بسم الله الرحمن الرحیم antidepressants range tricyclics tetracyclics ssri ...
TRANSCRIPT
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بسم الله الرحمن بسم الله الرحمن بسم الله الرحمن بسم الله الرحمن الرحیمالرحیم
الرحیمالرحیم
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Antidepressants
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Range
Tricyclics Tetracyclics SSRI SNRI MAOI Oddities Adjuvants
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Factors Influencing Choice
Features of illness, e.g. agitation, hypersomia
Suicide risk Other therapy Other illness. Side effects Cost Special problems e.g.
Age, driving, pregnancy
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Drug Failure
Non compliance. Inadequate dosage. Other drugs e.g. alcohol, caffeine. Unresolved outside problems. Up to 25% failure even if above
don’t apply.
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Tricyclics & Tricyclics & tetracyclics TCAStetracyclics TCAS
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Imipramine Imipramine AmitriptylineAmitriptyline Tertiary aminesTertiary amines trimipramintrimipramin TCASTCAS CloimpramineCloimpramine
Secondary Amines DesipramineSecondary Amines Desipramine NortriptylineNortriptyline
Tetracyclic Tetracyclic AmoxpineAmoxpine MaprotilineMaprotiline
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PharmacokineticsPharmacokinetics Peak plasma Peak plasma 2-8hr2-8hr Half- lives Half- lives 10-70 10-70 hrhr
P 450 enzyme P 450 enzyme systemsystem
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PharmacodynamicsPharmacodynamics Block the reuptake Block the reuptake NENE 5HT5HT Antagonists at:Antagonists at: Muscarinic AchMuscarinic Ach Histamine Histamine H1 H1 alfa alfa 11adrenergicadrenergic alfa alfa 22adrenrgicadrenrgic
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Indications Indications
Major depressive disMajor depressive dis Secondary depression Secondary depression Medical Medical
dis dis Movement disMovement dis DementiaDementia
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Panic dis ( Imipramine)Panic dis ( Imipramine) Generalized anxiety dis (doxepine)Generalized anxiety dis (doxepine) Obsessive – compulsive dis Obsessive – compulsive dis ClomipramineClomipramine SSRIsSSRIs Eating dis (imipramine,desipramine)Eating dis (imipramine,desipramine) Pain disPain dis EnuresisEnuresis (Imipramine) (Imipramine) Peptic ulcer Peptic ulcer (doxepin) (doxepin) NarcolepsyNarcolepsy
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Premature Premature EjaculationEjaculation(( clomipramine)clomipramine)
NightmareNightmare PTSDPTSD ADHDADHD Sleepwalking disSleepwalking dis Separation anxiety disSeparation anxiety dis Sleep terrorSleep terror
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Adverse Adverse reactionsreactions
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Psychiatric: ManiaPsychiatric: Mania PsychosisPsychosis
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Anticholinergics:Anticholinergics:
Dry mouth ( Gum)Dry mouth ( Gum) Constipation (laxative)Constipation (laxative) Blurred visionBlurred vision Urinary retention Urinary retention
(Bethanechol) (Bethanechol) Impotence ( “ ) Impotence ( “ ) Narrow angle glaucoma (mioitc Narrow angle glaucoma (mioitc
agent)agent)
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CNS antichcoli:CNS antichcoli: Confusion Confusion
( physostigmine)( physostigmine) deliriumdelirium
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SedationSedation serotonergicserotonergic CholinergicCholinergic HistaminergicHistaminergic
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Autonomic effectsAutonomic effects Orthostatic hypotensionOrthostatic hypotension
(fludrocortisone 0—05mg (fludrocortisone 0—05mg X2)X2)
SweatingSweating PalpitationsPalpitations Blood pressure Blood pressure
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CardiacCardiac effects effects Tachycardia Tachycardia Flattened T wavesFlattened T waves Prolonged QTProlonged QT S.T S.T Quinidinelike effect Quinidinelike effect
PVCPVC
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At high plasma concentrations At high plasma concentrations arrhythmogenicarrhythmogenic Hypertensive episodes during Hypertensive episodes during
surgerysurgery
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Neurological effectsNeurological effects SedationSedation Delirium Delirium Psychomotor stimulationPsychomotor stimulation Myoclonic twitchesMyoclonic twitches Speech blockage Speech blockage ParesthesiaParesthesia Peroneal palsiesPeroneal palsies AtaxiaAtaxia Seizure ( maprotiline)Seizure ( maprotiline) Lower the seizure threshold (Clomipramine – Lower the seizure threshold (Clomipramine –
Amoxapin) Amoxapin)
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Allergic effectsAllergic effects
Exanthematous 4-5%Exanthematous 4-5%((marprotilinemarprotiline) )
JaundiceJaundice
