Depressive Disorders PDF

Depressive Disorders 2/7//24 ➔ Depression- common & serious medical illness that negatively affects how you feel, the way you think & how you act ◆ More than sadness ◆ Pervasive- affecting all aspects of life ◆ Multiple physical, em...

Depressive Disorders 2/7//24 ➔ Depression- common & serious medical illness that negatively affects how you feel, the way you think & how you act ◆ More than sadness ◆ Pervasive- affecting all aspects of life ◆ Multiple physical, emotional, genetic etiologies ◆ Depression is leading cause of disability worldwide & is major contributor to global burden of disease ◆ Only 10% get treatment for depression ◆ MC in females Descriptive Terms ➔ Sadness- emotional state of unhappiness, mild to extreme; usually caused by loss ➔ Dysphoria- ‘Bad Feeling’ mood characterized by generalized discontent & agitation ➔ Anhedonia- No pleasure from anything (DX criteria) ➔ Fatigability- Tired or easily tired ➔ Diurnal Mood Variation- Worse in AM, better in PM ➔ Early Morning/Mid Cycle awakening from sleep ➔ Psychomotor Retardation: slow speech w/ long pauses before answers, slowness in thinking, decreased body movements (like jello) Precursors ➔ Loss: relationship, employment, home, money, environment (loss rekindles loss) ➔ Previous dx/tx for depression ➔ Current/hx substance abuse, physical, mental & sexual abuse ➔ Adverse Childhood experiences ➔ Chronic/Debilitating illness ➔ Medical conditions ➔ Family hx ➔ If you see a person w/ serious dz, think depression Risk for Illness ➔ Coronary Artery Dz ◆ 4x more likely to develop heart attack w/ hx of illness ◆ Increased risk of sudden cardiac death & re-infection ➔ Diabetes ◆ Poor glycemic control ◆ Increased micro/macro vascular complications ➔ Increased C Reactive Protein: inflammation marker Associated Health Habits ➔ Addictions- tobacco & alcohol ➔ Unhealthy Diet: high fat, low fiber, few fruits/veggies, processed meats, red meat, excess alcohol; negatively affects microbiome ➔ Overeating/Sedentary lifestyle Causes of Depression 1. Genetics- all humans carry at least some depressive gene a. 1st family members have 2-4x risk (40% Heritability) b. Epigenetics: modifying gene expression instead of altering genetic code itself (loading vs pulling the trigger) 2. Neuroticism a. Family neuroticism/depression b. Perfectionism/high achieving c. Regular experience of (-) emotions: Anxiety, Irritability, Frustration, Nervousness, Worry, Guilt 3. Learned Helplessness a. Dog experiments b. People who have been in abusive, captive type situations who can’t change environment c. Conditioned behavior that needs to be unlearned Cultural Related Issues ➔ Presents as somatic sx, insomnia, loss of energy, discrimination against people who are depressed Assessing Depression (SIG E CAPS)  ➔ Sad/Sleep/Sex ➔ Interest Diminished (Anhedonia) ➔ Guilt ➔ Energy Reduction ➔ Concentration ➔ Appetite/Weight gain/loss ➔ Psychomotor Retardation/Pain ➔ Suicide Thoughts PHQ-2 ➔ Formal Assessment for Depression- the first 2 questions of PHQ-9 ◆ Little Interest/Pleasure in doing things ◆ Feeling down, depressed, hopeless ➔ Interpretation: (+) if 3+ points (Administer PHQ-9) ◆ 0- Not at all ◆ 1- Several Days ◆ 2- More than ½ the day ◆ 3- Almost everyday PHQ-9 Assesses for Depression ➔ MC used instrument in US Major Depressive Disorder (MDD) Criteria ➔ Depressive Signs & Sx present for most days during 2 week period ◆ Depressed mood or anhedonia ◆ Not due to another condition ➔ 5 Symptoms Required for Dx (SIG E CAPS) Dysthymia ◆ Sleep Disorder (insomnia or opposite) → Depression ◆ Appetite Loss/Gain ◆ Fatigue/Loss of Energy ◆ Low Self Esteem With melancholic Features ➔ Depressed mood ➔ Anhedonia ➔ Weight Loss/Gain ➔ Psychomotor retardation/agitation ➔ Guilt → Depression Atypical Features ➔ Mood reactivity- mood brightens in response to actual/potential + events ➔ 2 or