Hello All,
I was looking for something in my files, and ran across this post dated
January 28, 1996 from Alan Bonander. Since there has been a lot of discussion
on this subject, I thought it may be helpful to read this.
Regards,
Margaret Tuchman(54yrs,dx1980) --NEW JERSEY
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From: [log in to unmask]
Subject: Depression in PD
Please read this slowly and understand that I am learning how to put a "gut
brain" together with a "normal" brain, finding pain in places where none
exists. PD is like fighting a war on many fronts and thanks to this list
server, each day I learn more about the enemy. Each time I look at my
generals researching the enemy as they see them, I realize the complexity of
the problem. We really need additional funding -- pass the Udall Bill and
other bills so the war can really begin.
Here is depression in Parkinson's disease. Please read slowly.
DEPRESSION IN PARKINSON'S DISEASE
(A Supplement to the Video)
by Alan Bonander
NOTE: This paper is a written supplement to the video of the presentation
called 'Depression in Parkinson's Disease' by Neal Slatkin, MD, a
presentation made at the state-wide meeting of YPSN of CA on June 10, 1995 in
Duarte, CA. Dr. Slatkin is a neurologist, parkinsonologist and director of
the Parkinson Center at the City of Hope Medical Center in Duarte,
California.
INTRODUCTION
Our sixteenth president, Abraham Lincoln, stated, "I am now the most
miserable man living. If what I feel were equally distributed to the whole
human family, there would not be one cheerful face on the earth. Whether I
shall ever be better, I cannot tell, I awfully forebode I shall not. To
remain as I am is impossible. I must die or be better, it appears to me."
This is one of the best statements on the problems of depression. An
eminent psychiatrist once said that more human suffering can be attributed to
depression than any other illness affecting mankind.
Approximately 6% of the US population will have a major depression sometime
during their life. A major depression is one which significantly limits
one's functionality. In the older population, depression is a very
significant problem. There are about 45 million people over the age of 65.
It is estimated that between 10% and 20% of these people are having a major
depression at any point in time. That means somewhere between 4.5 million
and 9 million older people are having a major depression at any point in
time.
If we look at a list of all causes of mortality in 1992, suicide is listed
between HIV(AIDS) and homicide. Surely if we have an epidemic of HIV(AIDS)
and an epidemic of crime in this country, we have an epidemic of suicide.
And suicide is only the tip of the iceberg when it comes to depression.
Costs are important in our society today. It is estimated that depression
costs $45.3 billion annually. That is composed of $14 billion for direct
costs (inpatient, outpatient, drugs), $7.5 billion for death from suicide,
$12.1 billion from decreased productivity and $11.7 billion from absenteeism.
DEPRESSION IN PD
Depression is the most common neuro-psychiatric disturbance among PD
patients. It is more common than psychosis, confusion and dementia. The
prevalence in PD, which is about 40%, is higher than for any other chronic
illness that is matched for similar degree of functional impairment. Of
those with depression, about 50% are having a major depression. The other
50% are having a minor or mild depression which only sucks all the joy out of
their lives.
In a study performed at Columbia in New York, it was found that the annual
incidence, (number of new cases), of depression among Parkinson's patients
was 1.90% which was over 10 times the annual incidence of depression in the
general population of 0.17%.
Depression seems to appear at anytime. It is often present at time of
diagnosis, after several years and with increasing physical impairments.
Depression can also appear during episodic periods. About 70% of those
experiencing random "ON-OFF" cycles are more depressed when they are "OFF."
This change can happen almost instantaneously when they turn "OFF."
It appears that more females have depression (this is questionable) and those
with a past history of depression. Also those experiencing rigidity,
bradykinesia and gait problems are more susceptible to depression.
Interestingly, those with PD more on their right side are more likely to
have depression. The patient current age, family history of PD, dementia and
tremor seem to not influence depression.
Young onset patients (those getting PD before age 50) are 3 times more likely
to have a major depression than those with normal onset (36% vs. 11%). Mild
or minor depression is about the same for any age of onset ( 16% vs. 14%).
Together, Young onset patients are about twice as likely to experience
depression than those with normal onset PD (52% vs. 25%).
