Drug Evaluation

Paroxetine
Siu Wa Tang† & Daiga Helmeste
†University of California, Irvine, California, USA 92697-1681

Background: Paroxetine is a widely used antidepressant that has received

1. Introduction attention regarding suicide risk in younger patients. Objective: The purpose of
2. Overview of the market this paper is to review the pharmacology, efficacy and safety of paroxetine
in the affective disorders. Methods: The authors performed a PubMed
3. Introduction to paroxetine
search for all literature in English crossing the words ‘paroxetine’ and ‘Paxil’
4. Conclusion
against the words ‘serotonin transporter,’ ‘clinical trials,’ ‘depression’ and
5. Expert opinion ‘SSRI’. A search for paroxetine-related information at the FDA website and
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Mercer University on 11/12/14

under the clinical trial register of the GSK website were also performed.
Results/conclusion: Paroxetine is a serotonin re-uptake inhibitor with good
selectivity and no significant active metabolites. Paroxetine is approved
(ages ≥ 18 years) for the treatment of major depressive disorder, panic
disorder, obsessive–compulsive disorder, social anxiety disorder (social phobia),
post-traumatic stress disorder, and generalized anxiety disorders.
Drug – drug interactions involving the CYP enzyme system have been
documented, as well as concern for increased suicidality risk in younger
adults and recent FDA alerts regarding teratogenicity, serotonin syndrome
and persistent pulmonary hypertension.
For personal use only.

Keywords: antidepressant, depression, paroxetine, serotonin re-uptake inhibitor,

serotonin transporter

Expert Opin. Pharmacother. (2008) 9(5):787-794

1. Introduction

Major depression is no longer a mystical or obscure illness in modern society. As

the fourth leading contributor to the global burden of disease (DALYs) in the
year 2000, depression is now projected to reach the second place by 2020 [1].
According to World Health Organization, depression is already the second
leading cause of DALYs in the age category of 15 – 44 years for both sexes
combined. With the diagnosis becoming more accepted as a medical diagnosis
rather than a social stigma or weakness of personality, many patients are no longer
afraid to seek treatment for their depression. Whereas many non-psychiatrist
physicians were prompt to refer their depressed patients to psychiatrists
previously, many physicians now seek training in managing depression. Diagnosis
and treatment of depression has become an essential part of everyday practice for
many family physicians. In this regard, the availability of the specific serotonin
re-uptake inhibitor (SSRI) group of antidepressant drugs certainly has played an
undeniably important role. Compared to the old tricylic antidepressant drugs
(TCAs), which possess many troubling and sometimes lethal side effects, the
SSRIs are much easier to use. Serious adverse effects or lethality with antidepressant
drug overdose are now rarely encountered and fewer unpleasant side effects also
result in better long-term compliance. Although there are voices regarding the
danger of overprescription, it is undeniable that the arrival of the SSRIs
has increased the percentage of depressed patients treated.

2. Overview of the market

Before the arrival of the new generations of antidepressant drugs such as the
SSRIs, antidepressant drugs with a tricylic (or tetracyclic) molecular structure

