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MAJOR DEPRESSIVE

DISORDER AND

GENERALIZED ANXIETY

DISORDER

Dana Bartlett, RN, BSN, MSN, MA

Dana Bartlett is a professional nurse and

author. His clinical experience includes 16

years of ICU and ER experience and over

20 years of as a poison control center

information specialist. Dana has published numerous CE and journal articles, written

NCLEX material and textbook chapters, and done editing and reviewing for publishers

such as Elsevier, Lippincott, and Thieme. He has written widely on the subject of

toxicology and was recently named a contributing editor, toxicology section, for

Critical Care Nurse journal. He is currently employed at the Connecticut Poison

Control Center and is actively involved in lecturing and mentoring nurses, emergency

medical residents and pharmacy students.

ABSTRACT

Major depressive disorder and generalized anxiety disorder are

psychiatric conditions with primary symptoms that often overlap. The

treatment of each condition is often similar. Medication, psychotherapy

and lifestyle changes are typically recommended as part of the patient

treatment plan. Although often diagnosed as separate conditions,

major depressive disorder and generalized anxiety disorder often co-

occur, and thoughtful consideration by psychiatric and primary care

providers and nurses of selective treatment strategies to target

primary symptoms will support patient compliance, progress and

remission.

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Continuing Nursing Education Course Planners

William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,

Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner

Policy Statement

This activity has been planned and implemented in accordance with

the policies of NurseCe4Less.com and the continuing nursing education

requirements of the American Nurses Credentialing Center's

Commission on Accreditation for registered nurses. It is the policy of

NurseCe4Less.com to ensure objectivity, transparency, and best

practice in clinical education for all continuing nursing education (CNE)

activities.

Continuing Education Credit Designation

This educational activity is credited for 2 hours. Nurses may only claim

credit commensurate with the credit awarded for completion of this

course activity.

Pharmacology content is 0.5 hour (30 minutes).

Statement of Learning Need

Nurses need to understand the diagnostic criteria, and treatment for a

major depressive disorder and generalized anxiety disorder in order to

best support and to educate patients and their families.

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Course Purpose

To provide nurses with knowledge of the common psychiatric

conditions of major depressive and generalized anxiety disorder.

Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses

and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Dana Bartlett, RN, BSN, MSN, MA, William S. Cook, PhD,

Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC - all

have no disclosures.

Acknowledgement of Commercial Support

There is no commercial support for this course.

Activity Review Information

Reviewed by Susan DePasquale, MSN, FPMHNP-BC.

Release Date: 1/1/16 Termination Date: 4/18/18

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

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1. Risk factors for major depressive disorder include:

a. Chronic disease and substance abuse.

b. Smoking and obesity.

c. Male gender and high socioeconomic status.

d. High level of education and age > 65.

2. People who have major depressive disorder are:

a. Depressed only during stressful life events.

b. Depressed once or twice a week.

c. Depressed almost every day.

d. Depressed only during episodes of substance abuse.

3. Screening for depression should be done:

a. If the patient has noticeable signs and symptoms.

b. For every patient ≥ age 18 if there is appropriate clinical

support.

c. Only during stressful life events.

d. Only for patients who request screening.

4. First-line medications used to treat major depressive

disorder would be:

a. Diazepam and imipramine.

b. Bupropion and phenelzine.

c. Amoxapine and trazodone.

d. Citalopram and fluoxetine.

5. True or false: ECT is effective for treating major depressive

disorder.

a. True.

b. False.

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Introduction

Major depressive disorder and generalized anxiety disorder are two of

the most common psychiatric disorders. These diseases are not as

prevalent as medical illnesses, such as cardiovascular disease and

diabetes, but they result in a significant cost to the individual and

society. This problem is compounded because major depressive

disorder and generalized anxiety disorder are chronic in nature and

often resistant to treatment. Psychotherapy and pharmacotherapy can

be effective, but availability, cost, patient compliance issues, and a

relative lack of clinical evidence supporting who should be treated,

how, and for how long have restricted the successful treatment of

major depressive disorder and generalized anxiety disorder.

Epidemiology Of Major Depressive Disorder

Major depressive disorder has been identified by the World Health

Organization (WHO) as the leading cause of disability worldwide.1

Approximately 20% of all adults will have an episode of major

depression at some point2 and the lifetime prevalence of major

depression has been estimated to be 7%-12% in men and 20%-25%

in women.3 These statistics vary depending on the clinical setting, and

there is strong and consistent evidence that major depression is often

undetected or underdiagnosed.

