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Anti depressant Drugs. Rezaei M. MD Psychiatrist. Tricyclics. Tertiary amines: Imipiramine Amitriptyline Clomipramine Trimipiramine Doxepin Secondary amines Desipiramine Nortriptyline protriptyline. Tetracyclics. Amoxapine Maprotiline Minaserin. Pharmacological actions.

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anti depressant drugs

Anti depressant Drugs

Rezaei M. MD

Psychiatrist

tricyclics
Tricyclics
  • Tertiary amines:
    • Imipiramine
    • Amitriptyline
    • Clomipramine
    • Trimipiramine
    • Doxepin
  • Secondary amines
    • Desipiramine
    • Nortriptyline
    • protriptyline
tetracyclics
Tetracyclics
  • Amoxapine
  • Maprotiline
  • Minaserin
pharmacological actions
Pharmacological actions
  • Absorbed from oral administration
  • Peak plasma concentration 2-8 hrs
  • Half life vary from 10 to 70 hrs ( nortriptyline, maprotiline and protriptyline may have longer half lives )
  • 5-7 days are needed to reach steady state plasma concentration
  • Metabolized in liver by cytochrome p-450 enzyme
  • Drug interaction with quinidine, cimetidine , fluxetine, serteraline, paroxetine , phenothiazine, carbamazepine
  • Genetic variability between persons are responsible for up to 40-fold differences in plasma concentrations of TCA`s
slide5

Mechanism of action:

    • Block the reuptake of NEP and serotonin
    • Competitive antagonists at the muscarinic acetylcholine, histamine H1, @1 and @2-adrenergic receptors.( Amoxapine, nortriptyline, desipramine, maprotiline have the least anticholinergic activity.

Doxepine has the most antihistaminergic activity,

clomipramine is the most sertonin-selective of the TCAs)

adverse effects
Adverse effects
  • Psychiatric effects
    • A major adverse effect is the possibility of inducing a manic episode in patients +/- history of BMD I disorder
  • Anticholinergic effects
    • Patient may develop a tolerance for these effects with continued treatment.
      • Amitriptyline
      • Imipramine
      • Doxepin
      • Trimipramine
    • Dry mouth, constipation, blurred vision , urinary retention,
    • Treatment
    • Beware of narrow angle glaucoma
    • Severe reactions may induce CNS anticholinergic syndrome with confusion and delirium
slide7

Sedation

    • Amitriptyline
    • Trimipramine
    • Doxepin
    • The least sedative effects are in desipiramine and protriptyline
  • Autonomic effects
    • Orthostatic HOTN ,Partly because of @1-adrenergic blockade
    • Nortriptyline least likely cause the problem
    • Fludrocortisone may be helpful
    • Other effects include sweating , palpitation, HTN
slide8

Cardiac effects

    • In the usual therapeutics doses: tachycardia, flattened T wave, prolonged QT interval, and depressed ST segment
    • Because the drug prolong conduction time, their use in patients with preexisting conduction defects is contraindicated.
    • The drug should be discontinued several days before elective surgery because of occurrence of hypertensive episodes during surgery in patients receiving TCAs.
slide9

Neurlogical effects

    • Desipramine and protriptyline are associated with psychomotor stimulation:
      • Myoclonic jerks and tremors of tongue and upper extremities
      • Speech block
      • Paresthesia
      • Peroneal palsy
      • Ataxia
    • Amoxapineis unique in causing
      • Parkinsonian symptoms
      • Akathisia
      • Dyskinesia
      • rarely; neuroleptic malignant syndrome
slide10

Maprotiline may cause seizures if

    • Dose increase too quickly
    • Dose keep at high level for too long
  • Overall TCAs have relatively low risk for inducing seizures, except in patients who are at risk for seizures.
allergic and hematological effects
Allergic and hematological effects
  • Rash in 4-5 % in maprotiline
  • Jaundice is rare
  • Agranulocytosis, leukopenia and leukocytosis are rare.
  • However , a patient with fever or sore throat during the first few months of TCA treatment, should have a CBC immediately.
slide12

Other adverse effects :

    • Weight gain
    • Impotence
    • Gynecomastia
    • Amenorrhea
    • Nausea
    • Hepatitis
    • Vomiting
    • SIADH
slide13
SSRI
  • Major differences between them is different pharmacokinetics profiles
  • Fluoxetine has the longest half life of 2-3 days, others of about 2o hrs.
  • All well absorbed orally and metabolized in the liver
  • Paroxetine and fluoxetine are metabolized by CYP 2D6, be careful in coadministration of drugs with the same enzyme metabolizer
  • Fluvoxamine inhibits the CYP 3A4, so interfere with terfenadine and astemizole.
  • If taken with food, it reduce nausea and diarrhea.
therapeutic indications of ssri
Therapeutic indications of SSRI
  • Depression ; they are first line in the general population ( mild and moderate Dep. ), the elderly, the medically ill and those who are pregnant.
  • Serteraline may be more effective for treatment of severe depression with melancholia
  • Over 50% of persons who respond poorly to one SSRI will respond favorably to another.
slide15

