DEPRESSION AND ANXIETY DIOSRODERS IN PRIMARY CARE PRESENTATION.pptx

the incidence of depression and anxiety disorders are so high in primary care and polyclinics as well as the prevalence of these disorders in chronic physical illness are so high

1. Depression & Anxiety disorders in primary care By Dr. ASHRAF SAAD ELSHAZLY CONSULTANT PSYCHIATRY

2. Body - mind interaction Satisfaction, love , joy , sorrow, fear, apprehension, anger provide the meaning of human existence. Without emotion man would be nothing but like a biological computer. So emotion is very important to and among human being. Strong interaction between body and mind means integrity of human being If one part is affected the other is suffering

3. Normal Physiology Normal physiology of mood, perception, emotion and behavior focuses majorly on neurotransmitters in the brain. There are over 46 neurotransmitters in the brain and many have more than one function. Neurotransmitters are chemical messengers that are released and received by synapses of neurons to mediate intracellular communication in the nervous system. Serotonin is involved with mood, H appiness , and sleep induction. Raphe-Serotonin System normally modulates homeostasis, emotionality, and tolerance to aversive experiences. Norepinephrine in the brain helps regulate alertness, mood functions, in dream sleep, and maintains arousal. It also can help in the response to stressful situations.

4. Normal Physiology The locus coeruleus has a group of norepinephrine containing cells implicated in global psychologic processes including attention, vigilance and orientation to stimuli. Dopamine in the brain regulates reward and motivation which could explain the loss of interest in patients with depression if it iss reduced. Dopamine motivates people to take action toward goals, desires, and needs, and issues a surge of reinforcing P leasure once they’ve been accomplished. Sufficient levels are needed for the brain to function properly and decreased levels have been found in patients with depression.

5. PLEASURE HAPPINESS 1-Pleasure is short-lived (about an hour, like a good meal). Get it, experience it, and get over it. Why do you think you can’t remember what you ate for dinner yesterday? 1-Happiness lasts much longer (weeks to months to years). It’s what happens when you have a working marriage or watch your teenager graduate from high school. 2-Pleasure is visceral in terms of excitement (e.g., a casino, a football game, or a strip club). It activates the body’s fight-or-flight system, which causes blood pressure and heart rate to go up. 2-Happiness is ethereal and calming (e.g., listening to soothing music or watching the waves of the ocean). It makes your heart rate slow and your blood pressure decline. 3-Pleasure can be achieved with different substances (e.g., heroin, nicotine, cocaine, caffeine, alcohol, and of course sugar). Each stimulates the reward center of the brain. Some are legal, some are not. 3-Happniess is not achievable with substance use. Rather, happiness is usually achieved with deeds (like graduating from college or having a child who can navigate his or her own path in life). 4-Pleasure occurs with the process of taking (like from a casino). Gambling is definitely a high: when you win, it is fundamentally rewarding, both viscerally and economically. 5-Pleasure is yours and yours alone. Your sense of reward does not immediately impact anyone else. 6-Pleasure when unchecked can lead into misery, like addiction. 7-Last and most important, Pleasure is driven by dopamine, 4-Happiness is often generated through giving (like giving money to a charity, or giving your time to your child, or devoting time and energy to a worthwhile project). 5-your happiness often impacts other people directly and can impact society at large. 6-Happiness when unchecked cannot lead into misery, like addiction. 7- Happiness is driven by serotonin.

6. Response to stressors

7. healthy ways to handle life’s stressors These are evidence-based tools to tackle it in healthy ways. S ocial support : Strong social support can  improve resilience to stress .  Seek good nutrition :  Acute stress can kill the appetite, but the release of the hormone cortisol during chronic stress can cause fat and sugar cravings. Relax your muscles : Combat stress with stretches, massage, or warm baths. Or try  progressive muscle relaxation . Meditate : A strong body of research shows that  mindful meditation   can reduce psychological stress and anxiety. Protect your sleep . Get physical exercises: 30-minute walk in the living room can do the trick. Take a moment in nature: Even  nature videos  can sped the recovery from stress. Keep your pleasurable activities :  reading a novel, singing along to your favorite tunes, or streaming your favorite comedy. Reframe your thinking : One of the most research-supported treatments for stress and anxiety is cognitive behavioral therapy, or CBT.  Seek help . Try to eliminate the stressors.

