Successfully reported this slideshow.
Your SlideShare is downloading. ×

Depression and Antidepressants

Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Upcoming SlideShare
Seminar On Antidepressants
Seminar On Antidepressants
Loading in …3
×

Check these out next

1 of 34 Ad
Advertisement

More Related Content

Slideshows for you (20)

Advertisement

Recently uploaded (20)

Depression and Antidepressants

  1. 1. DEPRESSION AND ANTIDEPRESSANT S DRUG
  2. 2.  INTRODUCTION  SYMPTOMS OF DEPRESSION  CLASSIFICATION OF DEPRESSION  TREATMENT OF DEPRESSION  ANTIDEPRESSANTS  ELECTROCONVULSIVE THERAPY
  3. 3. Introduction
  4. 4. "Depression" is a very common psychiatric disorder that is related to the "mood" (affective disorder).  Changes in mood are associated with depression and/or mania.  Disorders of mood rather than disturbance in thought or cognition.  Clinical depression: feeling sad for more than two weeks.
  5. 5. 1- Emotional Symptoms  Intense feelings of sadness, hopelessness and despair  Inability to experience ordinary pressure or to cope with ordinary life events  Feeling of guilt and ugliness  Indecisiveness and loss of motivation  Loss of energy and interest
  6. 6. 2- Biological symptoms 1- Retardation of thought and action 2- Loss of libido 3- Loss of appetite and sleep disturbance DEPRESSION IS THE MOST COMMON CAUSE OF SUICIDE
  7. 7. Classification of Depression A) According to severity of symptoms: 1. Mild depression---------self-limiting 2. Moderate depression -------difficulties at home and work 3. Severe depression --------serious, associated with suicidal thoughts
  8. 8. B) According to type 1- Unipolar depression (major depression):  mood swings are always in the same direction  about 75% of cases non-familial  accompanied by symptoms of anxiety and agitation  Associated with stressful life events  25% familial  unrelated to external stresses  endogenous depression 2- Bipolar depression (manic-depression):  in which depression alternates with mania  enthusiasm and self-confidence, accompanied by impulsive actions
  9. 9. I. Psychotic depression II. Postpartum depression III. Atypical depression What are the possible mechanisms of depression? • Depression is associated with insufficient central release of NA and 5-HT • Led to development of the Biogenic Amine Hypothesis
  10. 10.  Proposed in 1965 and states that DEPRESSION is caused by a functional deficit of Monoamine transmitter at certain sites in the brain, while MANIA results from functional excess.  The Theory is based on the ability of known antidepressat drugs (TCAs and MAOIs) to facilitate monoaminergic transmission and of drugs as Reserpine to cause depression.
  11. 11. Normal synapse, no depression.
  12. 12. Neurotransmitter deficiency lead to Depression
  13. 13.  5-HT deficiency may cause the sleep problems, irritability and anxiety associated with depression  Decreased level of NE, which regulates mood, alertness, arousal, appetite, reward & drives, may contribute to the fatigue and depressed mood of the illness  However, dopamine is important for pleasure, sex & psychomotor activity
  14. 14. TREATMENT OF DEPRESSION 1. Psychological treatment 2. Pharmacological treatment 70 % of depressed patients respond to antidepressants 3. ECT ( electroconvulsive therapy) for very severe depression, which has not responded to other treatments or for patients who cannot take antidepressants
  15. 15. ANTIDEPRESSANTS  Antidepressants do not act immediately (show clinical effects after 2 weeks) indicating that secondary adaptive changes in the brain are important.  The most consistent adaptive change seen with antidepressant drugs is the downregulation of beta-, alpa-2 and 5-HT2 receptors. Alpha-1 is not affected.  Affect only people who are depressed.  Effect does not increase with increasing doses.  Antidepressants are not habit-forming.  Antidepressants differ widely in side effects.
  16. 16. 1) Tricyclics (TCAs) and Tetracyclics Imipramine Doxepin Desipramine Amoxapine Trimipramine Maprotiline Clomipramine Amitriptyline Nortriptyline Protriptyline 2) Monoamine Oxidase Inhibitors (MAOIs) Tranylcypramine Phenelzine Moclobemide 3) Selective Serotonin Reuptake Inhibitors (SSRIs) Fluoxetine Fluvoxamine Citalopram Sertraline Paroxetine Escitralopram
  17. 17. 4) Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) Venlafaxine Duloxetine 5) Norepinephrine and Dopamine Reuptake Inhibitor (NDRI) Bupropion 6) Noradrenaline Reuptake Inhibitor (NRI) Reboxetine 7) Serotonin Reuptake Enhancer Tianeptine
