Depression/Anxiety by 1R9mes7

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									Depression and Anxiety

Purpose: The purpose of this course is to provide an overview of two of the most

common psychiatric disorders seen in primary care: depression and anxiety. The

incidence, pathophysiology, signs and symptoms, diagnostic criteria, and

treatment for each disorder will be discussed.

Objectives:

       After completion of this course, the participant will be able to

      demonstrate familiarity with the pathophysiological changes in depression

       and anxiety

      identify the diagnostic criteria for depression and anxiety

      demonstrate familiarity with the SIG-E-CAPS pneumonic in the diagnosis

       of depression

      demonstrate familiarity with the treatment modalities for depression

      demonstrate familiarity with the treatment modalities for generalized

       anxiety disorder and other anxiety disorders

      demonstrate familiarity with the role of lifestyle in management of

       depression and anxiety

Case

   A 32-year-old white female, who is the mother of three, presents to the

primary care clinician with lack of energy, back pain, early morning wakening and

irritability. She reports that she is so engrossed in her children’s lives that she

has no time to do anything herself. On the rare evening that she has an evening

free she chooses to go to sleep instead of going out.
   Her physical exam is unremarkable. Her past medical history is unremarkable

except for three healthy vaginal births. She is on no medications and has no

allergies to medications.

Introduction

   Depression is one of the most common disorders encountered by the primary

care clinician. Unfortunately, it remains under diagnosed and under treated.

   While depression has obvious implications on quality of life it can also affect

quantity of life. Those who suffer from depression are more likely to commit

suicide, have medical illness poorly controlled, abuse substances, lose work time

and have problems in their personal lives.

  Anxiety is also a common medical diagnosis. Many different types of anxiety

exist from generalized anxiety disorder to obsessive compulsive disorder. Death

rates are higher among anxious individuals as anxiety negatively affects the

endocrine and immune system. Those with anxiety also have a higher rate of

suicide1.

  Both conditions have a negative social stigma, which partly explains why these

conditions are under diagnosed. Patients and physicians are often reluctant to

bring up the topic of depression or anxiety. Many times depression and anxiety

co-exist.

   Depression affects 20 percent of women and 12 percent of men across a

lifespan. Anxiety incidence is variable depending on the type of anxiety 1.

      Generalized anxiety disorder (GAD) 4.1-6.6%

      Social phobia 2.6 – 13.3%
      Panic disorder 2.3-2.7%

      Obsessive compulsive disease 2.3-2.6

      Post traumatic stress disorder – 1-9.3%

   The prevalence of anxiety is high, one estimate proposes that 18% of primary

care patients are afflicted with an anxiety disorder and around 7% are

generalized2. Only 60% of those diagnosed with generalized anxiety disorder

were treated in 20023.

   GAD disrupts the lives of about 10 million Americans4 and is often a

predecessor to major depression. GAD is also associated with other mood

disorders, functional impairment and alcohol and other substance dependence

disorders4.

   The white population is more commonly affected with depression than the

black population9. Panic disorder has equal incidence in the white, black and

Hispanic population1. Females are more commonly diagnosed with both

depression and anxiety than males.

   Depression rates peak between the ages of 25 and 449. Generalized anxiety

disorder has its onset in the 20’s or early 30’s, but as children they are often

characterized by being nervous about grades and social events. Panic disorder is

most common in the late teens and early 20’s and than again the late 40’s and

early 50’s. OCD is typically diagnosed in the mid 20’s to early 30’s1.

   Many disease states increase the risk of mental health disease. Chronic

disease is associated with increased rates of depression and anxiety. Some

diseases are more prone to mental health conditions than others. Chronic
obstructive pulmonary disease (COPD) patients are at much higher risk for

developing depression than the general population5. A recent study suggested

that the risk of depression in COPD is higher than those with diabetes5.

   Heart disease is also linked to depression. Recent guidelines recommend

that patients who have had a recent heart attack should be screened for

depression regularly6.

   Individuals afflicted with metabolic syndrome are more likely afflicted with

depression than those without the condition7. This is important to recognize as

patients with metabolic syndrome need to make lifestyle changes to prevent

complications of the disease and depressed patients are less likely to make

these changes. Individuals with metabolic syndrome are at risk for diabetes,

heart disease and stroke.

   Infertile couples are also noted to be at higher risk of depression and other

mental health conditions. Women were noted to have more binge-eating than

fertile women. Men were noted to have increased rates of social phobia and

obsessive-compulsive disorder, but both conditions were noted to be subclinical8.

   A more lasting, but milder form of depression is called dysthymia. It can last

for years before it is treated or recognized. It is diagnosed when a patient has a

depressed mood on most days for most of the day for at least two years. These

patients are withdrawn, pessimistic, irritable and are unable to find joy in life.

Many people – including the patient themselves - mistakenly think these

individuals are just this way by nature.
    Pathophysiology

   The exact pathophysiological mechanism responsible for both anxiety and

depression are not known. The role of neurotransmitters is strongly implicated in

the pathogenesis of both conditions. Serotonin, norepinephrine and dopamine

are three neurotransmitters that have been looked at.

  Many factors contribute to psychiatric illness beyond the absolute level of

neurotransmitters. The receptor regulation and sensitivity are also linked to

mental disease. Likely there needs to be neuronal receptor regulation over time

to affect mood9. The role of pathophysiology is important in the pharmacologic

treatment of depression.

Signs and Symptoms

   For the diagnosis of major depression the patient must demonstrate at least

one of the following: depressed mood and/or reduction of interest or pleasure in

activities. In addition, they must exhibit at least four physical symptoms such as

weight/appetite changes, decrease in energy, fatigue, concentration difficulties,

and sleep disturbance for a minimum of two weeks. Bereavement, general

medical conditions, medications, drug or alcohol abuse cannot account for these

symptoms. Bereavement is normal after certain events (e.g. death of a loved

one), but symptoms should not persist beyond two months. The symptoms must

result in significant impairment of social, occupational or school functioning10.

A well known pneumonic is often used for the clinician to diagnose depression:

SIG-E-CAPS (table 1).
Table 1: SIG-E-CAPS pneumonic

S            Sleep disturbance – either insomnia or hypersomnia.

I            Loss of interest in everyday activities – anehdonia.

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.

    Sleep disturbance is most commonly early morning wakening, known as

terminal insomnia.

    Passive suicidal ideation is common with depression, which is not thoughts of

suicide, but a preference to not be alive. Risk factors for suicide include: the

existence of a mental health disorder (the presence of anxiety and depression

increases the risk), lack of social support, substance abuse and availability of a

weapon. Health care providers need to evaluate for a plan and a method to carry

that plan out.

    Mania is important to rule out. This would indicate bipolar disease or manic-

depression. To assess for this ask the patient if he/she ever feels the opposite of

depressed. Do they ever feel really charged up and do not sleep or spend a lot

of money? Mania is a feeling of elation that lasts greater than 3 weeks and is

associated with pressured speech, decreased need for sleep, feelings of
grandiosity, impaired functioning, increased activity, flight of ideas, easy

distractibility and poor decision making such as excessive spending or sexual

indiscretion.