8. Depression & Anxiety comorbidity The prevalence of comorbidity between anxiety disorder and major depressive disorder is frequent, up to 25% Panic disorder and Generalized Anxiety Disorder have been most studied as part of an anxiety-depression comorbid state All (or almost all) anxiety disorders appear to show comorbidity with at least some depressive symptoms, if not full MDD General practitioner who sees 40 patients a day can expect that eight will require support or treatment for anxiety or depression(20%) ,, and that is not counting those whose disorders go unrecognized

9. Core Symptoms of Anxiety Cognitive symptoms Fear of dying or going mad and crazy Decreased attention & concentration and memory impairment Somatic symptoms Cardiovascular:-palpitation , chest pain, tachycardia, flushing Respiratory : hyperventilation , shortness of breathing Neurological: dizziness , headache , parasesthesia , vertigo Gastrointestinal: choking, dry mouth, nausea, , vomiting , diarrhea Musculoskeletal : muscle ache and tension , restlessness Psychological Derealization , depersonalization , speeding or slowing of thoughts , distractibility , irritability , insomnia , vivid dreams

10. Core Symptoms of Depression *Main Symptoms 1-Depressed mood(sad, down , blue) and or 2-Anhedonia (reduced interest or pleasure) *Somatic Symptoms 1-Change in appetite 2-Change in sleep pattern 3-Reduced energy level 4-Psychomotor agitation or retardation *Cognitive Symptoms 1- poor concentration /attention /memory/easy distraction 2- inappropriate guilt /self reproach 3- thought of death , dying , suicide 5 out of 9 at least 2 weeks

11. MIXED ANXIETY DEPRESSION CERTERIA * The patient has three or four of the symptoms of major depression( which must include depressed mood and or anhedonia ), and they are accompanied by anxious distress. *The patient has symptoms of anxious distress, two or more of the following symptoms ; irrational worry , preoccupation with unpleasant worries , having motor tension, fear that something bad may happen. *The symptoms must have lasted at least 2 weeks and no other DSM diagnosis of anxiety od depression must be present , and they are both occurring at the same time

12. Impacts of Major Depressive &Anxiety Disorders Disorder Individual Impacts Family Impacts Decreased Quality of Life Even up to 60% of remitted patients still have reduced QOL Income Loss Increased days missed of work and decreased work performance Social Isolation Higher risk of developing chronic and neurodegenerative diseases CAD, DM, Parkinson’s, MCI, others Caregiver Burnout Higher risk of worse outcomes with preexisting chronic and neurodegenerative diseases Familial Pessimism Higher all-cause mortality 50-100% greater (ex 39% greater in cancer pts, 200% greater in DM females) Increased Alcohol Abuse Shorter life expectancy 11-15 years shorter in males, 7-13 years shorter in females Divorce Higher incidence of suicide (27x greater in MDD than in Gen Pop) Decreased Bonding/attachment to children Higher risk of death to homicide (2.6x greater in MDD than in Gen Pop) Higher risk of death in accidents (2x greater in MDD than in Gen Pop)

13. Differentiating Anxiety and depression

14. Etiology of depression and anxiety disorder

15. Why is it Important in Primary Care? Depression & Anxiety disorder comorbidity is COMMON: lifetime prevalence of depression & anxiety disorder comorbidity is 25% OFTEN MANAGED EXCLUSIVELY BY GENERAL MEDICAL PROVIDERS (~70%) COMMON CAUSE OF DISABILITY : 2 nd leading cause of disability – both in USA & worldwide RECURRENT : 75% of patients successfully treated by PCP experience another episode in the decade following their initial treatment HIGHLY COMORBID WITH MEDICAL PROBLEMS

