nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2
Continuing Nursing Education Course Director & Planners:
William A. Cook, PhD, Director; Douglas Lawrence, MS, Webmaster;
Susan DePasquale, CGRN, MSN, FPMHNP-BC, Lead Nurse Planner
Accreditation 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.
Credit Designation:
This educational activity is credited for 2.5 hours. Nurses may only
claim credit commensurate with the credit awarded for completion of
this course activity.
Course Author & Planner Disclosure Policy Statements:
It is the policy of NurseCe4Less.com to ensure objectivity,
transparency, and best practice in clinical education for all continuing
nursing education (CNE) activities. All authors and course planners
participating in the planning or implementation of a CNE activity are
expected to disclose to course participants any relevant conflict of
interest that may arise.
Statement of 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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3
Course Purpose:
To provide nurses with knowledge of the common psychiatric
conditions of major depressive and generalized anxiety disorder.
Learning Objectives:
1. Identify risk factors for major depressive disorder and generalized
anxiety disorder.
2. Identify environmental stressors that contribute to the etiology of
these diseases.
3. Identify screening tests used to detect major depressive disorder
or generalized anxiety disorder.
4. Identify signs or symptoms associated with major depressive
disorder and generalized anxiety disorder
5. Identify the first-line medications used to treat these diseases.
Target Audience:
Advanced Practice Registered Nurses, Registered Nurses, Licensed
Vocational Nurses, and Associates
Course Author & Director Disclosures:
Dana Bartlett, RN, BSN, MA, MSN, William S. Cook, PhD,
Douglas Lawrence, MS, Susan DePasquale, CGRN, MSN, FPMHNP-BC -
all have no disclosures.
Acknowledgement of Commercial Support: There is none.
Activity Review Information:
Reviewed by Susan DePasquale, CGRN, MSN, FPMHNP-BC.
Release Date: 4/18/15 Termination Date: 4/18/18
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4
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.
Please take time to complete the self-assessment Knowledge Questions
before reading the article. Opportunity to complete a self-assessment of
knowledge learned will be provided at the end of the course.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5
a. True.
b. False.
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6
b. chronic and often does not respond to treatment.
c. characterized by rapid, progressive worsening.
d. is typically characterized by rapid, progressive improvement.
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10
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
screening test that is often used, it is availble without charge, and it
has been shown to be accurate, specific, and sensitive.32-36
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11
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
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,
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12
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
many non-specific somatic complaints.3,28, 39,40 These complaints
should be evaluated, but it should be remembered that many patients
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15
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.
Table 5: Currently Available Antidepressants/Atypical Anti-Depressants
Monoamine Oxidase Inhibitors
Isocarboxazid
Phenelzine
Selegiline, transdermal
Tranylcypromine
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16
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
Aytical Antidepressants (unrelated to serotonin, tricyclic,
tetracyclic, and MAO inhibitors)
Bupropion (Wellbutrin)
Mirtazapine (Remeron)
Nefazadone (Serzone)
Trazodone (Desyrel)
Vilazodone (Viibryd)
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17
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.
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19
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
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21
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.
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)
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25
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
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26
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
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).
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27
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).
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28
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
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29
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.
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30
than was previously thought, and that using them in combination with
an antidepressant and psychotherapy can be very effective.117
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
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31
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
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 the NURSECE4LESS.COM course planners evaluate
nursing knowledge needs met following completion of this course by
completing the self-assessment Knowledge Questions after reading the
article. Correct Answers, page 34.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33
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.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34
Correct Answers:
REFERENCE SECTION
The reference section of in-text citations include published works
intended as helpful material for further reading. Unpublished works
and personal communications are not included in this section, although
may appear within the study text.
1. Marcus M, Yasamy T, van Ommeren M, Chisholm D, Shekhar S,
WHO Department of Mental Health and Substance Abuse.
Depression. A global public health concern. 2012. Retrieved
March 25, 2015 from
http://www.who.int/mental_health/management/depression/wh
o_paper_depression_wfmh_2012.pdf?ua=1.
2. Fakhoury M. New insights into the neurobiological mechanisms of
major depressive disorders. Gen Hosp Psychiatry. 2015;37:17-7.