   It is important to assess for psychosis as this may indicate depression with

psychotic features or schizo-affective disorder. Ask the patient if

delusions/hallucinations are present? Do they have special powers?

   It is also important to ask about homicidal thoughts. Depressed patients are

at risk to physically or verbally attack other people. Anyone with homicidal

thoughts should be hospitalized.

   Generalized anxiety disorder (GAD) is characterized by excessive anxiety or

worry without proof or out of proportion to the given situation. The patient is in a

continual state of tension and anxiety. The symptoms persist beyond six months

and the anxiety is in response to various stressors. The DSM IV lists the criteria

for GAD as three or more of the following symptoms - which impair normal

functioning, cause distress and are not due to another medical or psychological

problem - needing to be present most days for the past 6 months10. These

symptoms include: irritability, sleep disturbance, fatigue, feeling restless, on edge

or keyed up, lacking concentration and muscle tension.

    GAD affects quality of life as it impairs functioning. Patients often

procrastinate, practice avoidance, have poor problem solving skills, miss work

and do not maintain daily responsibilities.

   The physical symptoms of anxiety include: elevated blood pressure, increased

respiratory and heart rate, muscle tension, and reduced blood flow to the
intestines resulting in nausea or diarrhea. Tremor, shaking, furrowed brow,

dilated pupils, cold clammy hands and diaphoresis may also be present.

Physical findings often do not point to the diagnosis of anxiety. Needle track

marks, ascites and hepatomegaly suggest substance abuse

   When evaluating a patient with non-specific or vague complaints, anxiety or

depression must be considered in the differential. Common complaints of

patients with GAD include: fatigue, sweating, dry mouth, flushing, nausea,

diarrhea, urinary frequency, insomnia, weakness, irritability, restlessness and

muscle tension and chills.

  Other conditions need to be evaluated for when anxiety is considering such as

substance abuse, withdrawal, reactions to medications. Many medications may

lead to signs and symptoms of anxiety. This includes prescription as well as

non-prescription or illegal drugs. Common prescription drugs that may lead to

signs and symptoms suggestive of anxiety include: thyroxin, theophylline,

digoxin, steroids and narcotics. Amphetamines, marijuana, cocaine and

withdrawal from alcohol, nicotine or sedative-hypnotics may also cause anxiety.

Social conditions that may be found on history include major life events such as a

death, marriage or divorce. A family history may be positive for mental illness.

   Medical conditions can mimic anxiety. Medical conditions to consider when

anxiety is present include: chronic obstructive pulmonary disease, angina,

myocardial infarction, arrhythmias, valvular disease, anemia, asthma, and

hypoglycemia.

   Psychological testing such as the Beck Anxiety Inventory, the Hamilton
Anxiety Rating Scale and the Anxiety Disorders Interview Schedule can be used

in the diagnosis of this condition.

   When the diagnosis of anxiety is made it is important to keep other diagnoses

as a consideration especially when treatments are not effective. Other clues that

anxiety is not causing the issue include: symptoms starting after age 35, anxiety

symptoms not related to life stressors, no avoidance behaviors and a lack of

childhood history of significant forms of anxiety are clues to the need for further

evaluation11. GAD should be a diagnosis of exclusion after other diseases have

been ruled out.

    Panic disorder is associated with recurrent episodes or panic attacks. Panic

attacks are short-periods of intense fear that come on very quickly. At least four

symptoms must be present to diagnose panic attack including: shortness of

breath, chest pain, palpitations, increased heart rate, sweating, trembling,

dizziness, fainting, nausea, abdominal distress, numbness, chills or hot flashes,

sensation of choking, depersonalization or fear of dying.

   Obsessive compulsive disorder (OCD) is a disorder characterized by

obsessions and compulsions that cause distress for the person suffering from

them. Obsessions are recurrent and persistent thoughts, images or impulses

that cause stress and anxiety. Compulsions are repetitive behaviors carried out

by the individual to reduce anxiety caused by the obsession.

   Phobia is a fear of something. Everyone is afflicted with specific fears, but

when does a phobia become a disease. Agoraphobia is a fear of a specific item.
Those with agoraphobia often fear being embarrassed by a public onset of a

panic attack and often become socially isolated.

   Social phobias, also known as social anxiety disorder (SAD), are persistent

fears in social situations that impair the ability to function socially. These

situations cause the person to feel anxiety which is excessive.

   Post-traumatic stress disorder (PTSD) happens after a trauma that included a

real or threatened death or injury. PTSD is characterized by at least one of the

following: re-experienced the event; recurrent dreams; flashbacks; intense

psychological distress from the previous trauma; or physiological changes when

exposed to trauma cues.

Diagnostic work up

   Ruling out other medical conditions is a critical part of the work-up of

depression and anxiety disorder. Laboratory evaluation should include:

       Complete blood count

       Basic metabolic panel

       Thyroid function test

       Drug screen and urinalysis

  Other tests to consider based on the initial presentation may include:

       Liver function tests

       Vitamin B-12 levels

       Erythrocyte sedimentation rate

       Antinuclear antibody

       Rapid plasma reagin
      Human immunodeficiency virus testing

      Arterial blood gas

      Dexamethasone suppression test (Cushing disease)

      Cosyntropin stimulation test (Addison’s Disease)

      Electroencephalogram

      Lumbar puncture

      CAT scan of the brain

      Cardiovascular work up

Treatment

   Many different treatments are available for depression and anxiety. Ideally a

collaborative method is recommended for best depression treatment as this

maximizes adherence, quality of life and treatment outcome12. Management

should include adequate follow up with monitoring of effectiveness of treatment.

The Institute of Clinical System Improvement12 recommends a team approach to

depression management with the involvement the primary care physician,

psychiatrist, and care manager.

  The primary goal of treatment is for the patient to have minimal symptoms and

achieve complete remission. Additional goals include: restoration of

functionality, prevention of further episodes, and prevention of a

neurodegenerative process.

   Patients need to be active members in the treatment of their depression.

Patients and families need to be educated about their disease and this is the

responsibility of not only the patient, but the treating clinicians as well as the
depression case manager. Ideally the involvement of a case manger would

improve education and adherence to treatment. Most depressed patients are

not assigned a care manager and the role of teaching, motivating the patient and

assuring follow up are the role of the treating clinician.

  The depressed patient is a clinical challenge with treatment as the disease is

often characterized by decreased energy and motivation, pessimism, and social

isolation.

   Patients who do not understand the disease are likely to have reduced rates

of treatment compliance. Patients need to understand the basics of the disease

including its cause, symptoms and the natural course of the disease12.

   Understanding how treatment affects the disease is another critical aspect to

the management of the disease. Patients need to understand that medications

work over a period of weeks to months. Patients who assume that they will feel

better after taking one to two doses of medication are much less likely to adhere

to treatment.

   Understanding side effects of treatments is another critical aspect of

treatment. Many side effects of medications used to treat depression are

temporary and will improve as the body adapts to the medications. Knowing this

may help get the patient through the initial weeks of therapy. Patients also need

to understand about the discontinuation syndrome so they do not attempt to stop

the medications abruptly without consulting their health care provider.