Major depressive disorder is more common in women, it is

substantially more common in people who have co-existing medical

problems such as coronary atherosclerosis, diabetes, Parkinson’s

disease, stroke, or traumatic brain injury,3 and the rate of major

depressive disorder increases with the seriousness of medical

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morbidity.4 Major depressive disorder is associated with a very high

risk for suicide5 and many people who suffer from major depressive

disorder never receive treatment.6

The pathogenesis of major depressive disorder is unknown, but it is

probably a complex interaction between genetic, biological, social or

environmental, and psychological factors.2,7,8 Risk factors for major

depressive disorder are listed in Table 1.

Table 1: Risk Factors for Major Depressive Disorder

Age (18-29)

Childhood adversity and/or trauma

Chronic diseases

Cognitive impairment, i.e., dementia

Gender (Female)

Low socioeconomic status

Poor social support

Race (White)

Serious medical illness

Stressful life events

Substance abuse

Unemployed

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Genetics:

Depression is to some degree an inherited disease.8 People who

have major depressive disorder are three times more likely to

have a first-degree relative (parent or sibling) who has or had

depression than people who do not,9 and twin studies have

estimated that the risk of developing depression is

approximately 30%-50% associated with genetic variations.10-12

However, despite a consistent body of evidence that indicates

people inherit a susceptibility to depression, genome-wide

association studies and gene-environment interaction studies

have not yet clearly defined the role and contribution of genetics

in the development of depression.8

Biological:

Biological causes of major depressive disorder include abnormal

changes in brain structures, impaired and/or abnormal

neurotransmitter function, and immune system dysfunction that

can cause inflammation and oxidative stress.2,13-22 Whether

these changes in structure and function are cause or effect has

been difficult to determine, given the heterogeneity of major

depressive disorder and the treatments for the disease.

Environmental:

Major life stressors are considered to be a strong predictor for

the development of major depressive disorder.2,6,23-27 Chronic

diseases such as cancer, chronic obstructive pulmonary disease,

diabetes, heart disease also increase the risk for developing

depression, as do acute illnesses such as stroke.

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Diagnostic Criteria For Major Depessive Disorder

The American Psychiatric Association’s diagnostic criteria for major

depressive disorder, located in the Diagnostic and Statistical Manual of

Mental Disorders, are listed in Table 1.28

Table 2: Diagnostic Criteria for Major Depressive Disorder

1. Five or more of the following symptoms have been present during a two

week period; they are a signficant change from the patient’s previous

mood and funcioning; at least least one of the symptoms is depressed

mood or loss of pleasure or interest, and; the symptoms are not caused by

a medical condition.

Depressed mood most of the day, nearly every day. The depressed mood

can be subjective (i.e., the patient reports feeling sad, hopeless) or can

be observed by others. In children or adolescents irritation is often

present.

Markedly diminished interest or pleasure in daily activities. This happens

nearly every day and is reported by the patient or by others.

Significant weight loss (> 5% of body weight) when not dieting or a

decrease or increase in appetite nearly every day. (Note: In children,

consider failure to make expected weight gain).

Insomnia or hypersomnia nearly every day.

Psychomotor agitation or retardation nearly every day: this should be

observable by others and not just the patient’s feelings of restlessness or

feeling lethargic.

Fatigue or loss of energy nearly every day.

Feelings of worthlessness or excessive or inappropriate guilt nearly every

day.

Diminished ability to think or concentrate, or indecisiveness, nearly every

day, reported by the patient or observed by others.

Recurrent thoughts of death; recurrent suicidal ideation without a specific

plan; a suicide attempt or a specific plan for committing suicide.

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2. The symptoms cause clinically significant distress or impairment in social,

occupational, or other important areas of functioning.

3. The episode is not attributable to a substance or another medical

condition.

4. The occurrence of the major depressive episode is not better explained by

schizoaffective disorder, schizophrenia, schizophreniform disorder,

delusional disorder, or other specified and unspecified schizophrenia

spectrum and other psychotic disorders.

5. There has never been a manic episode or a hypomanic episode.

Screening For Depression

Screening for depression is recommended by the U.S. Preventive

Service Task Force (The Guide to Clinical Preventive Services) in non-

pregnant adults 18 years and older when staff-assisted depression

care supports are in place to provide accurate diagnosis, effective

treatment, and follow-up.29 Screening for depression should also be

considered in certain high-risk populations, i.e., people who have

cancer or cardiovascular disease, people who have recently had a

stroke or a myocardial infarction, or people who have chronic pain.

