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  1. 1. Antidepressants in Psychiatric Disorders
  2. 2. Antidepressants? <ul><li>Are drugs that relieve the symptoms of depression </li></ul><ul><li>Were first developed in the 1950s </li></ul><ul><li>There are approx. 30 different kinds of antidepressants available today and are of 5 main types: </li></ul><ul><ul><li>MAOIs (Monoamine oxidase inhibitors) </li></ul></ul><ul><ul><li>Tricyclics </li></ul></ul><ul><ul><li>SSRIs (Selective Serotonin Reuptake Inhibitors) </li></ul></ul><ul><ul><li>SNRIs (Serotonin and Noradrenaline Reuptake Inhibitors) </li></ul></ul><ul><ul><li>NASSAs (Noradrenaline and Specific Serotoninergic Antidepressants) </li></ul></ul>[email_address]
  3. 3. Classes of Antidepressants <ul><li>SNRIs: newer form of antidepressant that work on both norepinephrine and 5-HT. They typically have similar side effects to the SSRIs. </li></ul><ul><ul><li>Desvenlafaxine, Duloxetine, Milnacipram, Venlafaxine </li></ul></ul><ul><li>SSRIs : work by preventing the reuptake of serotonin by the presynaptic neuron, thus maintaining higher levels of 5-HT in the synapse </li></ul><ul><ul><li>Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, </li></ul></ul><ul><li>Tricyclics: block the reuptake of certain neurotransmitters such as norepinephrine (noradrenaline) and serotonin </li></ul><ul><ul><li>Amitriptyline, Clomipramine, Imipramine, Nortriptyline </li></ul></ul><ul><li>MAOIs : work by blocking the enzyme monoamine oxidase which breaks down the neurotransmitters dopamine, serotonin, and norepinephrine (noradrenaline). </li></ul><ul><ul><li>MAOIs can be as effective as tricyclic antidepressants, although they can have a higher incidence of dangerous side effects (as a result of inhibition of cytochrome P450 in the liver </li></ul></ul><ul><ul><li>Isocarboxazid, Phenelzine </li></ul></ul>[email_address]
  4. 4. map of TCAs and SNRI pharmacological properties [email_address]
  5. 5. [email_address] Advantages Disadvantages / Side Effects <ul><li>Often effective in reducing panic attacks and elevating depressed mood. </li></ul><ul><li>Well researched. </li></ul><ul><li>Usually a single daily dose </li></ul>Anticholinergic : dry mouth, blurred vision constipation, urinary retension Antihistaminergic : Sedation Alpha blockade : Postural hypotension
  6. 6. Action of antidepressants and other drugs at serotonergic synapses [email_address]
  7. 7. [email_address]
  8. 8. Uses of Antidepressants <ul><li>Moderate to severe depressive illness (Not mild depression) </li></ul><ul><li>Schizophrenia </li></ul><ul><li>Severe anxiety and panic attacks </li></ul><ul><li>Obsessive compulsive disorders </li></ul><ul><li>Post-traumatic stress disorder </li></ul><ul><li>Chronic pain </li></ul><ul><li>Eating disorders </li></ul>[email_address]
  9. 9. Depression <ul><li>A common mental disorder that presents with </li></ul><ul><ul><li>Depressed mood </li></ul></ul><ul><ul><li>Loss of interest or pleasure </li></ul></ul><ul><ul><li>Feelings of guilt or low self-worth </li></ul></ul><ul><ul><li>Disturbed sleep or appetite </li></ul></ul><ul><ul><li>Low energy and </li></ul></ul><ul><ul><li>Poor concentration. </li></ul></ul><ul><li>Major Types: </li></ul><ul><ul><li>Major depressive disorder, </li></ul></ul><ul><ul><li>Dysthymic disorder </li></ul></ul><ul><ul><li>Bipolar disorder </li></ul></ul><ul><ul><li>Cyclothymic </li></ul></ul><ul><li>Prevalence </li></ul><ul><ul><li>20 – 25% of women (35 – 45 years) </li></ul></ul><ul><ul><li>7-12 % of men (after 55 years) </li></ul></ul><ul><ul><li>50 – 75 % remain undiagnosed & untreated. </li></ul></ul>[email_address]
