1. Mood Disorders Compiled By Salina Chan, R3 Asia Karakoc, R2 2013

2. Today We’ll Talk About… Major Depressive Disorder Treatments Bipolar Treatments Persistent depressive disorder (dysthymia) Cyclothymia Adjustment d/o

3. Major Depressive Disorder

4. Major Depression Stats Public Health Agency of Canada/ Statistics Canada: Lifetime prevalence of major depression: 12.2%, past- year episodes: 4.8% The peak annual prevalence occurred in the group aged 15 to 25 years. Female to male ratio 2:1 Worldwide, major depression is the leading cause of years lived with disability.

5. Major Depressive Disorder M - SIGECAPS Mood Mood Sleep Sleep Interest Interest Guilt Guilt Energy Energy Concentration Concentration Appetite Appetite Psychomotor Psychomotor Suicidal ideation Suicidal ideation

7. Major Depressive Disorder Criteria Depressed Mood; OR Markedly diminished Interest/pleasure 4 other symptoms (5/9 total) Most of the day, almost every day 2 weeks duration Other Symptoms Weight or appetite changes Fatigue or loss of energy Feelings of worthlessness or excessive or inappropriate guilt Diminished ability to think/concentrate or indecisiveness Insomnia or hypersomnia Psychomotor agitation or retardation Recurrent thoughts of death, recurrent SI, SA

8. Major Depressive Disorder Change from previous function Symptoms cause clinically significant distress or impairment in social, occupation or other important area of functioning Episode not attributable to physiological effects of a substance or to another medical condition Not better accounted for by SczA, Scz, delusional d/o or other psychotic d/o Never been manic or hypomanic episode

9. Major Depressive Episode Specifiers Melancholic Loss of pleasure or lack of mood reactivity + 3 of: Distinct depressed mood, worse in morning early awakenings psychomotor changes weight loss guilt Atypical Mood Reactivity + 2 of: Chronic rejection hypersensitivity leaden paralysis hypersomnia increased appetite

10. Major Depressive Episode Specifiers Peri-Partum Onset of episode during pregnancy or within 4 weeks postpartum With Seasonal Pattern Onset and offset at particular times of year MDE never in a different season in past 2 years With Psychotic Features Hallucinations or delusions With Anxious Distress Feeling 2 or more of keyed/tense, restless, difficulty conc b/c of worries, fearing something awful may happen, feeling might lost control

11. Major Depressive Episode MSE Appearance Normal to Poor kempt/hygiene Psychomotor retardation or agitation Objective or subjective Mood & Affect May deny being sad but look it “depressed”, “down in dumps”, “sad”, “hopeless”, “discouraged”, “blah”, “have no feelings”, “anxious” Irritability, down, depressed, low, heavy, anxious, tense Lability, Range restriction

12. Major Depressive Episode MSE Speech & Thought Latency (may be long!) Circumstantial may be preoccupied with somatic complaints, death, hopelessness, personal defects Ruminations about past failings Delusions of guilt guilt/responsibility not limited to being sick and not meeting occupational/interpersonal responsibilities

13. MDD Video https://www.youtube.com/watch?v=4YhpWZCdiZc

14. MDD Differential Manic episode with irritable mood or mixed episodes Mood d/o due to another medical condition Substance/medication-induced depressive disorder ADHD Adjustment d/o with depressed mood Normal sadness

15. Bereavement MDE Primary feelingsEmptiness/ lossDepressed mood, loss of pleasure TimingWaves of grief, ↓intensity Persistent low mood ThoughtsPreoccupation with deceased Self-critical, pessimistic Self-esteemPreservedWorthlessness/self-loathing Suicide“joining deceased”Worthless, hopeless, pain

16. Depressive Symptoms d/t… Medical Conditions MS Stroke Hypothyroidism Anemia Medications Anticonvulsants Beta blockers CCB Estrogen Opioids

17. MDD Treatment Lifestyle nutrition, exercise, socialize, Omega 3s Meds SSRIs SNRIs NDRI Mirtazapine Tricyclics, MAOIs Psychotherapy Cognitive-Behavioral Therapy, Interpersonal Therapy, Family ECT

18. Antidepressants: SSRIs SSRI – Selective Serotonin Reuptake inhibitor Fluoxetine (Prozac): 10 to 60 mg Fluvoxamine (Luvox): 50 to 300 mg Sertraline (Zoloft): 25 to 250 mg Paroxetine (Paxil): 10 to 60 mg Citalopram (Celexa): 10 to 60 mg Escitalopram (Cipralex): 10 to 20 mg First line: any, escitalopram- some evidence for superiority, or “select one based on patient’s presentation & med SE profile”

19. Common SEs of SSRIs Headaches or dizziness Weight/appetite fluctuations Nausea, loss of appetite, diarrhea. Anxiety or irritability. Problems sleeping or drowsiness. Loss of sexual desire or ability.