There are a variety of screening tools available and comparative

studies indicate that they are reasonably equal in effectiveness and

ease of use.30,31 The Patient Health Questionnaire - 9 (PHQ-9) is a

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screening test that is often used, it is availble without charge, and it

has been shown to be accurate, specific, and sensitive.32-36

Table 3: The Patient Health Questionnaire-9

Over the Last 2 weeks, How Often

Have You Been Bothered by Any

of the Following Problems?

Not

At

all

Several

Days

More Than

Half the

Days

Nearly

Every

Day

1. Little interest or pleasure in doing things 0 1 2 3

2. Feeling down, depressed, or hopeless 0 1 2 3

3. Trouble falling or staying asleep, or sleeping

too much 0 1 2 3

4. Feeling tired or having little energy 0 1 2 3

5. Poor appetite or overeating 0 1 2 3

6. Feeling bad about yourself — or that you are

a failure or have let yourself or your family

down

0 1 2 3

7. Trouble concentrating on things, such as

reading the newspaper or watching television 0 1 2 3

8. Moving or speaking so slowly that other

people could have noticed? Or the opposite —

being so fidgety or restless that you have

been moving around a lot more than usual

0 1 2 3

9. Thoughts that you would be better off dead or

of hurting yourself in some way 0 1 2 3

0 +

______

+

______ +

______

=Total Score: ______

If you checked off any problems, how difficult have these problems made it for

you to do your work, take care of things at home, or get along with other

people?

Not difficult at all Somewhat difficult Very difficult Extremely difficult

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A score of 10 or higher indicates the posssibility of a depressive

disorder, and scores of 5, 10, 15, and 20 indicate the presence of mild,

moderate, moderately severe and severe depression, respectively.37

The diagnosis of depression requires that there is a score of 2 or

higher on one of the first two questions.37 A shortened version, the

PHQ-2, uses the first two questions of the PHQ-9 and it appears to

offer good sensitivity and specificity as well.37

The SIGECAPS mnemonic is another useful screening tool for detection

of major depressive disorder.38

Table 4: SIGECAPS Mnemonic

S Sleep disturbance – either insomnia or hypersomnia.

I Loss of interest in everyday activities – anhedonia.

G Guilt – helplessness, hopelessness, worthlessness

E Lack of energy

C Difficulty concentrating

A Appetite disturbance – either increased or decreased

P Psychomotor blunting or agitation

S Suicidal thoughts, thoughts of death

Also ask the patient if they feel depressed.

Patients who have a major depressive disorder often complain of lack

of energy, decreased appetite, dizziness, inability to concentrate or

think, fatigue, insomnia, pain, restlessness, and they frequently have

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many non-specific somatic complaints.3,28, 39,40 These complaints

should be evaluated, but it should be remembered that many patients

who are depressed may have somatic complaints but will not admit to

or cannot express feelings of depression.3,39-41 These somatic

complaints and patients not reporting feelings of depression may

contribute to a missed diagnosis,42 and Deneke et al., (2014) noted

that there is evidence that many cases of depression are not detected

by primary health care providers or in a medical setting.3.43

Learning Break:

Is screening for depression effective? Williams et al., (2014) states that

depression is frequently undetected if targeted screening is not done and that

screening is not harmful.39 There is also evidence that for screening to be helpful

beyond increasing detection and diagnosis rates it must be used in conjunction

with appropriate follow-up and effective care; i.e., screening alone is not

enough.39,43

Clinical Course Of Major Depressive Disorder And

Consequences Of The Disease

The clinical course of major depresive disorder is quite variable.3 The

disease typically has its onset when the patient is in his or her mid-20s

or 30s28,43 but a later onset is not uncomon.44 Most patients who have

major depessive disorder will eventually remit, but some patients will

never have a remission (two months or more with no symptoms, or

one or two symptoms to a mild degree) and others may have many

years in which they have no signs and symptoms of depression.28

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Early recognition and treatment and a short duration of depressive

symptoms are associated with spontaneous recovery, a better

response to treatment, and a higher chance of remission.28,45,46

Patients who have had severe depression or who have had an onset at

a relatively young age are more likely to have recurrent depression,28

and depression accompanied with anxiety, personality disorders, or

psychotic features has a poor prognosis for remission.28 Gender and

age do not seem to affect the progression of major depressive

disorder.28

Major depressive disorder is associated with a high mortality risk and

most of this risk is from suicide. Major depressive disorder is

considered to be a signficant risk factor for suicidal behavior,47 and

suicide attempts or threats of suicide are considered to be consistent

risk factors for suicide in patients who have major depressive

disorder.48 Major depressive disorder is a risk factor for the

development of chronic diseases (and it negatively influences the

progression of these diseases) such as cardiovascular diseases,

diabetes, and neurological disorders.43,49-51 People who have major

depressive disorder are more likley to smoke, abuse alcohol and

drugs,49 they report a lower quality of life, and this disorder has a

profound effect on the patient’s family life, personal relationships, and

professional and social life.

