Depression

This ppt will provide a complete information on the topic Depression. It Will also provide the types of depression, pathophysiology involved, causes, drugs used in Depression and its management.

1. Depression Presented by: Abhishek .S. Joshi First Year M.Pharm (Pharmacology) SSR College of Pharmacy, Silvassa 1

2. Points of discussion. History Introduction & definition Different types of depression Epidemiology or prevalence of the disease Etiology or causes Pathophysiology Clinical manifestations (Signs and symptoms) Diagnosis and Investigative tests Treatment approaches 2

3. History 3 Hippocrates Galen Emil Kraepelin Four Humors or Internal fluids--Blood -Black bile -Yellow bile -Phlegm Excess of black bile-Melancholic state Distinguished Melancholia into: -Manic Depression -Dementia Praecox Melancholic person =Depressed person

4. 4 Sigmund Freud “Mourning and Melancholia”

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6. 6 Hamilton Rating scale for Depression Beck Depression Inventory Gold Standards

7. Introduction & definition According to oxford dictionary- Depression is feeling of severe despondency, or dejection and the disorder of mood. Leading cause of disability. More than 264 million people suffer from depression worldwide.  Clinical depression and just feeling sad both are different. Is persistent alteration in one's mood , persistent – ve mental state more focused on the past. Anxiety and depression both are different. Anxiety more focused to the future. Anxiety= “What if”, “Sense of uncertainty” Depression- more focused on the past 7

8. Introduction & definition (continued) Can also disturb sleep and appetite. Poor concentration and tiredness are common. Definition(WHO)- A common mental disorder that presents with depressed mood , loss of interest or pleasure ( anhedonia ), feeling of guilt, low self worth , disturbed sleep or appetite, low energy or poor concentration. Another definition- State of low mood and aversion (dislike) , to activity that can affect a person’s thoughts, behavior, feelings and sense of well being. 8

9. Introduction & definition (continued) Some very common symptoms include- S I G E C A P S S- Sleep Disturbances (Insomnia or Hypersomnia) I- Interest (reduced) ( Anhedonia ) G- Guilt E- Energy (reduced) C- Concentration (reduced) A- Appetite (reduced) P- Psychomotor retardation (Decreased thinking and movement) S- Suicidal thoughts 9

10. Introduction & definition (continued) According to psychiatric guidelines- Diagnosis of depression is mandatory if at least 5 of the symptoms seen in the individual. According to National Institute of Mental Health- It takes a depressed person, 10 yrs for asking of help. Depression can be : Major(depression for very long time) and Bipolar 10 Hippocampus

11. Different types of depression Major Depressive Disorder (MDD) Treatment Resistant Depression Sub- syndromal Depression (SSD) Persistent Depressive Disorder (PDD) Premenstrual Dysphoric Disorder (PMDD) Bipolar Depression (Manic Depression) Disruptive mood dysregulation disorder (DMDD) Postpartum (or perinatal ) depression Seasonal Affective Disorder (SAD) Substance-induced mood disorder Psychotic Depression Depression due to illness Situational Depression (Reactive Depression/Adjustment Disorder) Atypical and Melancholic Depression 11

12. 1. Major Depressive Disorder (MDD) Very common type of depression. Aka- Clinical depression or Unipolar depression. According to APA for MDD diagnosis- at least 5 symptoms (S I G E C A P S) persisting for 2 weeks or more. One episode can occur or more often several. People show dysphoria, anhedonia, physical changes(altered weight, appetite, sleep, energy) Impaired social life and distress. 12

13. 2. Treatment Resistant Depression Those MDD patients who don’t respond to the treatment . One after the other antidepressants are tried but depression stubbornly hangs on. According to some researchers- 4 different treatments should be tried. How to overcome? Proper diagnosis Counseling on proper dosage and duration Switching to different class of the drugs. Antipsychotics are also sometimes beneficial 13

14. 3. Sub- syndromal Depression (SSD) Patients do not meet all the criteria of MDD diagnosis. Symptoms similar to clinical depression (MDD) DSM-5 (Diagnostic & Statistic Manual of mental Disorders) classify it in “other specified depressive disorder” At least 3 or 4 symptoms (S I G E C A P S) persisting for 1 week- patient is sub- syndromally depressed. SSD can worsen to MDD if untreated. Treatments include 14 Cognitive behavioral therapy Transcranial Magnetic Stimulation

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16. 16 Transcranial Magnetic Stimulation(TMS)