   Other points of education that are critical to convey to the patient include12:

      Signs and symptoms suggestive of relapse
      The amount of time treatment will take

      How to communicate with the health care provider

      Prognosis

   Patients should understand that depression is a very treatable medical

disease and not a problem with their internal character. American society

strongly stigmatizes against mental disease. Depressed patients should be

treated. If active treatment is stopped, recurrence rates are high and patients

should be educated about what to look out for that would indicate relapse.

   Lifestyle changes are primary interventions that should be encouraged in all

patients. This includes activities such as exercise, nutrition, smoking cessation

and alcohol restriction.

   Exercise is an effective strategy in the management of depression. Exercise

in the depressed individual can be associated with other barriers due to the

disease. These include: low energy level and feelings of guilt if exercise

sessions are missed. Developing a plan that will maximize adherence is a critical

aspect in the prescription of exercise. Discuss with the patient what type of

exercise he/she enjoys (walking, swimming, group exercise). People comply

with exercises that they enjoy much more readily. Provide information about

aerobic exercise prescription guidelines so patients can derive benefits from

exercise.

   Patients should be taught about the FITT principal. This is a pneumonic to

help patients remember how to exercise aerobically. F stands for frequency,

which should occur 3-7 times a week. Exercise ideally should occur most days of
the week, but this is not the ideal strategy for someone who has low energy or

deconditioned. Use clinically judgment to determine how often a depressed

patient should exercise, encouraging them to gradually increase the number of

days they exercise as conditioning and energy levels allow.

   I stands for intensity. The intensity is how hard one exercises during an

exercise session. Multiple methods are available to gauge intensity. Patients

should exercise hard enough to increase the breathing rate and heart rate, but

not hard enough so they cannot carry on a conversation while exercising. More

sophisticated methods to gauge intensity exist – such as monitoring the heart

rate and exercising at 50-80% of the heart rate reserve (see table 2).

Table 2: Determining the heart rate for exercise using the heart rate reserve method
220-age = maximal heart rate

Maximal heart rate – resting heart rate = heart rate reserve

(0.5-0.8 x heart rate reserve) + resting heart rate = Exercise heart rate training zone

For example:

A thirty year old male has a maximal heart rate of (220-30) or 190 beats/minute. His

resting heart rate is at 70 beats per minutes. His heart rate reserve is therefore 190

– 70 or 120. To determine his heart rate training zone 120 is multiplied by 0.5 and

0.8 to yield: 60 and 96. To this the resting heart rate is added to yield the heart rate

that the exerciser should be in during his aerobic training session. (60 + 70) to (96 +

70) or 130 to 166 beats per minute.



   T stands for time. Exercise should occur for at least 30 minutes during each

exercise session. This may not be a realistic goal when initiating an exercise
program, but should be a goal for all patients. Exercising up to 60 minutes a day

is realistic in those who have the time, energy and conditioning to do so.

 The last T stands for type of exercise. Aerobic exercise should involve

exercises that use large muscle groups such as the legs. Appropriate aerobic

exercises include: walking, jogging, biking, swimming and group exercise

classes.

   While lifestyle interventions should be recommended for all patients, the use

of medications versus psychotherapy is a question of some debate. Determining

the severity of the depression is a factor in determining which treatment option is

recommended. For severe depression both psychotherapy and medications are

recommended12. When depression is mild or moderate either option is

appropriate12.

   Psychotherapy is effective. It often takes longer to see improvements in

treatment with psychotherapy than medications. It is recommended to

reconsider treatment options at 8-10 weeks before re-evaluation of the treatment.

It is most effective in individuals with severe psychological or psychosocial

issues. It is especially helpful in patients with chronic depression. It repairs

psychosocial and occupational functioning, improves depression symptoms and

prevents relapse12.

   One of the most popular methods of psychotherapy is cognitive-behavioral

therapy (CBT). CBT is one of the more popular forms of talk therapy. This type

of therapy often involves many tasks for the patient to involve themselves in,

such as journaling and other home work assignments. This method has been
made popular by David D. Burns in his book the Feeling Good Hand Book.

Cognitive behavioral therapy looks to modify negative thought processes and

behavior patterns to help the patient have more joy and less depression and

anxiety.

  Other types of therapy include interpersonal therapy, problem-solving

treatment, and short-term psychodynamic psychotherapy.

   Talk-therapies are an effective management strategy in the treatment of

depression. Part of their benefit is that they provide regular contact with the

health care system and helps the patient develop some responsibility.

Medications

   Medications are a mainstay for the treatment of depression. All

antidepressant have equal effectivness9. More important than which medication

is prescribed is how well the patients adheres to therapy.

  As discussed earlier, education is important in the treatment of depression, it is

very important when prescribing medications to patients. The length of treatment

is between 6-12 months after there is a remission. Side effects may initially be

more severe. As time elapses side effects often lessen. Nausea, a common

side effect with many medications, tends to abate after about a week. Teaching

patients to hang in there with mild side effects until the body adapts to the

medication is critical to enhancing adherence. Teach patients that they will not

feel better for a number of weeks. Early follow up is necessary to monitor for

response at which time a dosage adjustment is sometimes needed or a change

in medication is needed.
   Follow up must also assess for risk of suicide. Research suggests that young

adults, children and adolescents are at risk of suicide after treatment with

antidepressants. This often occurs after a depressed patient gets some energy

back and now has the energy to complete an act of suicide. Any increase in

irritability, agitation or another unusually psychiatric symptom may herald the

onset of a suicide attempt and must be evaluated.

   Multiple medications are available for the medical treatment of depression and

determining which medication to use requires evaluation of multiple factors.

Evaluation of any other medications tried in the past can be helpful. A positive or

negative response could steer the clinician toward or away from a particular

agent. An evaluation of co-morbid medical and psychiatric conditions should be

done. The clinician should evaluate other medications the patient is on to

evaluate for any medication interactions. Another consideration is the provider’s

familiarity with the medication. Having a complete understanding in regard to its

dosing, side effects, drug interactions and clinical effectiveness may only be

possible with a few medications.

   First line treatment for depression is the serotonin reuptake inhibitors (SSRIs).

These medications work by increasing the amount of the neurotransmitter

available in the brain. These are now considered first line treatment mainly

because of their safety profile.

   The tricyclic antidepressants (TCAs) were available before the SSRIs and

while effective, there were real safety concerns with these medications.

Foremost, they are unsafe in overdose. This is a critical point in the depressed
patient who may be at risk for suicide. Taking a handful of TCAs is likely to be

fatal, while a handful of SSRIs, while not recommended, is much less likely to be

fatal.

   TCAs, while as effective as first line agents, are not used as often due to side

effect profiles. They are associated with urinary retention, blurred vision, dry

mouth and constipation. They can also lead to orthostatic hypotension or cardiac

arrhythmia.

   TCAs are broken down into secondary (nortriptyline and desipramine) and

tertiary amines. Tertiary amines (amitriptyline, doxepine, and imipramine) are

linked to more sedation, cognitive changes and cardiac problems such as

orthostatic hypotension.

   TCAs are particularly effective in older patients in the treatment of depression,

but there is concern over side effects. Nortriptyline is considered the best first line

medication for the older adult in the treatment of depression and it should be

started at a low dose, titrated slowly and monitored closely for side effects.

Tertiary amines TCA should be avoided in older individuals.