Treatment For Major Depressive Disorder

Antidepressant medication and psychotherapy are the two primary

treatments for major depressive disorder. They will be discussed

separately, but they can be and often are used together.

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Antidepressant Medication

The antidepressant medication used to treat major depressive disorder

are often classified as first-generation or second-generation. First

generation refers to the monoamine oxidase inhibitors (MAOIs) such

as phenelzine and selegiline and the tricyclic anti-depressants (TCAs)

such as amitriptyline and nortriptyline; second-generation refers to all

other drugs used to treat major depressive disorder.

These terms are still commonly used, but the antidepressants cannot

be easily or usefully divided into these two categories. These

medications work by affecting the activity or level of

neurotransmitters, but the mechanism of action is specfic to each

drug.

Learning Break:

The MAOIs and the TCAs are called first-generation simply because these drugs

were developed and used many years before the advent of the so-called second-

generation antidepressants.

The generic name is provided first and the trade name is in

parentheses. Some of the older medications are rarely if ever

prescibed with trade names.

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Table 5: Currently Available Antidepressants/Atypical Anti-Depressants

Monoamine Oxidase Inhibitors

Isocarboxazid

Phenelzine

Selegiline, transdermal

Tranylcypromine

Selective Serotonin Re-Uptake Inhibitors/Receptor Partial Agonists

Citalopram (Celexa)

Escitalopram (Lexapro)

Fluoxetine (Prozac)

Fluvoxamine (Luvox)

Paroxetine (Paxil)

Sertraline (Zoloft)

Vilazodone (Viibryd)

Serotonin-Norepinephrine Re-Uptake Inhibitors

Desvenlafaxine (Pristiq)

Duloxetine (Cymbalta)

Milnacipran (Ixel)

Venlafaxine (Effexor)

Tricyclic and Tetracyclic Anti-Depressants

Amitriptyline

Amoxapine

Clomipramine

Desipramine

Doxepin

Imipramine

Maprotiline

Nortriptyline

Protriptyline

Trimipramine

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Aytical Antidepressants (unrelated to serotonin, tricyclic,

tetracyclic, and MAO inhibitors)

Bupropion (Wellbutrin)

Mirtazapine (Remeron)

Nefazadone (Serzone)

Trazodone (Desyrel)

Vilazodone (Viibryd)

A drug that is representative of each of these categories is briefly

discussed below. However, it is important to remember that the

mechanism of action described (and thus the category each medication

is placed in) is the primary way the drug works; and, to lesser or

greater degree, all of the antidepressants can affect other

neurotransmitters and bind to other receptor sites.52 For example, the

antidepressant effect of the TCAs is mediated through re-uptake of

norepinephrine and serotonin but the TCAs also bind to peripheral α-

adrenergic receptors and histamine receptors, and postural

hypotension and anticholinergic effects such as dry mouth and

dizziness are common side effects of the TCAs.

Bupropion:

The mechanism(s) of action of bupropion is not completely

understood, but it most likely affects adrenergic and

dopaminergic activity.

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Phenelzine:

Phenelzine inhibits the activity of monoamine oxidase, an

enzyme that is responsible for the breakdown of endogenous

dopamine, norepinephrine, and serotonin.

Fluoxetine:

Fluoxetine inhibits the re-uptake of serotonin, thus increasing

cental nervous system (CNS) concentrations of serotonin.

Venlafaxine:

Venlafaxine inhibits the re-uptake of norepinephrine and

serotonin, thus increasing the CNS concentration of these

neurotransmitters.

Nortriptyline:

Nortriptyline and the other TCAs are believed to have

antidepressant effects by inhibiting the re-uptake of

norepinephrine and serotonin. However, these drugs also down-

regulate beta and serotonin receptors and as previously

mentioned they have other important pharmacologic effects, i.e.,

binding to peripheral alpha receptors and histamine receptors.

