times they feel sad and don’t enjoy life. For some people the emotional pain
becomes so severe or prolonged that it becomes a problem. This is depression.
Because there seem to be different patterns of depression that respond to
different treatment, psychiatrists have divided depression into categories.
Depression is the most severe form of depression. It
involves low mood or loss of enjoyment in most activities for two or more weeks.
This is accompanied by such symptoms as change in sleep and appetite, loss of
energy, loss of self-esteem, difficulty concentrating and preoccupation with
death or suicide. In some cases depressed people become irrationally convinced
that something terrible is happening to them, such as poverty or fatal disease.
The depressed person may withdraw from friends and family, and be unable to
work. Studies show that between 6 and 19% of the population will suffer from
major depression at some time in their life. It appears to be a “biological”
illness in that the tendency to develop this condition can run in families,
that depression can occur for no apparent reason and when the person has
experienced no significant changes in their life, and that the misery can
resolve with medication treatment alone in some cases.
symptoms are less intense than in Major Depression, Dysthymic Disorder
lasts for years. In fact the low mood and associated symptoms must be present on
most days for at least two years to qualify for this diagnosis. About 6% of the
population will experience this form of depression.
several other important forms of depression. Adjustment Disorder with
Depressed Mood involves a drop in mood in response to a specific stressful
circumstance. Bipolar disorder involves low
mood periods similar to Major Depression, but with periods of elevated or
irritable mood as well. Depression can also occur as a biological reaction to
certain physical illnesses (e.g. strokes affecting the left frontal cerebrum,
hypothyroidism, pancreatic cancer) or to chemical substances (e.g. alcohol,
methamphetamine, ß-blocking antihypertensive medications).
treatment depends on the type of depression. Patients with Major Depression
may be treated with medication, psychotherapy, or electro convulsive therapy (ECT).
The choice depends on the symptoms (severity and type), patient preference and
history of treatment response during prior depressive episodes. With more severe
forms of Major Depression it is generally necessary to use either medication or
ECT. Specific psychotherapies can be used along with medication, or as a sole
form of treatment in the case of less severe forms of Major Depression.
Major Depression are usually treated with medication (about 70% of people
respond well) or ECT (about 80% response rate). Psychotherapy may be an
important adjunct to treatment. Psychotherapy can help the person to decrease
the impact of the depressive symptoms and to sustain hope.
Dysthymic Disorder have historically been treated with psychotherapy
alone. In recent years however, it has become apparent that more than half
(50-60% response rate) of patients with Dysthymic Disorder will respond to most
types of antidepressants.
Since the medications that have been available in the past 10-15 years are
relatively non-toxic, it is often worth trying antidepressant medication with
psychotherapy, even when the depression seems related to psychological factors.
approaches to dysthymic disorder include Cognitive
Psychotherapy, Interpersonal Psychotherapy, and where conflicts are an
important part of the problem, Psychodynamic Psychotherapy.
Psychotherapy is based on the recognition that when
people are depressed they think differently. Pessimism causes the depressed
person to expect the worst, and to behave as if this were a certainty. This
results in not trying new things (“it won’t work” or “I probably
wouldn’t enjoy it”), in withdrawing from friends (“they will be bored with
me”). Cognitive therapy helps a person to examine the distorted assumptions
that go with depression, and that maintain the person thinking and acting in
ways that keep them depressed.
Psychotherapy investigates the ways in which problems
with relationships (role disputes, role transitions, unresolved grief and social
deficits) can have a profound impact on mood and functioning.
Psychotherapy explores the roots of adult dysfunction
in unresolved childhood conflicts. By doing so it helps explain why the person
would choose to do things that seem harmful to them. It permits a reevaluation
of assumptions about oneself and others, so that the person can deal more
effectively with others and themselves.
