Antidepressant Drugs

• An antidepressant, in the most common usage, is a psychiatric medication thought to alleviate

clinical depression or dysthymia ('milder' depression). Drug groups known as MAOIs, tricyclics and
SSRIs are particularly associated with the term. These medications are now amongst the most
commonly prescribed by psychiatrists and general practitioners, and their effectiveness and
adverse effects are the subject of many studies and competing claims. Other antidepressants are
also widely used, notably St John's Wort.
• Antidepressants have a delayed onset of action and are usually taken as a course over several
weeks, months or years. They are generally considered separately from stimulants, and drugs used
for an immediate euphoric effect only are not generally considered antidepressants. Despite the
name, antidepressants are often used in the treatment of other conditions, including
anxiety disorders, bipolar disorder, obsessive compulsive disorder, eating disorders and
chronic pain. Some have also become known as lifestyle drugs or "mood brighteners". Other
medications not known as antidepressants, including antipsychotics in low doses[1] and
benzodiazepines[2] are also widely used to manage depression.
• The term antidepressant is sometimes applied to any therapy (e.g. psychotherapy,
electro-convulsive therapy, acupuncture) or process (e.g. sleep disruption, increased light levels,
regular exercise) found to improve clinically depressed mood. An inert placebo tends to have a
significant antidepressant effect, so establishing something as an antidepressant in a clinical trial
involves demonstrating a significant additional effect.
 Introduction
• An antidepressant, in the most common usage, is
a psychiatric medication thought to alleviate
clinical depression or dysthymia ('milder'
depression). Drug groups known as MAOIs,
tricyclics and SSRIs are particularly associated
with the term. These medications are now
amongst the most commonly prescribed by
psychiatrists and general practitioners, and their
effectiveness and adverse effects are the subject
of many studies and competing claims. Other
antidepressants are also widely used, notably
St John's Wort
• Antidepressants have a delayed onset of action and are usually taken as a
course over several weeks, months or years. They are generally
considered separately from stimulants, and drugs used for an immediate
euphoric effect only are not generally considered antidepressants. Despite
the name, antidepressants are often used in the treatment of other
conditions, including anxiety disorders, bipolar disorder,
obsessive compulsive disorder, eating disorders and chronic pain. Some
have also become known as lifestyle drugs or "mood brighteners". Other
medications not known as antidepressants, including antipsychotics in low
doses[1] and benzodiazepines[2] are also widely used to manage
depression.
• The term antidepressant is sometimes applied to any therapy (e.g.
psychotherapy, electro-convulsive therapy, acupuncture) or process (e.g.
sleep disruption, increased light levels, regular exercise) found to improve
clinically depressed mood. An inert placebo tends to have a significant
antidepressant effect, so establishing something as an antidepressant in a
clinical trial involves demonstrating a significant additional effect.
• [edit] Mechanisms of action
• The therapeutic effects of antidepressants are believed to be
related to their effects on neurotransmitters.
Monoamine oxidase inhibitors (MAOIs) block the break-down of
monoamine neurotransmitters (serotonin and norepinephrine) by
inhibiting the enzymes which oxidize them, thus leaving higher
levels still active in the brain (synaptic cleft).
• Tricyclic antidepressants (TCAs) prevent the reuptake of various
neurotransmitters, including serotonin, norepinephrine, and
dopamine. Selective serotonin reuptake inhibitors (SSRIs) more
specifically prevent the reuptake of serotonin (thereby increasing
the level of active serotonin in synapses of the brain). Other novel
antidepressants specifically affect serotonin and other
neurotransmitters.
• Neurotransmitter levels are altered as soon as the antidepressant
chemicals build up in the bloodstream, but effects on mood appear
to occur several days or weeks later.
• One explanation of this holds that the "down-regulation" of
neurotransmitter receptors— an apparent consequence of excess
signaling and a process that takes several weeks — is actually the
mechanism responsible for the alleviation of depressive symptoms.
Another hypothesis is that antidepressants may have some longer-
term effects due to the promotion of neurogenesis in the
hippocampus, an effect found in mice [28][29]Other animal research
suggests that antidepressants can also affect the expression of
genes in brain cells, by influencing "clock genes". [30]
• New research suggests that delayed onset of clinical effects from
antidepressants indicates involvement of adaptive changes in
antidepressant effects. Rodent studies have consistently shown
upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP)
• system induced by different types of chronic but
not acute antidepressant treatment including
serotonin and norepinephrine uptake inhibitors,
monoamine oxidase inhibitors, tricyclic
antidepressants, lithium and electroconvulsions.
cAMP is synthesized from
adenosine 5-triphosphate (ATP) by adenylyl
cyclase and metabolized by cyclic nucleotide
phosphodiesterases (PDEs).[31]Data also suggest
antidepressants to have the ability of modulating
neural plasticity in longterm administration.[32]
• [edit] Therapeutic efficacy
• There is a large amount of research evaluating the potential
therapeutic effects of antidepressants, whether through
efficacy studies under experimental conditions (including
randomized clinical trials) or through studies of "real
world" effectiveness. A sufficient response to a drug is often
defined as at least a 50% reduction in self-reported or
observed symptoms, with a partial response often defined
as at least a 25% reduction. The term remission indicates a
virtual elimination of depression symptoms, albeit with the
risk of a recurrence of symptoms or complete relapse. Full
remission or recovery signifies a full sustained return to a
"normal" psychological state with full functioning.
• [edit] Tolerance and dependence
• Most antidepressants, including the SSRIs and
tricyclics, are known to produce tolerance (i.e. a
patient receiving antidepressant therapy for
some years will often have to increase the dose
over time, or add other drugs, to receive the
same therapeutic effect), and withdrawal
(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
addictive qualities as other substances such as nicotine
, caffeine, cocaine, 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. [citation needed]
• psychological withdrawal symptoms, a
phenomenon known as "SSRI discontinuation
If an SSRI
medication is suddenly discontinued, it may prod
uce both
somatic and 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 anxiety, or can
make a patient aggressive, dysphoric or acutely suicidal. In
certain cases, an antidepressant can induce a switch from
depression to mania or hypomania, can accelerate and
shorten a manic cycle (i.e. promote a rapid-cycling pattern),
or can induce the development of psychosis (or just the re-
activation of latent psychosis) in a patient with depression
who wasn't 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: Nausea, diarrhea, headaches. Sexual
side effects are also common with SSRIs, such as loss of
libido, failure to reach orgasm 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, dizziness, 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
liver inflammation, heart attack, stroke, and
seizures.