Choosing an Antidepressant

Effectiveness, safety and tolerability are the primary factors to

consider when choosing an antidepressant; the patient’s co-

morbidities, other prescription medications that she or he takes, and

patient preference, must also be considered. The effectiveness of the

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antidepressants is considered to be essentially comparable,53-55 but at

this time the selective-serotonin re-uptake inhibitors are usually the

first choice.56 These medications, along with serotonin-norepinephrine

re-uptake inhibitors, are the most commonly prescribed

antidepressants,52 primarily because when compared to the MAOIs and

the TCAs they have more tolerable side effects and are far less

dangerous when taken in overdose.56-58

Common adverse effects or side effects of the antidepressants are

listed in Table 6.56 The incidence of, and risk for these, varies for each

drug.

Table 6: Adverse Effects and Side Effects of Antidepressants

Agitation

Anticholinergic signs/symptoms, i.e., dizziness, dry mouth

Constipation

Drowsiness

Gastrointestinal effects

Insomnia

Orthostatic hypotension

Palpitations

Restlessness

Serotonin syndrome

Sexual dysfunction

QTc prolongation

Weight gain

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Learning Break:

The selective serotonin re-uptake inhibitors are required to include a boxed

warning (typically called a “black box” warning) in the prescribing information that

states that the use of these drugs has been associated with an increased risk for

suicidal thinking and behavior in children, adolescents, and young adults. These

medications can be prescribed for these patient populations but only with close

monitoring for emergence and/or worsening of suicidal behavior or thoughts.

A response to an antidepressant is usually considered to be a > 50%

reduction in symptoms as measured by an assessment tool such as

the PHQ-9.58 Responses are usually seen in one to two weeks56 but

longer response times are possible.58 If the patient does not respond

the clinician can decide to: 1) increase the dose; 2) wait several more

weeks to see if a response occurs; 3) prescribe a different drug; or,

4) add another antidepressant or an adjunctive treatment to the

regimen.

The addition of psychotherapy is an adjunction treatment option,

which will be discussed in a later section. These approaches have their

own risks and benefits and there is no universal consensus as to which

one is best.59,60 Clinicians should also be aware that non-adherence to

antidepressant therapy is relatively common,61-63 and if the patient is

not responding he or she should be questioned about the level of

compliance. The goal of treatment is full remission of symptoms. If an

antidepressant or antidepressants are an effective regimen, then

treatment is usually continued for at least six months to a year.63,64

Most patients should be started on a single antidepressant. There is no

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conclusive evidence that dual therapy for initial treatment provides an

advantage, and it increases the risk for side effects.65

Discontinuing and Switching Antidepressants

The topic of discontinuing and switching antidepressants will not be

discussed in depth. A discontinuation syndrome with withdrawal signs

and symptoms can occur when antidepressants are stopped.66

Tapering the dose over a period of two to four weeks rather than

abruptly stopping treatment is recommended,67 but there is some

doubt as to whether this strategy is truly effective for preventing

discontinuation syndrome.66 Regardless, patients should be instructed

not to abruptly discontinue their antidepressant medications or to

decrease the dose. The approach to switching from one antidepressant

to another is specific to the drug being stopped and the one being

started.

Other Treatments/Therapies for Major Depressive Disorder

There are many treatments aside from antidepressants that have been

used to treat major depressive disorder, however, a complete review

of these would be too extensive for this study. Deep brain stimulation,

transcranial magnetic stimulation, and vagus nerve stimulation are

used much less often than the therapies discussed in the module and

they will not be described. Other medications that have been and can

be used to treat major depressive disorder is listed in Table 7.68,69

Clinical experience with these drugs is limited and they are considered

adjunctive therapy.

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Table 7: Other Medications for Treatment of Major Depressive Disorder

Amphetamine

Aripiprazole (Abilify)

Buspirone (Buspar)

Carbamazepine (Tegretol)

Ketamine

Lithium

Methylphenidate, long-acting

Olanzapine (Zyprexa)

Pindolol

Quetiapine (Seroquel)

Thyroid hormone

(including other Atypical Antipsychotics and Psychostimulant drugs)

Lifestyle interventions, i.e., abstinence from alcohol, drug, and tobacco

use, changes in diet, exercise patterns, and sleep patterns have been

investigated for a beneficial effect on depression.58 A sensible,

moderate diet, regular exercise, smoking cessation, moderate alcohol

use, and abstaining from drug use all have undeniable health benefits,

but there is no substantial evidence that theses interventions or other

lifestyle changes have a strong effect on alleviating depression.70,71

Animal-assisted therapy, music therapy, meditation, and various types

of relaxation therapy have shown some benefit for treating major

depressive disorder, but a recent review noted that more clinical

experience and controlled trials are needed before they can be judged

to be effective.58

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Electroconvulsive therapy (ECT) is considered to be an effective

therapy for treatment-resistant depression, i.e., patients who have not

responded to two drugs from a different class used for a sufficient

length of time or patients who have not responded to four or more

different therapeutic regimens.72,73 It can also be used for geriatric

patients, patients who have depression and Parkinson’s disease,

patients who have severe major depression,58 those whose depression

is accompanied by catatonia or psychotic features, or patients who

have been, or may be non-compliant with medication regimens.