   Fluoxetine (Prozac) was the first SSRI made available. This medication has a

long half-life (5 days). This makes the medication less likely to have the

discontinuation syndrome. The body naturally tapers the medication. It is dosed

20 mg once a day to start, with a maximum dose of 80 mg once a day. The

doses can be split into an AM dose and a noon dose. Fluoxetine also comes in a

weekly formulation as Prozac weekly, which is dosed once a week. It may

potentiate warfarin, digoxin, carbamazepine and phenytoin. Fluoxetine is
indicated for depression, bulimia nervosa, panic disorder and obsessive-

compulsive disorder.

   Fluoxetine is approved for depression in children (over the age of 8) and

adolescents, but it carries a black box warning (like all other SSRIs). There is an

increased risk of suicide noted when SSRIs are used in depressed adolescents.

Since the introduction of this warning there has been fewer cases of depression

diagnosed and decreased use of the medication in adolescents. Any adolescent

treated needs to be monitored closely – office visits every week for 4 weeks and

than every 2 weeks for one month and than every month for the next three

months. Any patient who the clinician is concerned about suicide should be

referred.

   Sertraline (Zoloft) has more of a sedating effect than fluoxetine and may be

useful in the management of an anxious depression. It is started at 25-50 mg

orally every day and than the dose can be increased gradually to 200 mg per

day. It may interact with cimetidine, warfarin, digoxin, and diazepam. It is

indicated for depression, premenstrual dysphoric disorder, panic disorder, PTSD,

OCD and social anxiety disorder.

   Paroxetine (Paxil) is most likely to cause discontinuation syndrome because

of its short half-life. It is comes in the standard form and an extended release

form the standard form is dosed 10 mg per day to start to a maximum of 50 mg

orally per day while the extended release form (Paxil CR) is dosed at 12.5 mg

once a day to a maximum of 62.5 mg orally every day.
   Paroxetine may interact with cimetidine, fosamprenavir, ritonavir, warfarin and

non-steroidal anti-inflammatory medications. It is indicated for depression,

premenstrual dysphoric disorder, panic disorder and social anxiety disorder.

        Fluvoxamine (Luvox) is indicated for obsessive-compulsive disorders but

    is often used off label in the treatment of depression and anxiety. The

    starting dose for adults is usually 50 mg once a day and 25 mg per day for

    children and adolescents. This medication has multiple drug interactions and

    notably interacts with many benzodiazepines.

   Citalopram (Celexa) is indicated for depression and is dosed at 20 mg once a

day and the dose can be increased to 40 mg once a day after one week. The

maximum dose is 60 mg once a day. The medication may be potentiated by

cimetidine, azole antifungal, macrolides or omeprazole. It is antagonized by

carbamazepine

   Escitalopram (Lexapro) is dosed 10 mg orally every day to start and it may be

increased to 20 mg everyday. It is indicated for depression and generalized

anxiety disorder. It interacts with carbamazepine, lithium, anticoagulants and

metoprolol (increases level).

  Side effects of SSRIs can vary between medications, but many side effects

have a class effect. Anorexia is common. Tremor and sweating also occur.

Headache and nausea can occur, but both will dissipate after the body gets used

to the medication. Sexual dysfunction can occur. Delay in orgasm is very

common – it can be used as a potential treatment for premature ejaculation.
   Increased risk of suicide is the most serious side effect. There is now a black

box warning for children and adolescents for this mediation. This works typically

by improving mood and energy to a point where the patient has the energy to act

on a suicidal plan. This is one of the major reasons that follow up is so

important.

   Serotonin syndrome is a condition characterized by an excess of serotonin in

the body. It is typically caused by an interaction of the SSRI with another

medication such as cocaine, amphetamines, Monoamine oxidase inhibitor

(MAOI) (the most common clinical interaction) or St John’s Wort. It is

characterized by a rapid onset of cognitive changes, elevated heart rate,

sweating, nausea, vomiting, hyperthermia, hyperreflexia, tremor, cognitive

changes. Treatment involves stopping the medication causing the syndrome and

supportive care including control of elevated body temperature, elevated blood

pressure, control of agitation; control of autonomic instability and in some cases

the administration of serotonin antagonists.

  The serotonin-norepinephrine reuptake inhibitors (SNRIs) are a newer class of

medication and have three medications in this class venlafaxine (Effexor),

duloxetine (Cymbalta) and desvenlafaxine (Pristiq). They effect both serotonin

and norepinephrine neurotransmitters.

   Venlafaxine – which is indicated for depression, GAD, panic disorder and

social anxiety disorder - is started at a dose of 37.5-75 mg orally once a day and

than titrated up by 75 mg no more than every four days. Generally pushing the

dose beyond 225 mg is not recommended in the outpatients setting. Possible
drug interaction can occur with venlafaxine and alcohol, non-steroidal anti-

inflammatory medications, cimetidine, diazepam, haloperidol, lithium,

ketaconazole, risperdal, imipramine and metoprolol. Common side effects

include nausea, constipation, sweating, dizziness, somnolence, dry mouth,

nervousness and sexual dysfunction including abnormal ejaculation. One

notable side effect is hypertension which is not common, but can be significant in

a patient with pre-existing cardiovascular disease or hypertension. Hypertension

is more common with higher doses.

   Duloxetine is indicated for depression, generalized anxiety disorder, diabetic

nerve pain and fibromyalgia. It is started at a dose of 20 mg twice a day for

depression and 60 mg once a day of GAD. It may be started at a lower dose of

30 mg once a day for GAD for the body to adapt to the medication. The dose

can be pushed to 30 mg twice a day for depression. It may interact with other

SSRIs, cimetidine, some fluoroquinolone antibiotics and tricyclic antidepressants.

   Desvenlafaxine (Pristiq) is the newest SNRI medication approved for treat

major depressive, generalized anxiety, social anxiety and panic disorders. The

recommended dose for Pristiq is 50 mg once a day. The most common side

effects are: nausea, constipation, dizziness, somnolence, anorexia, male sexual

dysfunction and anxiety.

   Other agents used to treat depression include: bupropion (Wellbutrin),

mirtazapine (Remeron) and nefazodone (Serzone).

   Bupropion is indicated for depression and seasonal affective disorder. It

should not be used in those with a seizure disorder, bulimia or anorexia nervosa.
Side effects include CNS stimulation with tremor, dizziness, difficulty sleeping,

and agitation, mania, dry mouth, nausea, palpitations, sweating, hypertension.

Because the side effects are very common symptoms of anxiety, those with co-

morbid anxiety disorder would not do as well on this medication.

   Mirtazapine is dosed at 15 mg per day to start and may be increased to 45

mg. It is typically dosed at bedtime because it is sedating. It may also lead to

weight gain as it increases appetite. Other side effects include: dizziness,

nausea, dry mouth and constipation. This drug is commonly used in nursing

home residents who are depressed and are losing weight as it may encourage

weight gain.

   Tricyclic antidepressants such as imipramine (Tofranil), amitriptyline (Elavil),

and nortriptyline (Pamelor) are effective older drugs used to treat depression but

are not used as frequently today because of the improved safety and side effect

profiles of the newer medications.

