How to take an antidepressant: it’s no longer enough to treat depression; it’s necessary to banish it. What’s the best drug for that? It boils down to what side effects you can tolerate in the long haul

How to take an antidepressant: it’s no longer enough to treat depression; it’s necessary to banish it. What’s the best drug for that? It boils down to what side effects you can tolerate in the long haul

Hara Estroff Marano

fifteen years ago, Prozac launched a revolution. It rendered depression a disorder that was–finally–safely treatable. The torrent of prose hailing Prozac and its chemical kin eventually made the mental illness dinner-party discourse. Today, a much quieter revolution in treatment is taking place. It, too, has its origins in Prozac and its siblings, the selective serotonin reuptake inhibitors.

Fifteen years of experience with reasonably safe treatments has given the mental health world a new understanding of the disorder and its true course: It’s no longer enough to merely treat depression; it’s necessary to banish it.

Increasingly, the aim of treatment is not to make patients better but to make them completely well. In the absence of full remission from an episode of depression, the disorder tends to recur. What’s more, studies now show that the longer patients remain sick, the harder it is for them to recover completely.

“It became very clear over the past several years that people who don’t achieve full remission are at high risk for relapse and for doing poorly,” says Jonathan Alpert, M.D., Ph.D., associate director of the depression research program at Massachusetts General Hospital in Boston. “Even if they don’t have a full relapse, they don’t do well in social and occupational function.”

There is no magic bullet; evidence indicates that the available antidepressants are equally effective. All of the drugs get 70 percent of people better within six to ten weeks, according to David Dunner, M.D., director of the Center for Anxiety and Depression at the University of Washington. However, “better” does not necessarily mean symptom-free. “There isn’t any difference among the drugs regarding that.”

Where the drugs do differ, however, is in the side effects they create, especially in the long haul. Side effects have become a central consideration in the new approach to depression treatment.

Long-term treatment is also critical. Data indicate that individuals should be treated for at least nine months following their first acute episode. If they have chronic depression–an episode lasting two years or more–they need to be treated for two years after remission. “And if they have recurrent depression marked by multiple episodes, perhaps forever,” notes Dunner.

However, the average duration of a prescription is about 100 days. “It’s a serious problem,” Dunner points out. “We’re not treating people nearly long enough.”

Nor is treatment aggressive enough, according to Alpert: “Really pushing for remission may mean using two antidepressants at once or pushing the close up higher than one would normally use.”

Pick your pill

For many experts, the most sensible approach to selecting an antidepressant is to factor in the presence of associated or co-occurring conditions. Anxiety disorders, for example, commonly accompany depression. The selective serotonin reuptake inhibitors (SSRIs) have been well studied for the major anxiety disorders: panic, social phobia, generalized anxiety disorder and obsessive-compulsive disorder.

“For someone who has depression and social phobia, it’s reasonable to use a medication whose effectiveness has been well documented for both disorders,” reports Alpert. The data also suggest that SSRIs are “reasonable first choices” for those with eating disorders.

But antidepressants don’t work if people don’t take them. Patients have to be willing to put up with side effects that range from drowsiness to seizures. As true as that is for short-term treatment, it’s even more the case with long-term treatment. “The issue is, what can we do to get these patients to stay on the drugs for the length of time the evidence now suggests is best?” explains Dunner.

In the long run, two side effects are especially bothersome: sexual dysfunction and weight gain. The SSRIs are strongly linked to sexual dysfunction in both sexes–diminished libido, erectile dysfunction and delayed, attenuated or absent orgasm. In one recent study, up to 70 percent of patients receiving the newer antidepressants reported sexual dysfunction when asked directly about it. That contradicts the 15 percent declared on product labels. Some of the atypical antidepressants–such as Wellbutrin (buproprion) and Remeron (mirtazapine)–do better at preserving sexual function.

In regard to weight gain, the SSRI antidepressants do not appear to be created equally. Paxil, for one, seems to cause more problems. One study, by Andrew Nierenberg, M.D., associate director at Massachusetts General’s clinical depression and research program, showed that after six months, patients put on more weight with Paxil than with the other antidepressants. Evidence favors non-SSRIs for avoiding weight gain, particularly bupropion and Serzone (nefazodone). Nefazadone, however, bears a Food and Drug Administration warning that it can cause liver failure in rare instances.

Paxil also causes more sexual dysfunction, which leads many individuals to discontinue their regimen. Teresa* found that Paxil stanched her anxiety and depression after only two weeks. “I was calmer. My emotions weren’t erupting,” recalls the 55-year-old social worker. But the flip side was a sense of muted emotions and diminished sexual appetite. “The libido isn’t just your sex drive, it’s your passion for life,” says Teresa. She plans to continue taking Paxil despite the side effects. “It did what I wanted it to do, which is take away the pain.”