Electroconvulsive therapy has been shown to achieve a substantial

remission rate,74 and a review of randomized controlled trials indicates

that ECT combined with medications is superior to the use of

medications alone for preventing relapse.75 Anterograde and

retrograde memory deficits and other cognitive deficits are relatively

common after ECT,76,77 but fortunately these are in most patients of

short duration.77 Electroconvulsive therapy is comparatively time

consuming and logistically complicated.

St. John’s wort is a flowering plant and extracts from the plant are

widely used to treat depression. St. John’s wort preparations are

available over-the-counter but the evidence for its effectiveness is

mixed,78,79 and it is not currently recommended as a treatment for

major depressive disorder.80 It should be used with caution as it can

interact with, and reduce the effectiveness of, many commonly used

medications such as antidepressants, digoxin, oral contraceptives, and

warfarin.80

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S-adenosyl methionine (SAMe) is an endogenous substrate that is

involved in metabolic processes. Synthesized SAMe preparations have

been used to treat depression and SAMe is available over-the-counter.

As with St. John’s wort, the evidence for the effectiveness of SAMe for

treating major depressive disorder is at best mixed and it is not

currently recommended as a therapy for this disease.81-83

Success Rate of Antidepressants

Aside from psychotherapy (which will be discussed in the next section)

antidepressants are the most commonly used therapy for major

depressive disorder. They are widely prescribed and the second-

generation antidepressants, particularly the SSRIs, are safe and

generally well tolerated and pharmacotherapy is less expensive and

more convenient than psychotherapy. However, many patients do not

respond to antidepressants; non-compliance with antidepressant

therapy is common, and relapses during remission and before recovery

are common features of antidepressant therapy.84 Continuing

antidepressant therapy for a period of time after remission has proven

to be successful in preventing relapses.85 However, poor patient

compliance and living for one to two years with antidepressant side

effects are significant limitations to this approach.

Psychotherapy for Major Depressive Disorder

There are many types of psychotherapy that are available for the

treatment of major depressive disorder. Several reviews indicate that

no type of psychotherapy is superior in effectiveness. 86-87

Psychotherapy alone can be an effective treatment,84,88 but there is

considerable evidence that psychotherapy combined with an

antidepressant is superior to either psychotherapy alone or

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antidepressants alone for treating major depressive disorder.84,88-92

The effectiveness of psychotherapy appears to be associated with the

number of sessions per week; more sessions being more effective.93

Generalized Anxiety Disorder

Generalized anxiety disorder is a common psychiatric condition.

Population studies have found a lifetime prevalence of generalized

anxiety disorder of 5.0%-5.7%.94,95 Generalized anxiety disorder is

more common in women and it is a common psychiatric disorder in the

elderly.96-98

Etiology Of Generalized Anxiety Disorder

The pathogenesis of generalized anxiety disorder is complex and

incompletely understood. Risk factors for generalized anxiety disorder

are listed in Table 8.99-102

Table 8: Risk Factors for Generalized Anxiety Disorder

Depression

Family history of psychiatric disorders

Financial strain

Female gender

Poor parenting

Negative life events

Physical ailments/disabilities

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Genetics:

Twin studies and other genetic research indicate that generalized

anxiety disorder is moderately heritable, but the genetic

influences have not been clearly identified.103-106

Biological:

There is data and research that suggest that brain function and

brain metabolism are signficantly different in patients who have

generalized anxiety disorder.107-109

Environmental:

Environmental influences are clearly associated with the

development of generalized anxiety disorder, i.e., stressful life

events, poor parenting, and physical ailments and disabilities.

Learning Break:

People who have generalized anxiety disorder often have personality traits of

chronic worry, difficulty recovering from emotional distress, emotional

hyperactivity and intensity, hypersensitivity, and hypervigilance.98

The American Psychiatric Association’s diagnostic criteria for

generalized anxiety disorder, located in the Diagnostic and Statistical

Manual of Mental Disorders, are listed in Table 9.28

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Table 9: Diagnostic Criteria for Generalized Anxiety Disorder

1. Excessive anxiety and worry, happening more days than not for at least

six months, about activities or events.