17. 17 TMS working and principle

18. 4. Persistent Depressive Disorder (PDD) Aka- Dysthymia Long term form of depression Symptoms lasts for 2 yrs or more Depressed mood, sadness last for a whole day for 2 yrs or more. Children/Teens- irritability symptoms lasts for 1 year 2 of the symptoms should be there- sleep problems, poor appetite or overeating, fatigue, low self esteem or concentration, hopelessness. Intensity of symptoms changes time to time 18

19. 5. Premenstrual Dysphoric Disorder (PMDD) 10% of childbearing age women experience PMDD Hormone based mood disorder. Severe form of PMS Trigger depression, sadness, anxiety, irritability in the week before a woman’s period. These women are sensitive to change of hormone levels. Estrogen affects dopamine, serotonin, norepinephrine . SSRI before 2 weeks of menstruation start or during menstruation- found effective. Light therapy improves sleep quality and mood. 19

20. 6. Bipolar Depression (Manic Depression) Extreme mood fluctuations. Feelings changes from suicidal thoughts to feeling of euphoria and endless energy. Extreme mood swings occur frequently. Young adulthood Worsen without the treatment. Effective treatments- mood stabilizers(Li), light therapy, talk therapy, atypical antipsychotics (FDA-approved cariprazine , lurasidone, olanzapine-fluoxetine combination and quetiapine) 20

21. 7. Disruptive mood dysregulation disorder (DMDD) Screaming and temper tantrums(anger followed by crying) are typical features Diagnosis generally in children Struggle with regulating their emotions Angry mood, irritable mood most of the day, every day Kids have strong emotional outbursts. Unable to contain their emotions. Chronic or persistent irritability is common DSM-5 classify- children who can not regulate emotion in age- appropriate way Current treatments- Psychotherapy, Parent training to deal with irritable child 21

22. 8. Postpartum (or perinatal ) depression One in 4 women & one in 8 men affected with postpartum depression In women- hormonal shift, fatigue In men- environmental, shifting roles, lifestyle changes with parenting “ Baby blues ”(sad feelings after childbirth)(mild mood disturbances in new mothers), subsides within a week or two If “Baby blues” condition last for several weeks or more- Postpartum depression According to DSM-5- mood swings, anxiety symptoms, “baby blues” during pregnancy increase risk of postpartum depression 22

23. Extreme cases of postpartum depression Two cases recent cases of Kerala (MONDAY, JANUARY 11, 2021) : Thiruvananthapuram & Kasaragod Kasaragod- 23-year-old women arrested- strangled her infant in earphone wires, killed him, covered him with a cloth, put infant under her bed. Investigating officials- she had a first child, disappointed that she’s pregnant soon. Experts- Post partum depression. Thiruvananthapuram - 29-year-old woman arrested- women killed her infant, buried the body behind her house. 23

24. 9. Seasonal Affective Disorder (SAD) Comes and goes with seasons Start- late autumn and early winter Ends- Spring and summer Increased craving for foods rich in carbohydrates therefore weight gain Patients- overreact, oversleep, withdrawal from social interaction, feeling of heaviness in legs and arms Women & young children are at higher risk Diagnosis- After at least 2 years of recurring seasonal symptoms Possible causes- imbalance of serotonin, overabundance of melatonin, insufficiency of vit. D 24

25. 10. Substance-induced mood disorder Sedating drugs causes change in mood. Substances such as alcohol(too much), opioid painkillers, benzodiazepines are responsible for mood changes. Depression, loss of interest, anxiety are symptoms Sedating drugs causes substance induce mood disorder. Diagnosis- Doctor may rule out the causes of depression. 25

26. 11. Psychotic Depression Severe depression with psychosis. Symptoms include hallucinations(to see and to hear things that aren’t present) & delusions (false belief of happenings) Disturbing fixed false beliefs are present Antidepressants + Antipsychotic, electroconvulsive therapy(ECT) 26

27. 12. Depression due to illness Disease such as HIV, cancer, multiple sclerosis, heart disease can be cause of depression itself. Inflammation also plays an important role in causing depression Inflammation Chemicals cross brain, triggering depression 27 Chemicals released by immune system

28. 13. Situational Depression (Reactive Depression/Adjustment Disorder) Short term, stress related type depression. Develop after a traumatic event or changes everyday life Examples include- divorce, retirement, loss of a friend, illness, relationship problems Within 90 days of triggering event- situational depression begins to occur. 28

29. 14. Atypical and Melancholic Depression Are subtypes of Major Depressive Disorder Atypical Depression Patient eats and sleeps lots Seen in young adults Emotionally reactive and very anxious Melancholic Depression Trouble in sleep Deeply think over guilt Seen more often in older adults 29