3. Eisendrath SJ, Cole SA, Christensen JF, Gutick D, Cole MJ,
Feldman MD. Depression. In: Feldman MD, Christensen JF,
Satterfield JM, eds. Behavioral Medicine: A Guide to Clinical
Practice, 4th ed. New York, NY: McGraw-Hill; 2014.
1. a
2. c
3. b
4. d
5. a
6. b
7. c
8. d
9. a
10. b
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35
4. Taylor WD. Clinical practice. Depression in the elderly. N Engl J
Med. 2014;371:1228-36.
5. Miret M, Ayuso-Mateos JL Sanchez-Moreno J, E. Vieta. Depressive
disorders and suicide: epidemiology, risk factors, and burden.
Neurosci Biobehav Rev. 2013; 37: 2372-74.
6. Slavich GM, Irwin MR. From stress to inflammation and major
depressive disorder: a social signal transduction theory of
depression. Psychol Bull. 2014 ;140:774-815.
7. Grosse L, Carvalho LA, Wijkhuijs AJ, Bellingrath S, Ruland T,
Ambrée O, et al. Clinical characteristics of inflammation-
associated depression: Monocyte gene expression is age-related
in major depressive disorder. Brain Behav Immun. 2015;44:48-
56.
8. Dunn EC, Brown RC, Dai Y, Rosand J, Nugent NR, Amstadter AB,
Smoller JW. Genetic determinants of depression: recent findings
and future directions. Harv Rev Psychiatry. 2015;23:1-18.
9. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of
major depression: review and meta analysis. Am J Psychiatry.
2000;157:1552-62.
10. Pasquini M, Berardelli I, Biondi M. Ethiopathogenesis of
depressive disorders. Clin Pract Epidemiol Ment Health.
2014;10:166-71.
11. Rice F, Harold G, Thapar A. The genetic aetiology of childhood
depression: a review. J Child Psychol Psychiatry. 2002;43:65-79.
12. Klengel T, Binder EB. Gene-environment interactions in major
depressive disorder. Can J Psychiatry. 2013;58:76-83.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36
13. Amico F, Meisenzahl E, Koutsouleris N, Reiser M, Möller HJ, Frodl
T. Structural MRI correlates for vulnerability and resilience to
major depressive disorder. J Psychiatry Neurosci. 2011;36:15-22.
14. Han KM, Choi S, Jung J, Na KS, Yoon HK, Lee MS, Ham BJ.
Cortical thickness, cortical and subcortical volume, and white
matter integrity in patients with their first episode of major
depression. J Affect Disord. 2014;155:42-8.
15. Kautto M, Kampman O, Mononen N, Lehtimäki T, Haraldsson S,
Koivisto PA, et al. Serotonin transporter (5-HTTLPR) and
norepinephrine transporter (NET) gene polymorphisms:
Susceptibility and treatment response of electroconvulsive
therapy in treatment resistant depression. Neurosci Lett. 2015;
590:116-20.
16. Zhao X, Huang Y, Ma H, Jin Q, Wang Y, Zhu G. Association
between major depressive disorder and the norepinephrine
transporter polymorphisms T-182C and G1287A: a meta-
analysis. J Affect Disord. 2013 Aug 15;150(1):23-8
17. Dunlop BW, Nemeroff CB. The role of dopamine in the
pathophysiology of depression. Arch Gen Psychiatry. 2007; 64:
327-337
18. Camardese G, De Risio L, Di Nicola M, Pucci L, Cocciolillo F, Bria
P, et al. Changes of dopamine transporter availability in
depressed patients with and without anhedonia: a 123I-N-ω-
fluoropropyl-carbomethoxy-3β- (4-Iodophenyl)tropane SPECT
study. Neuropsychobiology. 2014;70:235-43.
19. Kobrosly R, van Wijngaarden E. Associations between
immunologic, inflammatory, and oxidative stress markers with
severity of depressive symptoms: an analysis of the 2005-2006
National Health and Nutrition Examination Survey.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37
Neurotoxicology. 2010;31:126-33.
20. Eisenberger NI, Inagaki TK, Mashal MN, Irwin MR. Inflammation
and social experience: an inflammatory challenge induces
feelings of social disconnection in addition to depressed mood.
Brain Behav Immun. 2010; 24: 558-63.
21. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P,
Drake DF, et al. A randomized controlled trial of the tumor
necrosis factor antagonist infliximab for treatment-resistant
depression: the role of baseline inflammatory biomarkers. JAMA
Psychiatry. 2013;70:31-41
22. Palta P, Samuel LJ, Miller ER 3rd, Szanton SL. Depression and
oxidative stress: results from a meta-analysis of observational
studies. Psychosom Med. 2014;76:12-9.
23. Harkness, KL, Tabari N, Monroe, SM, Slavich, GM, Gotlib IH,
24. Bagby, RM. Sex differences in life events prior to onset of major
depressive disorder: The moderating effect of age. J Abnorm
Psych. 2010;119: 791-803-803.
25. Monroe, SM, Slavich GM, Gotlib IH. Life stress and family history
for depression: The moderating role of past depressive episodes.
J Psychiatr Res. Advance online publication.
doi:10.1016/j.jpsychires.2013.11.005.
26. Slavich, G M, Monroe SM, Gotlib IH. Early parental loss and
depression history: Associations with recent life stress in major
depressive disorder. Journal of Psychiatr Res. 2011;45:1146-52.
27. Slavich GM, O’Donovan A, Epel ES, Kemeny ME. Black sheep get
the blues: A psychobiological model of social rejection and
depression. Neurosci Biobehav Rev. 2011;35:39-45.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38
28. Monroe SM, Slavich GM, Gotlib IH. Life stress and family history
for depression: the moderating role of past depressive episodes.
J Psychiatr Res. 2014;49:90-5.
29. American Psychiatric Association. Diagnostic and Statistical
Manual of Psychiatric Disorders. DSM-V, 5th ed. Arlington, VA:
American Psychiatric Association; 2013.
30. U.S. Preventive Services Task Force. Depression in adults,
screening In: U.S. Preventive Services Task Force, Agency for
Healthcare Research and Quality. The Guide to Clinical Preventive
Services 2014. Retrieved April 5, 2015 from
http://www.ahrq.gov/professionals/clinicians-
providers/guidelines-recommendations/guide/cpsguide.pdf.
31. Williams JW, Pignone M, Ramirez G, Stellato Perez C. Identifying
depression in primary care: a literature synthesis of case-finding
instruments. Gen Hosp Psychiatry. 2004;24:225-37.
32. Williams JW, Noël PH, Cordes JA, Ramirez G, Pignone M. Is this
patient clinically depressed? JAMA. 2002;287:1160-70.
33. Kiely KM, Butterworth P. Validation of four measures of mental
health against depression and generalized anxiety in a
community based sample. Psychiatry Res. 2015;225:291-8.
34. Martin A, Rief W, Klaiberg A, Braehler E. Validity of the Brief
Patient Health Questionnaire Mood Scale (PHQ-9) in the general
population. Gen Hosp Psychiatry. 2006;28:71-7.
35. Wittkampf KA, Naeije L, Schene AH, Huyser J, van Weert HC.
Diagnostic accuracy of the mood module of the Patient Health
Questionnaire: a systematic review. Gen Hosp Psychiatry.
2007;29:388-95.
36. Gilbody S, Richards D, Brealey S, Hewitt C. Screening for
depression in medical settings with the Patient Health
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39
Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern
Med. 2007;22:1596-602.
37. Narayana S, Wong CJ. Office-based screening of common
psychiatric conditions. Psychiatr Clin North Am. 2015;38:1-22.
38. Carlat DJ. The psychiatric review of symptoms: a screening tool
for family physicians. Am Fam Physician. 1998;58:1617-24.
39. Williams J, Nieuwsma J. Screening for depression. UpToDate.
March 24, 2014. Retrieved April 6, 2015 from
40. Deneke DE, Schultz HE, Fluent TE. Screening for depression in
the primary care population. Psychiatr Clin North Am.
2015;38:23-43.
41. Bell RA, Franks P, Duberstein PR, Duberstein PR, Epstein RM,
Feldman MD, Fernandez y Garcia E, et al. Suffering in silence:
reasons for not disclosing depression in primary care. Ann Fam
Med. 2011; 9:439-46.
42. Timonnen M, Liukkonen T. Management of depression in adults.
BMJ. 2008;336:435-9.