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Hematological effects Hematological effects AgranulocytosisAgranulocytosis
LeukocytosisLeukocytosis LeukopeniaLeukopenia EosinophiliaEosinophilia
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Sore throat Sore throat CBCCBC
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Other adverse effectsOther adverse effects Weight gainWeight gain ImpotenceImpotence GynecomastiaGynecomastia AmenorrheaAmenorrhea SIADHSIADH HepatitisHepatitis
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Drug – Drug Drug – Drug InteractionsInteractions
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TCAS Block: TCAS Block: propranololpropranolol ClonidineClonidine GuanethidineGuanethidine
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TCAS increas : Antipsychotics TCAS increas : Antipsychotics levellevel
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TCAS+ sympathomimetics TCAS+ sympathomimetics serious serious CardiovascularCardiovascular effectseffects
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Oral contraceptives TCAOral contraceptives TCA
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AcetazolamideAcetazolamide AspirinAspirin Cimetidine TCACimetidine TCA ThiazideThiazide FluoxetineFluoxetine Sodium bicarbonateSodium bicarbonate
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Ascorbic acidAscorbic acid Ammonium chloridAmmonium chlorid BarbituratesBarbiturates Cigarette smoking TCACigarette smoking TCA Chloral hydrateChloral hydrate LithiumLithium PrimidonePrimidone
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TCAS additive effects:TCAS additive effects: Opioids Opioids AlcoholAlcohol AnxiolyticsAnxiolytics HypnoticsHypnotics Over – the – counter Over – the – counter
coldcold
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GuidelinesGuidelines CBCCBC LFTLFT ElectrolytesElectrolytes ECGECG
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DosageDosage TCAS: 150-300 mgTCAS: 150-300 mg Nortriptyl : 50-150 Nortriptyl : 50-150
mgmg
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Overdose Overdose AttemptsAttempts
AgitationAgitation DeliriumDelirium ConvulsionsConvulsions Hyperactive deep tendon reflex'sHyperactive deep tendon reflex's Bowel and bladder paralysisBowel and bladder paralysis Dysregulation of (BP) and temperatureDysregulation of (BP) and temperature Mydriasis Mydriasis Coma Coma Respiratory depression Respiratory depression Cardiac arrhythmias (3-4days)Cardiac arrhythmias (3-4days)
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Treatment – resistant Treatment – resistant DepressionDepression
Lithium ( 900-1200 mg)Lithium ( 900-1200 mg) Liothyronine( T3 ) ( 25-50 mg)Liothyronine( T3 ) ( 25-50 mg) T4T4
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Selective Serotonin reuptake Inhibitors
SSRIs
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SSRIs Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram Escitalopram
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Indication Depression Sertraline Fluoxetine Obsessive – Compulsive Disorder (OCD) Floxentine Panic dis citalopram Eating dis Bulimia Fluoxetine Anorexia Fluoxetine B.P.D Social phobia Paroxetine PTSD PMS Premataure Ejaculation Fluoxtine Sertraline
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Sexual obsessions ADHD Autistic dis Fluoxetine Neuropathic pain Fibromyalgia Headache Psychosomatic conditions Fluoxetine Syncope sertraline CopD sertraline
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Pharmacokinetics
half life = 1-3 daysmetabolized : liverP4 5O – Cyp 2D6
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Pharmacodynamics Inhibition of serotonin Reuptake
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Augmentation Strategies
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Pregnancy
Fluoxetine IQ Language delays Behavioral problems Neonatal Jitteriness Tachypnea
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Depression in Mechicallyill
Dression in Mechicallyill
Treatment of Depression
Excessive Physical morbidity
Myocardial InfarctionProlonged hospitalization Death
Depression in Medically ill
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Fluoxetine 20-80 mgSertraline 50-200 mgParoxetine 40-60 mgCitalopram 20-60 mgFluvoxamine 50-300 mg
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Adverse Reactions
¾ no side effects 10-15% no tolerate
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Sexual dysfunction Inhibited orgasm Decreased libido Bupropion Yohimbine Cyproheptadine Bromocriptine Amantadine Sildenafil Amphetamine(5mg)
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Gastrointestinal adverse effects
Nausea Diarrhea Anorexia Vomiting Dyspepsia
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Weight gain Paroxetine
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Headaches 18-20% Fluoxetine
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AnxietyFluoxetine