30. Epidemiology Statistics of India Every year 10 th of October- celebrated as World Mental Health Day to spread awareness. This year theme- “Mental Health for all due to Covid-19” Causes of depression in covid 19 pandemic- increased anxiety, fear, isolation, social distancing, emotional distress. Acc. to WHO- Mental Health workforce – not at all up to the mark in India Huge shortage of Psychiatrist and Psychologists WHO estimated- 7.5% Indians suffer from mental disorder. 20% of Indians will suffer by the end of 2020 India accounts 36.6% of global suicides 30

31. Statistics of the globe More than 264 million people suffer from depression (WHO 2020) 63.8% of adult and 70.77% adolescent- have severe impairment (NMIH 2017) Severe depression among colleges students- rose from 9.4% to 21.1% (2018) 70-80% woman- experience baby blues 10-20% woman suffer from PDD 2/3 rd of those who commit suicide struggle with depression. Suicide is the leading cause for death for 15-19yr olds From 2013-2018- suicide attempts increased from 0.7 to 1.8% 31

32. Etiology or causes 32 Genetic Causes Genes play important role in depression. 80 genes linked to depression Genetic variation- affects nerve connections in parts of brain, control decision making. Increased variation, increased risk of developing depression. Environmental Causes Synthetic chemicals, food additives, preservatives, pesticides, hormones, GM foods, industrial by products Nonchemical sources- noise pollution, electrical pollution, natural disasters, catastrophic events Acc. to some researchers- childhood abuse, long term stress at home or work, coping with loss of loved ones. “Sick building syndrome (SBS)”(Being in a building with poor air quality) Electrical pollution- EM waves are generated by modern appliances- thus promotes depression.

33. 33 Majority of genetic diseases are studied using this fly

34. Biochemical Factors Traumatic events, blood sugar imbalances, medical illness- neurotransmitter imbalances The Biogenic Monoamine Hypothesis- deficiency of neurotransmitters (serotonin, NA, DA) Endocrine Factors Addison’s disease, Acromegaly- brings depressed mood, anxiety, agitation Endocrine- Nervous system work together- Hypothalamic Pituitary System- homeostatis Eg - T 3 & T 4 hormone produced by thyroid gland T 3 has major role in mental health T 3 receptors- more concentrated in the brain If thyroid underperforming- T 3 &T 4 not in enough quantity T 3 not gets into the brain, thus increased depression. Another eg - Adrenal gland (help regulate internal stress response. If stress present- adrenal not function properly), cortisol (uncontrolled stress- cortisol not produced) 34

35. Poor nutrition Carbohydrates Proteins Fatty acids Vitamin Female Sex hormones Drugs 35

36. Pathophysiology 1. Biogenic Monoamine Hypothesis Serotonin Hypothesis Catecholamine Hypothesis 2. Inflammation and depression 3. Connective abnormalities in cortico -limbic network 36

37. 37 Cortico - Limbic Region

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39. Clinical manifestations (Signs and symptoms) 39 Does all individual have same symptoms? NO

40. 40 Symptoms of depression that goes unnoticed

41. Diagnosis and Investigative tests DSM-5 Diagnostic Criteria for Depression Depressed mood most of the day, nearly every day. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day. Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day. A slowing down of thought and a reduction of physical movement (observable by others, not merely subjective feelings of restlessness or being slowed down). Fatigue or loss of energy nearly every day. Feelings of worthlessness or excessive or inappropriate guilt nearly every day. Diminished ability to think or concentrate, or indecisiveness, nearly every day. Recurrent thoughts of death , recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. 41

42. Investigative tests or Screening tools Hamilton Depression Rating Scale (HDRS) Beck Depression Inventory (BDI) Patient Health Questionnaire (PHQ) Major Depression Inventory (MDI) Center for Epidemiologic Studies Depression Scale (CES-D) Zung Self-Rating Depression Scale Geriatric Depression Scale (GDS) 42

43. Treatment approaches 43

44. Brief history of development of antidepressants Monoamine oxidase inhibitors Isoniazid ( Isonicotinyl hydrazide) and Iproniazid (isopropyl isonicotinyl hydrazide) Fox and Gibas (1953) Tricylic antidepressants Imipramine Selective Serotonin Reuptake inhibitors Fluoxetine (1974) and Nisoxetin (1975) Atypical Antidepressants Bupropion (1989), Venlafaxine (1993), Vortioxetine (2013) 44

