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Ssri n snri
 

Ssri n snri

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  • Difference f c nd s??Paroxetine== most A/Es…Fluvoxamine- nausea
  • antidepressants, which affect other monoamine neurotransmitters as well.
  • 5-hydroxytryptamine 5-HT.. 14 distinct downstream serotonin receptors (5-HT receptors).
  • Hypo nd midbrain e beshi
  • They act upon two neurotransmitters in the brain that are known to play an important part in mood, namely, serotonin and norepinephrine. This can be contrasted with the more widely-used selective serotonin reuptake inhibitors (SSRIs), which act only on serotonin.
  • Sertraline- 200max. Though >100mg no help. TCA- 75-100
  • Life threatning
  • CP450 inhibitors
  • When SS occurs?
  • Receptor rebound…..Onset within 5 dayz f stopping treatment. Or during tapper or in missed dose….treatment??– mild- no rx others- reintroduce or another f same class with longer half life..
  • SIADH… 5Ht regulation f ADH…So SSRI n SNRI more…..
  • citalopram
  • Vascular injury------ platelet---- release f 5HT---- Vaso constricton. 5HT s a weak platelet aggregator. SSRI inhibit the 5HT transporter responsible fr uptake f 5HT n platelet
  • Fluoxetine--- insulin req reduced, HBA1c improved, wt loss…. Limited data n venla
  • Citalopram- QT prolong…. Dnt go fr SNRI. Tolerance…bp
  • 10 mg start n hepatic
  • – active monitoring, individual guided self-help, CBT or exercise are preferred in these cases

Ssri n snri Ssri n snri Presentation Transcript

  • SSRIs and SNRIs:In adults Dr. Syed Faheem Shams Student of MD (Part-II) Psychiatry, BSMMU
  • Depression
    • 3 rd largest cause of burden of disease
    • GLOBAL BURDEN OF DISEASE STUDY 1995 SHOWS UNIPOLAR DEPRESSION 2nd to Coronary disease by 2020 ; 1 st by 2030
  • Prevalence in Bangladesh
    • WHO + NIMH---- ‘03-‘05
    • Psychiatric disorder ---- >18 yrs --- 16.05%.
    • MDD--- 4.6%
    • GAD--- 2.9%
    • Somatoform D--- 1.4%
    • Panic--- 1.3%
    • Agorophobia—0.9%
    • OCD--- 0.5%
    • Simple Phobia--- 0.3%
  • Antidepressants
      • Tricyclic antidepressants (TCA)
      • Monoamine oxidase inhibitors (MAOI)
      • Selective Serotonin Re-uptake Inhibitors (SSRI)
      • Other and atypical antidepressant
        • Serotonin-2 Antagonists/Reuptake Inhibitors (SARI)
        • Serotonin and Noradrenaline Reuptake Inhibitors (SNRI)
        • Noradrenaline and Dopamine Reuptake Inhibitors (NDRI)
        • Noradrenaline Reuptake Inhibitors (NaRI)
        • Noradrenergic/Specific Serotonergic Antidepressants (NaSSA)
    • HOW DOES THE MOST ANTIDEPRESSANTS WORK??
  • Neurotransmitter Receptor Hypothesis of Antidepressant Action Decreased state due to up-regulation of receptors Stahl S M, Essential Psychopharmacology (2000)
  • Neurotransmitter Receptor Hypothesis of Antidepressant Action Antidepressant blocks the reuptake pump, causing more NT to be in the synapse Increase in NT causes receptors to down-regulate Stahl S M, Essential Psychopharmacology (2000)
  • SSRI’s
    • Citalopram
    • Escitalopram
    • Fluoxetine
    • Sertraline
    • Fluvoxamine
    • Paroxetine
    Fluoxetine Sertraline
    • SNRI---
    • Venlafaxine
    • Duloxetine
    • NaSSA ---
    • Mirtazapine
    • SARI---
    • Trazodone
    • NDRI---
    • Buproprion
    • NaRI---
    • Reboxetine
  • Why selective??