43. Deneke DE, Schultz HE, Fluent TE. Screening for depression in
the primary care population. Psychiatr Clin N Am. 2015;38:23-
43.
44. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas
KR, et al. The epidemiology of major depressive disorder: results
from the National Comorbidity Survey Replication (NCS-R). JAMA.
2003; 289:3095-3105.
45. Ghio L, Gotelli S, Cervetti A, Respino M, Natta W, Marcenaro M,
et al. Duration of untreated depression influences clinical
outcomes and disability. J Affect Disord. 2015;175:224-8
46. Ghio L, Gotelli S, Marcenaro M, Amore M, Natta W. Duration of
untreated illness and outcomes in unipolar depression: a
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40
systematic review and meta-analysis. J Affect Disord. 2014;152-
154:45-51.
47. Wang Y, Sareen J, Afifi TO, Bolton SL, Johnson EA, Bolton JM. A
Population-based longitudinal study of recent stressful life events
as risk factors for suicidal behavior in major depressive disorder.
Arch Suicide Res. 2015 Jan 6. [Epub ahead of print].
48. Oquendo MA, Currier D, Mann JJ. Prospective studies of suicidal
behavior in major depressive and bipolar disorders: what is the
evidence for predictive risk factors? Acta Psychiatrica
Scandinavica. 2006;114:151-8.
49. Jia H, Zack MM, Thompson WW, Crosby AE, Gottesman II.
Impact of depression on quality-adjusted life expectancy (QALE)
directly as well as indirectly through suicide. Soc Psychiatry
Psychiatr Epidemiol. 2015 Feb 7. [Epub ahead of print]
50. Yu M, Zhang X, Lu F, Fang L. Depression and risk for diabetes: A
meta-analysis. Can J Diabets. 2105 Mar 13. pii: S1499-
2671(14)00707-2. doi: 10.1016/j.jcjd.2014.11.006. [Epub ahead
of print]
51. Seligman F, Nemeroff CB. The interface of depression and
cardiovascular disease: therapeutic implications. Ann NY Acad
Sci. 2015 Mar 24. doi: 10.1111/nyas.12738. [Epub ahead of
print].
52. Bang-Andersen B, Sánchez C. Emerging mechanisms and
treatments for depression beyond SSRIs and SNRIs. Biochem
Pharmacol. 2015 Mar 24. pii: S0006-2952(15)00156-2. doi:
10.1016/j.bcp.2015.03.011. [Epub ahead of print].
53. Malhi GS, Hitching R, Berk M, Boyce P, Porter R, Fritz K.
Pharmacological management of unipolar depression Acta
Psychiatrica Scandinavica. 2013 (Supplement 443);127:6-23
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41
54. Gartlehner G Thaler K, Hill S, Hansen RA. How should primary
care doctors select which antidepressants to administer? Curr
Psychiatry Rep. 2012;14:360-9.
55. Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux L, Van Noord
M, et al. Comparative benefits and harms of second-generation
antidepressants for treating major depressive disorder: an
updated meta-analysis. Ann Int Med. 2011;155:772-85.
56. Ciechnaowski P. Uniploar major depression in adults: Choosing
initial treatment. UpToDate. January 17, 2015. Retrieved April 7,
2015 from http://www.uptodate.com/contents/unipolar-major-
depression-in-adults-choosing-initial-
treatment?source=search_result&search=Unipolar+major+depre
ssion&selectedTitle=1%7E150.
57. Halverson JL. Depression. eMedicine. February 23, 2015.
Retrieved April 8, 2015 from
http://emedicine.medscape.com/article/286759-
treatment#aw2aab6b6b2.
58. Bentley SM, Pagalilauan GL, Simpson SA. Major depression. Med
Clin N Am. 2014;98:981-1005.
59. Souery D, Calati R, Papageorgiou K, Juven-Wetzler A, Gailledreau
J, Modavi D, et al. What to expect from a third step in treatment
resistant depression: A prospective open study on escitalopram.
World J Biol Psychiatry. 2014 Dec 23:1-11. [Epub ahead of print].
60. Bschor T, Bauer M, Adli M. Chronic and treatment resistant
depression: diagnosis and stepwise therapy. Dtsch Arztebl Int.
2014111:766-75.