10.1517/14656566.9.5.787 © 2008 Informa UK Ltd ISSN 1465-6566 787

 Paroxetine
dominated the market. These antidepressant drugs share a
common high potency in inhibiting neuronal serotonin
(5-HT) and norepinephrine (NE) re-uptake while differing
widely in their ability to affect other receptors [2,3]. The high
affinities for other receptors, transporters and enzymes are
commonly associated with side effects, some of which are
either unpleasant or potentially serious. This made it difficult
for inexperienced clinicians to use them and at the same
time has resulted in a poor quality of life for patients.
To increase the specificity of the NE and 5-HT re-uptake
blockade properties while decreasing the unwanted side
effects, new antidepressant compounds with alternate
structures were developed. A pyridylallylamine zimelidine,
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with a bicyclic structure, was found to be an antidepressant
with powerful 5-HT re-uptake blockade property when
searching for antihistamines similar to chlorphenamine. It
became the first SSRI to be marketed, but unfortunately
had to be taken off the market due to dangerous
neuropathic and other hypersensitivities. Zimelidine was
followed by the arrival of fluvoxamine and fluoxetine [4].
These new SSRIs greatly enhanced the ease of treatment of
depressed patients when serious side effects and overdose-
related fatalities previously seen with tricyclics were sub-
stantially reduced. The market for antidepressant drugs
For personal use only.
continued to grow and pursuance of other potent and
specific 5-HT re-uptake blockers resulted in the synthesis of
a number of popular SSRIs, namely paroxetine, sertraline,
citalopram and escitalopram in the subsequent years. All the
SSRIs share the common property of nanomolar affinity for
the 5-HT uptake transporter and high potency in inhibiting
5-HT re-uptake. Due to this specific and high potency
in 5-HT re-uptake inhibition compared to their action
on other targets, the SSRIs rapidly established themselves as
the main antidepressant drugs in the market.
3. Introduction to paroxetine
Although the availability of fluoxetine started the decline of
TCAs, the arrival of paroxetine heralded the rapid expansion
of the SSRI group of antidepressant drugs. In many countries,
paroxetine became one of the best selling antidepressant
drugs. Paroxetine is marketed in the UK as Seroxat and in
the US as Paxil. Paxil is approved for the treatment of major
depressive disorder (MDD), panic disorder, obsessive–
compulsive disorder, social anxiety disorder (social phobia),
post-traumatic stress disorder, and generalized anxiety
disorders. Paxil CR (controlled-release) is approved for the
treatment of MDD, panic disorder, social anxiety disorder
and premenstrual dysphoric disorder. Both Paxil and Paxil
CR have not been approved in Europe or North America for
the treatment of patients aged < 18 years.
3.1 Chemistry
Paroxetine and other SSRIs, while sharing the property of
5-HT re-uptake blockade seen with the tricyclic or tetracyclic
788 Expert Opin. Pharmacother. (2008) 9(5)
antidepressants, are chemically different. Paroxetine is a
phenylpiperidine and is available as a hydrochloride
salt when used as an SSRI antidepressant drug. The
chemical name is (-)-trans-4R-(4′-24 fluorophenyl)-
3S-([3′,4′-methylenedioxyphenoxy] methyl) piperidine
hydrochloride hemihydrate, the empirical formula
is C19H20FNO3·HCl·1/2H2O, with molecular weight of
374.8 Da (329.4 Da as free base). GSK manufactured
paroxetine HCl tablets under the trade name Paxil. It is also
available as Paxil CR an enteric, film-coated, controlled-
release tablets. Many other pharmaceutical companies
manufacture generic paroxetine HCl tablets in similar
strengths and also in chronic release or suspension format.
3.2 Pharmacodynamics
3.2.1Receptor profile and serotonin
re-uptake inhibition
In receptor binding studies, paroxetine and other SSRIs
demonstrated a very different profile compared to the TCAs.
Paroxetine has high affinity for the serotonin transporter but
little affinity for α-adrenergic (1 and 2), β-adrenergic,
dopamine (D2), 5-HT (1 and 2), muscarinic and histamine
H1 receptors [5], thus explaining its relative lack of side
effects compared to the TCAs. By comparison, tritiated
imipramine (3H-IMI), which was the first compound
widely used to label the transporter protein [6-10], showed
target promiscuity and was not an ideal compound for
labeling the 5-HT transporter. Paroxetine was subsequently
discovered to label the transporter with very high affinity
(Kd: 0.08 nM) [11]. Of all the SSRIs, paroxetine is the most
potent in terms of 5-HT re-uptake blockade, whereas
escitalopram is the most specific [12]. Both paroxetine
and escitalopram are excellent candidates for labeling
5-HT transporter proteins.
The known amino acid sequence [13] and proposed three-
dimensional (3-D) structure of the 5-HT transporter
protein suggested that TCAs or SSRIs bind to the
transporter protein and distort the 3-D coil structure of the
transporter thus blocking the passage of the 5-HT molecule.
This action gives these drugs the name of 5-HT re-uptake
inhibitors. It can be further visualized that SSRIs and
antidepressant drugs with different structures may bind to
different parts of the transporter and effect a distortion of
the protein. The serotonin transporter protein is very large
(∼ 630 amino acids) and has 12 segments that traverse the
cell membrane (transmembrane domains: TM 1 – 12).
Thus, there are a number of potential binding sites for
antidepressant drugs. This was shown in the early studies
using the 3H-IMI label, in which the presence of allosteric
binding sites on the transporter protein was suspected.
Temperature sensitivity experiments [7-9] suggested that the
binding of antidepressant drugs to the transporter protein is
very much affected by the configuration of the transporter
protein. Later work with 3H-citalopram and 3H-escitalopram,
examining modulation of antidepressant binding to the

