Tolerance and dependence
Most antidepressants, including the SSRIs and tricyclics, are known to
produce
tolerance (i.e. a decrease in the effects of a drug over time), and
ithdrawal
(particularly if abrupt) may produce adverse effects, which can range from mild
to extremely severe.
Antidepressants do not seem to have all of the same
ddictive
qualities as other substances such as
icotine,
affeine,
ocaine, or
other
stimulants - in other words, while antidepressants may cause dependence and
withdrawal they do not seem to cause uncontrollable urges to increase the dose
due to
euphoria or
pleasure, and thus do not meet the strict definition of an addictive
substance. However, antidepressants do meet the
World Health Organisation definition of "dependency-inducing", and indeed
the SSRIs are listed by the organisation as among the most strongly
dependency-inducing substances in existence.
If an
SSRI medication is suddenly discontinued, it may produce both
omatic
and
psychological withdrawal symptoms, a phenomenon known as "SRI
discontinuation syndrome" (Tamam & Ozpoyraz, 2002). When the decision is
made to stop taking antidepressants it is common practice to "wean" off of them
by slowly decreasing the dose over a period of several weeks or months, although
often this will reduce the severity of the discontinuation reaction, rather than
prevent it. Most cases of discontinuation syndrome last between one and four
weeks, though there are examples of patients (especially those who have used the
drugs for longer periods of time, or at a higher dose) experiencing adverse
effects such as impaired concentration, poor short-term memory, elevated anxiety
and sexual dysfunction, for months or even years after discontinuation.
It is generally not a good idea to take antidepressants without a
prescription. The selection of an antidepressant and dosage suitable for a
certain case and a certain person is a lengthy and complicated process,
requiring the knowledge of a professional. Certain antidepressants can initially
make depression worse, can induce
nxiety, or
can make a patient aggressive, dysphoric or acutely
suicidal. In certain cases, an antidepressant can induce a switch from
depression to ania
or ypomania,
can accelerate and shorten a manic cycle (i.e. promote a rapid-cycling pattern),
or can induce the development of
sychosis
(or just the re-activation of latent psychosis) in a patient with depression who
was not psychotic before the antidepressant.
Side effects
Antidepressants can often cause
side effects, and an inability to tolerate these is the most common cause of
discontinuing an otherwise working medication.
Side effects of SSRIs:
ausea,
iarrhea,
eadaches.
Sexual side effects are also common with SSRIs, such as loss of
ibido, failure
to reach rgasm
and
erectile problems.
Serotonin syndrome is also a worrying condition associated with the use of
SSRIs. The Food and Drug Administration has included Black Box warnings on all
SSRIs stating how they double suicidality (from 2 in 1,000 to 4 in 1,000) in
children and adolescents who are prescribed these drugs.
Side effects of TCAs (tricyclic antidepressants): Fairly common side effects
include
dry mouth, blurred vision,
drowsiness,
izziness,
tremors, sexual problems,
skin rash, and weight gain or loss.
Side effects of MAOIs (monoamine oxidase inhibitors): Rare side effects of
MAOIs like
phenelzine (brand name: Nardil) and
tranylcypromine (brand name: Parnate) include
iver
inflammation,
heart attack,
stroke, and
seizures.erotonin
syndrome is a side effect of MAOIs and SSRIs when they are combined.
General Although recent drugs may have fewer side effects, patients sometimes report
severe side effects associated with their discontinuation, particularly with
aroxetine
and
venlafaxine. Additionally, a certain percentage of patients do
not respond to antidepressant drugs. Another advantage of some newer
antidepressants is they can show effects within as few as five days, whereas
most take four to six weeks to show a change in mood. However, some studies show
that these medications might be even more likely to result in moderate to severe
sexual dysfunction. However, there are medications in trials that appear to show
an improved profile in regard to sexual dysfunction and other key side effects.
MAO inhibitors can produce a potentially lethal hypertensive reaction if
taken with foods that contain high levels of
yramine,
such as mature cheese, cured meats or yeast extracts. Likewise, lethal reactions
to both prescription and over the counter medications have occurred. Any patient
currently undergoing therapy with an MAO inhibiting medication should be
monitored closely by the prescribing physician and always consulted before
taking an over the counter or prescribed medication. Such patients should also
inform emergency room personnel and information should be kept with one's
identification indicating the fact that the holder is on MAO inhibiting
medications. Some doctors even suggest the use of a medical alert ID bracelet.
Although the reactions in question are dramatic when they happen, the total
number of deaths due to interactions and dietary concerns are comparable to
over-the-counter medications.
Antidepressants should be used with great care, usually in conjunction with
mood stabilisers, in the treatment of
bipolar disorder, as they can exacerbate symptoms of
ania. They have
also been known to trigger
ania or
ypomania
in some patients with bipolar disorder and in a small percentage of patients
with depression.17]
SSRIs are the antidepressants most frequently associated with this side effect.
In particular, it has been noted that the most dangerous period for
uicide in a
patient with depression is immediately after treatment has commenced, as
antidepressants may reduce the symptoms of depression such as
psychomotor retardation or lack of motivation before mood starts to improve.
Although this appears to be a paradox, studies indicate the suicidal ideation is
a relatively common component of the initial phases of antidepressant therapy,
and it may be even more prevalent in younger patients such as pre-adolescents
and teenagers. It is strongly recommended that other family members and loved
ones monitor the young patient's behavior, especially in the first eight weeks
of therapy, for any signs of suicidal ideation or behaviors.