more: Increased Weight Gain/Appetite, Hypersomnia, Leaden Paralysis, (Heavy feelings in arms/legs), Interpersonal rejection (not limited to episodes of mood disturbance) Specifier ➔ With Psychotic Features: Mood congruent/incongruent (Hallucinations) ➔ Catatonia ◆ Unresponsiveness to external stimuli & apparent inability to move normally in a person who is apparently awake ◆ Lack of movement/communication OR combativeness & agitated movement ➔ Seasonal Features: Seasonal Affective Disorder (SAD), recurring ➔ With Anxious Distress: presence of at least 2 of following in MDD or PDD ◆ Feeling keyed up/tense ◆ Unusual restlessness ◆ Difficulty concentrating because of worry ◆ Fear something awful might happen ◆ Feeling individual may lose control of themselves Medical Workup ➔ Through History & Physical ◆ Family Hx including race/ethnicity, Social Hx (environmental exposure, sleep apnea screen ‘Epworth sleepiness scale’), History of abuse/trauma/military experience/ACEs Medication & Street Drugs  ➔ MDMA, Alcohol, Cocaine, Heroin, Opioids, Spice, Sedative Hypnotics, Anti-Anxiety, Mefloquin, Levodopa, Antihypertensives (Methyldopa, Beta Blockers), H2 Blockers/PPis, Contraceptives, Corticosteroids Laboratory ➔ More dependent on history, CBC w/ dif & ESR, CMP, Lipid Levels, UA & Tox, BHcG Serum, RPR/VDRL (Syphilis), ANA, RF, TSH, B12, Folate, Thiamine, HIV, Lyme Antibody (IgG), Vit D Routine Screening ➔ Pap/HPV, Mammogram, Colon Cancer (FIT), Spiral CT (Smokers), +/- PSA ➔ Neuro Imaging done w/ atypical presentation/when H&P/Labs indicate Behavioral Care- 2x as many patients significantly improved by 12 months ➔ If left untreated, independent risk for subsequent cognitive decline & possible dementia Persistent Depressive Disorder (Dysthymia) ➔ 2 or more of following for >2 years (1 year if child) ◆ Poor Appetite/Overeating, Insomnia/Hypersomnia, Low Energy/Fatigue, Low Self Esteem, Poor concentration/Difficulty making decisions, Feelings of hopelessness, People w/ dysthymia are still functional Antidepressant Medication ➔ Pretreatment ◆ Amenable to taking meds, Aware of benefits & SE of meds, Have capacity/motivation to be adherent, Able to monitor effects of meds, Read meds ‘package insert’ ➔ Suicide Risk: benefits of antidepressants outweigh their risks ➔ Increased risk of dementia w/ anticholinergic SE (like tricyclics) ➔ Therapy Goals SILDE 50 ◆ Remission- complete resolution of depressive sx ◆ Recovery= remission >1 year (long term end point goal of tx) ◆ Prevention of relapse & recurrence ➔ Less Than Optimal Outcomes ◆ Responder: >50% improved but 1 year, then relapse ➔ Antidepressant Trial ◆ After 1st Trial- 33% complete remission ◆ 67% have residual sx (sx that remained after responding) ◆ 67% in remission after 4 wks treatment (complete resolution) Selective Serotonin Reuptake Inhibitors (SSRIs)- 1st line antidepressants ➔ Escitalopram- Least amount of SE (Prolonged QT) ➔ Sertraline, Citalopram, Fluoxetine, Fluvoxamine, Paroxetine ➔ Efficient, tolerable, generally safe ➔ Inhibits serotonin reuptake pump & increases postsynaptic serotonin receptor occupancy ➔ Has little affinity for other types of receptors ➔ Also used for OCD, PTSD, Anxiety ➔ Side Effects: Sexual problems, Weight Gain (after taking it for a while), Reduced + feelings, Dependency on meds, Emotional numbness, Nausea, Insomnia, Decr appetite, Incr sweating, Tremors, Sleepiness, Prolonged QT interval (specifically Citalopram, Escitalopram), Restless leg syndrome, incr bleeding, May worsen IBS Norepinephrine & Dopamine Reuptake Inhibitors (NDRIs) ➔ Bupropion (MC) used for major depression, seasonal affective disorder, ADHD, psychomotor retardation, over eating, tobacco dependence & obesity ◆ Side Effects- Seizures(if hx of this can decrease threshold)**, decr appetite, watch out in pt’s w/ HTN, poss sexual enhancement ➔ CI w/ hx of MAOI use in past 2 