Extracellular surface
Cell membrane
Cytoplasm
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Mercer University on 11/12/14
Figure 1. Hypothetical model of the 5-HT transporter
embedded in cell membrane. The 5-HT transporter protein is
composed of a long amino acid chain containing 12 transmembrane
helices (cylinders in figure) with both termini in the cytoplasm [48-50].
Based on site mutation experiments, certain amino acids of the
polypeptide chain have been identified to be important for the
primary 5-HT binding site (where TCAs and other 5-HT uptake
inhibitors bind) and the allosteric site (where paroxetine and
escitalopram bind), respectively [51-54]. Binding of 5-HT uptake
For personal use only.
inhibitors are thought to distort the configuration of the helices,
lock it in an inactive state and block the passage of 5-HT through
the transporter.
5-HT: Serotonin; TCA: Tricyclic antidepressant.
serotonin transporter, suggested that there is at least one
binding site on the transporter protein for serotonin uptake
inhibitors (TCA or SSRI classification), and the presence of
one or two allosteric binding sites to which paroxetine and
the enantiomers of citalopram (R- and S-citalopram) bind,
respectively [14]. Paroxetine shares with citalopram enantiomers
(R- and S-citalopram) the ability to inhibit dissociation of
uptake inhibitors from the serotonin transporter protein
(SW Tang and D Helmeste, unpublished research data) and
this property is not shared by all antidepressants. Whether
this property is critical in differentiating the onset or clinical
efficacy for different types of patients is the subject of much
current research.
Mutation experiments have confirmed that certain amino
acids are important for antidepressant binding to the
serotonin transporter protein, and that more than one site
is involved (Figure 1). For example, citalopram binding is
strongly dependent on TM 1 and 3, whereas the allosteric
modulatory sites of the binding are strongly dependent on
TM 10 – 12. In addition, amino acid residues important for
citalopram binding (TM1: Y95F; TM3: I172M) differ from
those needed for paroxetine binding to the serotonin
transporter [15-17]. These differences allow the development
of 5-HT transporter modulators, which act on differing
segments of the transporter protein. It is debatable
whether another SSRI is needed in the present oversaturated
Expert Opin. Pharmacother. (2008) 9(5)
Tang & Helmeste
SSRI antidepressant market, or whether antidepressant
compounds of a different class and different mechanism
of action would better serve the clinical needs of SSRI
treatment-resistant patients.
The predominant metabolites of paroxetine are essentially
inactive as 5-HT re-uptake inhibitors. By comparison,
norfluoxetine, a desmethyl metabolite of fluoxetine, is a
serotonin re-uptake inhibitor and contributes to the long
duration of action of fluoxetine [5]. Thus, paroxetine and
other SSRIs such as citalopram, without potent active
metabolites, are generally safer than fluoxetine in overdose
and drug – drug interaction situations. However, there
are still current drug therapy issues such as concomitant
paroxetine with pimozide or thioridazine with the potential
for QTc prolongation and arrhythmia.
3.3 Pharmacokinetics and metabolism
Absorption of paroxetine is not affected by food. First-pass
metabolism of paroxetine is extensive and it is metabolized
in the liver by both CYP2D6 and CYP3A4. The mean
elimination half-life for healthy subjects appears to be ∼ 24 h,
shorter than the ∼ 37 h for citalopram or 4 days for fluoxetine.