  10. 10. [email_address]
  11. 11. Frequently prescribed antidepressants for Depression Aaron M. Koenig; First‑line pharmacotherapies for depression – what is the best choice?; POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ 2009; 119 (7-8) [email_address]
  12. 12. Schizophrenia <ul><li>Is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality </li></ul><ul><li>Characterized by psychosis, hallucinations, delusions, cognitive defects, occupational and social dysfunction </li></ul><ul><ul><li>Onset in late teens or early 20s in males; sometime later in females </li></ul></ul><ul><li>Incidence : 1 - 3 % </li></ul><ul><li>Gender : Affects males and females equally </li></ul><ul><ul><li>Males in the early 20’s </li></ul></ul><ul><ul><li>Females in early 30’s </li></ul></ul>[email_address]
  13. 13. Schizophrenia Etiology and Pathophysiology <ul><ul><li>Etiology </li></ul></ul><ul><ul><ul><li>Genetic predisposition </li></ul></ul></ul><ul><ul><ul><li>Intrauterine, birth or postnatal complications </li></ul></ul></ul><ul><ul><ul><li>Viral CNS infections </li></ul></ul></ul><ul><ul><ul><li>Environmental stressors (biochemical or social) </li></ul></ul></ul><ul><ul><li>Pathophysiology </li></ul></ul><ul><ul><ul><li>Increased dopamine in mesolimbic pathways causes delusions and hallucinations </li></ul></ul></ul><ul><ul><ul><li>Dopamine deficiency in mesocortical and nigrostriatal pathways causes negative symptoms (apathy, withdrawal) </li></ul></ul></ul><ul><ul><ul><li>Hallocinogens produce effect through action on 5-HT2 receptors </li></ul></ul></ul>[email_address]
  14. 14. Schizophrenia <ul><li>Positive symptoms </li></ul><ul><ul><li>Hallucinations </li></ul></ul><ul><ul><li>Delusions </li></ul></ul><ul><ul><li>Disordered thinking </li></ul></ul><ul><ul><li>Disorganized speech </li></ul></ul><ul><ul><li>Combativeness </li></ul></ul><ul><ul><li>Agitation </li></ul></ul><ul><ul><li>Paranoia </li></ul></ul><ul><li>Negative symptoms </li></ul><ul><ul><li>Social withdrawal </li></ul></ul><ul><ul><li>Emotional withdrawal </li></ul></ul><ul><ul><li>Lack of motivation </li></ul></ul><ul><ul><li>Poverty of speech </li></ul></ul><ul><ul><li>Blunted affect </li></ul></ul><ul><ul><li>Poor insight </li></ul></ul><ul><ul><li>Poor judgement </li></ul></ul><ul><ul><li>Poor self-care </li></ul></ul>[email_address]
  15. 15. Antidepressants in Schizophrenia <ul><li>Studies show that depressive symptoms are common in all phases of Schizophrenia </li></ul><ul><li>In one study, improvement in treatment scores was significantly greater in 58 schizophrenics given the neuroleptic Perphenazine after a two-week washout than in the 29 patients given placebo. Half the Perphenazine-treated group also had Amitriptyline; these showed a significantly greater improvement than the placebo group as regards flatness of effect and in other sub-scores on the Wing scale, but they did not improve significantly more than patients given perphenazine alone </li></ul>Reference: Use of antidepressants in schizophrenia; BRITISH MEDICAL JOURNAL; 1037 [email_address]
  16. 16. Study of 35 outpatient schizophrenics who had developed true depressive symptoms showed that depressive symptoms responded better in the group given Amitriptyline together with perphenazine, but three-quarters of those receiving combined treatment had an increase in blood pressure and body weight. In another study of schizodepressives chlorpromazine alone appeared to be as good as chlorpromazine combined with amitriptyline. Thus the value of antidepressants even for schizophrenics with definite depression has yet to be firmly substantiated. Reference: Use of antidepressants in schizophrenia; BRITISH MEDICAL JOURNAL; 1037 Antidepressants in Schizophrenia [email_address]