wks Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) ➔ Watch out in patients w/ HTN & Seizures ➔ Duloxetine- fibromyalgia indication ➔ Venlafaxine- off label for fibromyalgia/chronic pain ➔ Milnacipran- fibromyalgia indication  ➔ Levomilnacipran- enantiomer of milnacipran ➔ Blocks presynaptic serotonin & norepi- transporter proteins ➔ Inhibits reuptake w/ incr stimulation of postsynaptic receptors Serotonin Modulators (NEWER) ➔ Vortioxetine- Increases serotonin, dopamine, NE, Ach; Useful for mild cognitive impairment ➔ Vilazodone used for IBS Tricyclic Antidepressants (TCAs) ➔ Primary: Amitriptyline & Imipramine ◆ Imipramine useful for General Anxiety including those w/o comorbid depression or manic disorder ➔ Secondary has fewer SE: Desipramine & Nortriptyline ➔ Side Effects: cardiac, anticholinergic, antihistamines, suicidal pts can overdose ◆ Blind as bat, mad as a hatter, red as a beet, Dry as a bone, Hot as a hare, Stuffed as a pipe Tetracyclic Antidepressants ➔ Trazodone used for sleep (Least effective, can cause priapism) ➔ Mirtazapine used for Sleepiness + Weight Gain ➔ Side Effects: Same as Tricyclics but less severe Monoamine Oxidase Inhibitors (MOA) ➔ Serotonin, Norepinephrine, Dopamine Enzyme Inhibitor, Tranylcypromine, Phenelzine, Selegiline Transdermal ➔ NO TYRAMINE- MAO blockade causes ‘Cheese Rxn” and ends up in general circulation instead of being metabolized normally → Hypertensive Crisis Starting Antidepressant Meds ➔ Start @ recommended dose, Allow 6 wks to work, Max 12 wks for trial, Stop herbals & alcohol ◆ Drugs that Incr Serotonin: St John’s Wart, SAMe, 5-HTP, Saffron, MDMA, PCP Serotonin Syndrome ➔ Dilated Pupils, Hyperreflexia, Clonus, Twitching, HARM (Hyperreflexia, Anxiety, Restlessness, Mydriasis) ➔ Treatment: Cyproheptadine blocks serotonin production, Benzodiazepines (Diazepam or Lorazepam) Major Depressive Disorder ➔ Tx: Maintenance tx x1 year; Pts w/ 2-3 relapses should be on for life; If want to stop meds, taper ◆ Suicidal Rate 15% (highest risk after starting meds especially for kids) ◆ CBT, Exercise (40 minutes), Diet (Mediterranean; Change microbiome b/c 90% Serotonin receptors located in gut), CBT ➔ Treating Non-Responders: Incr dose, Change meds/class, Add other med; Perform genetic testing, consider small amounts of T3, Add lithium if suicidal (Normally used to tx Bipolar Disorder) Add 2nd gen antipsychotic (Risperidone or Aripiprazole), Refer to psych Premenstrual Dysphoric Disorder (PMDD) ➔ Improves after menses starts & includes a total of 5 of: ◆ Anger/increased interpersonal conflicts ◆ Specific food cravings ◆ Breast Tenderness/Swelling ◆ Joint/Muscle Pain ◆ Bloating sensation/Weight gain ➔ Tx: ◆ SSRIs: Intermittent during luteal phase or during sx, use @ low doses ◆ OCs w/ drospirenone (Yaz, Loryna, Yasmin, Zarah, Syeda) Postpartum Depression (PPD) ➔ Up to 85% women experience ‘Baby Blues’ (worry, unhappiness, fatigue x1-2 wks post delivery) ➔ Tx: SSRIs (Paroxetine & Sertraline 1st line) ◆ Compatible w/ breast feeding ◆ AVOID Bupropion & Doxepin ◆ Enhanced w/ SGA (Aripiprazole, Risperidone, Olanzapine), Lithium, Triiodothyronine, Estrogen supplement (refer to OB), Brexanolone ◆ ECT for non-responders or if pt is actively suicidal/having infanticidal thoughts Treatment Resistant Depression (TRD) Dissociatives ➔ Ketamine, Esketamine, Used w/ oral antidepressants ➔ Done if pt tried 2 antidepressants for 6 wks minimum w/o remission of 50% increase in mood ➔ Transcranial magnetic stimulation ➔ Electroconvulsive Therapy: Safe in pregnancy, poss memory loss ◆ Most effective tx for depression Major Mood Disorder: Depression What is depression? o More than sadness, affects all aspects of life Statistics o *Depression is LEADING cause of disability worldwide + major contributor to global burden of disease o *only 10% of people ever receive tx o More common in females Depression Descriptive