61. Hung CI. Factors predicting adherence to antidepressant
treatment. Curr Opin Psychiatry. 2014;27:344-9.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42
62. Hansen RA, Dusetzina SB, Dominik RC, Gaynes BN. Prescription
refill records as a screening tool to identify antidepressant non-
adherence. Pharmacoepidemiol Drug Saf. 2010;19:33-7.
63. Jaffray M, Cardy AH, Reid IC, Cameron IM. Why do patients
discontinue antidepressant therapy early? A qualitative study. Eur
J Gen Pract. 2014;20:167-73.
64. Baldessarini RJ, Lau WK, Sim J, Sum MY, Sim K. Duration of
initial antidepressant treatment and subsequent relapse of major
depression. Clin Psychopharmacol. 2015;35:75-6.
65. Trivedi M. Unipolar depession in adults: Treatment with
antidepressant combinations. UpToDate. April 4, 2015. Retrieved
April 9, 2015 from http://www.uptodate.com/contents/unipolar-
depression-in-adults-treatment-with-antidepressant-
combinations?source=search_result&search=unipolar+depression
&selectedTitle=4%7E150.
66. Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal
symptoms after selective serotonin reuptake inhibitor
discontinuation: A systematic review. Psychother Psychosom.
2015;84:72-81. [Epub ahead of print].
67. Hirsch M, Birnbaum RJ. Antidepressant medications in adults:
Switching and discontinuing medication. UpToDate. January 16,
2015. Retrieved April 9, 2015 from
http://www.uptodate.com/contents/antidepressant-medication-
in-adults-switching-and-discontinuing-
medication?source=search_result&search=Antidepressant&select
edTitle=1%7E150.
68. Epstein I, Szpindel I, Katzman MA. Pharmacological approaches
to manage persistent symptoms of major depressive disorder:
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43
rationale and therapeutic strategies. Psychiatry Res. 2014;220
Suppl 1:S15-33.
69. DeWilde KE, Levitch CF, Murrough JW, Mathew SJ, Iosifescu DV.
The promise of ketamine for treatment-resistant depression:
current evidence and future directions. Ann NY Acad Sci. 2015
Feb 3. doi: 10.1111/nyas.12646. [Epub ahead of print].
70. Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, et
al. Exercise for depression. Cochrane Database Syst Rev. 2013
Sep 12;9:CD004366. doi: 10.1002/14651858.CD004366.pub6.
71. Sarris J, O'Neil A, Coulson CE, Schweitzer I, Berk M. Lifestyle
medicine for depression. BMC Psychiatry. 2014 Apr 10;14:107.
doi: 10.1186/1471-244X-14-107.
72. Oremus C, Oremus M, McNeely H, Losier B, Parlar M, King M, et
al. Effects of electroconvulsive therapy on cognitive functioning in
patients with depression: protocol for a systematic review and
meta-analysis. BMJ Open. 2015 Mar 11;5(3):e006966. doi:
10.1136/bmjopen-2014-006966.
73. Youssef NA, McCall WV. Relapse prevention after index
electroconvulsive therapy in treatment-resistant depression. Ann
Clin Psychiatry. 2014;26:288-96.
74. Kellner C. Unipolar major depression in adults: Indications for
and efficacy of electroconvulsive therapy (ECT). UpToDate.
January 29, 2015. Retrieved April 9, 2015 from
http://www.uptodate.com/contents/unipolar-major-depression-
in-adults-indications-for-and-efficacy-of-electroconvulsive-
therapy-
ect?source=search_result&search=electroconvulsive+therapy&sel
ectedTitle=4%7E60
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44
75. Brown ED, Lee H, Scott D, Cummings GG. Efficacy of
continuation/maintenance electroconvulsive therapy for the
prevention of recurrence of a major depressive episode in adults
with unipolar depression: a systematic review. J ECT.
2014;30:195-202.
76. Cleary M, Horsfall J. Electroconvulsive therapy: issues for mental
health nurses to consider. Issues Ment Health Nurs. 2014;35:73-
6.
77. Martin DM, Katalinic N, Ingram A, Schweitzer I, Smith DJ, Hadzi-
Pavlovic D, et al. A new early cognitive screening measure to
detect cognitive side-effects of electroconvulsive therapy? J
Psychiatr Res. 2013;47:1967-74.
