Antidepressants

465 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
465
On SlideShare
0
From Embeds
0
Number of Embeds
9
Actions
Shares
0
Downloads
8
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Antidepressants

  1. 1. Drugs Used in Affective Disorders
  2. 2. MOOD/MOOD DISORDER • Sustained emotion
  3. 3. INCIDENCE • Higher in women than in men • Between ages 25 to 44
  4. 4. Etiology of Depression Biogenic Amine Hypothesis • Depression and mania are due to an alteration in neuronal and synaptic catecholamine concentration at adrenergic receptor sites in the brain. – Depression: deficiency of catecholamine, especially norepinephrine – Mania: excess amines
  5. 5. ETIOLOGY • Biogenic amine theory • Dysregulation theory • Family history
  6. 6. Range of emotions • Euthymia • Hypomania • Euphoria • Mania • Dysthymia • Dysphoria • Depression
  7. 7. Clinical features of major depression One of the following must be present: – Depressed mood – Anhedonia (i.e., loss of interest or pleasure) Plus four or more of the following: – Decreased or increased appetite – Unintentional weight loss or gain – Insomnia or hypersomnia – Psychomotor agitation or retardation – Fatigue or loss of energy – Feelings of worthlessness or excessive or inappropriate guilt – Diminished ability to think or concentrate or indecisiveness – Recurrent thoughts of death and/or suicidal ideation – Suicide attempt
  8. 8. Treatment • Psychotherapy • Pharmacotherapy • ECT
  9. 9. Treatment phases for depression Treatment phase Duration Goal Acute 6 weeks Resolve symptoms Continuation 6-9 months Prevent relapse Maintenance 3-5 years of lifelong Prevent recurrence in high risk patients
  10. 10. Drug selection/administration • All drugs are equally effective • Half the lowest dose • 1-2 wks • 4-6wks • Try onother class
  11. 11. Changing antidepressant • 2 wks • 5 wks with fluoxetine
  12. 12. Clinical manifestations of serotonin syndrome and serotonin withdrawal syndrome Classification of dysfunction Serotonin syndrome Serotonin withdrawal syndrome Cognitive- behavorial dysfunction Confusion Hypomania Agitation none Autonomic nervous system dysfunction Diarrhea Diaphoresis Shivering Fever Changes in blood pressure Nausea and vomitting Flu-like symptoms Dizziness Light headedness Chills Sleep disturbances Neuromuscular dysfunction Myoclonus Hyperreflexia Tremor Seizure Death Lethargy Myalgia sensory disturbances (e.g., paresthesia)
  13. 13. Selective 5-HT uptake inhibitors (SSRI) • 1st line for depression • Actions similar in efficacy & time course to TCA • Acute toxicity is less than that of MAOI or TCA • Side-effects include nausea, insomnia & sexual dysfunction. • dangerous 'serotonin reaction' – (hyperthermia, muscle rigidity, cardiovascular collapse) can occur if given with MAOI. • Long half-lives
  14. 14. SSRI • Fluoxetine • Fluvoxamine • Nefazodone • Paroxetine • Sertraline • Trazodone • venlafaxine
  15. 15. SSRIs • Am bec of its stimulatory effect • Metabolize via cytochrome P450
  16. 16. SSRI’s • Fluoxetine- bulimia – Most stimulatory – For depression with negative symptoms • Paroxetine – Most sedating – Depression with anxiety and insomnia • Sertraline – Less stimulatory and less sedating
  17. 17. Tricyclic antidepressants (TCA) • TCA are chemically related to phenothiazine • 2nd line of choice • Inhibit reuptake of serotonin and norepinephrine • Important side-effects: – sedation (H1-block), postural hypotension (α-adrenoceptor block), dry mouth, blurred vision, constipation (muscarinic block), occasionally mania and convulsions. – Risk of ventricular dysrhythmias through potassium channel block.
  18. 18. Cyclic Antidepressants • Tricyclic antidepressants—primary: amitriptyline (Elavil), doxepin (Sinequan), imipramine (Tofranil) • Tricyclic antidepressants—secondary: desipramine (Norpramin), nortriptyline (Aventyl), protriptyline (Vivactil) • Tetracyclic antidepressants: amoxapine (Asendin), maprotiline (Ludiomil)
