. Epidemiologic investigations report that 50% of patients with

chronic pain will satisfy the criteria for a depressive disorder.

251 Anxiety disorders

are also commonly reported in this population as well. On the other hand, 65% of

individuals with major depression will experience some symptoms of somatic pain,

often presenting with pain as their chief complaint. Researchers have theorized that

this comorbid phenomenon can be explained by deficiencies in the neurotransmitters

serotonin and NE, which influence mood disorders in the prefrontal cortex and

limbic system, as well as module pain sensitivity via descending projections down

the spinal column. Other theories implicate elevations in cytokine activity, which

commonly occur during the course of mood disorders, as well as mediating

inflammatory activity occurring within the context of chronic pain.

251,252

Treatment plans for depressed patients with chronic pain should target both of

these conditions in order to achieve optimal outcomes. In regard to the selection of

antidepressants, preference is often given to medications that can address both sets of

symptoms associated with these comorbid conditions. For instance, antidepressant

agents with pain-relieving properties and agents that promote sleep and relieve

anxiety are often preferred. Antidepressants that enhance 5-HT and NE (TCAs and

SNRIs) have proven to be quite effective for the management of neuropathic pain

conditions, in addition to their benefits on anxiety and depression.

5,251,252 SSRIs are

much less effective primarily due to the lack of NE enhancement which is critical for

analgesia.

5

Drug interactions are often a major consideration in the selection of

antidepressants. For example, the combination of SNRI antidepressants with the

analgesic tramadol has been linked to a few case reports of serotonin syndrome, and

concomitant use of these agents should be discouraged. Certain opioid analgesics are

prodrugs and require metabolic transformation to generate the active species. These

analgesics include codeine (metabolized to morphine), hydrocodone (active

metabolite: hydromorphone), and oxycodone (oxymorphone), as well as tramadol (odesmethyl tramadol). Patients who require these medications would benefit from

antidepressants that do not effect CYP 450 (Table 86-8).

D.C. meets the criteria for an acute episode of major depression, and medication is

clearly indicated. Among the alternatives, SSRIs have not proven to be effective for

neuropathic pain. SNRIs and TCAs are effective for neuropathic pain conditions, as

well as depression and anxiety. However, there are substantial tolerability and

toxicity risks with TCAs not shown with the SNRI class. Additionally, she has

experienced significant weight gain with a low-dose TCA (50 mg amitriptyline). An

SNRI would be a good choice for the treatment of her depression and chronic pain.

Given

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D.C.’s history of nausea from venlafaxine, an alternate SNRI, such as

levomilnacipran or duloxetine, should be initiated. Duloxetine inhibits CYP450 2D6,

and this should be taken into consideration if other medication changes are

considered in the future.

Summary

Depressive episodes have a significant morbidity impact and can result in mortality,

usually via suicide. Treatment has been shown to reduce acute impact and prevent

future episodes. All antidepressants are considered generally equal in regard to

efficacy. Comorbid drug–disease and drug–drug interactions help identify best firstchoice options. Overall, SSRIs are considered the best first choice due to good

tolerability, safety in overdose, and low cost. Of these, sertraline and escitalopram

may have a slight advantage. Previous treatment successes or failures and family

history of medication response are important determining factors when disease and

drug issues are not present. Minimal treatment duration should be 6 months after

remission has been achieved though many patients will require lifelong

pharmacotherapy. Patient education and safety monitoring are critical aspects once

the patient enters into treatment. Outcomes for treatment are predictably beneficial

with improvements in quality of life and reduction of suicidal events.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Cleare A et al. Evidenced based guidelines for treating depressive disorders with antidepressants: a revision of the

2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015;29(5):459–525. (5)

Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. Arlington, VA:

American Psychiatric Association. 2010. (10)

Spina E et al. Clinically significant drug interactions with newer antidepressants. CNS Drugs. 2012;26(1):39–67.

(138)

Key Websites

American Psychiatric Association. http://www.psychiatryonline.org.

National Alliance on Mental Illness. http://www.nami.org.

National Institute of Mental Health. http://www.nimh.nih.gov.

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