Approximately two-thirds (64%) of ingested paroxetine is
eliminated through the kidney, in contrast to citalopram,
which is eliminated primarily via the liver (85%) [18,19]. In
patients with either liver or renal impairment, this differential
elimination route between the two SSRIs might be an
important factor in their selection. In elderly subjects,
increased steady-state plasma concentrations and prolongation
of the elimination half-life were observed compared to
younger adult controls. Therefore, elderly patients should be
initiated and maintained at the lowest daily dosage.
Steady-state plasma concentrations of paroxetine are
generally achieved in ∼ 1 – 2 weeks. Thus, one should wait
until 2 weeks after cessation of paroxetine before starting
drugs that interact with paroxetine, such as monoamine
oxidase inhibitors. At steady-state, the mean plasma
concentration for paroxetine 20 mg was ∼ 41 ng/ml [20,21].
Metabolism and pharmacokinetics of paroxetine is heavily
affected by its high plasma protein binding and its CYP
profile. At therapeutic concentrations, the plasma protein
binding of paroxetine and fluoxetine are both ∼ 95% [18].
The administration of either of these SSRIs to a patient
taking other drugs that are also tightly bound to protein
(e.g., warfarin, digitoxin) may cause a shift in plasma
concentrations potentially resulting in an adverse effect.
Paroxetine inhibits CYP2D6 [22] and may elevate plasma
levels of coadministered drugs, which are also metabolized by
this enzyme and these include many TCAs (imipramine, [23]),
phenothiazine neuroleptics (e.g., perphenazine and
thioridazine) as well as many second-generation antipsychotic
drugs (e.g., risperidone) and atomoxetine. Plasma levels
of paroxetine may also be elevated or lowered when
coadministered with CYP2D6 inhibitors such as cimetidine
or enzyme inducers such as phenytoin, respectively.
789
 Paroxetine
Consequences of such drug – drug interaction through
the CYP enzymes could be serious, such as in the case of
warfarin. Fluoxetine, similar to paroxetine also inhibits
CYP2D6, whereas citalopram is only a weak inhibitor of
CYP2D6 and CYP2C19 and a weak or negligible inhibitor
of CYP3A4 and CYP1A2 [24,25].
3.4 Clinical efficacy
Paroxetine has been shown to be an effective antidepressant
drug in many studies.
3.4.1 Major depressive disorder
MDD was established in six placebo-controlled studies
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of patients aged 18 – 73, measured by the Hamilton
Depression Rating Scale (HDRS), the Hamilton depressed
mood item, and the Clinical Global Impression
(CGI)-Severity of Illness.
A study of out-patients with MDD who had responded
to Paxil during an 8-week open-treatment phase and then
randomized to Paxil or placebo for 1 year demonstrated
a significantly lower relapse rate for patients taking
Paxil (15%) compared with those on placebo (39%).
3.4.2 Obsessive–compulsive disorder
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Obsessive–compulsive disorder was established in two
12-week multicenter placebo-controlled studies of adult
out-patients suffering from moderate-to-severe obsessive–
compulsive disorder (DSM-IV). Treatment comprised fixed
doses of 20, 40 or 60 mg of paroxetine/day. Daily doses
of paroxetine 40 and 60 mg were found to be effective.
Long-term maintenance of efficacy was demonstrated in
a 6-month relapse prevention trial.
3.4.3 Panic disorder
Panic disorder was etablished in three 10- to 12-week
multicenter, placebo-controlled studies of adult out-
patients (DSM-IV). Long-term maintenance of efficacy
was demonstrated in a 3-month relapse prevention trial.