2. The individual finds it difficult to control the worry.

3. Anxiety and worry are associated with three (or more) of the following

six symptoms and some of the symptoms have been present more days

than not for the prior six months. Only one of these is required to be

present in children.

a. Restlessness, feeling keyed up or on edge.

b. Easily fatigued.

c. Difficulty concentrating, mind goes blank.

d. Irritability.

e. Muscle tension.

f. Difficulty falling asleep or staying asleep, restless or unsatisfying sleep.

4. The anxiety, worry, or physical symptoms cause clinically significant

distress or impairment in social, occupational, or other important areas

of functioning.

5. The disturbance is not attributable to the physiological effects of a

substance (i.e., a drug of abuse, a medication) or another medical

condition (i.e., hyperthyroidism).

6. The disturbance is not better explained by another mental disorder (i.e.,

anxiety or worry about having panic attacks in panic disorder, negative

evaluation in social anxiety disorder [social phobia], contamination or

other obsessions in obsessive-compulsive disorder, separation from

attachment figures in separation anxiety disorder, reminders of traumatic

events in posttraumatic stress disorder, gaining weight in anorexia

nervosa, physical complaints in somatic symptom disorder, perceived

appearance flaws in body dysmorphic disorder, having a serious illness in

illness anxiety disorder, or the content of delusional beliefs in

schizophrenia or delusional disorder).

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Screening For Generalized Anxiety Disorder

Patients who have generalized anxiety disorder typically have a wide

range of physical and psychiatric complaints. The primary symptoms

include anxiety, difficulty concentrating, fatigue, headache, insomnia,

and pain. If no medical explanation for the patient’s complaints can be

found a screening test for anxiety should be applied.

Screening tools for detecting generalized anxiety disorder include the

Beck anxiety inventory, the generalized anxiety disorder-7 or 2 (GAD-

7, GAD-2), the hospital anxiety and depression scale (HADS), the

Symptoms Driven Diagnostic System-Primary Care (SDDS-PC), and

the Prime MD tool.37 The GAD-7 is free, and it has good sensitivity and

specificity, and it can also help identify patients who suffer a disability

from the disorder.110 The specificity and sensitivity of the GAD-7 may

be population-specific.111

Table 10: The GAD-7

Over the last 2 weeks, how often have you been bothered by the following

problems.

Not at all Several days More than half the days Nearly every day

1. Feeling nervous, anxious or on edge.

2. Not being able to stop or control worrying.

3. Worrying too much about different things.

4. Trouble relaxing.

5. Being so restless that it is hard to sit still.

6. Becoming easily annoyed or irritable.

7. Feeling afraid as if something awful might happen

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Scores for the answers are 0, 1, 2, or 3, respectively. If the score is ≥ 8 then a

provisional diagnosis of generalized anxiety disorder can be made.

If you checked off any problems, how difficult have these problems made it for

you to do your work, take care of things at home, or get along with other people?

Not difficult at all Somewhat difficult Very difficult Extremely difficult

Clinical Course And Consequences Of

Generalized Anxiety Disorder

Generalized anxiety disorder is typically a chronic disease and most

patients experience fluctuations in the severity of symptoms.96,99

Complete and lasting remission can occur but the incidence of lasting

remission is not high and for many patients who do have remission,

some levels of anxiety remain.99 Unfortunately, many patients who

have generalized anxiety disorder do not respond to therapy.99

The consequences of generalized anxiety disorder can be serious. It is

associated with significant functional impairment;96,112 and, is

associated with an increased risk for depression96 and cardiovascular

disease. It also has been associated with an increased incidence of

suicidal ideation and suicide attempts,99,113 and has a significant

negative effect on a person’s quality of life.

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Treatment For Generalized Anxiety Disorder

Pharmacotherapy

The selective serotonin re-uptake inhibitors (SSRIs) and the serotonin-

norepinephrine re-uptake inhibitors (SNRIs) are considered the first-

line drugs for the treatment of generalized anxiety disorder.114,115

These medications have been shown to be effective and, although

there is little evidence, available data suggests that all of the selective

serotonin re-uptake inhibitors are comparable in effectiveness for this

purpose.114

A response is usually seen within four weeks of initiation of therapy. If

there has been no response in six to eight weeks then the original

medication should be tapered and a new one started.114

Second-line drugs for treating generalized anxiety disorder are the

benzodiazepines (i.e., alprazolam, diazepam) and the tricyclic

antidepressants (TCAs).114 The TCAs and the benzodiazepines have

been shown in some reports to be equally effective for treating

generalized anxiety disorder.116 Concerns for the TCAs were discussed

in the section on major depressive disorder, and the benzodiazepines

are not without risk, i.e., dependency, overdose, and significant side

effects such as drowsiness, tolerance, and withdrawal. However a

2014 study noted that long-term use of benzodiazepines may be safer

than was previously thought, and that using them in combination with

an antidepressant and psychotherapy can be very effective.117

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Learning Break:

Benzodiazepines bind to a specifc receptor that is associated with gamma-

aminobutyric acid (GABA) receptors. Gamma aminobutyric acid is one of the

major inhibitory neurotransmitters and when benzodiazepines bind to

benzodiazepine receptors this action increases the activity and duration of

GABA, thus causing sedation and anxiolysis.