The bargaining table

Psychiatrists believe that side effects are a matter of negotiation. “Some of the most teary exchanges in my office have involved women who don’t want to gain weight on a drug,” confides John Herman, M.D., director of clinical services in psychiatry at Mass General. “The patients come in tearful because they’re depressed; then they come in no longer depressed but distraught because they are way overweight.”

“It’s a stealth side effect,” observes Jerrold Rosenbaum, M.D., chief of psychiatry at Massachusetts General. “It emerges subtly over time and surprises everybody.”

Physicians must consider what is tolerable in exchange for a medication’s primary effects and understand that the bar has been raised. “As the cookie lady Mrs. Fields once said, `Good enough is not good enough,'” says Dunner. “Just because a patient improves doesn’t mean the treatment should be stopped.”

Sometimes the problem lies with patients themselves. Often, they feel better and stop their medication, thinking it’s no longer needed. “Although an individual patient might win, it’s a mistake,” observes Dunner. “The odds are against her.”

At least as often, side effects interfere with long-term patient compliance. Therefore, clinicians must know how to manage the dosage or try to augment the antidepressant with another medication so the patient will stay on course. Psychostimulants such as Dexedrine, Ritalin and Adderall are widely used as antidepressant adjuncts, even though their primary indication is for attention deficit disorders or narcolepsy. Provigil, recently approved for the treatment of narcolepsy, is also used to boost the efficacy of antidepressants or reduce the drowsiness they cause. Thyroid hormones and natural remedies such as omega-3 fatty acids and SAM-e are also being explored.

Leading psychopharmacologists contend that antidepressant treatment can be delivered in a way that instills confidence in patients–enough to ride out early difficulties. “I try to emphasize the early side effects that might occur and how to manage them,” reports Dunner. “So if a patient suffers from them, he doesn’t say, `What is all this about?'”

It’s also important for patients to know that taking one pill will not instantly make them better; in fact, the drugs are not likely to begin working for three to four weeks. Treatment will then progress in eight to twelve weeks.

Some 30 percent of depressed patients do not respond to the first drug they try. If there is no improvement after a patient uses a medication at an adequate dose and for an adequate duration of time, a switch is in order. A drug with a different mechanism of action may be preferred. The trial, though, isn’t lost. The patient may have lost time, but valuable information has been gained.

“We’re trying to get the patient over that last little hump,” says Dunner. “Granted, we can improve most patients, but can we actually get them back to normal? I think we can do this with many more patients than we used to.”

LEARN MORE ABOUT IT:

Night Falls Fast Kay Redfield Jamison (Vintage, 2000)

The Noonday Demon Andrew Solomon (Touchstone, 2002)

Depression and Bipolar Support Alliance: www.ndmda.org

Psychology Today: www.psychologytoday.com

American Psychological Association: www.apa.org

National Institute of Mental Health: www.nimh.nih.gov/publicat/medmenu.cfm

THE DEFINITIVE GUIDE TO ANTIDEPRESSANTS

DRUG CLASS TRADE NAME GENERIC

(Date Drug NAME

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) citalopram

co-morbid anxiety disorders; no Lexa-Pro (2002) escitalopram

clear indication whether as Prozac (1987) fluoxetine

effective as MAOIs for atypical Luvox (1994) fluvoxamine

depression, but favored as Paxil (1992) paroxetine

first-line agents in general Zoloft (1993) sertraline

because of ease of use; may

have strong negative effect on

sleep patterns, with increased

awakening and movement; more

likely to be associated with

sexual dysfunction than other

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) nefazodone

useful for melancholic depres- Desyrel (1982) trazodone

sion; associated with positive

effect on sleep patterns, in-

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Effexor (1997) venlafaxine

cially useful for melancholic

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) bupropion

Remeron (1996) mirtazapine

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s) isocarboxazide

certain forms of depression Nardil (1960s) phenelzine

such as atypical depression or Parnate (1960s) tranylcypromine

depression resistant to other

medications; may be useful for

anxiety disorders including co-

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol,

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

DRUG CLASS TRADE NAME MANUFACTURER

(Date Drug

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) Forest

co-morbid anxiety disorders; no Lexa-Pro (2002) Forest

clear indication whether as Laboratories

effective as MAOIs for atypical Prozac (1987) Eli Lilly

depression, but favored as Luvox (1994) Solvay

first-line agents in general Paxil (1992) Glaxo

because of ease of use; may Smithkline

have strong negative effect on Zoloft (1993) Pfizer

sleep patterns, with increased

awakening and movement; more

likely to be associated with

sexual dysfunction than other

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) Bristol-Myers

useful for melancholic depres- Squibb

sion; associated with positive Desyrel (1982) Bristol-Myers

effect on sleep patterns, in- Squibb

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) Wyeth

cially useful for melancholic

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) Glaxo

Smithkline

Remeron (1996) Organon

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s) Roche

certain forms of depression Nardil (1960s) Parke-Davis

such as atypical depression or Parnate (1960s) Glaxo

depression resistant to other Smithkline

medications; may be useful for

anxiety disorders including co-

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol,

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

DRUG CLASS TRADE NAME PRIMARY

(Date Drug APPLICATION(S)