78. Grobler AC, Matthews G, Molenberghs G. The impact of missing
data on clinical trials: a re-analysis of a placebo controlled trial of
Hypericum perforatum (St Johns wort) and sertraline in major
depressive disorder. Psychopharmacology (Berl).
2014;231:1987-99.
79. Sarris J. St. John's wort for the treatment of psychiatric
disorders. Psychiatr Clin North Am. 2013;36:65-72.
80. National Institutes for Health. National Center for Complementary
and Integrative Medicine. St. John’s Wort and Depression.
September, 2103. Retrieved April 10, 2015 from
https://nccih.nih.gov/health/stjohnswort/sjw-and-depression.htm.
81. Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI,
Baer L, et al. A double-blind, randomized, placebo-controlled
clinical trial of S-adenosyl-L-methionine (SAMe) versus
escitalopram in major depressive disorder. J Clin Psychiatry.
2014;75:370-6.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45
82. Chitiva H, Audivert F, Alvarez C. Suicide attempt by self-burning
associated with ingestion of S-adenosylmethionine: a review of
the literature and case report. J Nerv Ment Dis. 2012;200:99-
101.
83. National Institutes for Health. National Center for Complementary
and Integrative Medicine. S-Adenosyl-L-Methionine (SAMe): An
Introduction. August 2013. Retrieved April 10, 2015 from
https://nccih.nih.gov/health/supplements/SAMe.
84. Hollon SD, DeRubeis RJ, Fawcett J, Amsterdam JD, Shelton RC,
Zajecka J, et al. Effect of cognitive therapy with antidepressant
medications vs antidepressants alone on the rate of recovery in
major depressive disorder: a randomized clinical trial. JAMA
Psychiatry. 2014;71:1157-64.
85. Huijbers MJ, Spijker J, Donders AR, van Schaik DJ, van Oppen P,
Ruhé HG, et al. Preventing relapse in recurrent depression using
mindfulness-based cognitive therapy, antidepressant medication
or the combination: trial design and protocol of the MOMENT
study. BMC Psychiatry. 2012 Aug 27;12:125. doi: 10.1186/1471-
244X-12-125.
86. Shinohara K, Honyashiki M, Imai H, Hunot V, Caldwell DM, Davies
P, et al. Behavioural therapies versus other psychological
therapies for depression. Cochrane Database Syst Rev. 2013 Oct
16;10:CD008696. doi: 10.1002/14651858.CD008696.pub2.
87. Cuijpers P, van Straten A, Andersson G, van Oppen P.
Psychotherapy for depression in adults: a meta-analysis of
comparative outcome studies. J Consult Clin Psychol.
2008;76:909-22.
88. Cuijpers P, Karyotaki E, Weitz E, Andersson G, Hollon SD, van
Straten A. The effects of psychotherapies for major depression in
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46
adults on remission, recovery and improvement: a meta-analysis.
J Affect Disord. 2014;159:118-126.
89. Cuijpers P, Dekker J, Hollon SD, Andersson G. Adding
psychotherapy to pharmacotherapy in the treatment of
depressive disorders in adults: a meta-analysis. J Clin Psychiatry.
2009;70:1219-29.
90. Kriston L, von Wolff A, Westphal A, Hölzel LP, Härter M. Efficacy
and acceptability of acute treatments for persistent depressive
disorder: a network meta-analysis. Depress Anxiety.
2014;31:621-30.
91. Ma D, Zhang Z, Zhang X, Li L. Comparative efficacy,
acceptability, and safety of medicinal, cognitive-behavioral
therapy, and placebo treatments for acute major depressive
disorder in children and adolescents: a multiple-treatments meta-
analysis. Curr Med Res Opin. 2014;30:971-95.
92. Köhler S, Hoffmann S, Unger T, Steinacher B, Dierstein N,
Fydrich T. Effectiveness of cognitive-behavioural therapy plus
pharmacotherapy in inpatient treatment of depressive disorders.
Clin Psychol Psychother. 2013;20:97-106.
93. Cuijpers P, Huibers M, Ebert DD, Koole SL, Andersson G. How
much psychotherapy is needed to treat depression? A
metaregression analysis. J Affect Disord. 2013;149:1-13.
94. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M,
Eshleman S, et al. Lifetime and 12-month prevalence of DSM-III-
R psychiatric disorders in the United States. Results from the
National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8-19
95. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters
EE. Prevalence, severity, and comorbidity of 12-month DSM-IV
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47
disorders in the National Comorbidity Survey Replication. Arch
Gen Psychiatry. 2005;62:593-602.
96. Baldwin, D. Generalized anxiety disorder: Epidemiology,
pathogenesis, clinical manifestations, course, assessment, and
diagnosis. UpToDate. November 6, 2014. Retrieved April 1, 2015
from http://www.uptodate.com/contents/generalized-anxiety-
disorder-epidemiology-pathogenesis-clinical-manifestations-
course-assessment-and-
diagnosis?source=search_result&search=generalized+anxiety+di
sorder&selectedTitle=2%7E84.
97. Zhang X, Norton J, Carrière I, Ritchie K, Chaudieu I, Ancelin ML.
Risk factors for late-onset generalized anxiety disorder: results
from a 12-year prospective cohort (The ESPRIT study). Transl
Psychiatry. 2015 Mar 31;5:e536. doi: 10.1038/tp.2015.31.
98. Vegas-Lopez O, Schneier FR, Wang S, Heimberg RG, Liu SM,
Hasin, DS, et al. Gender differences in generalized anxiety
disorder: results from the National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC). J. Clin. Psychiatry.
2008; 69:1606-16.
99. Newman MG, Llera SJ, Erickson TM, Przeworski A, Castonguay
LG. Worry and generalized anxiety disorder: a review and
theoretical synthesis of evidence on nature, etiology,
mechanisms, and treatment. Annu Rev Clin Psychol. 2013;9:275-
97.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48
100. King M, Bottomley C, Bellón-Saameño JA, Torres-Gonzalez F,
Švab I, Rifel J, et al. An international risk prediction algorithm for
the onset of generalized anxiety and panic syndromes in general
practice attendees: predictA. Psychol Med. 2011;41:1625-39.
101. Moreno-Peral P, Luna Jde D, Marston L, King M, Nazareth I,
Motrico E. Predicting the onset of anxiety syndromes at 12
months in primary care attendees. The predictA-Spain study.
PLoS One. 2014 Sep 3;9(9):e106370. doi:
10.1371/journal.pone.0106370. eCollection 2014.
102. Kendler KS, Gardner CO, Gatz M, Pedersen NL. The sources of
co-morbidity between major depression and generalized anxiety
disorder in a Swedish national twin sample. Psychol Med.
2007;37:453-62.
103. López-Solà C, Fontenelle LF, Alonso P, Cuadras D, Foley DL,
Pantelis C, et al. Prevalence and heritability of obsessive-
compulsive spectrum and anxiety disorder symptoms: A survey
of the Australian Twin Registry. Am J Med Genet B
Neuropsychiatr Genet. 2014;165B:314-25.
104. Mackintosh MA, Gatz M, Wetherell JL, Pedersen NL. A twin study
of lifetime Generalized Anxiety Disorder (GAD) in older adults:
genetic and environmental influences shared by neuroticism and
GAD. Twin Res Hum Genet. 2006;9:30-7.
105. Kendler KS, Walters EE, Neale MC, Kessler RC, Heath AC, Eaves
LJ. The structure of the genetic and environmental risk factors for
six major psychiatric disorders in women. Phobia, generalized
anxiety disorder, panic disorder, bulimia, major depression, and
alcoholism. Arch Gen Psychiatry. 1995;52:374-83.
106. 106. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ.
Major depression and generalized anxiety disorder. Same genes,
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49
(partly) different environments? Arch Gen Psychiatry.
1992;49:716-22.
107. Hettema JM, Kettenmann B, Ahluwalia V, McCarthy C, Kates WR,
Schmitt JE, et al. Pilot multimodal twin imaging study of
generalized anxiety disorder. Depress Anxiety. 2012;29:202-9.
108. Wu JC, Buchsbaum MS, Hershey TG, Hazlett E, Sicotte N,
Johnson JC. PET in generalized anxiety disorder. Biol Psychiatry.
1991;29:1181-99.
109. Nitschke JB, Sarinopoulos I, Oathes DJ, Johnstone T, Whalen PJ,
Davidson RJ, et al. Anticipatory activation in the amygdala and
anterior cingulate in generalized anxiety disorder and prediction
of treatment response. Am J Psychiatry. 2009;166:302-10.