3.4.4 Social anxiety disorder
Social anxiety disorder was established in three 12-week,
multicenter, placebo-controlled studies (DSM-IV criteria).
Effectiveness in long-term treatment of social anxiety
disorder for > 12 weeks has not been systematically
evaluated in adequate and well-controlled trials.
3.4.5 Generalized anxiety disorder
Generalized anxiety disorder was demonstrated in two
8-week, multicenter, placebo-controlled studies of adult
out-patients (DSM-IV criteria). Maintenance efficacy was
observed for up to 24 weeks in a placebo-controlled trial.
3.4.6 Post-traumatic stress disorder
Post-traumatic stress disorder was demonstrated in two
12-week, multicenter, placebo-controlled studies of adult
790 Expert Opin. Pharmacother. (2008) 9(5)
out-patients (DSM-IV). Efficacy for > 12 weeks has not
been systematically evaluated in placebo-controlled trials.
3.5 Safety and tolerability
The SSRIs as a group do not cause as many adverse effects
compared with the TCAs. Paroxetine does not generally
produce clinically significant cardiovascular changes such as
blood pressure, heart rate or ECG. The most commonly
observed adverse effects were nausea and somnolence,
sweating, tremor, dizziness, insomnia and sexual dysfunction
(ejaculatory delay). Other complications listed by
FDA [26] for paroxetine include bleeding problems,
especially if taken with aspirin, NSAIDs (ibuprofen
or naproxen) or other drugs that affect bleeding. Mania,
conversion of patients from depression to mania, and
seizures are also risks of SSRIs. Other rare, but potentially
dangerous, adverse effects associated with potent SSRIs such
as paroxetine include 5-HT syndrome, hyponatremia
and inappropriate antidiuretic hormone secretion. It is inad-
visable to discontinue paroxetine abruptly as patients may
experience acute discontinuation effects such as dizziness,
gastrointestinal complaints, headache, agitation/restlessness
and sleep disturbance. A special withdrawal syndrome in new-
borns of mothers on paroxetine is described in Section 3.5.3.
Overdose attempts have been reported with paroxetine up to
850 mg alone and in combination with other agents, but
no deaths occurred in these reports and recovery was
uneventful. This contrasts with TCA overdose fatalities,
which are reported to be much higher [27,28].
Special and important medical risks associated with
the use of paroxetine have triggered FDA alerts and wide
attention among the medical community and patients. These
are described in the following sections.
3.5.1 Suicidal behavior
Alleged suicidal behavior and ideation induced in younger
patients or children by paroxetine and some other SSRIs
raised a tremendous amount of anxiety among the medical
community and patients regarding antidepressant drugs.
This culminated in 2005 when the FDA asked manufacturers
to add a black box warning to the labeling of all antidepressants
to describe this risk and to emphasize the need for appropriate
monitoring particularly for younger patients [29].
In addition, the FDA directed manufacturers to develop
medication guides to be distributed at the pharmacy with
each prescription or refill of a medication. Also in 2005,
FDA began a comprehensive review of 295 individual
antidepressant trials that included over 77,000 adult patients
with MDD and other psychiatric disorders, to examine the
risk of suicidality in adults on antidepressants. Drug placebo
differences in increased cases of suicidality per 1000 patients
treated were as follows:
• increases compared to placebo: < 18 (14 additional cases);
18 – 24 (5 additional cases)