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) major depres-

co-morbid anxiety disorders; no sive disorder

clear indication whether as Lexa-Pro (2002) major depres-

effective as MAOIs for atypical sive disorder

depression, but favored as Prozac (1987) major depres-

first-line agents in general sive disorder

because of ease of use; may Luvox (1994) OCD

have strong negative effect on Paxil (1992) major depres-

sleep patterns, with increased sive disorder

awakening and movement; more Zoloft (1993) major depres-

likely to be associated with sive disorder

sexual dysfunction than other

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) major depres-

useful for melancholic depres- sive disorder

sion; associated with positive Desyrel (1982) major depres-

effect on sleep patterns, in- sive disorder

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) major depres-

cially useful for melancholic sive disorder

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) major depres-

sive disorder

Remeron (1996) major depres-

sive disorder

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s) major depres-

certain forms of depression sive disorder

such as atypical depression or Nardil (1960s) major depres-

depression resistant to other sive disorder

medications; may be useful for Parnate (1960s) major depres-

anxiety disorders including co- sive disorder

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol,

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

DRUG CLASS TRADE NAME SECONDARY

(Date Drug APPLICATION(S)

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998)

co-morbid anxiety disorders; no Lexa-Pro (2002)

clear indication whether as Prozac (1987) 1 2 5

effective as MAOIs for atypical Luvox (1994) major depres-

depression, but favored as sive disorder

first-line agents in general Paxil (1992) 5 6 7 8 9

because of ease of use; may Zoloft (1993) 5 6 7

have strong negative effect on

sleep patterns, with increased

awakening and movement; more

likely to be associated with

sexual dysfunction than other

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994)

useful for melancholic depres- Desyrel (1982)

sion; associated with positive

effect on sleep patterns, in-

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) 9

cially useful for melancholic

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) 10

Remeron (1996)

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s)

certain forms of depression Nardil (1960s)

such as atypical depression or Parnate (1960s)

depression resistant to other

medications; may be useful for

anxiety disorders including co-

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol,

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

DRUG CLASS TRADE NAME PRESUMED

(Date Drug MECHANISM OF

Introduced) ACTION

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) inhibits neu-

co-morbid anxiety disorders; no ronal reuptake

clear indication whether as of serotonin

effective as MAOIs for atypical Lexa-Pro (2002) inhibits neu-

depression, but favored as ronal reuptake

first-line agents in general of serotonin

because of ease of use; may Prozac (1987) inhibits neu-

have strong negative effect on ronal reuptake

sleep patterns, with increased of serotonin

awakening and movement; more Luvox (1994) inhibits neu-

likely to be associated with ronal reuptake

sexual dysfunction than other of serotonin

new agents; sexual dysfunction Paxil (1992) inhibits neu-

and agitation occur with all ronal reuptake

SSRIs; agitation may be averted of serotonin

by starting on low dose Zoloft (1993) inhibits neu-

ronal reuptake

of serotonin

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) serotonin

useful for melancholic depres- receptor

sion; associated with positive antagonist

effect on sleep patterns, in- Desyrel (1982) serotonin

creasing sleep efficiency and receptor

reducing awakenings; less antagonist

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) inhibits neu-

cially useful for melancholic ronal serotonin

depression; may be effective in and norepine-

co-morbid panic disorder phrine reup-

take, to lesser

extent dopamine

reuptake

OTHER ATYPICALS

Wellbutrin (1996) unknown: pos-

sible dopamine

effect, pos-

sible nore-

pinephrine

effect

Remeron (1996) serotonin re-

ceptor agonist;

enhances cen-

tral noradre-

nergic and

serotonergic

activity

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s) by inhibiting

certain forms of depression monoamine oxi-

such as atypical depression or dase, increases

depression resistant to other epinephrine,

medications; may be useful for norepinephrine

anxiety disorders including co- and serotonin

morbid panic disorder and concentration

social phobia; all MAOIs Nardil (1960s) by inhibiting

contraindicated with Demerol, monoamine oxi-

many cold and cough medica- dase, increases

tions, tyramine-rich foods, epinephrine,

most other antidepressants norepinephrine

and serotonin

concentration

Parnate (1960s) by inhibiting

monoamine oxi-

dase, increases

epinephrine,

norepinephrine

and serotonin

concentration

DRUG CLASS TRADE NAME MAJOR SIDE

(Date Drug EFFECTS

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) C E G H I

co-morbid anxiety disorders; no Lexa-Pro (2002)

