Photosensitivity

Anxiety and panic disorder associated with peginterferon/ribavirin may stem from a

malfunction of the neurobiologic substances norepinephrine, serotonin, and dopamine,

causing excitation of nerve impulses. These neurotransmitters regulate mood, movement,

and blood pressure. Gamma-aminobutyric acid inhibits neurotransmission in the brain

and is closely associated with benzodiazepine receptors. Theories regarding the cause of

the malfunction include chemical excess or deficit, or oversensitivity to chemical

Approximately 19.1 million American adults aged 18 to 54 years suffer from anxiety, and

approximately 2.4 million suffer from panic disorder.1 Anxiety appears to affect twice as

many women as men. However, psychologists believe that men are less likely to report or

even acknowledge having an anxiety disorder, so the disparity between the sexes may not

be so wide.2 Anxiety can be the result of physical or psychological factors, and is

ACUTE2,3: Manifests as episodes commonly called panic attacks. A panic attack is an

instance in which the body’s natural “fight or flight” reaction occurs at the wrong time.

This is a complex, involuntary physiologic response, with increased production and

release of hormones, especially adrenaline, and norepinephrine. These attacks are abrupt

and intense, can occur at any time, and can last from a few seconds up to half an hour,

with the patient incorrectly believing they are having a myocardial infarction or stroke.

The patient often reports being overwhelmed by a sense of impending disaster or death,

hence they are unable to think clearly. Other side effects at this time may include

dyspnea; a smothering, claustrophobic sensation; tachycardia; palpitations; chest pain;

dizziness; hot flashes and/or chills; trembling; numbness or tingling of the extremities;

diaphoresis; nausea; abdominal pain; diarrhea; a feeling of unreality; and a distorted

perception of the passage of time. The attacks themselves are unpredictable; some

experience one every few weeks, while others report several per day. Many fear having a

panic attack while alone or in public, which can lead to social isolation and diminished

CHRONIC2,3: Chronic anxiety is a milder, more generalized form of the disorder. In this

instance, patients suffer a vague sense of anxiety most of the time, although the intensity

of the feeling does not reach the level of those experiencing a panic attack. Chronic

unease, especially in the presence of other people, combined with a tendency to startle

easily, is often seen in this type of anxiety. Headaches and chronic fatigue are common

complaints among people with this form of anxiety. Although chronic anxiety can begin

at any age, onset usually occurs in a person’s 20s or 30s, and appears to run in families.

Mitral valve prolapse patients have an increased incidence of this form of anxiety.

Finally, people with chronic anxiety disorder exacerbation often report being under

Eventually, the disorder can have cumulative effects, such as generalized aches and

pains, muscular twitching and stiffness, depression, insomnia, nightmares, early waking,

decreased libido, and abnormal feelings of tension with an accompanying inability to

relax. Women often report changes in their menstrual cycles and increased premenstrual

symptoms. Other sequelae of incorrectly managed anxiety and panic include alcohol and

drug abuse, sexual dysfunction, increased physical illness, depression, and suicidal

ideation and risk. In individuals with depression, symptoms of anxiety may develop as

they begin to have increasing difficulty initiating or completing even the simplest

1. Educate the patient regarding disease, treatment, subcutaneous injection, side effects,

2. Provide contact numbers—office nurse, local hepatitis C support group, and “buddy,”

3. Perform pretreatment assessment for current/past history of anxiety or panic disorder,

and/or depression. Consider prescription antidepressants prior to or concomitantly

with therapy to prevent progression of the disorder. See “Depression” section for

4. Discuss expectations of therapy including side effects and management, and make

specific plans for behavior modification in individuals with prior psychiatric history.

This may prevent onset of symptoms or prompt reporting of the development of new

5. Involve family members in education and treatment planning to minimize “sick role.”

1. Reduce or eliminate alcohol, caffeine, nicotine, and other stimulants, and to eat

· Certain medications; illegal drugs · Food allergies/sensitivities · Hypoglycemia

· Caffeine-based products and other stimulants · Crowded environments · Mitral valve prolapse

· Unfamiliar surroundings/situations · Hormone-secreting tumors · No apparent cause

exercises and tapes, guided imagery, and meditation. Talking with family or friends

4. Exercise: walking, swimming, yoga, aerobics, etc. Conversely, assess for and ensure

1. Re-educate patient as necessary regarding hepatitis C, treatment, potential side

effects, symptom management, and stimulants and other causes or triggers of panic

2. Instruct patient how to manage panic attacks: Inhale to a count of four, exhale slowly

to a count of four, do nothing to a count of four; repeat until the attack subsides.