Medications appear to work by increasing the
availability of certain chemicals in the brain. These chemicals, called
neurotransmitters, are necessary for each nerve in the brain to send messages to
other nerves. Several parts of the brain are important in maintaining our usual
range of mood. The information needed to maintain mood is conveyed in part with
chemical signals. In some forms of depression, these chemical signals may be too
weak. Antidepressants can serve to strengthen the signal and help return the low
mood to a normal range. The chemical messengers most commonly affected by these
medications are serotonin (also called 5-hydroxytryptamine or 5HT) and
norepinepherine. Often it takes two to four weeks for depression to respond
fully to these medications, although some people may respond in a matter of
days. About 70% of patients with major depression respond to
relatively safe and effective medications to treat depression became available
over forty years ago. These were the tricyclics antidepressants, named
for the presence of three rings in their chemical structure. They are just as
effective as the most recently marketed antidepressants. The primary effect of
most of the tricyclics antidepressants is to block the reuptake of
norepinepherine and/or serotonin, but in contrast to the ‘selective’
medications, their effects are more diverse. They frequently block effects of
other neurotransmitters like acetyl choline (causing dry mouth, blurry vision,
constipation, urinary hesitancy urinary obstruction, heart palpitations),
histamine (causing weight gain and sedation) and the a1-adrenergic (norepinepherine)
receptor (causing low blood pressure on standing (dizziness, fainting and heart
palpitations) and sexual dysfunction). They can cause heart arrhythmias and
seizures (rarely in usual doses, but more commonly with overdoses). Thus, these
medications can be more dangerous than the more recently introduced
antidepressants, if taken as an overdose. This is of major concern since very
severely depressed patients are at greatest risk to attempt suicide.
find medications with fewer and less serious side effects, led to the discovery
of other groups of medication that act more selectively. These include the
“selective serotonin reuptake inhibitors” or SSRI’s: fluoxetine (Prozac),
sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil) and citalopram (Celexa);
venlafaxine (Effexor; a selective serotonin and norepinepherine reuptake
inhibitor), trazodone and nefazadone (Desyrel and Serzone, “serotonin
modulators”), mirtazepine (Remeron, a serotonin and norepinepherine enhancer),
and bupropion (Wellbutrin, a norepinepherine enhancer)
of antidepressants is the “monoamine oxidase inhibitors” or MAOI’s.
This group has been around about as long as the tricyclics antidepressants
(1950’s). They can be very effective antidepressants, and for certain people
can be the best treatment. But because of some potentially dangerous
interactions with a number of foods and medications, they are not usually tried
unless other treatments fail. They work by preventing the chemical messengers (serotonin
and norepinepherine) between nerve cells from being destroyed by the enzyme
monoamine oxidase. As with the other antidepressants, this increases the
strength of the chemical signal. The problem with these medications is that
there are a number of foods that contain a chemical, tyramine, which can raise
blood pressure if it is not destroyed in the intestines before it gets into the
blood stream. Normally the enzyme monoamine oxidase (present in the intestines
as well as the brain) destroys the tyramine before it can be absorbed. However
if a person takes the MAOI drugs, the enzyme is blocked and the result can be a
dangerous elevation in blood pressure. Many of the foods that need to be avoided
are high in protein and have been partially acted on by bacteria: aged cheese,
hard sausages (pepperoni, salami), pickled herring. Also several varieties of
wine and beer (but not distilled liquor) must be avoided. In addition there are
several medications that should not be taken with the MAOI’s, including
pseudoephedrine (Sudafed), diet pills with phenolpropanolamine (Dexatrim), and
most other antidepressants.
the dietary and medication interactions, the MAOI’s have several possible side
effects, including reduced blood pressure, sexual dysfunction, weight gain,
sedation, dry mouth and constipation.
to use as antidepressants these medications are also used to treat panic
disorder and social phobia.
The two most
commonly used MAOI’s are tranylcypromine (Parnate) and phenelzine (Nardil).
(Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil) and
citalopram (Celexa): These
medications enhance the signals in nerves that transmit messages with serotonin.
The some common side effects include nausea, diarrhea, headache, anxiety,
insomnia or somnolence, tremor, sexual dysfunction, reduced motivation. When
these occur they are generally not dangerous, but annoying. In addition, some of
these SSRI’s are associated with a ‘discontinuation syndrome’ if they are
stopped abruptly. While also not dangerous, symptoms include nausea, anxiety,
insomnia and headache. This occurs most frequently with paroxetine, fluvoxamine
and venlafaxine (see below); it is much less common with sertraline, and rarely
occurs with fluoxetine.
to their use as antidepressants, SSRI’s have also been used to treat panic
disorder, bulimia, obsessive compulsive disorder, excessive anger/aggression and
a-2 adrenergic receptor antagonist (by blocking presynaptic inhibition of
noradrenergic neurons it increases activity on noradrenergic neurons) and 5HT2
& 5HT3 blocker. Side effects include dry mouth,
sedation and weight gain, but it is not frequently associated with sexual
problems. It may have some anxiolytic effects. Typically, treatment begins at
7.5 mg and increases to the 15 to 45 mg/day range.