Terms o Sadness: emotional state of unhappiness, mild to extreme, usually caused by loss o Dysphoria: “bad feeling” mood w/ generalized discontent and agitation o Anhedonia: no pleasure from anything o Fatigability: tired or easily tired o Diurnal mood variation: worse in AM, better in PM o Early morning/mid-cycle awakening from sleep o Psychomotor retardation: slow speech w/ long pauses before answers, slowness in thinking, decreased body movements Common Depression Precursors o Loss o Previous diagnosis/tx for depression o A concurrent/ hx of substance abuse o A concurrent/hx of physical, mental, sexual abuse o Adverse childhood experiences (ACEs) o Chronic/ debilitating illness o Medical conditions o Family hx o When you see a pt w/ a serious disease, think of depression Depression as a Risk for Illness o Coronary Artery Disease o Diabetes o C-Reactive Protein o When you see a pt with depression, evaluate the whole person Major Depression Associated Health Habits o Addictions o Unhealthy diet o Overeating o Sedentary lifestyle Class Q: Which means the inability to experience pleasure from any activities? (Anhedonia) What Causes Depression- Genetics o All humans carry at least some genetic variants that can increase the risk of developing depression o 1st family members have 2-4 x risk o Epigenetics: modification of gene expression rather than alteration of the genetic code itself (loaded gun vs pulling the trigger (aka the stressor)  Adverse Childhood Experiences (ACEs) o Physical abuse, emotional abuse, sexual abuse, domestic violence, parental substance abuse, mental illness, suicide or death, crime or imprisoned family Depression- Loss of Nerve Synapses o Long term stress and anxiety can decrease nerve connections o People w/ depression have same serotonin levels as non-depressed individuals o Increased neurotransmitters increase number of synapses What Causes Depression- Neuroticism (negative emotions) o Family neuroticism/depression o Perfectionism/ high achieving What Causes Depression- Learned Helplessness o People who have been in abuse, captive type situations who could not change their environment o Conditioned behavior which needs to be unlearned Depression and Cultural Related Issues o Present as somatic symptoms, insomnia, loss of energy o Discrimination against people who are depressed *Assessing for Depression- SIG E CAPS o Sleep/Sex/Sad, Interest-diminished (anhedonia), Guilt, Energy Reduction, Concentration, Appetite or weight gain/loss, Psychomotor retardation/Pain, Suicide thoughts Formal Assessment for Depression- PHQ-2 o Is the first 2 questions of the PHQ-9 ▪ Little interest or pleasure in doing things (rate 0-3) ▪ Feeling down, depressed, or hopeless (rate 0-3) o Positive if 3 or more points o Administer PHQ-9 if positive (is most commonly used screening instrument in US) Major Depressive Disorder (MDD) Diagnostic Criteria o Depressive signs and symptoms present for most days during a *2-week period: ▪ depressed mood or anhedonia must be present, no signs of mania, episode is not a result of grief/bereavement, not due to another medical condition o DSM 5 MDD Diagnostic Criteria o >5 of the following symptoms required: depressed mood, anhedonia, sleep disorder, appetite loss/weight loss OR appetite gain/weight gain, fatigue/loss of energy, psychomotor retardation or agitation, trouble concentrating/making decisions, low self-esteem or guilt, recurrent thoughts of death or suicidal ideation Persistent Depressive Disorder (PDD) (aka Dysthymia or depression lite) o 2 or more for > *2 years (1 year for adolescents and children) o People w/ dysthymia are still functional MDD Specifiers o Mild = minor impairment o Moderate = between mild and severe o Severe = symptoms substantially in excess to make diagnosis, serious distress, markedly interfere w/ social and occupational functioning o W/ psychotic