WHAT IS DEPRESSION
Question: Is depression merely the exaggeration of a normal mood state
(sadness) or is it a qualitatively different mood state? Temperature and
mood can be viewed on a continuous scale. A temperature of 104 degrees is
qualitatively very different than a temperature of 100 degrees. Similarly,
sadness and depression are qualitatively very different.
Question: Is depression primarily caused by psychological stress and
conflict or is it related primarily to a biological abnormality? There are
two different types of depression: Endogenous which is biological such as
neurochemical, and exogenous which is situational coming from the
environment. Normally a depression is composed of some combination of both
endogenous and exogenous causes.
Studies have been done on the neurochemical component of depression. It has
been found that the neurochemicals of serotonin and norepinephrine are
involved in depression. Everyone knows that there is a deficiency of
dopamine in PD. It turns out that norepinephrine is manufactured from
dopamine. Dopamine is manufactured from tyrosine and levodopa with the help
of an enzyme called ENZ. Thus if there is a deficiency of dopamine there is
reason to believe there could be a deficiency of norepinephrine.
Serotonin is manufactured form a substance called tryptophan. This process
uses the same enzyme called ENZ. As fewer and fewer neurons are available to
produce dopamine, there is a cannibalistic effect on the neurons producing
serotonin. The process to create dopamine form levodopa enters the serotonin
cells and takes the ENZ, leaving little for the manufacture of serotonin.
Thus serotonin levels could fall for that reason.
SYMPTOMS OF DEPRESSION
Sadness
Depressed mood (especially in the morning)
Hopelessness, helplessness and self-blame
Loss of interest & pleasure in activities
Loss of energy - fatigue - leading to inactivity
Decreased concentration - indecisiveness which has led some doctors to
diagnosis dementia incorrectly
Sleep disturbance
Preoccupation with negative thoughts - seeing the world through maroon
colored glasses rather than rose colored.
Poor appetite and weight loss
Thoughts of death and suicide and in some cases actually doing it
DIAGNOSING DEPRESSION IN PD
DEPRESSION -->> MOTOR IMPAIRMENTS -->> DEPRESSION
Most people can understand that motor impairments can cause depression. It
is more difficult to understand that depression can cause motor impairments.
We have no difficulty believing that the mind can heal the body. It is more
difficult to grasp that the mind can cause physical impairments. Dr. Slatkin
states that when he tells a patient that the mind is causing physical
impairment, they do not believe him. He says they are going to be offended
and angry with him. They think I am telling them that their symptoms are not
"real" and that I feel in some way they are faking it. This is truly not the
case.
Mood state and physical state are interrelated. Solving only one side of the
problem does little. Both mood state and physical state must be evaluated
together. When there is an rapid deterioration in the physical state of a PD
patient keep in mind that adding the Parkinson's medications alone may not
help. Dr. Slatkin is convinced, from his many years of working with PD
patients, that when a patient is depressed, the medications for PD do not
work. Thus both sides of the equation must be addressed. Ways of improving
mood state are exercise, increased activity, antidepressants and counseling.
Ways of improving the physical state are with Parkinson's medications.
Clinical Features of Depression
Sad faces
Fatigability
Sleep disturbance
Speech: slow, ... ,
Stooped posture
Constipation
Diurnal variation
Low mood
Motivation loss
Hopelessness
Loss of interest
Feel inadequate
Suicidal wishes
Indecisiveness
Conscious guilt
Loss of appetite
Cry in interview
Looking at the clinical features of depression, there is an overlap of
clinical features with PD. The first seven symptoms are common to both
depression and PD. This means that if a PD patient goes in to his physician
with one or more of the common symptoms, what are the chances that the
physician will recognize these as depression and not PD?
There is no objective test of depression. What doctors rely on are tests
such as the Beck Depression Inventory, Geriatric Depression Scale, SCL-90,
MMPI and Hamilton Rating Scale. These combined with time spent with the
patient, good patient history and a proper physical examination help the
physician diagnosis depression. The "Mask of Depression" is there to remind
us that depression is often masked by physical symptoms. The symptoms are
chronic and recurrent pain, fatigue, memory loss, problems with sleep and
sexual dysfunction. Often no physical cause of these symptoms can be found.
What is found is that these are physical symptoms of the underlying
depression.
A study was performed that found that 58% of PD patients said, "Fatigue is
among my three most disabling symptoms." Fatigue was highly correlated with
depression. It as also found that 67% were found to have "fatigue with PD
was different in quality or severity" than that experienced before the
diagnosis. Fatigue was not correlated with disease severity.