16. Major Depressive Disorder A common, chronic, treatable mood disorder that typically follows a remitting and relapsing course of depressive episodes. Pervasive – affects not only patient but family, friends, and colleagues Underrecognized and undertreated Most cases will never reach a specialist Major stigma associated with it (although improving) Depression and Anxiety commonly co-occur

17. Prevalence of MDD A UK study showed that PCPs identified depression in almost half of cases. 35% to 50% of MDD cases go unrecognized; in addition, MDD is often untreated when diagnosed. PCPs manage the majority of patients with MDD. Higher rates among Women than men --Young adults (18-29)---People with lower incomes Lifetime prevalence for women, 10-25%; men, 5-12% Rates are equal for boys and girls before puberty ; rates in women following menarche are twice that of men. Age of onset is typically in early twenties, but earlier and later onset occur. Increased risk if female ; middle-aged; widowed, separated, or divorced; or low-income High comorbidity with anxiety disorder, substance use disorders, general medical conditions

18. Suicide Suicide rates in the US have risen by 30% from 2000-2016 Age-adjusted suicide rate in 2017: 14/100,000 2 nd leading cause of death ages 10-34 4th leading cause of death ages 35-54 2/3 of those who die by suicide had depression at time of the act

19. Comorbid Medical Conditions Asthma-Pain-Arthritis-Cardiovascular disease-Stroke-Diabetes-Obesity CVD and Depression Patients with cardiovascular disease (CVD) more likely to experience depression Patients with depression 1.6 times more likely to develop coronary artery disease (CAD); even more likely with MDD Also 4 times more likely to experience a myocardial infarction (MI) Post-MI patients with depression less likely to follow lifestyle changes Diabetes increases risk of depression . Depression twice as prevalent in those with diabetes More prevalent in women with diabetes than in men with diabetes Obesity and depression 65% of the US population is overweight or obese More obese women than men (54% vs. 46%) BMI ≥30 in women associated with nearly 50% increase in lifetime prevalence of depressive disorders

20. MDD & Medical comorbidity CI=confidence interval; HF=heart failure; IBD=inflammatory bowel disease; MDD=major depressive disorder; MI=myocardial infarction; MS=multiple sclerosis; RA=rheumatoid arthritis; SLE=systemic lupus erythematosus; T1DM=type 1 diabetes mellitus; T2DM=type 2 diabetes mellitus Gold et al. Nat Rev Dis Primers 2020;6(1):69 22 Prevalence of comorbid MDD in patients with chronic disease 40 25 20 15 10 5 General population Older adults (≥75) General inpatients Cancer (general) Lung Colorectal Prostate Gynaecological Breast Ovarian Brain MI HF Hypertension T2DM Neurological (general) 30 35 Epilepsy MS Stroke Parkinson disease T1DM RA SLE Psoriasis IBD Alzheimer disease Cancer Cardiometabolic General patient groups Neurological Inflammatory Point prevalence of comorbid MDD (percent, 95% CI) Figure adapted from: Gold et al., 2020

21. Treatment aspects Pharmacotherapy Psychotherapy Behaverrioal Activities

22. Moderate to Severe Depression Mild Depression Medications Monotherapy or Combined Cognitive Behavioral Therapy Adjunctive Interpersonal Therapy Adjunctive Behavioral Activation Adjunctive Exercise (30m mod intens 3x/wk) Adjunctive Light Therapy (am 30-60min qd) Adjunctive Electroconvulsive Therapy Monotherapy (*refractory, suicidal, psychotic) Transcranial Magnetic Stimulation Monotherapy (*after 1 med failure) Medications Monotherapy or Combined with therapy Cognitive Behavioral Therapy Monotherapy or Combined with meds Interpersonal Therapy Monotherapy or Combined with meds Behavioral Activation Monotherapy or Combined with meds Exercise (30m mod intens 3x/wk) Monotherapy or Combined with meds/thx Improve style of life with good nutrition Monotherapy or Combined with therapy