Augmentation strategies

    • In depressed persons with partial response :
      • Bupropion
      • Lithium
      • Levothyroxine
      • Sympathomimetics
      • Pindolol
      • Clonazepam
slide16

Suicide

    • Markedly reduce the risk of suicide
  • Depression during pregnancy
    • No documented adverse reaction
    • SSRI may produce a self limited neonatal withdrawal syndrome that consist of jitterness and mild tachypnea, it begins several hrs after birth and may persist for days to a few weeks. It is rare and does not interfere with feeding.
slide17

Postpartum depression(+/- psychotic feature)

  • Depression in the Elderly and Medically ill
    • Precise diagnostic evaluation to rule out dementia and delirium.
    • They are less well tolerated by persons with preexisting GI symptoms.
  • Chronic depression
    • They have to continue taking SSRI`s for at least 1 year.
slide18

Depression in children

    • Children of depressed adults are at increased risk of depression.
    • Adverse effects in children includes GI symptoms, insomnia, motor restlessness, social disinhibition, and hypomania or mania; so SSRI use with small doses.
  • OCD
    • Fluvoxamine and Serteraline are approved for treatment of pediatric OCD
    • Effective dose for OCD is higher than those required for depression.
slide19

Panic Disorders

    • SSRI`s are far superior to benzodiazepines for treatment of panic disorder with depression.
    • Are effective for childhood panic symptoms
  • Social Phobia
  • Posttraumatic Stress Disorder
    • SSRI`s are more effective than TCAD and MAO`s inhibitor
    • Marked improvement of both intrusive and avoidant symptoms.
  • Specific phobias, GAD, separation anxiety
slide20

Bulimia Nervosa and other Eating Disorder

    • Fluoxetine
  • Obesity ; fluoxetine in combination with behavioral program
  • PremensturalDysphoric Disorder
    • Fluoxetine and Serteraline
slide21

Adverse Reactions of SSRI`s

    • Sexual dysfunction: inhibited orgasm and decreased libido.
    • Gastrointestinal : nausea, diarrhea, vomiting, dyspepsia, anorexia.
    • Weight Gain
    • Headaches; 18-20 %
    • Anxiety
    • Insomnia and Sedation
    • Vivid dreams and Nightmares
    • Seizures
    • Extrapyramidal Symptoms
    • Galactorrhea
    • Hypoglycemia , rarely hyponatremia and SIADH
serotonin syndrome
Serotonin Syndrome
  • Concurrent administration of an SSRI with MAOI, l-tryptophan, or lithium can rise plasma serotonin concentration
    • Diarrhea
    • Restlessness
    • Agitation , hyperreflexia, autonomic instability, rapid fluctuations of vital signs
    • Myoclonus , seizures, hyperthermia, rigidity,
    • Delirium , coma, cardiovascular collapse and death.
ssri s withdrawal
SSRI`s Withdrawal
  • Dizziness
  • Weakness
  • Nausea
  • Headaches
  • Rebound depression
  • Anxiety
  • Insomnia
  • Poor concentration
  • Upper respiratory symptoms
  • Paresthesia
  • Migranelike symptoms
bupropion
BUPROPION
  • More effective against symptoms of depression than those of anxiety.
  • Half life 12 hrs.
  • Blockade of dopamine reuptake
  • Therapeutic indications:
    • Depression
    • Bipolar Disorders
    • ADHD
    • Cocaine Detoxification
    • Smoking cesation
bupropion1
BUPROPION
  • Adverse reaction
    • Headache
    • Insomnia
    • Upper respiratory symptoms
    • Nausea
    • Restlessness
    • Agitation
    • Irritability
    • Weight loss 25%
    • Dry mouth
      • constipation
trazodone
Trazodone
  • Half life is 6-11 hrs
  • Specific inhibitor of serotonin reuptake
  • Depressive Disorder
  • Insomnia
venlafaxine
Venlafaxine
  • May have faster onset of action than other antidepressant
  • Most effective drugs for treatment of severe depression with melancholic features & GAD
  • Half life 3.5 hrs( SR-form 9 hrs )
  • Inhibitor of serotonin & norepinephrine reuptake and weak inhibitor of dopamine reuptake
  • Therapeutic indications
    • Depression
    • GAD
    • OCD
    • Panic
    • Agarophobia , social phobia, ADHD
slide28

Adverse reactions:

    • Nausea
    • Somnolence
    • Dry mouth
    • Dizziness
    • Constipation
    • Asthenia
    • Anxiety
    • Anorexia
    • Blurred vision
    • Abnormal ejaculation and orgasm
    • Errectile disturbance and impotence
duloxetine
Duloxetine
  • Inhibitor of serotonin and norepinephrine
maio drugs
MAIO Drugs
  • Used less frequently than others
  • Increase biogenic amine neurotransmitter level
  • There are two type of MAO : A & B
  • MAOA metabolize NEP, SER, EPI
  • MAOB metabolize DOP, TYR
  • Therapeutic indications:
    • Depression, Atypical depression
    • Panic
    • Agarophobia
    • PTSD
    • Eating Disorder
    • Social phobia
    • Pain Disorder