This document summarizes the pharmacological properties and clinical uses of the selective serotonin and norepinephrine reuptake inhibitors (SNRIs) venlafaxine and duloxetine. It describes how both drugs work by inhibiting the reuptake of serotonin and norepinephrine, and discusses their approved therapeutic indications for depression, generalized anxiety disorder, social anxiety disorder, panic disorder, and neuropathic pain. The document also reviews precautions, adverse effects, dosage and administration for each drug.

1. SELECTIVE SEROTONIN
“NOREPINEPHRINE
REUPTAKE INHIBITORS
Dr. Soumya Nath Maiti
IMO
Chairperson
Dr. F.A Sattar,
Department of Psychiatry,
VIMS n RC

2. Overview
 Introduction
 Venlafaxine
 Pharmacological Actions
 Therapeutic Indications
 Precautions and Adverse Reactions
 Dosage and Administration
 Duloxetine
 Pharmacological Actions
 Therapeutic Indications
 Precautions and Adverse Reactions
 Dosage and Administration

3. Introduction
 Venlafaxine and duloxetine are selective
serotonin norepinephrine reuptake inhibitors
(SNRIs).
 Venlafaxine and duloxetine are not unique with
respect to their dual action.Tricyclic and
tetracyclic antidepressants (TCAs) also inhibit
reuptake of norepinephrine and serotonin.TCAs,
however, also possess numerous other receptor
properties, such as muscarinic, adrenergic, and
histaminergic effects, and thus are not
considered selective.

4. Venlafaxine
 Pharmacological Actions –
 Venlafaxine is well absorbed from the
gastrointestinal (GI) tract.The extended-release
formulation reach peak plasma concentrations in 5.5
hours to 9 hours.
 Venlafaxine has a half-life of about 3.5 hours, It is
metabolized by hepatic cytochrome P450.
 Venlafaxine is a potent inhibitor of serotonin and
norepinephrine reuptake and a weak inhibitor of
dopamine reuptake. It does not have activity at
muscarinic, nicotinic, histaminergic, opioid, or
adrenergic receptors.

5. Therapeutic Indications
Depression –
 US Food and Drug Administration (FDA) does
not recognize any class of antidepressant as
being more effective than any other.This does
not mean that differences do not exist.
 There is some evidence to suggest that
venlafaxine has a potential to induce higher rates
of remission in depressed patients.This
difference of the venlafaxine advantage is about
6 percent.

6.  Generalized Anxiety Disorder
 The extended-release formulation of venlafaxine
is approved for treatment of generalized anxiety
disorder.
 In clinical trials lasting 6 months, dosages of 75
to 225 mg a day were effective against insomnia,
poor concentration, restlessness, irritability, and
excessive muscle tension related to generalized
anxiety disorder.

7. Social Anxiety Disorder
The extended-release formulation of
venlafaxine is approved for treatment of
social anxiety disorder.
Panic Disorder
The extended-release formulation of
venlafaxine is also approved for treatment
of panic disorder.

8.  Other Indications
Case reports and uncontrolled studies have
indicated that venlafaxine may be beneficial in the
treatment of obsessive-compulsive disorder,
agoraphobia, attention-deficit/hyperactivity
disorder (ADHD), and in patients with a dual
diagnosis of depression and cocaine dependence

9. Precautions and Adverse
Reactions
 Most common adverse reactions- Nausea, somnolence,
dry mouth, dizziness, nervousness, constipation,
asthenia, anorexia, blurred vision, abnormal ejaculation
or orgasm, erectile disturbances, and impotence.
Sweating is also more common with venlafaxine than the
SSRIs
 Abrupt discontinuation of venlafaxine use can produce a
discontinuation syndrome consisting of dizziness,
anxiety, nausea, somnolence, paresthesias, and
insomnia.Therefore, venlafaxine use should be tapered
gradually over 2 to 4 weeks.

10.  Hyperetnsion -Venlafaxine can cause an increase
in blood pressure (BP) in some persons
 Mydriasis -Venlafaxine can cause mydriasis, so
patients with raised intraocular pressure or those
at risk for acute narrow-angle glaucoma should be
monitored during venlafaxine treatment.
 Hepatic Cirrhosis - The pharmacokinetic
dispositions of venlafaxine are altered in patients
with hepatic cirrhosis.Venlafaxine elimination
half-life is prolonged by about 30 percent and
clearance decreased by about 50 percent Dosage
adjustment, thus, is necessary in patients with liver
disease.