   Monoamine oxidase inhibitors (MAOI) are effective but rarely used today

because of the strict dietary restrictions, possible risk for hypertensive crisis and

multiple drug interactions. As a result, MAOI are rarely used for patients with

major depression and if they are used are used under the care of psychiatrist.

Patients who are most effectively treated are those with depression with atypical

features12.

   Early discontinuation is not recommended as it can be associated with

multiple negative effects. Early discontinuation is associated with relapse or

recurrence of symptoms. Early discontinuation is often self-prescribed and
therefore not done properly. Discontinuation often needs to happen gradually to

avoid a discontinuation syndrome.

   If the medication is going to be discontinued it should be tapered over 2-3

months. Discontinuation syndrome presents with flu-like symptoms, dizziness,

imbalance, insomnia, nausea and hyper arousal. With abrupt discontinuation of

medications the symptoms may last 1-2 weeks and sometimes longer. Cutting

the dose by 25% per week is a reasonable tapering schedule, but the patient

should be watched closely for any indication of discontinuation syndrome.

Certain medications are more prone to discontinuation syndrome including

agents with shorter half-lives, such as paroxetine, than in those with longer half-

lives, such as fluoxetine.

   Moreover, data is lacking regarding the optimal duration of treatment of

depression. A conservative estimate would be 6 to 12 months of antidepressant

therapy if the patient was experiencing their first episode of major depression9 13.

   Accordingly, any patient male or female, who is severely depressed, is having

suicidal ideation or has not responded to an adequate antidepressant trial,

should be referred to a psychiatrist for further evaluation and treatment.

Symptoms of psychosis are an indication for an emergency psychiatric

evaluation and/or hospitalization.

   Depression in pregnancy is a common problem. Depression can lead to risk

for both the mother and the fetus and needs to be evaluated for during

pregnancy. Untreated depression increases the risk of preterm labor,

preeclampsia and spontaneous abortion12.
   Treatment of depression in pregnancy is often done with behavioral

adjustment such as psychotherapy. Antidepressant therapy has not been

rigorously studied in pregnancy, but is considered relatively safe. Paroxetine is

the only medication that has shown some possible increase in risk12. The

remaining antidepressants have shown no increase in the risk of fetal

malformations, pregnancy complications, intrauterine death or behavioral

toxicity12. Paroxetine is associated with a slight increased risk of cardiovascular

malformations when compared to other antidepressants. This was only noticed

in patients who were on paroxetine in doses greater than 25 mg in the first

trimester.

   Another risk of depression in mothers is the risk of depression or another

mental illness in their child. Mothers with untreated depression have children

that have an 8% increased risk of having a psychiatric diagnosis. Children

whose mothers have treated depression have a11% reduced risk of psychiatric

diagnosis14.

   Caution should be used when prescribing antidepressants in breastfeeding

mothers. Small amounts of the medication will show up in the breast milk. It is

theoretically problematic when small amounts of medications show up in the

neonate’s blood as their immature clearance systems may lead to higher levels

in the blood. It is currently unknown if there will be any negative long-term

effects on the developing central nervous system. Therefore, it is generally not

recommended that breastfeeding mothers take antidepressants.
    Herbal treatment

   Herbal treatments are often tried in the management of depression. Multiple

agents are available for the management of depression, but none have been

rigorously studied and therefore should be used with extreme caution.

   Hypericum perforatum (St. John’s wort) is one of the most popular

medications. Data on the use of St. John’s Wort is variable. It has not been

proven to be overwhelmingly effective in the management of major depression12.

Some research shows that it is as good as traditional antidepressants while

some data shows that it is only minimally effective15.

   It is also associated with multiple drug-herb interactions. It interferes with

beta-blockers, digoxin, cyclosporine, oral contraceptives, simvastatin, warfarin,

fexofenadine and benzodiazepines. Side effects are not common and include

allergic reactions, nausea, insomnia, restlessness, irritability, dizziness, vivid

dreams, anxiety and dry mouth.      It is linked to the serotonin syndrome and

should not be taken when the patient is also taking a prescription antidepressant.

Dosing is inconvenient with 300 mg taken three times a day. It takes about one

month until effects are noticed

   SAM-e (S-adenosyl methionine ) is another alternative treatment used in the

management of disease. SAM-e is similar in efficacy to TCAs in the treatment of

major depression12. Side effects include: anorexia, nausea, constipation, dry

mouth, insomnia, dizziness, nervousness and sweating. It can be given

intramuscularly or orally. It is dosed between 400-1600 mg per day.

Follow up
   Follow up should initially occur on a weekly basis. The follow up can be via

phone or in person. When the patient stabilizes the follow up can be extended to

every 2-4 weeks. The goal during follow up is to help the patient reach remission

and at follow up appointments the medications or doses may need to be

adjusted.

   Response to treatment can be measured on formal scales such as the HAM-

D or the PHG-9. A full response is a greater than 50% reduction is symptoms

while a partial response is a 25-50% reduction in symptoms12.

   Once the patient has stabilized on the medication the patient should remain

on treatment for at least 6-12 months. Some patients are candidates for

continued pharmacotherapy or psychotherapy. Between 50-85% of people with

an episode of major depression have a repeat episode within 2-3 years12.

   Some patients do not respond to the initial treatment even when the dose is

pushed to the maximal dose. When there is not adequate response, other

conditions must be considered such as substance abuse, bipolar disease and

personality disorders. If other issues are present they must be addressed to

achieve control of symptoms. Evaluation of treatment compliance is another

issue that should be addressed. Clinicians often make the mistake of not

pushing the dose to the tolerable upper limit.

   If major depression remains the diagnosis another treatment approach should

be considered. Switching to different antidepressant medications may be

warranted. Recent trails showed some success when therapy was switched to

another medication in the same class or a different class of antidepressant
medications14. Adding psychotherapy is another option to achieve a remission.

Augmentation of therapy should also be considered in the management of

resistant depression (discussed below).

   Maintenance therapy is recommended for certain groups of depressed

patients to prevent another episode of major depression. Individuals who have

had two previous episodes of major depression, severe depression, a family

history of depression or old age at onset of depression (greater than 60) are

candidates for maintenance therapy. Those with a co-morbid anxiety disorder or

substance abuse disorder should also be considered for maintenance therapy.

Other factors that increase the risk of reoccurrence include: unable to achieve

remission, recurrence of symptoms when dose was decreased or lowered, and

preexisting dysthymic. For individuals with two episodes of depression,

medication should be continued for 3 years.

Expert consultation

   Primary care providers can manage depression just as well as specialty

care14. There are times that specialty care can be helpful. Patients who are

candidates for psychotherapy should be referred to a psychologist or a

psychiatrist with special training in talk therapy. Individuals with co-morbid

psychiatric conditions such as mania, personality disorder or substance abuse

should be considered for referral. Those at high risk for suicide are candidates

for expert care. Resistant depression may be better managed by a mental health

expert.

Augmentation therapy
   Those who fail to achieve remission on one medication could have there

therapy augmented by the addition of another medication. When augmentation

is considered a referral to an expert is recommended. Augmentation often

involves the use of medications that work through different mechanisms.

   Adding bupropion or mirtazapine to a SSRI is one strategy. Adding thyroid

hormone in the form of T3 between 25-50 mcg/day may be helpful.