Until the black box warnings on these drugs were issued by FDA as well as by
agencies in other nations, side effects and alerting families to risk were
largely ignored and downplayed by manufacturers and practitioners. This may have
resulted in some deaths by suicide although direct proof for such a link is
largely anecdotal. The higher incidence of suicide ideation reported in a number
of studies has drawn attention and caution in how these drugs are used.
People under the age of 24 who suffer from depression are warned that the use
of antidepressants could increase the risk of suicidal thoughts and behaviour.
Federal health officials unveiled
Proposed changes to the labels on antidepressant drugs in December 2006 to
warn people of the inherent danger.
On September 6, 2007, the
Centers for Disease Control and Prevention reported
uicide rate
in
American
adolescents (especially
girls, 10 to 24 years old) increased 8% (2003 to 2004), the largest jump in
15 years.
Specifically, in 2004 - 4,599 suicides in Americans ages 10 to 24, up from 4,232
in 2003, for a rate of 7.32 per 100,000 people that age. Before, the rate
dropped to 6.78 per 100,000 in 2003 from 9.48 per 100,000 in 1990. The findings
also reinforced the fact that antidepressant
drugs reduce suicide risk. Psychiatrists found that the increase is due to the
decline in
prescriptions of antidepressant
drugs like Prozac to young people since 2003, leaving more cases of serious
depression untreated. In a December 2006 study,
The American Journal of Psychiatry said that a decrease in antidepressant
prescriptions to minors of just a few percentage points coincided with a 14
percent increase in suicides in the
United States; in the
Netherlands, the suicide rate was 50% up, upon prescription drop.
The critics of this study contend that the US "2004 suicide figures were
compared simplistically with the previous year, rather than examining the change
in trends over several years".
The pitfalls of such attempts to infer a trend using just two data points (years
2003 and 2004) are further demonstrated by the fact that, according to the new
epidemiological data, the suicide rate in 2005 in children and adolescents
actually declined despite the continuing decrease of SSRI prescriptions. "It is
risky to draw conclusions from limited ecologic analyses of isolated
year-to-year fluctuations in antidepressant prescriptions and suicides. One
promising epidemiological approach involves examining the associations between
trends in psychotropic medication use and suicide over time across a large
number of small geographic regions. Until the results of more detailed analyses
are known, prudence dictates deferring judgment concerning the public health
effects of the FDA warnings."
Subsequest follow-up studies have supported the hypothesis that antidepressant
drugs reduce suicide risk.
However, the conclusion that societal suicide rate decreases are due to
antidepressant prescription is extraordinarily dubious given the plethora of
confounding variables.
Sexual
Sexual dysfunction is a very common side effect, especially with
SSRIs. Common sexual side effects include problems with
ibido (sexual
desire), lack of interest in sex, and
norgasmia
(trouble achieving orgasm).
[18] Although usually reversible, these sexual side effects can, in rare
cases, last for months or years after the drug has been completely withdrawn.
This disorder is known as
Post SSRI Sexual Dysfunction.
upropion,
a dual reuptake inhibitor (NE and DA), in many cases results in a moderately
increased libido, due to increased dopamine activity. This effect is also seen
with dopamine reuptake inhibitors, CNS stimulants and dopamine agonists, and is
due to increases in testosterone production (due to inhibition of prolactin) and
increased nitric oxide synthesis.
Apomorphine,
efazodone
and
nitroglycerin have been shown to reverse some sexual dysfunction via
increased nitric oxide activity.
MAOIs are reported to have fewer negative effects on sexual function and
libido, particularly
moclobemide at a 1.9% rate of occurrence. Betanechol has been reported to
reverse MAOI-induced sexual dysfunction via its cholinergic agonist properties
(Gross 1982).
In order for the physician to select the appropriate response, the patient
should provide the physician with information to distinguish between reduced
libido (little or no desire for sex), reduced sexual function (mpotence,
vaginal dryness) and
norgasmia,
as these have separate causes and prompt different treatment.
Thymoanesthesia Closely related to sexual side effects is the phenomenon of emotional
blunting, or mood anesthesia. Many users of SSRIs complain of apathy, lack of
motivation, emotional numbness, feelings of detachment, and indifference to
surroundings. They may describe this as a feeling of "not caring about anything
anymore." All SSRIs, SNRIs, and serotonergic TCAs are liable to cause this
effect to varying degrees, especially at higher dosages.
REM Sleep It is well recognized that virtually all major antidepressant drugs but
trimipramine suppress
REM sleep and it has, in fact, been proposed that the clinical efficacy of
these drugs largely derives from their suppressant effects on REM sleep. The
three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs),
tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs),
profoundly suppress REM sleep.19]
The MAOIs virtually completely abolish REM sleep, while the TCAs and SSRIs have
been shown to produce immediate (40-85%) and sustained (30-50%) reductions in
REM sleep. Abrupt discontinuation of MAOIs can cause a temporary phenomenon
known as "REM rebound" in which the patient experiences extremely vivid dreams
and nightmares.
Weight Gain Many antidepressants in all categories are associated with weight gain
usually in the range of 10-50 pounds but not uncommonly upwards of 100 pounds.
The specific cause is unknown, but it is known that antidepressants are
associated with increased cravings (usually for high fat carbohydrates), an
inability to feel full despite ingestion of adequate calories, low energy levels
and increased daytime sleepiness which can lead to overeating and a lack of
desire to exercise, and dry mouth which can lead to ingestion of calorie-laden
beverages. Eating low fat, low protein carbohydrate snacks and carbohydrate-rich
dinners allows the brain to make serotonin which then controls appetite and
balances mood. Carbohydrates thus eaten, as part of a balanced diet, by virtue
of their effect on brain serotonin levels, thus support weight loss in the
setting of antidepressant weight gain.
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