23. Treatment of Depression in Adults Second generation antidepressants SSRIs and SNRIs Psychotherapy models with similar effectiveness: CBT interpersonal therapy (IPT) behavioral therapy cognitive therapy psychodynamic therapy supportive therapy Select medication based on factors: Specific depressive symptoms Comorbid conditions Safety Side effect profile (e.g., sedating, weight gain, impact on sexual functioning) Concurrent medications (potential interactions) Ease of use (e.g., frequency of administration) Patient preference or expectations Cost and insurance coverage Response to antidepressants during prior episodes Family (first degree relative) history of response to antidepressants

24. Medication Med Step When Use Is Preferred Escitalopram A Anxiety, PMDD, OCD, PTSD, elderly with complicated medical probs Sertraline B If Escitalopram doesn’t work, partial efficacy, or mild AEs, but no reasons to do below Venlafaxine ER B (*A) *If chronic pain comorbid, can try as step A Mirtazapine B (*A) *If insomnia, failure to thrive are prominent, can try as step A Bupropion XL B (*A) *If prominent lethargy, amotivation, psychomotor slowing, clearly established comorbid ADHD or SAD, or Nicotine Use Disorder (that patient desires to treat) are present, can try as step A Recommended Steps for Primary Care Pharmacotherapy for Major Depressive Disorder Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

25. Medication Initial Dosing* Final Dosing* Anx Pain Sleep Other Benefits Interactions Adverse Effects Line** FDA aprvd Citalopram 20mg qd 20-40mg qday x PMDD, OCD, PTSD - 1 x Escitalopram 10mg qd 10-20mg qday x PMDD, OCD, PTSD - 1 x Fluoxetine 20mg qam 20-80mg qday x PMDD, OCD, PTSD, Bulimia ++ 2d6, 2d19 + 1 x Paroxetine 20mg qd 20-50mg qday x PMDD, OCD, PTSD ++ 2d6 ++ 1 x Sertraline 50mg qd 50-200mg qday x PMDD, OCD, PTSD + 2d6 + 1 x Venlafaxine XR 37.5mg qd 75-225mg qday x x PMDD, OCD, PTSD ++, w/d 1 x Duloxetine 40mg qday 40-120mg qday x x + 2d6 +, w/d 1 x Amitriptyline 25mg qhs 50-150mg qhs or div x x x IBS, Migr ++ 2d6 +++ 2 x Nortriptyline 25mg qhs 75-150mg qhs or div x x x ++ 2d6 ++ 2 x Imipramine 25mg qhs 50-150mg qhs or div x x x enuresis ++ 2d6 +++ 2 x Desipramine 25mg qhs 100-200mg qhs or div x x x ADHD ++ 2d6 ++ 2 x Trazodone D: 150mg div I: 50mg qhs D: 150-600mg div I: 50-300mg qhs x x +, priap 2 x Mirtazapine 15mg qhs 15-45mg qhs x x PTSD ++ 1 x Bupropion XL 150mg qam 150-450mg qam ADHD, SAD, NicotineUD + 2d6 +, NO SEX Dysfxn 1 x MAOIs Several several x +++ +++, tyramine rxn 3 x FDA approved generic antidepressants with good evidence for efficacy in Major Depressive Disorder *Stahl’s Essential Psychopharmacology, Prescriber’s Guide, 5 th Edition, 2014 **Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

26. Why Escitalopram? Bec. It was comparably effective and well tolerated in depressed patients with and without mental and/or somatic comorbidity . Patients with MDD treated with Escitalopram achieved remission independently of baseline anxiety severity. Escitalopram was found to be effective and generally well-tolerated in post-stroke depression patients Escitalopram significantly improved depressive symptoms in patients with MDD and comorbid diabetes as early as week 3 Escitalopram improved depressive symptoms † in patients with comorbid MDD and breast cancer Escitalopram 10–20 mg significantly improved the quality of life for patients with GAD compared to placebo