  19. 19. Cyclic Antidepressants Mechanism of Action • Block reuptake of neurotransmitters, causing accumulation at the nerve endings. • It is thought that increasing concentrations of neurotransmitters will correct the abnormally low levels that lead to depression.
  20. 20. Cyclic Antidepressants Mechanism of Action—Drug Effects Blockade of norepinephrine: – antidepressant, tremors, tachycardia, additive pressor effects with sympathomimetic drugs Blockade of serotonin: – antidepressant, nausea, headache, anxiety, sexual dysfunction
  21. 21. Cyclic Antidepressants Therapeutic Uses • Depression • Childhood enuresis (imipramine) • Obsessive-compulsive disorders (clomipramine) • Adjunctive analgesics • Trigeminal neuralgia
  22. 22. TCA – PM DOSAGE ALL- SEDATING ACTIVITY – 4-6 WKS- FULL RESPOSE – 1 WK ASSYMPTOMATIC RELIEF – ANTICHOLINERGIC SIDE EFFECTS
  23. 23. Cyclic Antidepressants Side Effects • Sedation • Impotence • Orthostatic hypotension • Older patients: – dizziness, postural hypotension, constipation, delayed micturation, edema, muscle tremors
  24. 24. TCA • TCA USER • HEALTHY • NONSUICIDAL • REFRACTORY TO NEWER DRUGS
  25. 25. Monoamine oxidase inhibitors (MAOI) • Action is long lasting (weeks) due to irreversible inhibition of MAO A & B. – Moclobemide has a short duration of action • 3rd line of choice • Main side-effects: – postural hypotension (sympathetic block) – atropine-like effects (as with TCA); – weight gain – CNS stimulation – Serotonin syndrome – liver damage (rare). ISOCARBOXAZID
  26. 26. Antidepressants: MAOIs Hypertensive Crisis and Tyramine • Ingestion of foods and/or drinks with the amino acid TYRAMINE leads to hypertensive crisis, which may lead to cerebral hemorrhage, stroke, coma, or death
  27. 27. Antidepressants: MAOIs Hypertensive Crisis and Tyramine Avoid foods that contain tyramine! • Aged, mature cheeses (cheddar, blue, Swiss) • Smoked/pickled or aged meats, fish, poultry (herring, sausage, corned beef, salami, pepperoni, paté) • Yeast extracts • Red wines (Chianti, burgundy, sherry, vermouth) • Italian broad beans (fava beans)
  28. 28. MAOI • ATYPICAL DEPRESSION • HYPERSOMNIA • AGITATION • ANXIETY
  29. 29. Monoamine oxidase inhibitors (MAOI) • Phenelezine,Tranylcypromine, • Isocarboxazid – Rarely clinical due to serotonin syndrome – hypertensive crisis- most common (tyramine-rich foods) – 3 -4 wks- do not discontinue – Insomnia effect – not at pm
  30. 30. Side effects • Othostatic hypotension • Weight gain • Edema • Sexual dysfunction • Hepatocellular damage-isocarboxacid
  31. 31. MANIA
  32. 32. Etiology • Genetics • Neurotransmitter level • GABA level • Calcium • G proteins • Psychosocial and physical stressors
  33. 33. Symptoms of mania • Grandiose ideations or expansive self-esteem • Decreased need for sleep • Pressured speech • Racing thoughts or flight of ideas • Distractability • Psychomotor agitation • Engaging in dangerous, high-risk activities
  34. 34. LITHIUM • Mechanism of Action –? –alters intracellular second messengers: adenyl cyclase-cyclic AMP system and the G protein-coupled phosphoinositide systems (NE and serotonin) –alters ion channel function –alters metabolism of GABA
  35. 35. LITHIUM • Adverse effects –Narrow therapeutic index –Therapeutic range: 0.5-1.5mEq/L –Minor S/E: tremors, polyuria, GI distress, memory problems, acne, weight gain –Long-term S/E: hypothyroidism –Toxic levels: ataxia, tremors, confusion, coma, sinus arrest, death
  36. 36. LITHIUM Baseline labs Adverse effects Thyroid function hypothyroidism BUN/Crea Renal insufficiency Electrolytes (esp.sodium) Dec. Na CBC leukocytosis
  37. 37. • Alternative mood-stabilising drugs (e.g. carbamazepine, valproate, gabapentin,clonazepam)
  38. 38. Summary • ANTICHOLINERGIC-TCA • CHLOMIPRAMINE-OC • IMIPRAMINE –NOCTURNAL • MAOI- HYPERTENSIVE CRISIS • SEIZURE-SE OF BUPROPION

×