• decreases compared to placebo: 25 – 64 (1 fewer cases);
> 65 (6 fewer cases)
In December 2006, FDA’s Psychopharmacologic Drugs
Advisery Committee agreed that labeling changes were
needed to inform healthcare professionals about the increased
risk of suicidality in younger adults using antidepressants.
The committee also noted product labeling needed to reflect
the apparent beneficial effect of antidepressants in older
adults and to remind healthcare professionals that the disorders
themselves are the most important cause of suicidality.
The most recent clarification on this issue was released
recently by FDA on May 2, 2007 [30]. It was proposed that
‘makers of all antidepressant medications update the existing
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black box warning on their products’ labeling to include
warnings about increased risks of suicidal thinking and
behavior, known as suicidality, in young adults aged 18 – 24 years
during initial treatment (generally the first 1 – 2 months). The
proposed labeling changes also include language stating that
scientific data did not show this increased risk in adults aged
> 24 years, and that adults aged ≥ 65 years taking antidepres-
sants have a decreased risk of suicidality. Discontinuation of
successful treatment may incur the risks of recurrent depres-
sion and the risk/benefit ratio should be carefully considered
by clinician and patient on a case-by-case basis.
For personal use only.
3.5.2 Teratogenicity
Use of medications by pregnant women always raises the
fear of birth defects, particularly if used on a chronic basis.
Study data raised the possibility that first-trimester exposure,
especially at dosage > 25 mg/day of paroxetine [31] might be
associated with a significant increase in cardiac malformation
risks [32]. However, others are of the opinion that specific
defects implicated are rare [33,34]. In view of the existing
controversies, the use of paroxetine in pregnant women
should be carefully weighed and possible alternatives be
considered. Discontinuation of successful treatment is
certainly not recommended as there could be severe
consequences such as postpartum depression and suicide.
3.5.3 Serotonin withdrawal symptoms in newborn
Up to 30% of newborns exposed to potent SSRIs
antidepressants towards the end of gestation showed
irritability, constant crying, shivering, increased tonus,
eating and sleeping difficulties, agitation and possibly
seizures [35]. All neonates exposed to SSRIs during the
last trimester should be observed for withdrawal symptoms
after birth.
3.5.4 Serotonin syndrome
Potent SSRIs such as paroxetine may cause a toxic state
called the serotonin syndrome, possibly as the result of
excess synaptic serotonin. The syndrome is characterized by
neuromuscular excitation (atypical chest pain, abnormal
muscle tone such as clonus myoclonus and rigidity),
Expert Opin. Pharmacother. (2008) 9(5)
Tang & Helmeste
autonomic stimulation (hyperthermia and sweating, abnormal
eye signs, sinus tachycardia, diaphoresis, tremor, excess
sweating and flushing) and changed mental state (headache,
anxiety, agitation, confusion or psychosis). Patients differ in
their susceptibility and tolerability to SSRIs and serotonin
syndrome could be from mild to severe. Combination of
paroxetine (and other SSRIs) and other drugs, particularly
those metabolized by CYP2D6, may result in elevation of
paroxetine levels and induce this syndrome. This has been
reported for the combination of tramadol with paroxetine
and some other SSRIs [36-39]. A recent FDA Alert
(July 2006) was issued regarding possible life-threatening
serotonin syndrome when 5-HT receptor agonists (triptans)
are used with SSRIs.
3.5.5 Infant persistent pulmonary hypertension
Chambers and co-workers [40] reported the occurrence
of persistent pulmonary hypertension in babies (6 – 12
per 1000 babies) whose mothers received SSRIs, including
paroxetine, after 20 weeks of pregnancy. An FDA Alert
(July 2006) was issued regarding this complication.
4. Conclusion
Paroxetine is a potent SSRI antidepressant drug devoid of
many of the side effects and dangers associated with the old
TCAs. The availability of generic paroxetine and some other
SSRIs have rendered the TCAs a second tier choice in many
countries. Although widely reported but relatively rare
adverse effects have affected its image, paroxetine has helped
many to recover from depression and remains one of the
popular antidepressant medications.
5. Expert opinion
5.1 Choice of selective serotonin
re-uptake inhibitors
The initial high price of SSRIs allowed the continuous use
of TCAs in many developing countries. This changed
rapidly when fluoxetine and some other SSRIs became
generic. The argument is now not so much whether
one should use SSRIs or tricylics but rather when tricylic
antidepressant drugs should be used, for example, as a choice
in SSRI treatment resistant patients and in certain pain
management situations.
Paroxetine is the most potent SSRI given its highest
affinity for the 5-HT transporter among all the SSRIs [12].
Interestingly, it also possesses respectable potency in
inhibiting NE re-uptake [41], making it a less-specific SSRI
when compared with citalopram [42]. This difference may
also explain why some patients who failed to respond to
one, may respond to another SSRI. It could be argued
that SSRIs differ among themselves in terms of transporter
binding chemistry and pharmacology. Whether these
differences translate into their suspected differences in
791
 Paroxetine