   The addition of stimulant medications may be helpful in the augmentation of

someone with a low energy depression. The use of methylphenidate has been

used with SSRIs, but this should not be used in those with cardiac problems or

on other stimulant medications.

  The combination of TCA-SSRI has been used. Caution must be used as the

TCA level can be elevated with this combination resulting in cardiac problems.

Citalopram and sertraline result in the most modest effects12.

   Lithium is another agent that is used with antidepressants. Caution must be

exercised as serotonin syndrome may occur with SSRIs and lithium. Recent

trails suggest that lithium is not as effective as thyroid hormone14.

   Atypical antipsychotic medications with antidepressants are used in the

management of resistant depression. Aripiprazole is approved by the FDA as an

agent to augment depression. Concerns about side effects of these agents need

to be considered included weight gain, glucose intolerance, akathisia and tardive

dyskinesia.

Other therapies
   Other therapies are available in the management of depression including: light

therapy and Electroconvulsive treatment (ECT) therapy. Light therapy is an

effective treatment for seasonal affective disorder, but it may work for other types

of depression. Some evidence suggests that it may enhance the effectiveness of

antidepressant medications.

   ECT involves shocks to the brain under anesthesia. It is one of the most

effective treatments for major depression. Some patients are more suited for

therapy with ECT than others, including: geriatric, co-morbid Parkinson’s

disease, the patient with catatonia or psychotic features, unsuccessfully treated

with other antidepressants, past history of positive response to ECT, medication

compliance is questionable or in those who medications are risky.

   Vagus nerve stimulation uses an implantable device that stimulates the left

vagus nerve intermittently. It is indicated for resistant depression.

   Other therapies are available but due to non-approval status and lack of

evidence based many are not used. These methods include: transcranial

magnetic stimulation, magnetic seizure therapy, deep brain stimulation and

acupuncture.

   Hospitalization may occur in those who are severely depressed or those at

risk to harm someone else or themselves. It may also occur when the doctor

wants to closely monitor therapy, augment therapy or monitor drug levels.

Treatment of Anxiety

   Treatment of anxiety bears resemblance to the treatment of depression.

Lifestyle interventions for the management of anxiety is critical. Exercise as
outlined in the depression section should be encouraged. Proper diet is helpful

in the management of anxiety as it can help make the body resilient to stressful

situations. Stress and anxiety increase the risk of over or under eating and the

abuse of alcohol.

   Sleep is an important aspect to assure that the body is in balance. Many

lifestyle changes should be encouraged to enhance quality sleep. Regular

exercise, not eating heavy meals before bed, avoiding caffeine or alcohol before

bed will assist in improved sleep patterns. Relaxing activities before bed such as

listening to pleasant music, light reading, watching a light television program may

help aide in sleep.

   Changing the way of thinking can help reduce anxiety. This often requires

the help of a trained therapist, but encouraging patients to change negative

thought and behavior patterns can help reduce anxiety. Patients should be

encouraged to make a conscious choice to avoid anger over trivial matters and

attempt to adopt a humorous outlook on life.

   Relapse is common upon the discontinuation of treatment for anxiety16. In

order to minimize the risk of relapse, treatment should be continued for at least

12 months. When treatment is discontinued, monitoring for early warning signs

of relapse is critical. A common early warning signs of relapse is functional

impairment.

   Non-pharmacological treatments of anxiety disorders include: cognitive-

behavioral therapy, interpersonal therapy, stress management, and biofeedback

therapies.
   Psychotherapy is an effective therapy for anxiety disorders. CBT is a

common and effective treatment of generalized anxiety disorder. It involves

changing maladaptive thinking as well as changing behaviors. It entails the

patient objectively recognizing the thoughts that fabricate and maintain anxiety

and change these thoughts using techniques that change behavioral response

and eradicate the anxiety reaction. The treatment can last between 3 and 5

months. Other techniques are available in the management of anxiety disorders

including panic disorders such as: systematic desensitization, exposure and

response treatment, modeling treatment and relaxation. Overall, relapse rates

after psychological treatment are about 60 to 80 % after one year17.

    Medications

   Multiple agents are available in the treatment of GAD including

benzodiazepines; buspirone; TCAs; and selective serotonin-reuptake inhibitors.

Benzodiazepines - alprazolam (Xanax) and clonazepam (Klonopin), diazepam

(Valium), lorazepam (Ativan), and chlordiazepoxide (Librium) - provide short-term

immediate relief of anxiety.

     SSRIs are first line treatment options for anxiety disorders and are

approved in GAD, SAD, PTSD and phobia. Difficulties with the SSRIs include a

delay prior to effectiveness, usually two to four weeks, and the potential for

temporary anxiety to occur initially. A combination of a benzodiazepine and an

antidepressant has been used to avoid initial anxiety symptoms and hasten relief

from anxiety. A selective serotonin reuptake inhibitor (SSRI) may be initiated at

low doses and titrated upward for full therapeutic response in the treatment of
generalized anxiety disorder. SSRIs used for the treatment of GAD include

fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa),

and fluvoxamine (Luvox).

   SSRIs have similar effectiveness in the management of anxiety. Paroxetine

and sertraline are equally effective for the treatment of GAD and SAD, but

paroxetine may be more likely to cause weight gain16 18 19. Similarly paroxetine

and escitalopram were studied with one study showing paroxetine more

efficacious and the other showing sertraline more efficacious for SAD. The two

drugs were found to be equally effective for GAD16 20 21.

   SSRIs are likely effective agents in the management of anxiety across the

lifespan. Older adults with GAD respond favorably to escitalopram. In a recent

study, 177 adults over the age of sixty were studied with 69% of those taking

escitalopram showing reduced anxiety levels compared with 51% of placebo

patients. In addition, individuals on escitalopram showed more improvement in

functioning, social function and activity level. One interesting aspect of the study

suggested that those treated with medication had a significant decrease in blood

pressure22.

   Likewise children showed an improvement in anxiety symptoms when treated

with SSRIs. The SSRI, sertraline, was given to children ages 7 to 17 and 55% of

patients improved. This was over double the number (24%) of patients on

placebo in this study who improved23.

   This study also looked at the effect of cognitive behavioral therapy on anxiety.

It showed that 60% of patients who had cognitive behavioral therapy as a
treatment for anxiety had an improvement. The most striking part of the study

suggested that the combination of medication and cognitive behavioral therapy

was most effective for the management of anxiety in children. Eighty-one

percent of those who got this combination showed improvement23.

   Multiple issues – mainly dependency, abuse and side effects – limit the use of

benzodiazepines in the treatment of anxiety. Side effects include daytime

drowsiness, psychomotor impairment and weight gain. Patients should be

cautioned not to combine alcohol and benzodiazepines. Experts differ on limiting

benzodiazepines to short term use or recommending relatively long-term use in

individuals with no history of substance abuse who can be closely monitored.

Some authorities do not recommend benzodiazepines as monotherapy or as

first-line treatments for generalized anxiety disorder4.