clear indication whether as Prozac (1987) C E G H

effective as MAOIs for atypical Luvox (1994) C E G H I

depression, but favored as Paxil (1992) C D E G H I

first-line agents in general Zoloft (1993) C E G H I

because of ease of use; may

have strong negative effect on

sleep patterns, with increased

awakening and movement; more

likely to be associated with

sexual dysfunction than other

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) C

useful for melancholic depres- Desyrel (1982) C

sion; associated with positive

effect on sleep patterns, in-

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) C E G H I

cially useful for melancholic

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) H J

Remeron (1996) C D

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s)

certain forms of depression Nardil (1960s) B C D E F

such as atypical depression or Parnate (1960s) B C E F

depression resistant to other

medications; may be useful for

anxiety disorders including co-

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol,

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

DRUG CLASS TRADE NAME PRECAUTIONS &

(Date Drug CONTRAINDICA-

Introduced) TIONS

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) MAOIs

co-morbid anxiety disorders; no Lexa-Pro (2002) MAOIs

clear indication whether as Prozac (1987) MAOIs,

effective as MAOIs for atypical Thioridazine

depression, but favored as Luvox (1994) MAOIs,

first-line agents in general Thioridazine,

because of ease of use; may Cisapride,

have strong negative effect on Pimozide,

sleep patterns, with increased Theophylline

awakening and movement; more Paxil (1992) MAOIs,

likely to be associated with Thioridazine

sexual dysfunction than other Zoloft (1993) MAOIs

new agents; sexual dysfunction

and agitation occur with all

SSRIs; agitation may be averted

by starting on low dose

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) MAOIs,

useful for melancholic depres- Cisapride,

sion; associated with positive Pimozide

effect on sleep patterns, in- Desyrel (1982) MAOIs

creasing sleep efficiency and

reducing awakenings; less

likely than SSRIs to cause

sexual dysfunction; sometimes

used in combination with SSRIs

to cut problems of sexual

dysfunction

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) MAOIs

cially useful for melancholic

depression; may be effective in

co-morbid panic disorder

OTHER ATYPICALS

Wellbutrin (1996) MAOIs, seizure

disorders,

bulimia,

anorexia

nervosa

Remeron (1996) MAOIs

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s) All MAOIs con-

certain forms of depression traindicated

such as atypical depression or with serotoner-

depression resistant to other gic agents in-

medications; may be useful for cluding SSRIs,

anxiety disorders including co- Demerol, epine-

morbid panic disorder and phrine and

social phobia; all MAOIs decongestants;

contraindicated with Demerol, pheochromocyto-

many cold and cough medica- ma, congestive

tions, tyramine-rich foods, heart failure,

most other antidepressants liver problems

Nardil (1960s) All MAOIs con-

traindicated

with serotoner-

gic agents in-

cluding SSRIs,

Demerol, epine-

phrine and

decongestants;

pheochromocyto-

ma, congestive

heart failure,

liver problems

Parnate (1960s) All MAOIs con-

traindicated

with serotoner-

gic agents in-

cluding SSRIs,

Demerol, epine-

phrine and

decongestants;

pheochromocyto-

ma, congestive

heart failure,

liver problems

DRUG CLASS TRADE NAME GENERAL

(Date Drug COMMENTS

Introduced)

SSRIs [selective serotonin reuptake inhibitors]

may be especially useful for Celexa (1998) “clean” side

co-morbid anxiety disorders; no effect profile;

clear indication whether as liquid formula-

effective as MAOIs for atypical tion available

depression, but favored as Lexa-Pro (2002) therapeutically

first-line agents in general refined form of

because of ease of use; may citalopram

have strong negative effect on molecule promi-

sleep patterns, with increased ses even

awakening and movement; more cleaner side

likely to be associated with effect profile,

sexual dysfunction than other possiblly fewer

new agents; sexual dysfunction drug interac-

and agitation occur with all tions; effec-

SSRIs; agitation may be averted tive at lower

by starting on low dose dosage than

other SSRIs

Prozac (1987) weekly dosage

form, liquid

formulation

available

Luvox (1994)

Paxil (1992) late emergence

of weight gain

(after 6

months); dis-

continuation

syndrome more

common than

with other

SSRIs; liquid

formulation

available;

controlled

release

formulation

available

Zoloft (1993)