110. Ruiz MA, Zamorano E, García-Campayo J, Pardo A, Freire O,
Rejas J. Validity of the GAD-7 scale as an outcome measure of
disability in patients with generalized anxiety disorders in primary
care. J Affect Disord. 2011;128:277-86.
111. Kertz S, Bigda-Peyton J, Bjorgvinsson T. Validity of the
Generalized Anxiety Disorder-7 scale in an acute psychiatric
sample. Clin Psychol Psychother. 2013; 20:456-64.
112. Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel
J, et al. 2009. The global burden of mental disorders: an update
from the WHO World Mental Health (WMH) Surveys. Epidemiol
Psichiatr Soc. 2009;18:23-33
113. Boden JM, Fergusson DM, Horwood LJ. Anxiety disorders and
suicidal behaviours in adolescence and young adulthood: findings
from a longitudinal study. Psychol. Med. 2007;37:431-40.
114. Bystritsky A. Pharmacological therapy for generalized anxiety
disorder. UpTo Date. October 9, 2104. Retrieved April 6, 2015
from
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50
http://www.uptodat.com/contents/pharmacotherapy-for-
generalized-anxiety-disorder?source=see_link.
115. Katzman MA, Copeland A, Klassen LJ, Chokka P, Brawman-
Mintzer O. Pharmacotherapy for generalized anxiety disorder.
Psychiatr. Ann. 2011;41:95-103.
116. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of
benzodiazepines versus antidepressants in anxiety disorders: a
systematic review and meta-analysis. Psychother Psychosom.
2013;82:355-62.
117. Starcevic V. The reappraisal of benzodiazepines in the treatment
of anxiety and related disorders. Expert Rev Neurother.
2014;14:1275-86.
118. McPherson F, McGraw L. Treating generalized anxiety disorder
using complementary and alternative medicine. Altern Ther
Health Med. 2013;19:45-50.
119. Cuijpers P, Sijbrandij M, Koole S, Huibers M, Berking M,
Andersson G. Psychological treatment of generalized anxiety
disorder: a meta-analysis. Clin Psychol Rev. 2014;34:130-40.
120. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological
therapies for generalised anxiety disorder. Cochrane Database
Syst Rev. 2007 Jan 24;(1):CD001848.
121. Hundt NE, Amspoker AB, Kraus-Schuman C, Cully JA, Rhoades H,
Kunik ME, et al. Predictors of CBT outcome in older adults with
GAD. J Anxiety Disord. 2014;28:845-50.
122. Mitte K. Meta-analysis of cognitive-behavioral treatments for
generalized anxiety disorder: a comparison with
pharmacotherapy. Psychol Bull. 2005;131:785-95.
123. Crits-Christoph P, Newman MG, Rickels K, Gallop R, Gibbons MB,
Hamilton JL, et al. Combined medication and cognitive therapy
nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51
for generalized anxiety disorder. J Anxiety Disord. 2011;25:1087-
94.
124. Power KG, Simpson RJ, Swanson V, Wallace LA. Controlled
comparison of pharmacological and psychological treatment of
generalized anxiety disorder in primary care. Br J Gen Pract.
1990;;40:289-94.
125. Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN,
Sherrill JT, et al. Cognitive behavioral therapy, sertraline, or a
combination in childhood anxiety. N Engl J Med. 2008;359:2753-
66.
The information presented in this course is intended solely for the use of healthcare
professionals taking this course, for credit, from NurseCe4Less.com.
The information is designed to assist healthcare professionals, including nurses, in
addressing issues associated with healthcare.
The information provided in this course is general in nature, and is not designed to
address any specific situation. This publication in no way absolves facilities of their
responsibility for the appropriate orientation of healthcare professionals.
Hospitals or other organizations using this publication as a part of their own orientation
processes should review the contents of this publication to ensure accuracy and
compliance before using this publication.
Hospitals and facilities that use this publication agree to defend and indemnify, and shall
hold NurseCe4Less.com, including its parent(s), subsidiaries, affiliates, officers/directors,
and employees from liability resulting from the use of this publication.
The contents of this publication may not be reproduced without written permission from
NurseCe4Less.com.