features (mood congruent/ incongruent, hallucinations) o Catatonia o Seasonal features (Seasonal Affective Disorder) o w/ anxious distress ▪ tense, restless, difficulty concentrating bc of worry, feeling something awful may happen, feeling like one might lose control  MDD w/ atypical features o Mood reactivity (mood brightens in response to potential positive events) o 2 or more: ▪ Weight gain/ increased appetite ▪ Hypersomnia ▪ Leaden paralysis ▪ Interpersonal rejection sensitivity Depressive Disorders w/ Mixed Features o Can have mixed features of both depression and mania Medication + Street Drugs Causing MDD Symptoms o MDMA, alcohol, cocaine, heroin o Sedative hypnotics o Anti-anxiety o Levodopa o Many antihypertensives (Even cardioselective beta blockers) o H2 blockers + PPIs o Contraceptives o Corticosteroids Medical Work Up o Lab ▪ CBC w diff and ESR ▪ CMP ▪ Lipid Levels ▪ UA and Tox screen ▪ BHCG (pregnancy) ▪ RPR/VDRL for syphilis ▪ ANA, RF (autoimmune) ▪ TSH ▪ B12, Folate, Thiamine ▪ HIV ▪ Lyme Antibody Test (IgG) ▪ Vit D Levels ▪ Homocysteine ▪ C Reactive Protein o Neurologic Imaging ▪ Only need if have headaches, visual disturbances, gait issues, etc. ▪ Lumbar puncture, CT/MRI, EEG, Genetic Testing Patient Integrated Behavioral Care: on avg, 2x as many pts significantly improved by 12 mths Risks of Untreated Depression: independent risk for subsequent cognitive decline and possibly dementia Antidepressant Medication: o Pretreatment Consideration ▪ Amenable to taking meds, aware of risks/benefits, capacity/motivation o Suicide Risk and Aggression ▪ 1) black box warning ages 6-24 ▪ 2) less substantial evidence for same adults over 24 ▪ 3) *follow up weekly at first and monitor for suicide/aggressive ideation ▪ Benefits of antidepressant meds likely outweigh risks to children and adolescents o Increased risk of dementia w/ anticholinergic side effects (like tricyclics) Antidepressant Therapeutic Goals  o Remission = complete resolution of depressive symptoms o Recovery = remission > 1 yr o Prevention of relapse and recurrence Less than Optimal Outcomes o Responder = pt is >50% improved but 1 yr, then relapse NIH Antidepressant Tx Study o Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study ▪ After 1st antidepressant trial: complete remission 33%, residual symptoms 67% ▪ 67% remission after 4 treatments Class Q: What is the long term end goal of depression tx? (Recovery) 3 Depression Related Neurotransmitters o Serotonin (satisfied, anti-anxiety, decreased impulsivity, decreased sex drive) o Dopamine (Motivation, attention, pleasure) o Norepinephrine (Concentration, energy) Antidepressant Selections o * SSRIs, SNRIs, Bupropion usual first line o Selective Serotonin Reuptake Inhibitors (SSRIs): ▪ First-line antidepressants: efficacy, tolerability, and general safety in overdose. ▪ They inhibit the serotonin reuptake pump and increase postsynaptic serotonin receptor occupancy. ▪ This initial action may cause subsequent changes involved in treating depression. ▪ They are selective and have little affinity for other types of receptors ▪ Also used for OCD, PTSD, Anxiety ▪ Common side effects include: nausea, sexual dysfunction, prolonged QT interval (esp. citalopram/ escitalopram), restless leg syndrome, increase in bleeding, headache, diarrhea, and constipation ▪ Escitalopram (Lexapro-least amount of ADEs), Citalopram (Celexa) sertraline (Zoloft), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), o Norepinephrine and Dopamine Reuptake Inhibitors (NDRIs) ▪ commonly used→ Bupropion (Wellbutrin) ▪ used to treat major depression, SAD, ADHD, tobacco dependence (Zyban), hypoactive sexual disorder, and obesity ▪ Contraindications: bulimia, anorexia, use of MAOIs the past two weeks, seizures Used cautiously in patients receiving other drugs that can lower seizure threshold ▪ Side effects: agitation, nausea, headache, loss