therapeutic efficacy needs more research. So far, there is no
clear evidence to suggest the existence of specific genetic
variations or defects in the transporter protein between
different patients suffering from depression when compared
with normal subjects. Large-scale trials such as the STAR*D
(Sequenced Treatment Alternatives to Relieve Depression
Study) project [43,44], which demonstrated differences in
response to different SSRIs and other antidepressant
compounds, showed some gain in switching non-responsive
patients to other antidepressant drugs, but these trials are
also limited by methodology such as drug dosages, diagnosis
and other factors, inherent in clinical trials of this sort.
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Mercer University on 11/12/14
mechanism of action after the SSRIs. They are unaware
that many TCAs are in fact dual NE and 5-HT re-uptake
blockers. The new dual blockers are superior in terms
of side-effect profiles, and not in terms of their ability
in blocking both NE and 5-HT re-uptake. Thus, the
concept of the new dual uptake blockers as antidepressant
drugs with superior efficacy is inaccurate. However,
the superior efficacy concept has been the subject of some
interesting studies regarding remission rates for various
antidepressants such as venlafaxine [46]. Nonetheless,
other 5-HT/NE re-uptake blockers [47] without a tricyclic or
tetracyclic structure represent an important path of
post-TCA antidepressant drug development and offer

5.2 Treatment resistance
Current antidepressant drugs alone or in combination with
other compounds benefit only about two-thirds of depressed
patients [45]. Some patients are treatment resistant, whereas
others never reach full remission. For many patients, their
response was only marginal and their depression easily
returned with minor stressful life events. Obviously there is
a great need for additional antidepressant drugs with new
mechanisms of action.
5.3 Selective serotonin re-uptake inhibitors versus
For personal use only.
the clinician a wider choice of antidepressant drugs when
the need for an alternate antidepressant drug arises in
the clinical setting. Under the dual 5-HT/NE re-uptake
blocker category of antidepressant drugs, venlafaxine was an
early stage compound in this development, followed rapidly
by a series of new compounds including duloxetine
and milnacipran, both with more balanced 5-HT/NE
re-uptake blockade profiles.
Declaration of interest

selective norepinephrine re-uptake inhibitors SW Tang received sponsorships, donations and research
Many clinicians nowadays mistakenly believe that dual grants from the following pharmaceutical companies:
re-uptake blockers are antidepressant drugs with a new Lundbeck, Astra Zeneca, GSK, Eli Lilly and Organon.

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Affiliation
Siu Wa Tang†1 MB PhD FRCP(C) &
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Mercer University on 11/12/14

Daiga Helmeste2 PhD

†Author for correspondence
1Emeritus Professor of Psychiatry

University of California,
Psychiatry North Campus Zot 1681,
Irvine, California, USA 92697-1681
Tel: +1 949 824 3557; Fax: +1 949 824 3557;
E-mail: swtang@uci.edu
2Visiting Professor

University of Hong Kong,

Psychiatry, Hong Kong, China
For personal use only.

794 Expert Opin. Pharmacother. (2008) 9(5)