  17. 17. Anxiety <ul><li>Anxiety disorders are extremes of normal anxiety. </li></ul><ul><li>Occur when normal anxiety system becomes dysregulated - excessive, inappropriate or deficient </li></ul><ul><li>Causes </li></ul><ul><ul><li>Genetic linkage </li></ul></ul><ul><ul><li>Structural abnormalities in the brain </li></ul></ul><ul><ul><li>Neurochemical dysfunction </li></ul></ul>[email_address]
  18. 18. Generalized Anxiety Disorder (GAD) <ul><li>Is an anxiety disorder characterized by chronic anxiety, exaggerated worry and tension, even when there is little or nothing to provoke it </li></ul><ul><li>Worries are accompanied by physical symptoms, especially fatigue, headaches, muscle tension, muscle aches, difficulty swallowing, trembling, twitching, irritability, sweating, and hot flashes </li></ul><ul><li>Usually begins at an earlier age and symptoms may manifest themselves more slowly than in most other anxiety disorders </li></ul>[email_address]
  19. 19. [email_address]
  20. 20. Drug Therapy for GAD Reference: NPS News; ISSN 1441-7421 October 2009 [email_address]
  21. 21. Reference: NPS News; ISSN 1441-7421 October 2009 [email_address]
  22. 22. Antidepressant as a Generalized Anxiolytics <ul><li>Recently, Venlafaxine XR became the first agent approved to treat both mood in depression and anxiety in GAD </li></ul><ul><li>Antidepressants are more effective than benzodiazepines for treating the uncontrollable worry associated with GAD </li></ul><ul><li>They do not produce tolerance or dependence </li></ul>[email_address]
  23. 23. Panic Attacks <ul><li>Sudden, unexpected attacks – overwhelming anxiety </li></ul><ul><li>Physical symptoms </li></ul><ul><ul><li>Palpitations, chest pain, choking sensation, dizziness, breathlessness, tingling in the hands and feet, sweating, faintness, nausea or abdominal distress </li></ul></ul><ul><li>Emotional and behavioral symptoms </li></ul><ul><ul><li>Fear of dying, losing control, going mad, feeling of unreality </li></ul></ul>[email_address]
  24. 24. Panic Attacks [email_address]
  25. 25. Panic attacks -Management <ul><li>SSRIs - Paroxetine, Citalopram </li></ul><ul><li>Benzodiazepines - good short term relief but high risk of dependency - Alprazolam </li></ul><ul><li>TCAs - Imipramine, Clomipramine </li></ul><ul><li>MAOIs - especially in mixed panic depressive states </li></ul>[email_address]
  26. 26. Obsessive Compulsive Disorders <ul><li>Repetitive unwanted obsessions or compulsive acts </li></ul><ul><li>Obsession is recurrent and intrusive thought, feeling, idea, image or impulses </li></ul><ul><ul><li>Usually distressing </li></ul></ul><ul><ul><li>Extreme need for orderliness </li></ul></ul><ul><ul><li>Persistent doubts </li></ul></ul>[email_address]
  27. 27. Obsessive Compulsive Disorders <ul><li>Pharmacotherapy </li></ul><ul><ul><li>SSRIs, Clomipramine </li></ul></ul><ul><ul><li>Augmentation with Quetiapine or Risperidone </li></ul></ul><ul><ul><li>Clonazepam </li></ul></ul>[email_address]
  28. 28. Post-Traumatic Stress Disorder <ul><li>Typically occur after a traumatic event (especially crimes, war) </li></ul><ul><ul><li>Symptoms : re-experiencing trauma (dreams, flashbacks), avoidance of anything associated with trauma, and constant state of hypervigilance </li></ul></ul><ul><li>Causes: Major Negative events in life </li></ul><ul><ul><li>War </li></ul></ul><ul><ul><li>Childhood abuse </li></ul></ul><ul><ul><li>Accidents </li></ul></ul><ul><ul><li>Earthquakes </li></ul></ul><ul><ul><li>Floods </li></ul></ul>[email_address]