of appetite, insomnia ▪ ADEs for Bupropion: can increase BP in some people, decreased appetite, weight loss, sexual enhancement o Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): ▪ Block presynaptic serotonin and NE transporter proteins. ▪ Inhibits reuptake of these neurotransmitters and leads to increased stimulation of post-synaptic receptors ▪ Duloxetine (Cymbalta), Venlafaxine (Effexor), Milnacipran (Savella), Levomilnacipran (Fetzima) ▪ Side effects: nausea, dizziness, dry mouth, constipation, insomnia, and diaphoresis ▪ WATCH OUT FOR PT WITH HTN + SEIZURES  o Newer Antidepressants ▪ Serotonin Modulators Vortioxetine (Trintellix) o Increases serotonin, dopamine, NE, Ach o Useful for mild cognitive impairment Vilazodone (Vybrid) o Works for IBS o Tricyclic Antidepressants (TCAs): ▪ Inhibits reuptake of both serotonin and NE ▪ Primary: amitriptyline (Elavil), Imipramine (Tofranil- useful w/ GAD) ▪ Secondary (Fewer effects) Desipramine (Norpramin), Nortriptyline (Pamelor) ▪ Side Effects: cardiac, anticholinergic, antihistaminic, decreased seizure threshold, sexual dysfunction, diaphoresis, and tremor ▪ An increased risk of cardiotoxicity and arrhythmias ▪ Suicidal patient can overdose ▪ Anticholinergic Toxidrome: blind as a bat, mad as a hatter, red as beet, dry as bone, hot as hare, stuffed as a pipe o Tetracyclic Antidepressants ▪ Combined reuptake inhibitors and receptor blockers Trazodone (Dysyrel) à used for sleep, one of least effective anti- depressants, “Trazabone” à can cause priapism Mirtazapine (Remeron) à sleepiness and weight gain ▪ Side effects: same as TCAs but not as severe o Monoamine Oxidase Inhibitors (MAOIs): ▪ the first class of antidepressants in clinical use ▪ serotonin, NE, Dopamine enzyme inhibitor ▪ Tranylcypromine (Parnate), Phenelzine (Nardil), selegiline transdermal ▪ Side effects: HTN, flushing and headache ▪ MAOI NO TYRAMINE DIET à hypertensive crisis o Herbals which can Raise Serotonin ▪ St. Johns Wart ▪ SAMe ▪ 5-HTP ▪ Saffron ▪ MDMA ▪ PCP Starting Antidepressant Medication o Begin at recommended starting dose o Report troublesome ADEs o Allow up to 6 weeks to work, may improve in 2 weeks o Maximum of 12 weeks for trial Major Depressant Disorder Medication Treatment o Maintenance treatment for 1 yr o Pts w/ 2-3 relapse probably should be on lifetime o Tape and watch for relapse Foods/meds to avoid with anti-depressants: alcohol (a depressant and can enhance drowsiness), fish oil, ibuprofen, aspirin because it enhances SSRI anti platelet affects o SSRI’s Black box warning age 6-24→ can lead to aggressive and suicide behavior Treating Non-Responders o Increase dose, change to another medication/class o Add/consider other non-pharm tx  o If not better, augment w/ meds in diff classes combined at a lower dose (SSRI w/ bupropion) o what to do: genetic testing, consider small amounts of thyroid hormone, add lithium (esp. if suicidal), add 2nd degree antipsychotic medication, refer to psychiatry What is the step approach to treating depression if the first drug does not work? o Switch classes Know which drugs to use with which concomitant conditions (sleepiness, sexual dysfunction, etc) How to evaluate a patient for suicide risk o Ask often all depressed, medicated, psychiatric patients ▪ How are you feeling? How is the medication working?, Do you feel suicidal? Do you feel like taking your life? o Ask if there was a previous attempt, a concurrent stressor, a desire to die, feeling overwhelmed, hopelessness o Triad of Death: Intention, Plausible plan, lethal means Criteria for routine and maintenance therapy? o Patient with 3 or more episodes of major depression Serotonin Syndrome o Usually occurs within several hours of taking a new drug or increasing the dose of a drug you’re already taking, signs and symptoms include ▪ Confusion, agitation/restlessness, dilated pupils, loss of muscle