Bupropion (Wellbutrin): Its mechanism of
action is unclear. It’s action may be mediated by it’s major metabolite,
hydroxybupropion, a norepinepherine reuptake inhibitor. In addition to its use
as an antidepressant, it may be used to treat nicotine addiction (smoking),
attention deficit disorder and social phobia. Side effects most commonly seen
include insomnia and nausea. It does not generally interfere with sexual
functioning. An increased risk of seizures is seen with higher doses of the
medication (>4% incidence at doses over 450 mg/day; <0.4% with lower doses).
Nefazadone (Serzone): This medication seems
to act primarily on the serotonin system. Apparently it blocks postsynaptic
serotonin receptors (5HT2A and 5HT2C), while a metabolite
stimulates the 5HT2C receptor. It is thought that these actions
indirectly stimulate the 5HT1A receptor. This antidepressant
typically is used in doses from 300 to 600 mg/day. It seems to have antianxiety
effects in addition to antidepressant actions. Side effects may include
sedation, nausea, headache and decreased blood pressure (via a-adrenergic
receptor blockade). There are seldom sexual side effects.
Venlafaxine (Effexor): In low doses (e.g. 75
mg/day), venlafaxine behaves much like an SSRI, with minimal effect on the
norepinepherine system, however in the higher dose range (e.g. 375 mg/day) it
also exhibits norepinepherine reuptake inhibition. This accords with the
observed side effects: Nausea, vomiting and sexual dysfunction starting at low
doses and increased sweating, dry mouth, increased blood pressure and heart rate
at higher doses.
antidepressants: Members of this group include imipramine (Tofranil),
amitriptyline (Elavil), doxepin (Sinequan), clomipramine (Anafranil),
protriptyline (Vivactyl), trimipramine (Surmontil), nortriptyline (Pamelor),
amoxepine (Asendin) and desipramine (Norpramin).
addition to the antidepressant uses of these drugs, one or more of them have
found use in treating: panic attacks ± agoraphobia (imipramine and clomipramine),
obsessive compulsive disorder (clomipramine), attention deficit disorder (imipramine),
primary incontinence (imipramine), neuropathic pain (doxepin, maprotiline,
amitriptyline), migraine headaches (amitriptyline and doxepin), bulimia (imipramine
and desipramine), generalized anxiety disorder (imipramine) and at times to
other anxiety disorders (doxepin), insomnia (amitriptyline and doxepine) and
ulcers (trimipramine and doxepin).
MAO inhibitors: The
two most commonly used members of this group are phenelzine (Nardil) and
tranylcypromine (Parnate). In recent years another MAOI, selegiline (Eldepryl)
has been used in low doses (5-10 mg) to treat Parkinson’s Disease. At these
lower doses it is selective enough that it does not required the dietary
restrictions needed with the others, however in the doses that are effective
treatment of depression (20-60 mg/day), the dietary restrictions must be
followed. Some side effects seen with MAO inhibitors include: low blood pressure
(feeling faint) when standing up, elevated blood pressure (if taken with certain
foods or medications), daytime sedation and/or insomnia at night, constipation,
dry mouth, weight gain and sexual dysfunction.
Therapy (ECT): This
treatment can be highly effective for patients with severe depression. Some
studies show an 80% response rate for treating major depression with ECT. Many studies comparing it
to antidepressant medication in major depression show it to be at least as
effective as medication, and possibly more so. The first reports describing the
effectiveness of this treatment came out around 1940.