45. 45 Presynaptic Neuron Postsynaptic Neuron

46. Current Classification Class A: Monoaminergic modulators I A : Monoaminooxidase inhibitors (MAOIs) a: Irreversible non-selective : Tranylcypromine, Phenelzine, Isocarboxazid b: Irreversible selective MAO-B inhibitor: Selegiline c: Reversible selective MAO-A inhibitor : Moclobemide II A : Neuronal reuptake inhibitors a: Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine b: Serotonin-noradrenaline reuptake inhibitors (SNRI) : Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran c: Noradrenaline and dopamine reuptake inhibitor (NDRI): Bupropion 46

47. Class III A : Alpha-2 ( α2) receptor antagonists Noradrenergic and specific serotonergic antidepressant ( NaSSA ) : Mirtazapine Class IV A : Multimodals a: Serotonergics : Vortioxetine, Vilazodone, Trazodone b: Noradrenergics : Mianserine , Maprotiline c: Noradrenergic and serotonergics (with significant muscarinic antagonism) : Imipramine, Clorimipramine , Amitriptiline , Desipramine, Nortriptiline Class B: Non-Monoaminergic modulators Melatonine receptors (MT1 and MT2) agonists : Agomelatine Class C: Drugs in research and development 47

48. Mirtrazapine Tetracyclic antidepressant Alpha 2 adrenergic receptor antagonists Thus it increases release of serotonin and NE Oral Bioavailability- 50% Plasma protein binding- 85% Metabolism occurs by CYP1A2, CYP2D6, CYP3A4 t1/2- 20 to 40 hrs Bupropion Inhibit NE and DA reuptake Unicyclic aminoketone Stimulate release of NE and DA from neurons 48

49. Vortioxetin New serotonergic antidepressant Mechanism not fully understood Believed to bind with high affinity SERT Also bind to 5-HT 3 , 5-HT 1A , 5-HT 7 Increase in dose increase causes more binding to receptor Agonist activity at 5-HT 1A Partial agonist activity at 5-HT 1B Antagonist at 5-HT 1D, 7, 3 Dose- 10mg/day Peak plasma conc. achieved after 7 to 11 hrs Bioavailability- 75% t1/2- 66 hrs 49

50. Vilazodone Similar action to vortioxetine Bioavailability- 72% t1/2- 25 hrs Plasma protein binding- 96%-99% Trazodone Inhibit both SERT and Serotonin type 2 receptors Inhibit serotonin reuptake, blocks histamine and α -1 adrenergic receptor. Evening dose- 75mg to 150mg before bedtime Dose increased every 3 rd day to about 300mg/day For elderly- 100mg/day 50

51. Mianserin Antagonist of serotonin and histamine receptor NE reuptake inhibitor H1 and α-1 blockade- sedation Bioavailability- 20 to 30% Plasma protein binding- 95% t1/2- 21 to 61hr Maprotiline Blockade of NE reuptake PP binding- 80 to 90% Peak plasma conc. Reached after 6hrs t1/2- 51 hr 51

52. Agomelatine Melatonergic M1and M2 receptor agonist Selective serotonergic 5-HT 2B, 2C receptor antagonist No effect on monoamine uptake Agomelatine resynchronizes circadian rhythm Antagonism of 5-HT 2C increase NA and DA in frontal cortex Aka as “ disinhibitor ” of NE-DA 52

53. Most commonly prescribed antidepressants Amitriptyline Nortriptyline Tianeptine Dothiapine Paroxetine Mirtrazepine Fluoxetine Desvenlafaxine 53

54. Non Pharmacological Treatments Food- Protein rich food (Rajasic foods) Hobbies- Those which involve all the 5 senses (e.g.- outdoor games) Routines- Walking, pranayamas , asanas(backward bending asanas), sufficient sleep (around 10 pm) Motivate to think positively, write down 10 + ve points before going to bed which made you happy during the whole day. 54

55. References Joseph H. Porter, Todd M. Hillhouse, A brief history of the development of antidepressant drugs: From monoamines to glutamate Sebastian A. Alvano , Luis M. Zieherb , An updated classification of antidepressants: A proposal to simplify treatment Bianca Nogrady , Antidepressant Approvals Could Herald New Era in Psychiatric Drugs Etiology of Depression: Genetic and Environmental Factors Radu V. Saveanu , MD, Charles B. Nemeroff , MD, PhD The Etiology of Depression - Depression in Parents, Parenting, and Children - NCBI Bookshelf 55

56. 6. The diagnosis of depression: current and emerging methods, Katie M. Smitha, Perry F. Renshawb , and John Bilelloa 7. Pathophysiology of depression and mechanisms of treatment, Brigitta Bondy 8. The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents Olumuyiwa John Fasipe 9. https://emedicine.medscape.com/article/286759-print 56

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