   A common problem with benzodiazepines is the loss of effectiveness over

time with continued use at the same dosage. Tolerance may develop to the

anxiolytic effects of benzodiazepines. Dependence can occur as early as three

months. Discontinuing benzodiazepines after long periods of use may result in

rebound symptoms such as sleep disturbances and anxiety, withdrawal

symptoms, including stomach distress, sweating and insomnia.

   Venlafaxine and duloxetine are indicated for the treatment of GAD and are

often chosen as first line agents in its management. Other medications used to

treat anxiety include: nefazodone (Serzone), which is indicated for depression

and panic disorder and mirtazapine (Remeron), a unique antidepressant known
as a 5-HT2 blocker, which may be effective for generalized anxiety disorder, but

is not indicated for GAD1.

   Azaspirones are a class of drugs proving useful in the treatment of

generalized anxiety disorder. Buspirone (BuSpar) is an azaspirone that has

been effective even with long-term use. It is not addictive and appears to have

less pronounced side effects and no withdrawal effects. It causes fewer CNS

effects such as sedation and psychomotor impairment than benzodiazepines and

may be better for those patients whose work requires mental acuity. It usually

takes 2 to 4 weeks to be effective9. Due to its low potential for abuse, buspirone

is useful in persons with anxiety and alcoholism. Common side effects include

dizziness, drowsiness, and nausea. Patients who have been taking

benzodiazepines may respond less well to buspirone.

   Other drugs used as alternatives to the benzodiazepines and SSRIs for the

treatment of anxiety disorders include the tricyclic antidepressants. Many prefer

them to benzodiazepines for the treatment of generalized anxiety disorders; and

they are better suited for medium or long-term therapy or when depression is

also present. For people with co-morbid conditions of generalized anxiety

disorder and depression, doxepin (Sinequan) has been beneficial. Imipramine

and doxepin are tricyclic antidepressants with the unlabeled use for treatment of

anxiety. Side effects often limit the use of tricyclic antidepressants and include

sleep disturbance, orthostatic hypotension, weight gain, sexual dysfunction, and

mental disturbance.
   Pregabalin (Lyrica) is used in the treatment of anxiety and effectively treats

symptoms of GAD. It is not indicated for these uses, but is sometimes used by

clinicians. It is associated with an onset of action in about one week.

Interestingly it may also improve co-morbid depression. Unlike SSRIs and

SNRIs it is associated with few withdrawal symptoms24.

   SAD is treated with medication and psychotherapy. SSRIs are first-line

medications in its management. Venlafaxine is another option in the

management of SAD. No agent is approved for individuals less than 18 years

old, but many medications are likely effective in the under 18 year old population.

Benzodiazepines, buspirone are also useful in the management of SAD.

Although infrequently used, MAOIs may be used as well. The beta-blocker,

propranolol, can mitigate the autonomic response in social phobia and reduce

heart rate and tremor. Levetiracetam and topiramate have been studied in the

treatment of SAD. They are well tolerated, although not approved for use, but

are often effectively used in the management of treatment resistant SAD16.

   Psychotherapy, CBT, is also used in the management of SAD. Gradual

desensitization, insight therapies are major parts of therapy in the management

of SAD.

   The treatment of OCD includes medications, behavior therapy, education and

family interventions. Surgery can be performed in rare cases of OCD. SSRIs,

clomipramine (Anafranil) and venlafaxine are commonly used to treat the

disorder. Many medications commonly used for OCD do not have an indication

for OCD.   Higher doses (than for depression) and up to 10 weeks is needed
until effect is noticed. Most patients do not obtain a full remission, but only a

reduction in symptoms with medications.

   The addition of CBT, with a trained psychotherapist, is helpful. An important

part of therapy is the exposure and response (or ritual) prevention (ERP).

Threatening situations are ranked and the person is gradually exposed to these

situations with the goal of decreasing the compulsive behavior to this response.

This process can be difficult and take a long time to succeed. Another important

aspect of CBT is recognizing and challenging the cognitive distortions of OCD

symptoms.

   For those individuals who do not respond to treatment should be referred for

expert care by a psychiatrist for advanced medication management. .

   PTSD is best treated if it can be done soon after the traumatic event. Like

other anxiety disorders it responds most favorable to a combination of

medications and therapy (group, individual, family etc). Children and teenagers

respond better to psychological therapy.

   Panic attacks are treated with SSRI as primary agents along with CBT.

Benzodiazepines can be used for quick relief and are often used while the SSRIs

take effect. They are used in some for long-term management but should only

be used in cases that do not respond to SSRIs or TCAs. Clonazepam is a

preferred agent as it has a longer half-life and should have fewer withdrawal

effects and less dependency issues than the more commonly used alprazolam.
   CBT should be used with medications and may be used alone. Therapy looks

at the patients distorted beliefs and looks to desensitize the patient to anxiety

provoking situations.

    Conclusion

   Depression and anxiety are conditions that have significant impact on the

quantity and quality of life. Identification of the disease is not complex, but both

diagnoses are often missed. Regularly evaluating patients for depression and

anxiety will improve identification and consequently improve outcomes.

Treatments for each disease are similar and include lifestyle modifications,

psychotherapy and medications.

Case Study Revisited

   The patients was given a quick screening in the office using the SIG-E-CAPS

criteria. While she denied depression she did test positive for Sleep disturbance,

loss of Interest (key criteria), lack of Energy, poor Concentration, excessive

Appetite and Psychomotor agitation. Based on these findings she was treated

with citalopram 20 mg everyday with a follow up in 10 days.