  18. 18.  TCAs are the oldest class of antidepressant drugs  They have characteristic three-ring nucleus  The first TCAs discovered was Imipramine Imipramine (Tofranil)
  19. 19.  Imipramine Desipramine  Clomipramine Amitriptyline  Nortriptyline Doxepin  Trimipramine TETRACYCLIC ANTIDEPRESSANTSTETRACYCLIC ANTIDEPRESSANTS  Maprotiline  Amoxapine
  20. 20. Blocking of receptors  TCAs also block :  Serotonergic receptors  Alpha adrenergic receptors  Histaminic receptors  Muscarinic receptors  Their role in therapeutic benefit is not known  These actions produce the adverse effects
  21. 21. 1- Elevate mood 2- Improve mental alertness 3- Increase physical activity # The antidepressant effect may develop after several weeks of continued treatment ( 2 - 3 weeks) 4- In non-depressed patients They cause sedation, confusion & motor incoordination
  22. 22. PHARMACOKINETICS of TCAs TCAs are "lipophilic" in nature, therefore they are well absorbed from the GIT and readily cross the blood brain barrier to penetrate the CNS. Elimination: hepatic oxidation TCAs are strongly bound to plasma proteins. Average t1/2: 24 hours ( 72 hours in overdose) Large T1/2 and large VD because TCA extensively bound to plasma protein (90-95 %)
  23. 23.  Amongst the first Antidepressants  Include: - Phenelzine - Tranylcypromine - Isocarboxazid - Moclobemide - Pargyline  Onset of antidepressant effect is delayed for 2-4 weeks.
  24. 24.  MAO is found in nearly all tissues and is located intracellularly associated with mitochondria.  Present in nerve terminals that release NA, DA or 5- HT.  Located on outer surface of mitochondrial membranes.  In neurons, MAO oxidatively deaminates and inactivates any excess norepinephrine, serotonin and dopamine, that may leak out of synapstic vesicles.  MAO is not involved in the inactivation of released transmitter
  25. 25. MAO exists in tow forms coded by separate genes MAO-A: Metabolizes norepinephrine, serotonin and tyramine. Inhibition of MAO-A produces Antidepressant effect . MAO-B: specific for dopamine. Inhibition of MAO-B produces Anti-parkinsonian effect.
  26. 26.  This occurs when Tyramine rich foods are taken with MAOIs.  Tyramine rich foods include Old cheese , Concentrated yeast products, Pickled or smoked fish, Red beans, Red Wine, Chicken liver, Sausages.  Tyramine in food is normally degraded in the gut by MAO-A.
  27. 27. - Fluoxetine (prozac) - Fluvoxamine - Paroxetine - Sertraline - Citalopram - Escitalopram
  28. 28. . Mechanism of Action of SSRIs
  29. 29. Adverse effects of SSRIs:  GIT symptoms: Nausea vomiting & diarrhea.  Changes in appetite ---weight loss/ gain.  Sleep disturbances: Drowsiness with Fluvoxamine.  Anxiety & Tremors.  Sexual dysfunction: Loss of libido , delayed ejaculation. Discontinuation syndrome:  Symptoms are headache ,malaise & flu like symptoms, agitation , irritability & nervousness
  30. 30. NE SELECTIVE REUPTAKE INHIBITORS (NRIS) Reboxetine Tomoxetine  Selective to NE uptake  May be more effective in noradrenaline deficiency syndrome (e.g., depression associated with fatigue, apathy, cognitive disturbances), or non responders to SSRIs.  Also act at presynaptic α2, postsynaptic α1, α2 and β adrenergic receptors (tremor, agitation, blood pressure). Advantages  Lacks antagonistic activity at histamine H1, muscarinic & adrenergic receptors or Na+ pump as with TCA.  Fewer unwanted cardiovascular effects than TCA’s.
  31. 31.  Serotonin norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders.  They act upon two neurotransmitters in the brain that are known to play an important part in mood, namely, 5HT and NE. This can be contrasted with the more widely-used selective serotonin reuptake inhibitors (SSRIs), which act only on serotonin.
  32. 32. Venlafaxine • It is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. Venlafaxine is the first and most commonly used SNRI. • Selective 5HT and NE uptake blockers Combines the action of SSRI and NRI. • Causes dual action on serotonin and adrenergic systems, thus amplifying these two systems synergistically. • But without α1, M1 cholinergic or H receptor blocking properties. Venlafaxine
  33. 33.  Stimulation through electrodes placed on either side of the head with the patient anaesthetized, paralysed with a NMB drugs to avoid physical injury and artificially ventilated  Response rates 60-80 %  The most effective treatment for severe suicidal depression  DISADVANTAGES Confusion, Memory loss lasting for days or weeks

×