SARIs [serotonin-2 antagonist/reuptake inhibitors]

dual action may be especially Serzone (1994) may be espe-

useful for melancholic depres- cially useful

sion; associated with positive in treating

effect on sleep patterns, in- depression with

creasing sleep efficiency and prominent in-

reducing awakenings; less somnia; less

likely than SSRIs to cause likely to cause

sexual dysfunction; sometimes weight gain and

used in combination with SSRIs sexual dysfunc-

to cut problems of sexual tion than

dysfunction SSRIs; can be

associated with

dry mouth,

nausea, consti-

pation, blurred

vision; rare

but serious

liver problems

can occur

Desyrel (1982) can be associa-

ted with seda-

tion, cardio-

vascular side

effects, sexual

dysfunction;

priapism can

occur in males

SNRIs [serotonin nonepinephrine reuptake inhibitors]

dual-action drugs may be espe- Efflexor (1997) often used af-

cially useful for melancholic ter failure of

depression; may be effective in trial of SSRIs;

co-morbid panic disorder may have nega-

tive effects on

sleep patterns

because of

stimulating

effects; can be

associated with

SSRI-like side

effects

although rela-

tive risk of

sexual dysfunc-

tion may be

lower than that

of standard

SSRIs; may be

especially use-

ful for older

patients be-

cause of rela-

tive lack of

drug interac-

tions; promi-

nent disconti-

nuation ef-

fects; extended

release

formulation

available

OTHER ATYPICALS

Wellbutrin (1996) often used as

adjunct to

SSRIs and other

antidepressants

to boost their

effects; limi-

ted data on

usefulness in

co-morbid

anxiety disor-

ders some

evidence not

well tolerated

in panic disor-

der due to

stimulating

effects (pro-

blem may be

averted by

starting with

half dose);

good side ef-

fect profile;

may be less

likely to cause

sexual dysfunc-

tion and weight

gain than

SSRIs; can be

associated with

headache,

tremor, sei-

zures sustained

release

formulation

available

Remeron (1996) dual action may

be especially

useful for

melancholic

depression; may

have positive

effects on

sleep patterns,

decreasing

awakening and

increasing

sleep efficien-

cy; may be

especially

useful for

older patients

by promoting

sleep and

weight mainte-

nance; may be

especially

useful in de-

pression with

prominent

insomnia;

sedating ef-

fects make drug

useful for

anxious-type

depressions;

unclear whether

suitable for

panic disorder;

sometimes used

to block SSRI

side effects,

such as nausea;

not associated

with sexual

dysfunction

causes weight

gain may be

associated with

sedation, dry

mouth; dis-

solvable wafer

available

MAOIs [monoamine oxidese inhibitors]

may be especially useful for Marplan (1960s)

certain forms of depression

such as atypical depression or

depression resistant to other

medications; may be useful for Nardil (1960s)

anxiety disorders including co-

morbid panic disorder and

social phobia; all MAOIs

contraindicated with Demerol, Parnate (1960s)

many cold and cough medica-

tions, tyramine-rich foods,

most other antidepressants

For all drugs in all classes, it takes an average of 2-4 weeks to begin

to see true antidepressant effects. No antidepressant has been

specifically approved for use in children.

SECONDARY APPLICATIONS KEY

1 bulimia

2 premenstrual dysphoric disorder (PMDD)

3 seasonal affective disorder (SAD)

4 dysthymia

5 obsessive-compulsive disorder (OCD)

6 panic disorder

7 post-traumatic stress disorder (PTSD)

8 social phobia

9 generalized anxiety disorder (GAD)

10 smoking cessation

SIDE EFFECTS KEY

A cardiac conduction delays

B orthostatic hypotension

C drowsiness

D weight gain

E sexual dysfunction

F severe hypertension, especially after

consuming certain goods

G gastrointestinal distress (nausea/diarrhea)

H insomia

I discontinuation side effects

J seizures

THE DEFINITIVE GUIDE TO ANTIDEPRESSANTS

DRUG CLASS TRADE NAME GENERIC

(Date Drug NAME

Introduced)

TRICYCLICS

may be useful for Elavil (1965) amitriptyline

melancholic depression; Asendin (1989) amoxapine

may be useful for co- Anafranil (1990) clomipramine

morbid attention defi- Norpramin desipramine

cit disorder, genera- (<1982)

lized anxiety disorder; Sinequan (1982) doxepin

may cause weight gain; Tofranil (1960) imipramine

can cause movement Pamelor, Aventyl nortriptyline

disorder; all tri- (1977)

cyclics can be lethal Ludiomil (<1982) maprotiline

in overdose; tricyclics Vivactil protriptyline

contraindicated with Surmontil (<1982) trimipramine

MAOIs, glaucoma,

urinary retention, some

forms of heart disease

MOOD STABILIZERS

Tegretol (1987) carbamazepine

Lamictal (1994) lamotrigine

Eskalith, Lithobid lithium

(1982)