TREATMENT OF DEPRESSION
Treatment of depression uses counseling, education, electro-convolsive
therapy (ECT), antidepressants, exercise and stimulants. Only two will be
discussed -- antidepressants and ECT. Drugs used are the following:
Antidepressants Used in Parkinson's Disease
Tricyclic
Elavil (amitriptyline)
Tofranil (lmipramine)
Pamelor (nortriptyline)
Norpramiln (desipramine)
Sinequan (doxepin)
Monoamine oxidase inhibitors (A & B)
Electroshock therapy (ECT)
Selective Serotonin Reuptake Inhibitors (SSRI)
Prozac (fluoxetine)
Zoloft (sertraline)
Paxil (paroxetine)
Miscellaneous
Desyrel (treazdone)
Wellbutrin (buproprion)
Effexor (ventafaxine)
Serzone (nofazodone)
The SSRI drugs inhibit the reuptake of serotonin. This allows more serotonin
to hang around in the synapse with hope more will cross the synapse to the
receptors of the receiving neuron. One thing that we do not want is dopamine
receptor blockade. The one antidepressant that is not good for PD patients
is Asenden (amoxapine) because of its dopamine receptor blockade function.
REMEMBER: Antidepressants take time work
Antidepressants have both a quick effect and a longer therapeutic effect.
Often the synoptic effect and the adverse side effects can show in hours or
days. The therapeutic effect usually takes from three to six weeks. Thus it
is important to stay on these drugs for a few weeks to determine if they can
help. If nothing happens in the first few days, this is correct. Many of
the tricyclic antidepressants are also good pain relievers -- especially for
nerve pain syndrome.
There is about a 70% response rate regardless of agent used. A drug is often
selected by looking at the side effects to be avoided. There are no good
biological response markers. Melancholic and persistent, recurrent
depression seem to respond best. The side effects of SSRI drugs are:
Side Effects of SSRI Drugs (Partial listing)
Nausea
Diarrhea
Sexual dysfunction (delayed ejaculation in men, lower libido in both
sexes)
Sleep or near sleep
General fatigue
Dry mouth
Constipation
Difficulty with urination
Memory loss (amnesia)
Dizziness from drop in blood pressure
Akathisia (need to move)
Worsening of PD symptoms
Serotonin Syndrome
Serotonin syndrome arises when an antidepressant that inhibits reuptake
reacts with a monoamine oxidase inhibitor. Drugs that increase serotonin
activity in the brain are: SSRI (Prozac, Zoloft, Paxil), TCAD (Elavil,
Pamelor, Desyrel), Lithium, Tryptophan. The Monoamine oxidase inhibitor is
Eldepryl (selegine, deprenyl). Pharmacists, if they know you are using both
Eldepryl and one of the antidepressants, are required to call your physician
to let them know they are prescribing drugs that may be contraindicated.
Always discuss the possible interaction with your physician.
Serotonin Syndrome Symptoms
Motor symptoms
Jerking of arms and legs
Increased stiffness and rigidity
Incoordination
Mental behavioral symptoms
Agitation
Confusion
Disorientation
Restlessness
Miscellaneous
Fever
Nausea, Diarrhea
Shriving, flushing
Sweating
Exceptional problems
High fever
Seizures
Coma, Death
ELECTRO-CONVULSIVE THERAPY
Electro-convulsive therapy has a long history of use. It was observed that
when a patient would have a seizure they would get better. Various methods
were used to cause seizures. In 1941 the first tests of ECT in the US were
done
in New York. Looking in a book on the use of ECT, one finds Parkinson's
disease on the list. ECT can be a very valuable therapy if the patient has
had a poor response to antidepressants or has a poor tolerance or compliance
with antidepressant medications or patients having problems due to manic
depressive disorder.
OTHER THERAPIES FOR DEPRESSION
EDITORAL COMMENT: Please note that this paper has discussed therapies
involving medications for depression in Parkinson's disease. These
therapies are important; however, the therapies of exercise, increased
activity and counseling should also be considered. Remember to be open with
your physician when discussing both mood state and physical state problems.
To be depressed is not unusual; but to stay depressed is unnecessary. END
Regards,
Alan Bonander