coordination/twitching muscles, muscle rigidity, diarrhea, shivering, goosebumps ▪ Severe serotonin syndrome can be life threatening→ high fever, seizures, irregular heartbeat, unconsciousness, death o H2ARM2 ▪ Hyperreflexia/ Hyperprexia ▪ Anxiety ▪ Restlessness ▪ Myoclonus/ Mydriasis o Herbs (St John’s warts) and supplement (5HTP) interacting with antidepressants to cause serotonin syndrome o Treatment: ▪ Cooling blankets/anti-pyrectics ▪ Benzodiazepines (Valium, Ativan) ▪ Cyproheptadine, antihistamine, blocks serotonin production ▪ Iv fluids ▪ Discontinuation of meds, herbs, drugs Non-medication treatments o Therapy: interpersonal, CBT, bibliotherapy, light therapy, humor therapy ▪ CBT is effective or more effective than medication o Exercise: studies support 40 minutes of aerobic; volunteering; pet: affection, need, walking; group support: therapy or “traditional” o Diet Premenstrual Dysphoric Disorder (PMDD) o Criteria ▪ More severe form of PMS ▪ Begins final week of cycle and improves after menses begins and includes total of 5: 1)Affective lability, 2) irritability (or anger or increased interpersonal conflicts), 3) depressed mood, feelings of hopelessness, or self-  deprecating thoughts, 4) anxiety, tension, and/or feelings of being keyed up or on edge AND 1) decreased interest in usual activates, 2) difficulty in concentration, 3) lethargy, easy fatigue, or marked lack of energy, 4) marked change in appetite, overeating, or specific food cravings, 5) hypersomnia/insomnia, 6) a sense of being overwhelmed or out of control, 7) physical sx: breast tenderness or swelling, joint or muscle pain, a sensation of “bloating” or weight gain (Acne) o Treatment ▪ SSRIs only: sertraline, fluoxetine, and paroxetine FDA approved Intermittent during luteal phase (14 days after menses) or during symptoms Start at lowest recommended dose ▪ OCs containing drospirenone YAZ , FDA approved Loryna, Yasmin, Zarah, Sydeda also have drosperienone Post-Partum Depression o Up to 85% experience “Baby Blues”: worry, unhappiness, and fatigue for 1-2 weeks after delivery ▪ Ask every post-partum woman o Similar Tx as MDD ▪ Competent help, sleep, psychotherapy, SSRIs (compatible w/ breast feeding) Paroexetine, sertraline first line AVOID bupropion and doxepin ▪ Estrogen supplementation ▪ ECT for non-responders and/or if pt is actively suicidal or having infanticidal thoughts ▪ Brexanolone à IV formulation of allopregnan Continuous, monitored IV infusion for 60 hours Seasonal Affective Disorder o Depression or dysthymia during winter months with less light o Tx ▪ Bright light therapy 60-90 mins per day for 2 weeks to assess effectiveness ▪ SSRIs, exercise, get outdoors if possible Treatment Resistant Depression (TRD) Disassociatives o Ketamine (outpatient clinic) o Esketamine (done in clinic) ▪ Both can cause disassociation, hallucinations, hypotension, headache o Transcranial Magnetic Stimulation (TMS) ▪ “can be done while watching TV” ▪ 1 hour, 5-6 x per week, 4-6 weeks ▪ Side effects: headache o Electroconvulsion Therapy (ECT) ▪ Under general anesthesia, electrodes placed transcranial and seizure provoked for 60 seconds ▪ Very effective in all type of MDD ▪ Few contraindications ▪ Greatest concern is transient memory loss ▪ Safe in pregnancy ▪ Relative CI w/ brain tumors  Major Depressive Disorder Prognosis o Chronic w/ relapses o Premorbid function may return but with episodes o Suicide rate estimate 15% ▪ Highest risk after initiating medical therapy, especially for adolescents/children Significance of Disruptive Mood Dysregulation Disorder in childhood o Frequent (>3 times/week) outbursts of temper lasting >1 year) o After age 6 and before age 18, usually leads to clinical depression, no more than 3 months period without symptoms, chronically irritated o Treatment: SSRIS, pediatric therapist, psychiatry, potential for suicide with medication