Antidepressant
From Wikipedia, the free encyclopedia
An antidepressant is a
psychiatric medication or other substance (nutrient or herb) used for
alleviating
depression or
ysthymia
('milder' depression). Drug groups known as
MAOIs,
tricyclics, and
SSRIs are particularly associated with the term. These medications are
now amongst the
drugs most commonly prescribed by
psychiatrists and as well as other physicians, and their
effectiveness and
adverse effects are the subject of many studies and competing claims.
Nutrients for which there are claims of antidepressant activity include
phenylalanine,
yrosine,
tryptophan,
5-Hydroxytryptophan, and
holine.
Most antidepressants have a delayed onset of action and are usually taken
over the course of weeks, months, or years. They are generally considered
distinct from
stimulants, and drugs used for an immediate
uphoric
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
and
benzodiazepines,
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
lacebo
tends to have a significant antidepressant effect, so establishing something
as an antidepressant in a
clinical trial involves demonstrating a significant additional effect.
History
Isoniazid and iproniazidIn 1951, two physicians from the Sea View Hospital on Staten Island, Irving
Selikoff and Edward Robitzek, began clinical trials to evaluate two new
anti-tuberculosis agents from Hoffman-LaRoche,
soniazid
and
iproniazid. Only the patients with poor
rognosis
were initially treated; nevertheless, their condition improved dramatically. In
addition, Selikoff and Robitzek noted "a subtle general stimulation... The
patients exhibited renewed vigor and indeed this occasionally served to
introduce disciplinary problems."
The promise of the cure for tuberculosis brought by the results of the Sea View
Hospital trials was also excitedly discussed in the mainstream press. In 1952,
learning of the stimulant-like side effects of the isoniazid, the Cincinnati
psychiatrist Max Lurie decided to try it on his patients. In the following year,
he and Harry Salzer reported that isoniazid improved the depression in two
thirds of their patients and also coined the term antidepressant to
describe its action.
A similar story happened in Paris, where Jean Delay, the head of psychiatry at
Sainte-Anne Hospital, found out from his
pulmonology colleagues from Cochin Hospital about the side effects of
isoniazid. In 1952, that is even earlier than Lurie and Salzer, Delay with the
resident Jean-Francois Buisson also reported the positive action of isoniazid on
depressed patients.
For the reasons unrelated to the efficacy, isoniazid as antidepressant was soon
overshadowed by more toxic iproniazid,
although it remains one of the mainstays of the
tuberculosis treatment. The mode of antidepressant action of isoniazid is
still unclear. It is speculated that its effect is due to the inhibition of
diamine oxidase coupled with a weak inhibition of
monoamine oxidase A.
Another anti-tuberculosis drug tried at the same time by Selikoff and
Robitzek,
iproniazid, was observed to have a greater "psychostimulant" effect, albeit
at the cost of a greater toxicity.
Subsequently to the publications on isoniazid, papers by Jackson Smith, Gordon
Kamman, George Crane, and Frank Ayd describing the psychiatric applications of
iproniazid also appeared, and Ernst Zeller found iproniazid to be a potent
monoamine oxidase inhibitor.
Nevertheless, iproniazid had remained relatively obscure until Nathan Kline, the
influential and flamboyant head of research at Rockland State Hospital, began
its popularization both in medical and popular press as a "psychic energizer".
While isoniazid was not patentable,
Roche put a significant marketing effort behind iproniazid, including promoting
its
off-label use for depression.
Its sales grew massively in the following years, until it was recalled from the
market in 1961 due to the cases of lethal
hepatotoxicity.
Imipramine The discovery that a
tricyclic ("three ringed") compound had a significant antidepressant effect
was also first made in the early 1950s, by
Roland Kuhn in a Swiss psychiatric hospital. By that time
antihistamine derivatives were coming in to use to treat surgical shock and
then as psychiatric neuroleptics. Although, in 1955,
eserpine
was indicated to be more effective than placebo in alleviating anxious
depression, neuroleptics (literally "to seize the neuron") were developing for
use as
sedatives and
antipsychotics.
In attempting to improve the effectiveness of one of them,
chlorpromazine, in conjunction with the
Geigy
pharmaceutical company, Kuhn discovered that compound "G 22355"
(manufactured and patented in the US in 1951 by H�fliger and Schinder) had a
beneficial effect in patients with depression with mental and motor retardation.
He first reported his findings on what he called a "thymoleptic" (literally
"taking hold of the emotions", by contrast with neuroleptics, "taking hold of
the nerves") in 1955/56 and they gradually became established, resulting in the
marketing of the first tricyclic antidepressant,
mipramine,
soon followed by variants.
Later history These new drug therapies became
prescription-only medications in the 1950s. It was estimated that no more
than 50 to 100 people per million suffered from the kind of depression that
these new drugs would treat and pharmaceutical companies were not enthusiastic.[itation
needed] Sales through the 1960s remained poor compared to
the
major tranquilizers (neuroleptics/antipsychotics) and
minor tranquilizers (such as benzodiazepines), which were being marketed for
different uses.
The term antidepressant is reported to have been coined by Lurie and to not
have been widely adopted until at least the 1960s.
Imipramine remained in common use and numerous successors were introduced. The
field of MAO inhibitors remained quiet for many years until "reversible" forms
affecting only the MAO-A subtype were introduced, avoiding some of the adverse
effects.
Most pharmacologists by the 1960s thought the main therapeutic action of
tricyclics was to inhibit
norepinephrine reuptake, but it was gradually observed that this action was
associated with energizing and motor stimulating effects whilst some
antidepressant compounds appeared to have differing effects through action on
erotonin
systems (notably proposed by Carlsson and Lindqvist (1969) and Lapin and
Oxenkrug (1969)).
Researchers began a process of
rational drug design to isolate antihistamine-derived compounds that would
'selectively' (specifically) target these systems. The first such compound to be
patented, in 1971, was
imelidine,
whilst the first released clinically was
ndalpine.
luoxetine
(Prozac), FDA approved for commercial use in 1988, became the first
blockbuster
SSRI. Fluoxetine was developed at
li Lilly
in the early 1970s by Bryan Molloy, David Wong and others.
While it had fallen out of favor in most countries through the 19th and 20th
centuries, the herb
St John's Wort had become increasingly popular in
ermany where
ypericum
extracts eventually became licensed, packaged and prescribed by doctors.
Small-scale efficacy trials were carried out from the 1970s and 1980s, and
attention grew in the 1990s following a
meta-analysis of these.
It remained an
over-the-counter drug (OTC) or supplement in most countries and research
continued to investigate its neurotransmitter effects and active components,
particularly
yperforin
SSRIs became known as "novel antidepressants" along with other newer drugs
such as NRIs and
NRIs with various different selective effects, such as
venlafaxine,
uloxetine,
efazodone
and
mirtazapine
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