Depakote (1982) valproic acid,

divalproex

sodium

IN DEVELOPMENT

N/A CRF antagonist

N/A duloxetine

(SNRI)

N/A gepirone

Mifeprex (TK) mifepristone

Zyprexa (TK) olanzapine

N/A reboxetine (NR)

N/A substance P

antagonists

Topamax topiramate

DRUG CLASS TRADE NAME MANUFACTURER

(Date Drug

Introduced)

TRICYCLICS

may be useful for Elavil (1965) Merck

melancholic depression; Asendin (1989) Watson

may be useful for co- Anafranil (1990) Novartis

morbid attention defi- Norpramin Aventis-Pasteur

cit disorder, genera- (<1982)

lized anxiety disorder; Sinequan (1982) Pfizer

may cause weight gain; Tofranil (1960) Novartis

can cause movement Pamelor, Aventyl Eli Lilly

disorder; all tri- (1977)

cyclics can be lethal Ludiomil (<1982) Mylan

in overdose; tricyclics Vivactil Merck

contraindicated with Surmontil (<1982) Wyeth-Ayerst

MAOIs, glaucoma,

urinary retention, some

forms of heart disease

MOOD STABILIZERS

Tegretol (1987) Novartis

Lamictal (1994) Glaxo Smithkline

Eskalith, Lithobid GlaxoSmithKline,

(1982) Solvay

Depakote (1982) Abbott

IN DEVELOPMENT

N/A

N/A Eli Lilly

N/A Organon

Mifeprex (TK) Danco

Zyprexa (TK) Eli Lilly

N/A Pharmacia

N/A

Topamax Janssen

DRUG CLASS TRADE NAME PRIMARY

(Date Drug APPLICATION(S)

Introduced)

TRICYCLICS

may be useful for Elavil (1965) major depressive

melancholic depression; disorder

may be useful for co- Asendin (1989) major depressive

morbid attention defi- disorder

cit disorder, genera- Anafranil (1990) OCD

lized anxiety disorder; Norpramin major depressive

may cause weight gain; (<1982) disorder

can cause movement Sinequan (1982) major depressive

disorder; all tri- disorder

cyclics can be lethal Tofranil (1960) major depressive

in overdose; tricyclics disorder

contraindicated with Pamelor, Aventyl major depressive

MAOIs, glaucoma, (1977) disorder

urinary retention, some Ludiomil (<1982) major depressive

forms of heart disease disorder

Vivactil major depressive

disorder

Surmontil (<1982) major depressive

disorder

MOOD STABILIZERS

Tegretol (1987) seizure disorder

Lamictal (1994) seizure disorder

Eskalith, Lithobid manic episodes of

(1982) bipolar disorder

Depakote (1982) manic episodes of

bipolar disorder;

seizure disorder

IN DEVELOPMENT

N/A

N/A

N/A

Mifeprex (TK) pregnancy

termination

Zyprexa (TK) antipsychotic

N/A

N/A

Topamax bipolar disorder

under study

DRUG CLASS TRADE NAME SECONDARY

(Date Drug APPLICATION(S)

Introduced)

TRICYCLICS

may be useful for Elavil (1965)

melancholic depression; Asendin (1989)

may be useful for co- Anafranil (1990) major depressive

morbid attention defi- disorder

cit disorder, genera- Norpramin

lized anxiety disorder; (<1982)

may cause weight gain; Sinequan (1982)

can cause movement Tofranil (1960)

disorder; all tri- Pamelor, Aventyl

cyclics can be lethal (1977)

in overdose; tricyclics Ludiomil (<1982)

contraindicated with Vivactil

MAOIs, glaucoma, Surmontil (<1982)

urinary retention, some

forms of heart disease

MOOD STABILIZERS

Tegretol (1987) bipolar disorder

Lamictal (1994) bipolar disorder

Eskalith, Lithobid

(1982)

Depakote (1982)

IN DEVELOPMENT

N/A

N/A

N/A

Mifeprex (TK)

Zyprexa (TK)

N/A

N/A

Topamax

DRUG CLASS TRADE NAME PRESUMED MECHANISM

(Date Drug OF ACTION

Introduced)