    • Affect only the reuptake pumps responsible for 5HT
    • Because of this, SSRIs lack some of the side effects of the more general drugs
  • History Of SSRI’s
    • SSRI’s were introduced in 1987
    • The first was Fluoxetine (Prozac:Eli Lilly & Company) FDA approved 1987
    • Sertraline (Zoloft; Pfizer, Inc) FDA approved 1991
    • Paroxetine (Paxil; GlaxoSmithKline) FDA approved 1992
    • Citalopram (Celexa; Forest Pharmaceuticals) FDA approved 2000
    • Escitalopram (Lexapro; Forest Pharmaceuticals) FDA approved 2002
  • Serotonin
    • Also known as 5-HT, derived from tryptophan (amino acid)
    • It is widely distributed in the animal and vegetable kingdoms
    • In mammals it is found in ---
    • gastrointestinal enterochromaffin cells
    • blood platelets
    • Brain
    • nerve tissue
    (McGraw-Hill Encyclopedia of Science and Technology, 2005)
  • Serotonin (contd.)
    • Serotonin is concentrated in certain areas of the brain---
    • the hypothalamus
    • midbrain
    • the cortex
    • Cerebellum
  •  
  •  
  • Other indications of SSRI
    • Anxiety disorders :
    • generalized anxiety
    • panic disorder
    • social phobia
    • obsessive-compulsive disorder
    • Bulimia nervosa
    • Pathological gambling
  • SNRIs
    • SNRIs were developed more recently than SSRIs
    • Relatively few
    • Their efficacy as well as their tolerability appears to be somewhat better than the TCA’s.
  • Venlafaxine
    • venlafaxine is approximately 3- to 5-fold more potent at inhibiting serotonin than noradrenaline reuptake
    • It has low affinity for cholinergic, histamine H1 and adrenergic receptors.
    • Venlafaxine is the first and most commonly used SNRI.
    Venlafaxine
  • Recognized minimum effective doses in MDD
    • SSRIs
      • Citalopram 20 mg/day
      • Escitalopram 10 mg/day
      • Fluoxetine 20 mg/day
      • Fluvoxamine 50 mg/day
      • Paroxetine 20 mg/day
      • Sertraline 50 mg/day
  • Recognized minimum effective doses – antidepressants (except TCAs)
    • Others
      • Duloxetine 60 mg/day
      • Mirtazapine 30 mg/day
      • Reboxetine 8 mg/day
      • Trazodone 150 mg/day
      • Venlafaxine 75 mg/day
  • Licensed Dosing
    • Citalopram--- 20-60mg/day
    • Escitalopram--- 10-20mg/day
    • Fluoxetine--- 20-60mg/day
    • Sertraline--- 50-200mg/day
    • Fluvoxamine--- 100-300mg/day
    • Paroxetine--- 20-60mg/day
  • Licensed Dosing
      • Duloxetine 60-120 mg/day
      • Mirtazapine 15-45 mg/day
      • Reboxetine 8-12 mg/day
      • Trazodone 150-300 mg/day
      • Venlafaxine 75-375 mg/day
  • Plasma half life Fluvoxamine Paroxetine Sertraline Fluoxetine Escitalopram Citalopram 17-22h 24h 26h 4-6 days 30h 33h
  • Adverse Effects (A/Es) of SSRIs
    • Nausea, vomiting, dyspepsia
    • Irritability/ agitation
    • Insomnia
    • Skin rash
    • Sexual dysfunction
    • Hyponatraemia
    • Cutaneous/ GI bleeding
    • Discontinuation syndrome
  • Adverse Effects (A/Es) of SSRIs Nausea+ Fluvoxamine Discontinuation sym++ Paroxetine A/E Sertraline Insomnia++ Agitation++ Rash+ Fluoxetine A/E Escitalopram Agitation, Insomnia Citalopram
  • Major interactions (CP 450 inhibitor) Fluoxetine Sertraline Fluvoxamine Paroxetine Citalopram Escitalopram Avoid - MAOi, St. John’s wort. Plasma level of some antipsychotics/some benzos/carbamazepine/TCAs plasma level of theophylline (Fluvo) Avoid - MAOi, St. John’s wort. Caution with alcohol, NSAID’s, Warferin
  • Serotonin syndrome
  • Features of Serotonin Syndrome
    • Classic clinical triad:
      • Mental status changes
      • Autonomic hyperactivity
      • Neuromuscular abnormalities
    • Wide ranging symptoms
  • Serotonin syndrome (contd.)
