A Look at Drug Treatments for Depression

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A Look at Drug Treatments for Depression

Thursday, December 30, 1999

[Everything from family autism to Y2k jitters can take its toll on our

mental health. This is especially true for many who may now suffer from the

holiday blues, aka Seasonal Affective Disorder (SAD). This excerpt comes

from the HealthGate Depression Center and focuses on drug treatments. This

is another in a series of FEAT's Parent Education Project reports.

Non-drug, or augmentative therapies are also reviewed at HealthGate's

website: http://www3.healthgate.com/hic/wcon/wcon-08.asp#01 ]

Most adult patients with major or chronic depression are given a trial

period of an antidepressant. Some form of psychotherapy is also usually

recommended; the type prescribed should be, like the medications, tailored

to the needs of the patient. The combination of antidepressants and therapy

appears to be more effective than either treatment alone for most patients,

possibly because patients are more likely to take their medications

regularly when they are also undergoing therapy. For those who fail

medications and psychotherapy, other techniques, such as electroconvulsive

therapy (ECT), are safe and effective. In severe cases that do not respond

to any conservative treatment, psychosurgery may be beneficial.

Treatment Guidelines for other Specific Patient Groups.

Children and Adolescents. Studies indicate that children and

adolescents with major depression respond as well to placebos so called

" sugar pills " as they do to tricyclic antidepressants. Although, they tend

to respond better to the newer antidepressants known as selective serotonin

reuptake inhibitors (SSRIs), some experts believe teenagers with mild to

moderate depression should receive psychotherapyespecially

cognitive-behavioral therapy or supportive therapybefore medications are

tried. For children and adolescents with very severe depression that does

not respond to psychotherapy, the American Academy of Child and Adolescent

Psychiatry now recommends SSRIs. These drugs should be combined during the

early acute phase with a mixture of psychotherapies, including

cognitive-behavioral, interpersonal, and psychodynamic therapies. Initial

drug treatments should continue for at least six months and a maintenance

phase should last another year or longer.

What Are the Drug Treatments for Depression?

General Guidelines.

Antidepressants are very effective; one study reported that up to 90%

of patients with major depression will improve with good compliance and

adequate doses of the right antidepressant drug. Side effects can be avoided

or moderated if the regimen is started at low doses and built up over time.

Current antidepressants are not addictive. A great deal of leeway exists in

choosing an appropriate antidepressant; overall, they seem to be equally

effective, although individual responses vary. Lack of compliance is

probably the major barrier to success; for example, according to one study,

as many as 70% of elderly depressed patients do not adhere to antidepressant

drug regimens. Some patients with accompanying problems, such as anxiety,

may require additional drugs that treat those symptoms.

For people who have never been treated for depression, medications are

usually maintained for six months or longer after depression has been

resolved. Patients who improve within two weeks of taking medications may

not require lengthy treatment. Some patients may require indefinite

maintenance therapy. These patients include those who have had three or more

recurrences of depression, people over 50 who have never had major

depression before, those with two episodes and a family history of

depression or bipolar disorder, and people who have had severe, sudden, or

life-threatening depressions within the past five years. Most patients have

a recurrence of depression within five years after treatment has stopped.

Virtually all antidepressants have side effects and complicated

interactions with other drugs, some are very serious. Some are mentioned in

the individual drug discussions below, but many are not, and patients should

inform the physician of any drugs they are taking, including over-the

counter-medications. There is an increased risk of oral health problems

caused by dry mouth associated with long-term use of all antidepressants.

The risks appear to be highest with heterocyclic antidepressants, with

multiple drug use, and with the presence of oral infections. Patients can

increase salivation by chewing gum, taking vitamin C tablets, using saliva

substitutes, and rinsing the mouth frequently. Abrupt withdrawal from many

antidepressants can produce severe side effects; no antidepressant should be

stopped abruptly without consultation with a physician.

Selective Serotonin-Reuptake Inhibitors and Other Designer

Antidepressants.

Selective serotonin-reuptake inhibitors (SSRIs) are now the first-line

treatment of major depression. They work by increasing levels of serotonin

in the brain. Because they act on serotonin specifically, they have fewer

side effects than tricyclic antidepressants, which affect a number of

chemicals in the body. SSRIs include fluoxetine (Prozac), sertraline

(Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa).

Benefits of SSRIs. SSRIs appear to help people with most forms of

depression including mild to moderately severe major depression, seasonal

affective disorder, and dysthymia. SSRIs are even proving to be effective

for premenstrual dysphoric disorder. In fact, in such cases, intermittent

fluoxetine therapy (taking the drug only during the 14-day premenstrual

period) may be as effective as continuous therapy and be associated with

fewer adverse effects. SSRIs also benefits people other disorders, including

obsessive-compulsive disorder, panic disorder, and bulimia. They also reduce

impulsive aggressive behavior in both psychiatric patients and in people

with no mental health problem. Patients taking SSRIs report not only relief

of depressive symptoms, but also a higher level of efficiency, more energy,

and better relationships with other people. Fluoxetine appears to be safe

for pregnant women and the developing fetus, although pregnant women should

avoid any medications, if possible. Antidepressants have been detected in

mother's milk, although one study found no adverse effects on one-year old

infants whose mothers took SSRIs while nursing their young.