11. Dosage and Administration
 Venlafaxine is available in 25-, 37.5-, 50-, 75-,
and 100-mg tablets and 37.5-, 75-, and 150-
mg extended-release capsules.
 The tablets and the extended-release
capsules are equally potent, and persons
stabilized with one can switch to an
equivalent dosage of the other.

12.  In depressed persons,The initial therapeutic
dosage is 75 mg a day, given once a day. Most
persons, however, are started at a dosage of 37.5
mg for 4 to 7 days to minimize adverse effects,
particularly nausea.
 The dosage can be raised to 150 mg per day after
day 4. As a rule, the dosage can be raised in
increments of 75 mg a day every 4 or more days.
It is approved by the FDA for use at dosages up
to 375 mg a day.
 The dosage of venlafaxine should be halved in
persons with significantly diminished hepatic or
renal function. If discontinued, venlafaxine use
should be gradually tapered over 2 to 4 weeks to
avoid withdrawal symptoms..

13. Duloxetine
 PharmacologicalActions
 Duloxetine is formulated as a delayed-release capsule to
reduce the risk of severe nausea associated with the drug.
 It is well absorbed, but a 2-hour delay occurs before
absorption begins. Peak plasma concentrations occur 6
hours after ingestion. Food delays the time to achieve
maximal concentrations from 6 to 10 hours and reduces the
extent of absorption by about 10 percent.
 Duloxetine has an elimination half-life of about 12 hours.
Elimination is mainly through the isozymes CYP 2D6 and
CYP 1A2. About 70 percent of the drug appears in the urine
as metabolites and about 20 percent is excreted in the
faeces.

14. Therapeutic Indications
 Depression and Generalized Anxiety
Disorder (GAD) - In contrast to venlafaxine, a
small number of studies have compared
duloxetine with SSRIs in depression.These
studies are suggestive of some advantage in
efficacy with duloxetine. In GAD higher doses
are also used with good results.

15.  Neuropathic Pain Associated with
Diabetes and Stress Urinary
Incontinence
 Duloxetine is the first drug to be approved by the
FDA as a treatment for neuropathic pain
associated with diabetes.The drug has been
studied for its effects on physical symptoms,
including pain, in depressed patients. Duloxetine
is currently awaiting approval as a treatment for
stress urinary incontinence,
 The action of duloxetine in the treatment of
stress urinary incontinence is associated with its
effects in the sacral spinal cord, which in turn
increase the activity of the striated urethral
sphincter.

16.  While duloxetine is approved for the
treatment of diabetic peripheral neuropathic
pain, it may worsen control of blood sugar
levels. Pooled data from clinical trials show
that short-term treatment with duloxetine
causes an increase in fasting glucose and
HA1c levels.
 Body weight decreased with short-term
duloxetine treatment, but increased during
long-term treatment.
 Modest increases in cholesterol may occur
during duloxetine therapy.

17. Precautions and Adverse
Reactions
 The most common adverse reactions Nausea, dry
mouth, dizziness, constipation, fatigue, decreased
appetite, anorexia, somnolence, and increased sweating.
Nausea was the most common side effect leading to
treatment discontinuation in clinical trials.
 Patients with substantial alcohol use should not be treated
with duloxetine because of possible hepatic effects. It also
should not be prescribed for patients with hepatic
insufficiency, end-stage renal disease or for patients with
uncontrolled narrow-angle glaucoma.
 Abrupt discontinuation of duloxetine should be avoided
because it can produce a discontinuation syndrome similar
to that of venlafaxine.

18. Dosage and Administration
 Duloxetine is available in 20-, 30-, and 60-mg
tablets.The recommended therapeutic, and
maximal, dosage is 60 mg per day.The 20- and
30-mg doses are useful for either initial therapy
or for twice-daily use as strategies to reduce side
effects.
 Difficulties in tolerability were seen, however,
with single doses above 60 mg. Accordingly,
when dosages of 80 and 120 mg per day were
used, they were administered as 40 or 60 mg
twice daily.

19. Summary
 Originally marketed as an antidepressant,
venlafaxine is now also indicated for the
treatment of generalized anxiety and social
anxiety disorders.
 Duloxetine is indicated for the treatment of
depression, generalized anxiety disorder, and
painful diabetic neuropathy and is awaiting
the indication for stress urinary incontinence

20. References
 Kaplan & Sadock's Synopsis of Psychiatry:
Behavioral Sciences/Clinical Psychiatry, 10th
Edition by Sadock, Benjamin James; Sadock,
Virginia Alcott p 1081- 1083

21. Thank You