TRICYCLICS

may be useful for Elavil (1965) inhibits neuronal

melancholic depression; reuptake of norepine-

may be useful for co- phrine and serotonin

morbid attention defi- and to some extent

cit disorder, genera- dopamine

lized anxiety disorder; Asendin (1989) inhibits neuronal

may cause weight gain; reuptake of norepine-

can cause movement phrine and serotonin

disorder; all tri- Anafranil (1990) inhibits neuronal

cyclics can be lethal uptake of serotonin

in overdose; tricyclics and norepinephrine

contraindicated with Norpramin inhibits reuptake of

MAOIs, glaucoma, (<1982) norepinephrine

urinary retention, some Sinequan (1982) inhibits reuptake of

forms of heart disease norepinephrine

Tofranil (1960)

Pamelor, Aventyl

(1977)

Ludiomil (<1982) inhibits uptake of

norepinephrine

Vivactil

Surmontil (<1982)

MOOD STABILIZERS

Tegretol (1987)

Lamictal (1994)

Eskalith, Lithobid alters excitability of

(1982) neurons

Depakote (1982)

IN DEVELOPMENT

N/A blocks receptors for

corticotropin relea-

sing factor, preven-

ting stress reactivity

N/A inhibits neuronal

uptake of serotonin

and norepinephrine

N/A serotonin receptor

antagonist

Mifeprex (TK) blocks stress hormone

cortisol

Zyprexa (TK)

N/A inhibits neuronal

reuptake of

norepinephrine

N/A blocks receptors for

neurokinin-I

(substance P)

Topamax

DRUG CLASS TRADE NAME MAJOR SIDE

(Date Drug EFFECTS

Introduced)

TRICYCLICS

may be useful for Elavil (1965) A B C D E I

melancholic depression; Asendin (1989) A B C D E I

may be useful for co- Anafranil (1990) A B C D E I J

morbid attention defi- Norpramin A B C D E I

cit disorder, genera- (<1982)

lized anxiety disorder; Sinequan (1982) A B C D E I

may cause weight gain; Tofranil (1960) A B C D E I

can cause movement Pamelor, Aventyl A B C D E I

disorder; all tri- (1977)

cyclics can be lethal Ludiomil (<1982) A B C D E I J

in overdose; tricyclics Vivactil A B C D E I

contraindicated with Surmontil (<1982) A B C D E I

MAOIs, glaucoma,

urinary retention, some

forms of heart disease

MOOD STABILIZERS

Tegretol (1987) C

Lamictal (1994)

Eskalith, Lithobid D G

(1982)

Depakote (1982) C D

IN DEVELOPMENT

N/A

N/A

N/A

Mifeprex (TK)

Zyprexa (TK)

N/A

N/A

Topamax

DRUG CLASS TRADE NAME PRECAUTIONS &

(Date Drug CONTRADICATIONS

Introduced)

TRICYCLICS

may be useful for Elavil (1965) MAOIs, recent beart

melancholic depression; attack, cardiac con-

may be useful for co- duction problems,

morbid attention defi- glaucoma, urinary

cit disorder, genera- obstructive disorders

lized anxiety disorder; Asendin (1989) MAOIs, recent heart

may cause weight gain; attack, cardiac

can cause movement conduction problems,

disorder; all tri- glaucoma, urinary

cyclics can be lethal obstructive disorders

in overdose; tricyclics Anafranil (1990) MAOIs, recent heart

contraindicated with attack, cardiac con-

MAOIs, glaucoma, duction problems,

urinary retention, some glaucoma, urinary

forms of heart disease obstructive disorders,

seizure disorders

Norpramin MAOIs, recent heart

(<1982) attack, cardiac con-

duction problems,

glaucoma, urinary

obstructive disorders

Sinequan (1982) MAOIs, recent heart

attack, cardiac con-

duction problems,

glaucoma, urinary

obstructive disorders

Tofranil (1960) MAOIs, recent heart

attack, cardiac con-

duction problems,

glaucoma, urinary

obstructive disorders

Pamelor, Aventyl MAOIs, recent heart

(1977) attack, cardiac

conduction problems,

glaucoma, urinary

obstructive disorders

Ludiomil (<1982) MAOIs, recent heart

attack, cardiac con-

duction problems,

glaucoma, urinary

obstructive disorders,

seizure disorders

Vivactil MAOIs, recent heart

attack, cardiac con-

duction problems,

glaucoma, urinary

obstructive disorders

Surmontil (<1982) MAOIs, recent heart

attack cardiac conduc-

tion problems,

glaucoma, urinary

obstructive disorders

MOOD STABILIZERS

Tegretol (1987)