  29. 29. PTSD - management <ul><li>SSRIs </li></ul><ul><li>Serotinergic TCAs </li></ul><ul><li>Zoloft (sertraline) has FDA approval for this indication </li></ul>[email_address]
  30. 30. Phobias <ul><li>Intense, irrational fear of a specific object or situation </li></ul><ul><li>Types of phobia: </li></ul><ul><ul><li>Agoraphobia </li></ul></ul><ul><ul><li>Social phobia </li></ul></ul><ul><ul><li>Specific phobias </li></ul></ul>[email_address]
  31. 31. Antideperssants for Anxiety <ul><li>Psychological therapies should be the first choice for most anxiety disorders to control symptoms and improve functioning. </li></ul><ul><li>If these do not provide sufficient benefit and drug therapy is needed, an antidepressant may be added </li></ul><ul><ul><li>Serotonin Selective Reuptake Inhibitors (SSRIs) - E.g. : Fluoxetine </li></ul></ul><ul><ul><li>Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) - E.g. : venlafaxine </li></ul></ul><ul><ul><li>Atypical Antidepressants </li></ul></ul><ul><ul><li>Tricyclic Antidepressants (TCAs) </li></ul></ul><ul><ul><li>Monoamine Oxidase Inhibitors (MAOIs) </li></ul></ul>[email_address]
  32. 32. Why Antidepressants for Anxiety?? Reference: Stephen M. Stahl; Mergers and Acquisitions among PsychotropicsClinical Neuroscience Update; J Clin Psychiatry 60:5, May 1999 [email_address]
  33. 33. Antidepressants for Anxiety?? Reference: Stephen M. Stahl; Mergers and Acquisitions among PsychotropicsClinical Neuroscience Update; J Clin Psychiatry 60:5, May 1999 [email_address]
  34. 34. Eating disorders <ul><li>An eating disorder is a condition which affects an individuals eating habits, either as a result of their own doing (self-inflicted), or as a bodily reaction to the consumption of food </li></ul><ul><li>Types: </li></ul><ul><ul><li>Anorexia Nervosa (It is an obsessive fear of gaining weight ) </li></ul></ul><ul><ul><li>Bulimia Nervosa (A person with bulimia eats a lot of food in a short amount of time) </li></ul></ul><ul><ul><li>Binge Eating (A binge eating disorder is characterized primarily by periods of uncontrolled, impulsive, or continuous eating beyond the point of feeling comfortably full) </li></ul></ul>[email_address]
  35. 35. [email_address]
  36. 36. Epidemiology <ul><li>Primarily affect women and girls, boys and men are also vulnerable </li></ul><ul><li>Lifetime prevalence </li></ul><ul><ul><li>Anorexia nervosa: 1% </li></ul></ul><ul><ul><li>Bulimia nervosa: 1-2% </li></ul></ul><ul><ul><li>Binge-eating disorder: 2.6% </li></ul></ul><ul><ul><ul><li>5-10% of the obese population </li></ul></ul></ul><ul><li>Women vs. men </li></ul><ul><ul><li>Anorexia and bulimia nervosa </li></ul></ul><ul><ul><ul><li>10x more common in women </li></ul></ul></ul><ul><ul><li>Binge eating disorder </li></ul></ul><ul><ul><ul><li>33% of those diagnosed are men </li></ul></ul></ul><ul><li>Median age onset: </li></ul><ul><ul><li>Anorexia & bulimia: 18-21 years old </li></ul></ul>[email_address]
  37. 37. [email_address]
  38. 38. Antidepressant for eating disorder [email_address]
  39. 39. Role of Antidepressant ineating disorders <ul><li>Trials have shown that binge eating and purging in people with bulimia nervosa can be reduced with antidepressant medicines </li></ul><ul><li>They can also improve a person’s perception about their body and weight </li></ul>National Prescribing Service Limited; Australian Prescriber; 2 august 2005 [email_address]
  40. 40. Thank You [email_address]