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Insomnia Fluoxetine Benzodiazepines
Trazodone
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–Sedation Citalopram
– Paroxetine
– Bupropion
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Vivid Dreams
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Seizures
– 0.1 - 0.2% Fluoxetine >100mg
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Extrapyramidal symptoms
Tremor 5-10%– Akathisia
Dystonia Cogwheel rigidity Torticollis Opisthotonos Gait dis Bradykinesia Tardive Dyskinesia Bruxism (Buspirone)
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Anticholinergic effects Paroxetine Dry mouth Constipation
Sedation
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Hematological adverse effects Paroxetine Fluoxetine Increase Bruisability
Neutropenia
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Electrolyte Glucose concentration Hyponatremia Secretion of inappropriate antidiuretic
Hormone ( SIADH)
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Endocrine Prolactin
mammoplasia
Galactorrhea
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Allergic reactions
Rashes Pulmonary system(fibrotic) Dyspnea
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Serotonin syndrome
MAOIS L-tryptophan Lithium
Diarrhea Restlessness Extreme agitation Hyperreflexia Autonomic instability
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Myoclonus Seizures Hyperthermia Shivering Rigidity Delirium Coma Status epilepticus Cardiovascular collaps Death
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Supportive careNitrvoglycerineCyproheptadineMethysergideCooling blanketsChlorpromazineDantrolene BenzodiazepinesArticonvulsants Mechanical ventilationParalyzing agents
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SSRI Withdrawal
DizzinessWeaknessNauseaHeadache AnxietyInsomniaPoor concentrationUpper respiratory symptoms ParesthesiaMigrain like symptome
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Drug – Drug interactions
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Fluoxetine Carbamazepine
Antineoplastic A.
Diazepam
Phenytoin
Warfarin
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Sertraline PT
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Paroxetine
PTCPP 2D6
Antidepressants PhenothiazinesAntiarrhythmic d.
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Fluvoxamine
Most Risk for interactions
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venlafexine, Effexor® 1st available as IR, not well tolerated Approval of XR resulted in better
tolerance at higher doses better efficacy Available in 37.5-75-150mg caps Dose range 75-300 in XR form Half life 5 hours steady state in 3 days,
longer with XR preparation Very effective with comorbid depression
and anxiety , OCD, panic
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Anti-anxiety effect present at higher doses >150mg QD
No weight gain Rare sedation Dizziness, lightheaded, restless,
disturbed sleep more common Sweating, headaches Side effects are usually transient at onset
of treatment
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Duloxitine, Cymbalta® Newest addition to SSRI/SNRI group Available 30-40-60mg caps Dose range 30-120mg QD Marketed as effective for patients with
somatic/pain issues More efficacious SNRI mg for mg than
venlafexine
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Very useful in the elderly with chronic pain, discomfort
Effective with FMS As effective as venlafexine in anxiety,
panic Not as efficacious as venlafexine in OCD,
by experience Well tolerated, no sedation, weight gain Dry mouth, headaches, restless, insomnia
dose related
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buproprion, Wellbutrin SR, XL® SNRI & dopamine reuptake inhibitor Available 100-150-200SR, 75-100-150IR,
100-150-300XL, tabs Dosage range 75-450mg QD rarely
exceeds 300mg QD Half life 20 hours, steady state 2-4 weeks Effective for depression with low mood ,
energy and motivation, (anhedonia)
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Effective at addressing cognitive symptoms associated with mood disorders.
Improves attention and concentration and mental energy.
Well tolerated no sedation, weight gain, no sexual dysfunction
Headaches, restless, rare agitation, insomnia
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Venlafaxine Selective Serotonin and
noradrenaline reuptake inhibitor – like amitryptyline.
Few other effects – unlike amitryptyline.
75-150mg / day minimum Dry mouth, somnolence, high BP,
nausea, headache and dizziness.
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The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete.
Moclobemide. Only MAOI-A. ? Role. ? Special place in anxiety
disorder. 300-600mg / day.
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Trazodone. Unique structure. Low cardiotoxicity, few
anticholinergic side effects. Drowsiness +. Nausea. 150 mg /day.