Other medications that are used to treat generalized anxiety disorder

include typical and atypical antipsychotics, buspirone (Buspar),

hydroxyzine (Vistaril), mirtazapine (Remeron), and pregabalin

(Lyrica).114 There is less clinical experience with these for treating

generalized anxiety disorder than with the first-line and second-line

medications, but if the first-line and second-line drugs are deemed

ineffective then these “third-line” medications can be prescribed.

Alternative and complementary medicine, herbal medicines, and

exercise have been used to treat generalized anxiety disorder and

there are some positive reports about these118 but the clinical

experience with their use is sparse.114

Psychotherapy

Psychotherapy, alone or in combination with drug therapy, can be an

effective treatment for generalized anxiety disorder,99,119 and cognitive

behavioral therapy is considered to be one of the most effective forms

of psychotherapy for this purpose.99,114,120,121 Cognitive behavioral

therapy has been compared to pharmacotherapy and the two have

been found to be equal in effectiveness for this patient population,122

but the data is limited. Combining cognitive behavioral therapy with an

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antidepressant or a second-line medication may be helpful but more

evidence supporting this approach is needed.123-125

Summary

Major depressive disorder and generalized anxiety disorder are very

common psychiatric disorders. They are associated with significant co-

morbidities, and they can have a profound negative effect on personal

health, social and professional life. The etiology of these diseases is

not completely understood, but they are to some degree inheritable,

they are perhaps precipitated by environmental stressors, and

abnormal brain function is either a cause or an effect that contributes

to their prolongation.

The preferred treatments for major depressive disorder and

generalized anxiety disorder are psychotherapy, pharmacotherapy or a

combination of both. Cognitive behavioral therapy is the most

commonly used psychotherapy for generalized anxiety disorder, and

selective serotonin re-uptake inhibitors are the first-line medications

for both of these disorders. Major depressive disorder and generalized

anxiety disorder are curable, but the rate of complete and lasting

remission for both is low.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the

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1. Risk factors for major depressive disorder include:

a. Chronic disease and substance abuse.

b. Smoking and obesity.

c. Male gender and high socioeconomic status.

d. High level of education and age > 65.

2. People who have major depressive disorder are:

a. Depressed only during stressful life events.

b. Depressed once or twice a week.

c. Depressed almost every day.

d. Depressed only during episodes of substance abuse.

3. Screening for depression should be done:

a. If the patient has noticeable signs and symptoms.

b. For every patient ≥ age 18 if there is appropriate clinical

support.

c. Only during stressful life events.

d. Only for patients who request screening.

4. First-line medications used to treat major depressive

disorder would be:

a. Diazepam and imipramine.

b. Bupropion and phenelzine.

c. Amoxapine and trazodone.

d. Citalopram and fluoxetine.

5. True or false: ECT is effective for treating major depressive

disorder.

a. True.

b. False.

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6. Risk factors for generalized anxiety disorder include:

a. Male gender and age > 16.

b. Depression and female gender.

c. Age > 65 and substance abuse.

d. Stressful life events and smoking.

7. Generalized anxiety disorder is a disease that:

a. Is typically brief in duration and responds easily to treatment.

b. Is typically chronic in nature but is almost always curable.

c. Is typically chronic in nature and the severity fluctuates over

time.

d. Is typically responsive only to psychotherapy.

8. First-line medication to treat generalized anxiety disorder

are:

a. Benzodiazepines.

b. Atypical antipsychotics.

c. MAOIs.

d. Selective serotonin reuptake inhibitors.

9. A common treatment for generalized anxiety disorder is:

a. Cognitive behavioral therapy.

b. Group therapy.

c. Psychoanalysis.

d. Behavioral therapy.

10. Generalized anxiety disorder is typically:

a. brief in duration and responds easily to treatment.

b. chronic and often does not respond to treatment.

c. characterized by rapid, progressive worsening.

d. is typically characterized by rapid, progressive improvement.

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Correct Answers:

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