Modern ECT takes place in a medical setting where careful monitoring of the
patient during treatment can take place. Prior to the treatments the patient
must be carefully evaluated to look for any complicating physical problems. At
the start of the procedure, a short-duration anesthetic is administered,
followed by medications to relax the muscles. The psychiatrist then positions
electrodes on the patient’s scalp and passes a current through them. This
produces a seizure lasting 30-45 seconds. Because a muscle relaxant is used,
there is generally little movement or chance of injury from muscle contractions.
Because short-acting anesthetic agents are generally used, the patient may begin
to regain consciousness within a matter of minutes after the treatment. The most
common side effects of the procedure include headache and transient memory
disturbances. Generally the patient receives two to three treatments a week,
with the end point being complete recovery or a failure to show further
improvement with additional treatments. It is fairly typical after the course of
treatments conclude to use antidepressant medication or periodic ‘maintenance
ECT’ to prevent relapse. The problem of memory disturbance has been studied in
detail. It depends to some extent on details of the treatment (electrode
placement, electric current wave-form, frequency of treatments) and of the
patient (advanced age, history of brain injury or brain disease). In general
memory problems resolve entirely over a few weeks to a few months. Studies have
shown no detectible memory deficit a year after the treatments.
John’s Wort (Hypericum
perforatum) has been used extensively in Europe to treat mild-to-moderate
severity depression. In Germany it accounts for 25% of antidepressant
prescriptions. Attempts have been made to standardize this herb (e.g. 300 mg of
plant extract containing 0.3% Hypericine). However, because it is not know what
the active ingredient might be, there is really no way to know precisely the
potency of a given batch. Most of the studies done on St. John’s Wort have
been poorly designed (often vague or broad criteria for depression and for
treatment response, lack of a placebo control group, comparison to low doses of
pharmaceutical antidepressants). There have been some more recent studies that
have attempted to address these shortcomings. Some of these studies show equal
efficacy to prescribed antidepressants)
while others indicate St. John’s Wort is less effective.
Some cautions now exist about the use of St. John’s Wort. It must be
remembered that even though it comes from a flowering vine, St. John’s Wort is
a drug. In addition to the fairly common side effect of nausea, it is known that
St. John’s Wort hastens the metabolism of certain other drugs, thereby
reducing the amount of the other medication in the patient’s body. These drugs
include oral contraceptives, theophylline, cyclosporine, warfarin and the AIDS
drug indinavir . The use of St. John’s Wort by patients depending on these
medications can reduce the medication’s effect (which in some cases could be
disastrous: at least two cases of incipient heart transplant rejection have been
traced to the use of St. John’s Wort by transplant patients taking the
anti-rejection drug cyclosporine). It may well be that St. John’s Wort will be
shown to be an effective treatment for mild or moderate depression. However as
we have discovered with all powerful and effective medications, there are
inevitably some risks that must be known and understood to use the medication
For some people, depressive episodes occur
regularly at one time of year (generally mid-winter). This form of depression is
often called Seasonal Affective Disorder (SAD) or
Winter Depression. While this type of depression often can respond to
medication, it has also been found to respond to bright light therapy. This
typically involves the use of special lights (much brighter usual indoor
illumination) before which the patient sits in the morning for perhaps 30
minutes each day. The advantage of bright light therapy over medication is that
when it works, it usually has no side effects provided the lights are designed
to produce the proper intensity (about 2000 lux). Interestingly SAD is seen more
frequently as one moves away from the equator where winter day-length becomes
(Centre for Evidence-Based Mental Health Journal Vol. 1, #4, December 1998,
Pg 111 or http://www.update-software.com/ccweb/cochrane/revabstr/ab001130.htm)
 Manual of Clinical
Psychopharmacology 3rd Edition; A. Shatzberg, J. Cole and C.
DeBattista; (1997) APA Press
Harvey, Rudolph and Preskorn Archives of General Psychiatry 2000; 57
Psychiatric Association: The Practice of Electroconvulsive Therapy:
Recommendations for Practice, Training, and Privileging. Task Force Report
on ECT. Washington, DC, American Psychiatric Association, 1990
U: L´elettroshock. Rivista Sperimentale Freniatria 64:209–310, 1940
Schrader, E. International Clinical Psychopharmacology 2000;15
Gaster B, Holroyd J: St. John’s Wort for depression Archives of
Internal Medicine 2000;160: 152-156