  • Serotonin syndrome (contd.)
  • Discontinuation Symptoms
    • Paroxetine commonest
    • Venlafaxine
  • Antidepressant-induced hyponatraemia
    • Risk factors
    • Old age
    • Female sex
    • Low body weight
    • Low baseline sodium concentration
    • Some drug treatments (e.g. diuretics, NSAIDs, carbamazepine, cancer chemotherapy)
    • Reduced renal function (especially acute and chronic renal failure)
    • Medical co-morbidity (e.g. hypothyroidism, diabetes, COPD, hypertension, head injury, CAD, various cancers)
    • Warm weather (summer)
  • Antidepressant-induced hyponatraemia- monitoring
    • All patients taking antidepressants should be
    • observed for signs of hyponatraemia
    • ( dizziness, nausea, lethargy, confusion,
    • cramps, seizures ).
    • Serum sodium should be determined (at
    • baseline and 2 and 4 weeks, and then 3-
    • monthly ) for those at high risk of drug-
    • induced hyponatraemia.
  • Special situations
    • Post stroke depression—
    • SSRIs
    • Mirtazapine
    • 30-40% stroke pts develop MDD.
  • Special situations
    • SSRIs and bleeding----
    • Pts with haemostatic defects
    • Pts taking warferin or antiplatelet drugs
    • NSAID’s
    • Steroids
    • P/h/o GI bleeding
  • Special situations
    • In Diabetes Mellitus ---
    • SSRI’s
    • SNRI’s
    • Mirtazapine
    • TCA
  • Special situations
    • In elder people–
    • SSRI’s
    • In Post MI patients-
    • SSRI’s
    • Mirtazapine
  • Special situations
    • In pregnancy- --
    • Fluoxetine
    • TCAs
    • In breast feeding mother- --
    • Sertraline
    • Paroxetine
  • Special situations
    • In renal impairment —
    • Citalopram
    • Sertraline
    • In hepatic impairment —
    • Citalopram
    • Paroxetine
  • Key points that patients should know
    • A single episode of depression should be treated for at least 6–9 months after remission
    • The risk of recurrence of depressive illness is high and increases with each episode
    • Those who have had multiple episodes may require treatment for many years .The chances of staying well are greatly increased by taking antidepressants
  • Key points that patients should know
    • Antidepressants are:
        • effective
        • not addictive
        • not known to lose their efficacy over time
        • not known to cause new long-term side effects
    • The medication needs to be reduced slowly under the supervision of a doctor
  • Key points that patients should know
    • Medication needs to be continued at the treatment dose. If side effects are intolerable, it may be possible to find a more suitable alternative
    • If patients decide to stop their medication, this must not be done suddenly, as this may lead to unpleasant discontinuation effects
  • NICE guidelines on the treatment of depression
    • Antidepressants are not recommended as first-line treatment in recent-onset, mild depression
    • Antidepressants are recommended for the treatment of moderate to severe depression and for dysthymia
  • NICE guidelines on the treatment of depression
    • For severe depression , a combination of an antidepressant and CBT is recommended
    • For treatment-resistant depression recommended strategies include augmentation with lithium, an antipsychotic or a second antidepressant
    • Patients with two prior episodes and functional impairment should be treated for at least 2 years
    • The use of ECT is supported in severe and treatment-resistant depression
  • NICE guidelines on the treatment of depression
    • When an antidepressant is prescribed, a generic SSRI is recommended
    • All patients should be informed about the withdrawal (discontinuation) effects of antidepressants
  • NICE guidelines on the treatment of anxiety disorders with SSRIs
    • ½ of the dose used in MDD.
    • Response – 6-8 wks
    • Duration of treatment-- ?? 6-8 months
  •  
  • Thank you all….
  • List of people with depression
    • Abraham Lincoln (US president)
    • William James & John B. Watson (pioneer psychologists)
    • Sir Winston Churchill (British Prime Minister )
    • Brooke Shields (American actress)
    • John Denver ( singer)