4. Advise the patient to create relaxation times throughout the day and evening,

6. Consider withholding interferon-based therapy until the patient is stable, or

neurotransmitters. This class of drugs is considered first-line. Initial starting dose is

generally lower than that used for depression to minimize exacerbation of anxiety.

benefit. Side effects may include nausea, diarrhea, loose stools (sertraline [Zoloft®]),

constipation (paroxetine [Paxil®]), insomnia, sedation (minimal and time-limited),

headache, dizziness, fatigue, tremor, nervousness and anxiety, sexual dysfunction

anorgasmia. Advantages include low level of toxicity and decreased lethal effect in

2. TCAs: various ratios of adrenergic/serotonergic reuptake inhibition. Proven effective.

Side effects may include dry mouth, blurred vision, increased intraocular pressure,

constipation, urinary retention, weight gain, sexual dysfunction, decreased seizure

threshold, and increased toxicity in the elderly and those with suicidal ideation. TCAs

3. Dual mechanism antidepressants: block serotonin and norepinephrine. Side effects

4. Midazolam (Versed®) or hydroxyzine (Vistaril®, Atarax®) may be utilized by

5. Benzodiazepines: may increase inhibiting effect of gamma-aminobutyric acid and

other inhibitory transmitters by binding to receptors in the CNS. Side effects may

include drowsiness, dizziness, hypotension, confusion, hypersensitivity, HA, stupor,

usually beneficial for a limited time period (1 month or less), can be addictive, and

withdrawal can lead to seizures and death if not managed carefully. These drugs have

1. National Institute of Mental Health. The Numbers Count: Mental Disorders in America:

Anxiety Disorders. Web site: www.nimh.nih.gov/publicat/numbers.cfm. Accessed October

2. Balch JF, Balch PA. Prescription for Nutritional Healing. 2nd ed. Garden City, NY: Avery

3. Knesper DJ, Riba MB, Schwenk TL. Primary Care Psychiatry. Philadelphia, Pa: W. B.

4. Renault P, Hoofnagle JH, Park Y, et al. Psychiatric complications of long-term interferon alfa

5. Valentine AD, Meyers CA, Kling MA, Richelson E, Hauser P. Mood and cognitive side

6. Drug Facts and Comparisons: 2000. 54th ed. St. Louis, Mo: Facts and Comparisons;

NOTE: See “Depression” section for antidepressant agents and further information.

IRRITABILITY/LABILE AFFECT

PATHOPHYSIOLOGY

Use of peginterferon/ribavirin therapy has been associated with personality changes, such

as irritability and labile affect. This pattern of personality changes is suggestive of

frontal-subcortical dysfunction. The brain dysfunction may be a clinical manifestation of

depression. Interferon causes depression by altering neuroendocrine or neurotransmitter

functions or by modulating the expression of cytokines.1 One of several potential

mechanisms is altered serum levels of tryptophan (a serotonin precursor), suggesting that

serotonin depletion might be responsible for the reported interferon-induced irritability

and labile affect.

PREVENTIVE STRATEGIES

1. Assess patients prior to and monthly during treatment for depression utilizing a

standardized tool (eg, CES-D).

2. Consider psychiatric evaluation prior to initiating antiviral therapy in patients with a

current episode of depression or a history of depression, history of psychiatric

hospitalization, history of substance abuse or chemical dependence, family history of

depression or suicide attempts, history of posttraumatic stress disorder, or history of

violent or abusive behavior.2,3

3. Follow closely patients with concurrent or previous problems with substance or

alcohol abuse. Look for relapse of substance abuse or signs of depression.

4. Be aware that some patients may minimize or deny symptoms of irritability and labile

affect because of embarrassment or fear of dose reduction or treatment cessation.

5. A high score on the CES-D self-assessment (particularly if the score was low or

normal prior to treatment, or if the score is increasing) strongly suggests the need for

a psychiatric evaluation.4

TREATMENT STRATEGIES

Patients should be encouraged to:

1. Engage in mild to moderate aerobic and/or anaerobic exercise, as a mechanism to

channel anger and irritability.

2. Try meditation/relaxation techniques (yoga, biofeedback, imagery, massage).

3. Maintain good sleep habits (consistent times for sleeping; avoid caffeine; consume

tryptophan-containing foods, such as warm milk, turkey, and salmon).

4. Avoid overstimulating environments (crowds, heavy traffic, loud noise).

5. Ensure adequate hydration (consumption in fluid ounces = one half body weight in

pounds; eg, a 160-lb person should consume 80 fl oz/d).

6. Enjoy small pleasures (movies, music, friends, pets, laughter, positive reminiscence).

7. Recognize and report warning signs (early detection and intervention are crucial).

Side Effects Management Handbook • XI. Psychologic • p. 12

Providers should consider:

1. Educating and supporting families to cope with unpredictable, difficult personality

changes and mood swings

2. Citalopram (Celexa®), escitalopram (Lexapro®), sertraline (Zoloft®), venlafaxine

(Effexor®), and mirtazapine (Remeron®): may offer the added advantage of fewer

potential interactions with other medications5

3. Nefazodone (Serzone®), bupropion (Wellbutrin®), and venlafaxine (Effexor®): firstline

antidepressants that have a sedating effect, reducing irritability and combative

behavior

4. Trazodone (Desyrel®): useful adjunct for sleep disturbance and is well tolerated

5. Gabapentin (Neurontin®): may prove useful for mild to moderate irritability or

impulsivity in the absence of depressive symptoms. Gabapentin has few significant

drug interactions and is not metabolized by the liver.

