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Anti-depressants - Selective Serotonin Re-uptake Inhibitors (SSRIs)
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Anti-depressants - Selective Serotonin Re-uptake Inhibitors (SSRIs)



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  • 1. Selective Serotonin Reuptake Inhibitors (SSRIs) Contents:  Introduction  List of drugs  Mechanism of action  Advantage over TCAs1 and MAOIs2  Indications  Pharmacokinetics  Adverse Drug Reactions (ADRs) / Side-effects  Discontinuation Syndrome  Serotonin Syndrome 1TCAs = Tri-cyclic Anti-depressants 2MAOIs = Monoamine Oxidase Inhibitors
  • 2. Introduction  SSRIs are the „drugs of choice‟ for treating depression.  Highly selective for serotonin transporter  gives them advantage over other drugs of this class.  Fluoxetine is the prototype drug.
  • 3. Drugs include: Can = Citalopram Effectively = Escitalopram Form = Fluoxetine Favorable = Fluvoxamine Potentials of = Paroxetine Serotonin = Sertraline
  • 4. 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- epinephrine transporter.
  • 5. 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 depression.
  • 6. Indications  Primary indication: Depression  Others: Panic Disorder  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.
  • 7. Pharmacokinetics  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 drugs.  Excretion: Urine. Sertaline and Paroxetine  Also fecal excretion.
  • 8. Side-effects  Sleep disturbances: Paroxetine and Fluvoxamine  sedating. 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.
  • 9. Discontinuation Syndrome  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 risk.  So, Fluoxetine  lowest risk for discontinuation syndrome.
  • 10. Serotonin Syndrome  “Excess of everything is harmful”  Administration of an SSRI in presence of another highly serotonergic drug such as MAOI  life-threatening „serotonin syndrome‟  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 Fluoxetine)