average, all antidepressants are equally effective. Although an individual
patient may preferentially respond to a certain anti-depressant, it is
difficult to predict this in advance. Without a personal or family history of
such a response, side effects are the most influential factors in choosing an
agent. Side effects may be particularly relevant in the following groups of
a high rate of depression in patients who have had a myocardial infarction and
the presence of depression adversely affects the prognosis of cardiac disease.
cardiovascular side effect of TCAs is orthos-tatic hypotension. This can be
clinically significant in both the hypertensive patient and the elderly
patient. Some of the tricyclic medications may have a lower risk of orthostatic
hypotension, notably nortriptyline and doxepin. The evidence for nortriptyline
causing little or no hypotension is convincing; for doxepin it is weaker (Roose
and Dalack, 1992).
not show a negative inotropic effect and do not seem to worsen congestive heart
failure. Patients with congestive heart failure may, however, be at a higher
risk for orthostatic hy-potension. Again, nortriptyline is the safest TCA in
conduction at the bundle of His. Their effect is analogous to type 1A
antiarrhythmic agents such as quinidine and procainamide. In therapeutic doses
they can slow cardiac conduction and in overdose they can cause
atrioventricular block-ade. These effects are of most concern in patients with
preexist-ing cardiac conduction defects. There is no evidence that any one
tricyclic medication is safer than another.
and coworkers (1993) recommend caution when using TCAs in all patients with
ischemic heart disease, particularly patients with ventricular arrhythmias that
follow a myocardial infarction.
serotonin reuptake inhibitors differ from the TCAs in that they do not prolong
the PR or heart wave (QRS) interval. Thus, they probably lack any of the
proarrhythmic and antiarrhythmic activities associated with TCAs. They do not
cause orthostatic hypotension. Most studies that exist suggest that SSRIs
should be safe in patients with heart disease.
has less proarrhythmic effect than the TCAs. However, there have been reports
of trazodone-related ventricular ectopy and complete heart block (Martyn et al., 1993). In patients with
preexisting heart disease, bupropion does not appear to cause the cardiac side
effects attributed to TCAs (Roose et al.,
pharmacokinetic changes are of great importance in ag-ing patients: decreased
efficiency of the hepatic microoxidase system and a decreased muscle–fat ratio.
Decreased efficiency of hepatic microoxidases results in the slower metabolism
of antidepressants and other drugs. Normal increases in body fat and a loss of
muscle mass result in an alteration of the volume of distribution for a
substance. Thus, lipophilic drugs, including all antidepressants, are more
widely distributed in the elderly body.
resulting slower metabolism and the increased volume of distribution increase
the half-lives of the various anti-depressants. The elderly, therefore, are
likely to have a greater incidence of side effects.
half-lives and steady state concentrations of the se-rotonin reuptake
inhibitors are only minimally affected by age. Paroxetine may be an exception
to this, and it may have an in-creased half-life in the elderly (Leonard,
assumption that elderly patients require lower blood levels of antidepressant
medication is not correct. Although pharma-cokinetic concerns may require
lowering of the medication dose, plasma levels are comparable to those in young
appears that antidepressants are as effective in the eld-erly as in the young,
although the elderly may have more diffi-culty tolerating these medications.
studies are available on the pharmacological treatment of depression in
medically ill patients, and even less on medically ill elderly patients. In
initiating treatment, the physician should understand the effects of various
illnesses on pharmacokinetics and the potential side effects that may result.
stimulants, antidepressants are the most common psy-chotropic medications
prescribed in children (Zito et al.,
2000) and adolescents (Jensen et al.,
1999) and the trend to use these medications in that group is on an increase.
It should be noted that the FDA has placed a “black box” warning related to
suicidal ideation in adolescents treated with SSRIs.
addition to depression, antidepressants are used in a number of nonaffective
disorders in children and adolescents, including enuresis,
attention-deficit/hyperactivity disorder, OCD and bulimia nervosa. They are
used to mitigate behaviors that are not part of a disease, for example, in
suicidal adolescents who do not have a concomitant depressive disorder
(American Academy of Child and Adolescent Psychiatry, 2001); however, there is
little empirical evidence that suggests that they can lower suicide risk
(Zametkin et al., 2001). Similarly,
they are used to dampen other impulsive behaviors.
should generally be treated with levels of medication comparable to those used
in adults, with the doses adjusted for body weight. As children have large
livers (relative to body weight), they tend to be efficient metabolizers of
substances, and may even need higher doses of medications (relative to body
weight) than do adults.
after the introduction of SSRIs, TCAs remained the most popular antidepressants
used in children. However, there have been concerns regarding the safety of
these medications. Sev-eral case studies have documented adverse cardiac
affects in children treated with TCAs, especially with desipramine. The Work
Group on Research of the American Academy of Child and Adolescent Psychiatry
(1990) conducted an exten-sive review of the available literature and concluded
that there is minimal or no increased risk of “sudden death” in children with
desipramine. It is probably wise, however, to perform an adequate cardiac
work-up before starting an antidepressant in a child.
these issues concerning cardiotoxicity, the serot-onin reuptake inhibitors have
become more popular for the treat-ment of children and adolescents. Most of the
newer agents have evidence for safety and efficacy in children, including
fluoxetine (Emslie et al., 1997) and
paroxetine (Keller et al., 2001).
Others of the SSRIs have data for their usefulness in anxiety disorders, such
as fluvoxamine (in OCD) (Riddle et al.,
2001) and sertra-line (which has open label data for social anxiety disorder
and OCD) (Compton et al., 2001).
Bupropion has been found safe and effective in children as well, although it
may exacerbate tics in Tourette’s disorder. Other antidepressants, including
most of the first-generation antidepressants, lack any positive efficacy
stud-ies in children or adolescents.
commonly used antidepressants, none show compel-ling evidence of
teratogenicity. Nonetheless, as is true for most medications, it is usually
best to discontinue antidepressants if a patient becomes pregnant. For all the
antidepressants, one must consider a risk–benefit decision, measuring the risk
of possible pregnancy-related side effects against the morbidity of a
pro-longed untreated depressive episode during pregnancy (Wisner et al., 2000). The FDA, in late 2005,
classified paroxetine as a class “D”
medication, indicating it should be used only with great caution in pregnancy.
antidepressants are secreted in breast milk. The levels of these agents are
difficult to predict, and their effect on the de-veloping infant is not known
(Cohen et al., 1991). There are no
systematic investigations of this issue. Given the level of uncer-tainty,
nursing should be deferred if antidepressant treatment is required.
of both world (Mann and Kapur, 1991) and the USA (Kapur et al., 1992) and a more recent study using prospec-tive data (Leon
et al., 1999) showed no unique
relationship be-tween fluoxetine (or any antidepressant) and suicidal
behaviors. However, as with any rare event, one cannot totally discount the
possibility that antidepressants may “trigger” suicidal ideation, either
through a direct neurochemical effect (e.g., through an acute decrease in
serotonergic transmission) or through nonspe-cific side effects of the drug
(e.g., the induction of akathisia). If such a phenomenon exists, it is very
uncommon, and probably not specific to any one antidepressant. There is,
however, now a “black box” warning regarding the emergence of suicidal idea-tion
in some adolescents taking SSRIs.
concerns must be balanced over the well-proven and much greater risk of
suicidal ideation and attempts when depression is not treated. Given this, and
the propensity of suicidal patients to choose medication overdose as the method
of suicide, the wide safety margin of the second- and third-generation
antidepressants makes them preferable to first-generation agents when suicide
is a concern. Bupropion has generally not been fatal in overdose, although
about a third of such cases experience a seizure.