Selective Serotonin Reuptake Inhibitors
List of drugs
Mechanism of action
Advantage over TCAs1 and MAOIs2
Adverse Drug Reactions (ADRs) / Side-effects
1TCAs = Tri-cyclic Anti-depressants
2MAOIs = Monoamine Oxidase Inhibitors
SSRIs are the „drugs of choice‟ for treating
Highly selective for serotonin transporter
gives them advantage over other drugs of
Fluoxetine is the prototype drug.
Can = Citalopram
Effectively = Escitalopram
Form = Fluoxetine
Favorable = Fluvoxamine
Potentials of = Paroxetine
Serotonin = Sertraline
Mechanism of Action
Primary aim in treatment of depression balance
levels of neurotransmitters to boost mood.
SSRIs act on serotonin transporter block
reuptake of serotonin in pre-synaptic neuron
more serotonin persists in the synaptic cleft
more post-synaptic neuronal activities.
Balancing of serotonin seems to help brain cells
send and receive chemical messages, which in
turn boosts mood.
Very selective for serotonin transporter 300- to
3000-fold more selective for serotonin than for nor-
Advantage over TCAs and MAOIs
TCAs and MAOIs affect re-uptake of serotonin
as well as nor-epinephrine.
Also have blocking activity at muscarinic, α-
adrenergic, histaminic H1 receptors.
SSRIs very selective for serotonin don‟t
exhibit antagonist activity at any other receptors.
Hence side effects associated with TCAs and
MAOIs like orthostatic hypotension, sedation, dry
mouth, blurred vision not seen with SSRIs
Fewer side effects, relatively safer in overdose and
equally effective as TCAs
Acquired status of first line treatment for
Primary indication: Depression
Generalized Anxiety Disorder
Post-traumatic Stress Disorder
Social Anxiety Disorder
Bulimia Nervosa (only Fluoxetine)
Obsessive – compulsive disorder
How? imbalance in the level of
neurotransmitters activates the „alarm-system‟ of
brain anxiety, obsessive-compulsive disorder etc
SSRIs balance the amount of neurotransmitter.
Well-absorbed after oral administration Fluoxetine
also available as sustained-release preparation.
Max. bioavailability in 2-8 hours and average half-lives
of 16-36 hours.
Fluoxetine longest half-life 50 hours, it‟s
metabolite (nor-fluoxetine) 10 days half-life.
Metabolized by cytochrome P450 enzyme system.
Enzyme-drug interactions: Inhibit various iso-enzymes
of CYP450 system (e.g. CYP2D6) hence, decreases
metabolism of drugs like TCAs, neuroleptic
drugs, antiarrhythmic, beta-adrenergic antagonist
Excretion: Urine. Sertaline and Paroxetine Also fecal
Sleep disturbances: Paroxetine and Fluvoxamine
Fluoxetine and Sertraline more activating.
Suicidal tendencies in children and teenagers.
Headache, sweating, anxiety, agitation, weakness,
fatigue, changes in weight.
GIT disturbances: nausea, vomiting, diarrhea
Overdose: Tendency to cause Seizures
How? by reducing seizure threshold.
Occurs on abrupt withdrawal of SSRIs.
Symptoms include: headache, malaise,
agitation, irritability, flu-like symptoms,
nervousness, changes in sleep pattern.
Agents with short half-lives, inactive
metabolites abrupt washout higher
So, Fluoxetine lowest risk for
“Excess of everything is harmful”
Administration of an SSRI in presence of
another highly serotonergic drug such as
MAOI life-threatening „serotonin
Excess of serotonin changes in mental
status and vital signs, hyperthermia, muscle
rigidity, muscle twitching.
Washout period of 2 weeks before
administration of an MAOI (6 weeks for