Duration of Effectiveness and Use. It takes two to four weeks for

SSRIs to be effective in most adults and longer up to 12 weeks in the

elderly and those with dysthymia. By 14 weeks, depression should be in

remission in everyone who responds to the drugs. Unfortunately, recurrence

is common once the drugs are stopped. One recent study of patients taking

fluoxetine suggested that patients should continue taking Prozac for 38

weeks to prevent relapse. Another study examined patients using paroxetine

and found that those who continued with the full dose of Paxil for 28 weeks

had half the chance for relapse when compared to those who reduced their

dose.

Side Effects of SSRIs. The most common side effects are nausea and

gastrointestinal problems. Others include anxiety, drowsiness, sweating,

headache, difficulty sleeping, and mild tremor. These effects usually wear

off over time. During the first few weeks of treatment, some patients lose a

small amount of weight, but, in general, they regain it.

Sexual dysfunction, including delayed or loss of orgasm and low sexual

drive, occurs in 30% to 40% of patients on SSRIs and account for a

substantial amount of noncompliance. (Citalopram, a newer SRRI, may pose a

lower risk than other SSRIs for this side effect.) Taking a supervised drug

" holiday " on the weekend may improve sexual function during that time.

(Withdrawal symptoms may develop and include return of depression, sleep

problems, exhaustion, and dizziness. Prozac, with its longer duration of

action, appears to be associated with a lower risk for withdrawal symptoms

than shorter-lasting SSRIs, but a weekend off this drug may not be long

enough to restore sexual function.)

Elderly people taking these drugs should take the lowest dose

possible, and those with heart problems should be monitored closely. SSRIs

can cause agitation, impulsivity, nausea, and dry mouthwhich can increase

the risk for cavities and mouth sores. The elderly are at increased risk for

falling. (It has been thought that SSRIs posed less of a risk for falls and

hip fractures than other antidepressants, but recent studies indicate that,

in this regard, they are no safer.) Over the years, some patients taking

SSRIs have reported a group of side effects, known as extrapyramidal

symptoms, which are similar to those in Parkinson's disease and affect the

nerves and muscles controlling movement and coordination. They are uncommon

and when they develop they tend to occur within the first month of

treatment.

High doses or interactions with other drugs may cause hallucinations,

confusion, changes in blood pressure, stiffness, and irregular heart beats.

Death from overdose is extremely rare. Serious interactions can occur with

certain drugs, including other antidepressants, such as tricyclics andof

particular noteMAOIs [see below]. Other serious interactions have occurred

with Demerol, illegal substances such as LSD, cocaine, or " ecstasy " , and the

antihistamines terfenadine (Seldane) and astemizole (Hismanal). (Seldane has

been taken off the market). Any medication must be taken with caution during

pregnancy. People may drink alcohol in moderation, although it may compound

the drowsiness experienced with SSRIs; some SSRIs increase the effects of

alcohol.

Heterocyclic and Other Designer Antidepressants. A number of drugs are

being designed that, like the SSRIs, target specific neurotransmitters that

regulate depression. Most act on mechanisms that elevate both serotonin and

noradrenaline and some may be more effective for severely depressed patients

than are the SSRIs. Some are known as heterocyclic antidepressants. These

drugs tend to have fewer adverse effects on sexual function than SSRIs, and

some people have reported enhanced sexuality with some of them. It should be

noted that most of these " designer " drugs are still new, and widespread use

may increase reports of adverse effects. Common side effects include

drowsiness, nausea, dizziness, and dry mouth, but drugs vary in others

effects. Dry mouth is a particular problem with long term use of

heterocyclics.

Bupropion. Bupropion (Wellbutrin) is particularly promising for a

number of conditions, including it use as a treatment for quitting smoking

(Zyban). It causes less sexual dysfunction than SSRIs. Side effects include

restlessness, agitation, sleeplessness, headache, rashes, stomach problems,

and in rare cases, hallucinations and bizarre thinking. Weight loss occurs

in about 25% of patients. High doses increase the risk for seizures,

particularly in those with eating disorders or those with other risk factors

for seizures.

Venlafaxine. Venlafaxine (Effexor) is another designer antidepressant

that is gaining popularity. In one comparison study, venlafaxine was similar

to fluoxetine (Prozac) in effectiveness and tolerability for most patients.

In a group who required higher doses of an antidepressant in order to obtain

a response, venlafaxine was slightly more effective. Venlafaxine has a

variety of side effects, and high blood pressure and depressed central

nervous system function can occur in high doses. Some patients report severe

withdrawal symptoms, including dizziness and nausea.

Nefazodone. Nefazodone (Serzone) has less severe side effects,

including sexual dysfunction, than SSRIs. The drug can also be combined with

SSRIs. However, it may cause an abrupt drop in blood pressure after standing

up suddenly.

Other Designer Antidepressants. Mirtazapine (Remeron) and maprotiline

(Ludiomil) are other effective antidepressants that have few side effects.

In one trial of patients with a high incidence of severe depression,

mirtazapine was more effective than fluoxetine and it had fewer side

effects. Maprotiline increases the chance for seizures in high-risk people

and may cause heart rhythm disturbances.

Lesser used drugs: Tricyclic Antidepressants, Monoamine Oxidase

Inhibitors (MAOIs).

Other Promising Chemical Treatments: Estrogen, 's Wort, Substance

P.

[For the full report go to:

http://www3.healthgate.com/hic/wcon/wcon-08.asp#01 ]________________________

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editor: Lenny Schafer schafer@...

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