27. Why Escitalopram? *Escitalopram demonstrated high response and remission rates in panic disorder * Long-term treatment with Escitalopram continuously improved functional disability in patients with panic disorder *In a meta-analysis, Escitalopram consistently demonstrated greater efficacy than placebo in patients with SAD *Escitalopram delivered significantly effective relief from symptoms of OCD. * Escitalopram demonstrated high remission rates and significant improvements in Depression and Anxiety symptoms over 24 weeks. * Escitalopram 10–20 mg significantly improved the quality of life for patients with GAD compared to placebo

28. Escitalopram is highly selective and potentially lesser side effects

29. The serotonin dual action of Escitalopram Sanchez. Basic Clin Pharmacol Toxicol 2006;99(2):91–95 Escitalopram Binds to primary & allosteric sites Serotonin reuptake inhibitor Binds to primary site

30. Escitalopram ( 10 mg and 20 mg) was generally well tolerated in patients with anxiety disorders and MDD AEs during 8 weeks of treatment in RCTs of escitalopram 10 and 20 mg completed by December 2006 AE, % Placebo (n=2,199) Escitalopram 10 and 20 mg (n=2,740) Patients with AEs 63.1 72.7 Headache 16.0 18.5 Nausea 8.5 17.7 Insomnia 5.0 8.4 Fatigue 3.4 8.1 Diarrhoea 4.9 7.7 Dry mouth 4.6 6.8 Dizziness 4.5 6.1 Somnolence 2.9 5.9 Ejaculation delayed (men) 0.6 5.4 Sexual dysfunction 2.1 10.3 Patients withdrawn due to AEs 2.8 7.3 Escitalopram was generally well tolerated in both acute and longer-term treatment for patients with anxiety disorders and MDD Escitalopram also had a comparable cardiovascular safety profile to placebo in this analysis Figure adapted from: Baldwin et al., 2007 32

31. Second-generation antidepressants are not equivalent in their potential for pharmacokinetic drug interactions 1 Cytochrome P450 isozyme inhibition in vitro/in vivo 0 = no inhibition; + = weak inhibition; ++ = moderate inhibition; +++ = strong inhibition Second-generation antidepressants are not equivalent in their potential for pharmacokinetic drug interactions. References: 1. Spina et al. Clinically Relevant Pharmacokinetic Drug Interactions with Second-Generation Antidepressants: An Update. Clinical erapeutics /Volume 30, Number 7, 2008. 3A4 2D6 1A2 2C19 2C9 Bupropion ++ Citalopram + Duloxetine ++ Escitalopram + Fluoxetine +/++ +++ + +/++ ++ Fluvoxamine ++ + +++ +++ ++ Nefazodone +++ + Paroxetine + +++ + + + Reboxetine + Sertraline + +/++ + + + Venlafaxine +

32. Indications and dosing References: 1. Cipralex® Summary of Product Characteristics . 2020. https://www.ema.europa.eu-/en/medicines/human/referrals/escitalopram. [Last accessed : September 2020]. Major Depressive Disorder Generalized Anxiety Disorder Panic Disorder Social Anxiety Disorder Obsessive Compulsive Disorder Dosage and directions for use: Cipralex® is administered as a single daily dose. Cipralex® may be taken without regard to food intake.

33. Key messages to give patients when starting antidepressants Side effects often precede therapeutic benefit. Side effects typically recede over time. Most people should be on medication at least 6-12 months after adequate response to the medicine. Although you may start feeling better in as little as 2 weeks, it takes more time for full response and remission. Take the medication as prescribed, even after you feel better. Do not stop taking the medication without calling your clinician.

34. WHEN TO REFER Referral to a psychiatrist is indicated if patient requires * adjunct anti-depressant treatment * has co-morbid psychiatric diagnoses including substance abuse, anxiety, panic attacks, or psychotic features such as hallucinations or delusions, or * has thoughts of death or harming others. *A person who is actively suicidal should be referred to the closest emergency department for hospitalization. *No response to medication trial one or two or drug side effects

35. Always remember… When you see anxiety, ask about depression When you see depression, ask about anxiety When a patient is not responding, look for comorbidity Choose drugs with known ‘broad spectrum’ effects Thoughtful dosage and titration adjustments (i.e. start low, go slow, and keep going)

36. Conclusions

37. THANK YOU