Adult Depression: Effective Treatments

Types

of Depression

Treatment

Overview

Psychotherapy

Medication

ECT

St.

John’s Wort

Phototherapy


Introduction

Everyone has

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.

 

Types

of Depression

Major

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.

While

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.

There are

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

The optimum

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.

Patients with

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.

Patients with

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[1].

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.

Psychotherapy

approaches to dysthymic disorder include Cognitive

Psychotherapy, Interpersonal Psychotherapy, and where conflicts are an

important part of the problem, Psychodynamic Psychotherapy.

Cognitive

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.

Interpersonal

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.

Psychodynamic

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.

Antidepressant

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

The first

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.

Attempts to

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)

Another group

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.

Apart from

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.

In addition

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).

 

Specific

Medications[2]

           

SSRI’s: fluoxetine

(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.

In addition

to their use as antidepressants, SSRI’s have also been used to treat panic

disorder, bulimia, obsessive compulsive disorder, excessive anger/aggression and

premenstrual dysphoria.

Mirtazepine

(Remeron):  an

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[3].

           

‘Tricyclic’

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).

In

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.

 

Other

Treatments:

           

Electroconvulsive

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[4]. 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[5].

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.

           

St.

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)[6]

while others indicate St. John’s Wort is less effective[7].

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

wisely.

Phototherapy:

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

shorter.

 



References

[1]

(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)

 

[2] Manual of Clinical

Psychopharmacology 3rd Edition; A. Shatzberg, J. Cole and C.

DeBattista; (1997) APA Press

[3]

Harvey, Rudolph and Preskorn Archives of General Psychiatry 2000; 57

(May): 503-509

[4]

American

Psychiatric Association: The Practice of Electroconvulsive Therapy:

Recommendations for Practice, Training, and Privileging. Task Force Report

on ECT. Washington, DC, American Psychiatric Association, 1990

[5]

Cerletti

U: L´elettroshock. Rivista Sperimentale Freniatria 64:209–310, 1940

[6]

Schrader, E. International Clinical Psychopharmacology 2000;15

(March):61-68

[7]

Gaster B, Holroyd J: St. John’s Wort for depression Archives of

Internal Medicine 2000;160: 152-156

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