6. Augmenting strategies combining two antidepressants, dose reductions, or drug

holidays: may be beneficial in controlling labile affect and irritability for patients

resistant to the above single-drug interventions

7. Referring for psychiatric consultation and/or family counseling

8. Discontinuing treatment if all other alternatives fail

Other Nervous System Side effects
The most frequent neurological side effects of interferon therapy are slowed thinking, difficulty concentrating, depression, lack of spontaneity, apathy, memory loss and confusion, and paresthesia, (an abnormal sensation, such as a burning, prickling feeling of the body). Some symptoms such as somnolence, insomnia, irritability, and anxiety are frequently reported. Be aware that the use of any depressants, tranquilizers, sedatives, narcotics, and alcohol may make these side effects worse.

Nervous System Side Effects... Depression
It is helpful to know that interferon affects the frontal lobe of the brain. The medication can cause depression in some people even if they have had no history of depression in the past. Not everyone on interferon therapy experiences depression, but for those whose lives are affected, it can be a very difficult time for the patient and the family. Knowing what to look for and what to do is very important.

First of all, learning that you have been diagnosed with hepatitis is difficult for anyone, and experiencing even a few weeks of sadness can be expected. But when your feelings begin to interfere with activities of daily living, it could mean that you are experiencing depression related to your therapy.

What are the signs and symptoms of depression? How can I tell if depression is affecting me? Your doctor or health care provider will be your best resource to evaluate your individual concerns. The following questions may help you determine if your emotions are being impacted by the interferon.

Is your mood depressed most of the day, nearly every day?
Are there feelings of sadness or emptiness everyday?
Do you feel a marked diminished interest or pleasure in all, or almost all activities, most of the day every day?
Is there a decrease in your appetite that is causing weight loss?
Are you having trouble falling asleep or wakefulness, (waking up after falling asleep)?
Do you feel like "sleeping-in" most days and prefer being alone more than before?

Severe depression can be very serious, and any thoughts of suicide should be reported to your doctor immediately. If you or your family member is having these side effects, you need to report them to your doctor or health care provider. Depression is a known side effect of this therapy and much can be done to manage it. You must be the one to reach out for help and discuss your feelings. There is effective treatment available for depression. Dont suffer in silence.

Fatigue
Fatigue is very common among people receiving interferon therapy. Fatigue is a feeling of tiredness that can keep you from doing the things you normally do or want to do. Factors such as hepatitis itself, low blood counts, nutritional problems and sleep problems contribute to fatigue. The exact cause of fatigue is not known.

Feeling weary or exhausted (physical, emotional, and/or mental exhaustion)
Feeling of heaviness, especially your arms and legs
Less desire to do normal activities like eating or shopping
Finding it hard to concentrate or think clearly

What can I do to manage my fatigue?
Everyone experiences fatigue and treatments differ. You may not feel tired while someone else does, or your fatigue may not last as long as someone else's does. Here are some tips to help you cope with fatigue:

Plan your day so that you have time to rest.
Take short naps or breaks rather than one, long rest period.
Eat a well-balanced diet and drink, at least, six 8-ounce glasses of fluid every day.
Administer your interferon at bedtime.
Take short walks or do light exercise if possible.
Try easier or shorter versions of activities you enjoy.
Try activities that are less strenuous, like listening to music or reading.
Keep a diary of how you feel each day. This will help you plan you daily activities.
Join a support group. Sharing your feelings with others may ease the burden of fatigue.
You may learn coping hints from talking about your situation.
Become comfortable having others do some things that you usually do.
See what helps you feel less tired, and make those activities a priority for you.
Save your energy for the most important things.
What symptoms should I report to a health care professional?
Call your nurse/ physician if you:

Get dizzy
Feel a loss of balance when walking
Feel a loss of balance when getting out of bed or out of a chair
Fall or hurt yourself
Have a problem waking up
Have a problem catching your breath
Have a sudden increase in fatigue

When is rest not the best treatment for interferon related fatigue?
You may be advised to "take it easy" and "get plenty of rest." Sometimes staying in bed over a long time can slow your body down and cause you to feel even more tired.

What can family or significant others do to help with interferon treatment related fatigue?

Do not push yourself to do more than you can do.
Ask your family or friends to help you with tasks you find difficult or taxing; like mowing the lawn or grocery shopping.
It may be difficult for family members to understand if rest does not make your fatigue go away. Explaining that the fatigue you feel is different from the fatigue you had before treatment may help them understand.

Toxins from a diseased liver may trigger feelings of rage and anger.
What's Eating you? by Nathaniel Mead