Lamictal (1994) divalproex sodium

Eskalith, Lithobid thiazide diuretics,

(1982) prescription-strength

nonsteroidal anti-

inflammatory agents;

angiotensin converting

enzyme inhibitors;

kidney or heart

disease, severe

debilitation, dehydra-

tion, sodium depletion

Depakote (1982) Lamortrigine

IN DEVELOPMENT

N/A

N/A

N/A

Mifeprex (TK)

Zyprexa (TK)

N/A

N/A

Topamax

DRUG CLASS TRADE NAME GENERAL COMMENTS

(Date Drug

Introduced)

TRICYCLICS

may be useful for Elavil (1965) anxiety-reducing

melancholic depression; sedative action; full

may be useful for co- therapeutic dose may

morbid attention defi- be difficult to tole-

cit disorder, genera- rate; low doses used

lized anxiety disorder; to treat pain

may cause weight gain; syndromes

can cause movement Asendin (1989)

disorder; all tri- Anafranil (1990) may be especially use-

cyclics can be lethal ful in melancholic

in overdose; tricyclics depression; anxiety-

contraindicated with reducing sedative

MAOIs, glaucoma, action

urinary retention, some Norpramin stimulating effect;

forms of heart disease (<1982) "cleaner" side effect

profile than other

tricyclics; does not

lower blood pressure;

also used to treat

ADHD especially in

adults

Sinequan (1982) anxiety-reducing seda-

tive action; has

potent antihistamine

effects

Tofranil (1960) oldest antidepressant

on market; may be

useful for co-morbid

OCD

Pamelor, Aventyl stimulating effect;

(1977) “cleaner” side effect

profile than some

other tricyclics; does

not lower blood

pressure

Ludiomil (<1982) anxiety-reducing

sedative action

Vivactil stimulating effect;

“cleaner” side effect

profile than other

tricyclics; does not

lower blood pressure

Surmontil (<1982) anxiety-reducing

sedative action

MOOD STABILIZERS

Tegretol (1987) FDA approved as anti-

convulsant; associated

with many drug inter-

actions; may produce

rash, low blood counts

Lamictal (1994) FDA approved as anti-

convulsant; efficacy

shown for bipolar

depression but not

major depression

Eskalith, Lithobid used as augmenter for

(1982) nonresponsive unipolar

depression

Depakote (1982) FDA approved as anti-

convulsant; extended

release formulation

available

IN DEVELOPMENT

N/A may be useful for co-

morbid PTSD; repre-

sents novel approach

to depression by dam-

pening hormonal

responses to stress

N/A dual-action drug may

be especially useful

for melancholic de-

pression; may also be

especially useful for

depression accompanied

by pain; FDA approval

possible in early 2003

N/A may be especially

useful for atypical

depression

Mifeprex (TK) long known as RU-486;

being tested for

psychotic depression

Zyprexa (TK) FDA approved as anti-

psychotic; may be of

use for refractory

depression in combina-

tion with SSRIs; com-

bined formulation with

Prozac now being

explored

N/A may be useful for co-

morbid attention de-

ficit disorder; asso-

ciated with less

weight gain and seda-

tion than other

agents; less sexual

dysfunction of the

type associated with

SSRIs; may be associa-

ted with dry mouth,

constipation, in-

creased sweating,

insomnia; currently

available in more than

50 countries

N/A represents novel ap-

proach to depression

by affecting neuro-

transmitter system

(neurokinin) com-

pletely different from

other antidepressants;

believed to dampen

emotional (and immune)

response to stress;

may be useful for

patients resistant to

other antidepressants;

MK-869 (Merck) is in

Phase III clinical

trials; also in trials

for chemotherapy-

induced nausea and

vomiting

Topamax FDA approved for

seizure disorders; may

cause cognitive

problems such as dif-

ficulty word-finding;

has unusual advantage

of not causing weight

gain and may help with

weight loss on other

psychotropic drugs

For all drugs in all classes, it takes an average of 2-4 weeks to begin

to see true antidepressant effects. No antidepressant has been

specifically approved for use in children.

SECONDARY APPLICATIONS KEY

1 bulimia

2 premenstrual dysphoric disorder (PMDD)

3 seasonal affective disorder (SAD)

4 dysthymia

5 obsessive-compulsive disorder (OCD)

6 panic disorder

7 post-traumatic stress disorder (PTSD)

8 social phobia

9 generalized anxiety disorder (GAD)

10 smoking cessation

SIDE EFFECTS KEY

A cardiac conduction delays

B orthostatic hypotension

C drowsiness

D weight gain

E sexual dysfunction

F severe hypertension, especially after

consuming certain goods

G gastrointestinal distress (nausea/diarrhea)

H insomia

I discontinuation side effects

J seizures

* Identifies have changed.

Hara Estroff Marano is the editor of Psychology Today’s Blues Buster newsletter as well as editor at large of PT.

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