   At the ten day follow up appointment she reported that she had some initial

nausea, but did notice that her sleep had improved. The nurse practitioner

increased her dose to 40 mg and had a follow up in one month. At the one

month appointment she reported that she felt much better. She reported that her

husband has made several comments on her reduced irritability. She has

recently became more active in her church group.
1
       Yates WR. Anxiety. 2008. (cited 2008 December 15). Available from:
URL: http://emedicine.medscape.com/article/286227-print
2
       Seitz DP. Screening mnemonic for generalized anxiety disorder.
Canadian Family Physician 2005; 51(10): 1340-1342.
3
       Healthy People 2010. DATA 2010. (cited 2008 December 26). Available
from: URL: http://wonder.cdc.gov/data2010/focus.htm
4
        Fredman S. & Korn M. Anxiety Disorders and Related Conditions. 2007.
(cited 2008 November 27). Available from: URL:
http://www.medscape.com/viewarticle/436399
5
       van den Bemt L, Schermer T, Bor H, et al. The risk for depression co-
morbidity in patients with COPD. Chest. 2009;135(1):108-114
6
       Green LA, Dickinson WP, Nease DE Jr, et al. AAFP guideline for the detection
and management of post-myocardial infarction depression. Annals of Family
Medicine 2009; 7(1): 71-9
7
       Dunbar JA, Reddy P, Davis-Lameloise, N et al. Depression: an important
co morbidity with metabolic syndrome in a general population. Diabetes Care.
2008; 31(12):2368-73.
8
       Volgsten H, Skoog-Svanberg A, Ekselius L et al. Risk factors for
psychiatric disorders in infertile women and men undergoing in vitro fertilization
treatment. Fertility and Sterility. 2008 Dec 30. [Epub ahead of print}.
9
       Bhalla RN & Moraille-Bhalla P. Depression. 2008. (cited 2008 December
15). Available from: URL: http://emedicine.medscape.com/article/286759-print
10
       American Psychiatric Association. Diagnostic and statistical manual of
mental disorders. 4th ed. Washington, D.C: American Psychiatric Association,
2000.
11
      Korn M & Pollock R. Anxiety Disorders: Science and Clinical
Understanding. (cited 2008 November 27). Available from: URL:
http://www.medscape.com/viewprogram/1974
12
       Institute for Clinical Systems Improvement. Major Depression in Adults in
Primary Care. Eleventh Edition, May 2008. Available from: URL: www.icsi.org
13
       Pies R & Rodges D. The Recognition and Treatment of Depression: A
Review for the Primary Care Clinician (cited 2008 November 8) Available from:
URL: http://www.medscape.com/viewprogram/4572_pnt
14
       Gaynes BN, Rush AJ, Trivedi MH et al. The STAR*D study: Treating
depression in the real world. Cleveland Clinic Journal of Medicine 2008; 75(1):
57-66.
15
       American Pharmacists Association. Popular Herbal and Dietary
Supplements. 2007. (cited 2009 January 8). Available from: URL:
http://www.nphealthcarefoundation.org/ce/otc/
16
       Starcevic V. Anxiety States: A Review of Conceptual and Treatment
Issues. Current Opinion Psychiatry 2006; 19(1): 79-83.
17
        Gliatto M. Generalized Anxiety Disorder. American Family Physician
2000; 62:1591-600,1602
18
        Bandelow B, Behnke K, Lenoir S, et al. Sertraline versus paroxetine in the
treatment of panic disorder: an acute, double-blinded non-inferiority comparison.
Journal of Clinical Psychiatry 2004; 65: 405-413.
19
        Ball SG, Kuhn A, Wall D et al. Selective serotonin reuptake inhibitor
treatment for generalized anxiety disorder: a double,-blind, prospective
comparison between paroxetine and sertraline. Journal of Clinical Psychiatry
2005; 66: 94-99.
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escitalopram in 12 and 24 week treatment of social anxiety disorder: randomized,
double-blind, placebo controlled, fixed-dose study. Depression and Anxiety.
2004; 19: 241-248.
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Medical Association 2009; Jan 21. [Epub ahead of print}.
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24
         Pohl RB, Geltner DE, Fieve RR et al. Efficacy of pregabalin in the
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2005 ;25(2): 151-8.
      Quiz
      1) Major depression is.
      Self limiting
      *Likely to reoccur
      Is not associated with higher death rates
      Is part of a normal grief reaction

      2) Which is a risk for major depression?
      African American
      *Having chronic obstructive pulmonary disease
      Being male
      Witnessing a traumatic event

      3) For anxiety, benzodiazepines:
      Do not help with situational, short-term anxiety
      Are associated with alcohol abuse
      *Are quicker in onset of action than selective serotonin reuptake inhibitors
(SSRIs)
      Are associated with reduced rates of depression

      4) Which symptom is least suggestive of anxiety:
      Irritability
      Insomnia
      *Flat affect
      Reduced ability to concentrate
       5) Dysthymia is a milder depression that tends to persist.
       *True
       False

        6) Diagnostic testing for a patients with depression should include all of
the following EXCEPT:
        Thyroid stimulating hormone levels
        Complete blood count
        *Lipid panel
        Basic metabolic panel

       7) Which medication is the best first line option for major depression:
       *Citalopram (Celexa)
       Nortriptyline (Pamelor)
       Alprazolam (Xanax)
       Mirtazapine (Remeron)

      8) When discontinuing SSRIs it important to taper them over a period of
weeks.
      *True
      False

     9) Tricylcic antidepressants are not used as first line medications in the
management of depression because of all of the following reasons EXCEPT:
     Association with confusion in the elderly
     Risk of constipation
     *It is associated with increasing anxiety
     They are often fatal in overdose

       10) Medication treatment of the first episode of major depression should
last _______ after remission :
       *6-12 months
       For life
       Two years
       3-6 months

       11) SSRIs are contraindicated in patients with glaucoma.
       True
       *False

       12) Which anti-depressant has the fewest sexual side effects:
       Venlafaxine
       Sertraline
       *Bupropion
       Paroxetine
      13) Which anxiety is characterized by a baseless morbid fear of
apparently harmless objects often leading to agoraphobia.
      Generalized anxiety disorder
      Obsessive compulsive disorder
      *Panic disorder
      Post-traumatic stress disorder

      14) Depressed patients should be encouraged to:
      Initiate an exercise program 5-7 times a week
      Exercise for 10-15 minutes each session
      Perform weight training as a type of aerobic exercise
      *Encourage up to an hour of exercise a day in those whose conditioning
and energy level allows

      15) The A in the SIG-E-CAPS mnemonic stands for:
      Anxiety
      Agitation
      *Appetite changes
      Anhedonia

      16) In teen-agers, which is the most effective treatment in the
management of anxiety:
      Watch and wait therapy
      Selective serotonin treatment
      Cognitive-behavioral therapy
      *Combination therapy with cognitive-behavioral therapy and a selective
serotonin therapy

      17) Which SSRI is least likely associated with the discontinuation
syndrome?
      *Fluoxetine
      Paroxetine
      Sertraline
      Citalopram

      18) Which is linked to depression?
      Chronic obstructive pulmonary disease
      Metabolic syndrome
      Myocardial infarction
      *All of the above

      19) Which medication is least likely to cause the serotonin syndrome
when combined with the SSRI sertraline:
      *Buspirone
      St. John’s Wort
      Venlafaxine
      Paroxetine

      20) The effects of buspirone may not be noticed for 2-4 weeks.
      *True
      False

     21) Which medication is associated with the highest risk in pregnant
women?
     Fluoxetine
     Sertraline
     *Paroxetine
     Citalopram

      22) Mirtazapine is associated with sedation.
      *True
      False

      23) Which medication is likely to interact with SSRIs?
      Warfarin
      Digoxin
      Cimetidine
      *All of the Above

      24) Tapering of SSRIs should occur by _____% every week.
      10
      *25
      50
      75

      25) Which of the following is NOT a symptom of abrupt withdrawal from
paroxetine?
      *Sexual dysfunction
      Dizziness
      Nausea
      Hyper-arousal

      26) Which medication is not recommended for the patient with anxiety?
      Paroxetine
      Sertraline
      Venlafaxine
      *Bupropion
       27) Which benzodiazepine is recommended due to fewer dependency
issues in the patient with panic attacks?
       Lorazepam
       Anafranil
       Alprazolam
       *Clonazepam

       28) Benzodiazepines are the first-line long-term treatment in panic
attacks.
       True
       *False

       29) Which statement is true regarding anti-depressant medication therapy
       Nausea typically persists for the first 2-3 months of therapy
       *Improvement in symptoms may not be noticed for 4-8 weeks.
       Abrupt discontinuation of the medication will result in minimal side effects
       Monoamine oxidase inhibitors are the most effective medication used to
treat depression

      30) Which of the following statements about St. John’s Wort is FALSE?
      It is dosed three times a day
      *Its effects are noticed in 10 days
      It has multiple drug-herb interactions
      Should not be used with paroxetine

								
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