20. Serotonin Syndrome Results from excess serotonergic activity centrally (5HT1a, 5HT2) Onset within 24 hours of initiating a serotonergic agent Signs and Symptoms Cognitive: agitation, delirium, hallucinations, coma Autonomic: shivering, diaphoresis, hyperthermia, hypertension, tachycardia, diarrhea Neurologic: myoclonus, hyperreflexia, tremor Untreated or unrecognized may lead to rhabdomyolysis, renal failure, seizures

21. Serotonin Syndrome Symptoms are self-limited with removal of offending agent(s) Supportive treatment targeting specific symptoms or medical consequences Cooling, hydration, antihypertensives, anticonvulsants, Benzodiazepines to manage agitation Serotonin receptor antagonists (cyproheptadine)

22. Other Antidepressants SNRI: Serotonin Norepinephrine Reuptake Inhibitor Venlafaxine (Effexor): 37.5mg to 450mg Desvenlafaxine (Pristiq): 50-400mg Duloxetine: (Cymbalta): 60 mg NDRI: Bupropion (Wellbutrin) Bupropion SR 100 mg to 450 mg Bupropion XL 150 mg to 400 mg NaSSA: Mirtazapine (Remeron) 15mg to 60 mg Serotonin-2 antagonist/reuptake inhibitor: Trazadone: 50 to 400 mg

23. Common adverse effects of antidepressants

24. Old Antidepressants MAOIs Not first line SE Hypertensive Crisis; if combined with foods containing tyramine (unpasteurized cheese, herring, unpasteurized meats, some beers and wines) Phenelzine (Nardil): 15 mg BID to TID Tranylcypromine (Parnate): 10 mg BID to TID Meclobemide (Mannerix) – reversible MAOI TCAs Not first line SE include: dizziness, sedation, blurred vision, urinary retention, constipation, dry mouth Risk of cardiac arrhythmias if OD Nortriptyline, Amitriptyline Desipramine, Imipramine

25. Starting Medications Start low, go mod-slow , aim for lowest efficacious dose, hold & assess, go up if still symptomatic, don’t go beyond usual highest dose Escitalopram: start at 5mg x 1-2 weeks, then increase to 10mg. Sertraline: start with 25mg and increase by 25mg every week until 150-200mg Venlafaxine: start 37.5mg and increase by 37.5mg per week till 150mg

27. Psychotherapy Details with Anxiety lecture! *Cognitive Behaviour Therapy Family Therapy Supportive Therapy *Interpersonal therapy Dialectic Behavior Therapy Psychodynamic Therapy

28. ECT Gold Standard treatment for depression Most efficacious with least side effects Main side effects: memory loss 1 st line for acute catatonia/psychosis/ suicidality/patient’s preference Also used for refractory cases May take up to 15 sessions before effect seen

29. BIPOLAR :):

30. Bipolar Disorder Criteria Abnormally elevated, expansive or irritable mood and Persistently increased goal-directed activity or energy Plus 3 (4 if mood = irritable) of possible associated symptoms

31. GST PAID by Bipolar Buyer

32. GST PAID Bipolar Disorder Grandiosity (inflated self esteem) Sleep (less) Talkative (Pressured speech or talking more) Pleasurable activities with painful consequences spending, sex, speed, substances, foolish investments, gambling Activity increased (Goal-directed or psychomotor agitation) Ideas, Flight of (or racing thoughts) Distractable

33. Bipolar Disorder Manic >7 days marked impairment in social/occupational functioning OR hospitalization Possible psychotic features Hypomanic >4 days Not severe enough to cause marked impairment/psychosis. No hospitalization needed No psychotic features

34. Bipolar Disorders Bipolar Type I At least one manic episode Bipolar Type II At least one Major Depressive Episode and one Hypomanic Episode

36. Q: What is a Mixed Episode? No longer a Dx Now a mixed features specifier for MDD or Bioplar MDD > 3 manic/hypomanic symptoms that don’t overlap with symptoms of major depression Hypomania/Mania the presence of at least three symptoms of depression in concert with the episode of mania/hypomania

37. Bipolar disorder stats Bipolar I disorder: 12mo prev 0.6%, mean age 18 Bipolar II disorder: 0.8%, early 20s Male: female ratio 1.1:1 (BPI) Females: more rapid cycling, mixed episodes, depressive symptoms 12% of originally diagnosed MDE  bipolar 5-15% of bipolar II  bipolar I

38. Bipolar MSE Appearance Flamboyant, better hygiene than normal Psychomotor activity: exaggerated hand gestures, getting up from chair frequently Intense eye contact Mood & Affect “anxious”, “happy”, “angry” Elevated, ecstatic, euphoric, irritable, worried Quick liability between extremes

39. Bipolar MSE Speech & Thought Form Pressured speech Flight of ideas Distractibility Tangential Thought Content Grandiosity Paranoia Religious preoccupation

40. Bipolar Video https://www.youtube.com/watch?v=zA-fqvC02oM

41. Bipolar Disorder Differential Bipolar I MDD Anxiety d/o Substance/Medication- induced ADHD Personality d/o Disorders with prominent irritability Biopolar II Bipolar II MDD Cyclothymic disorder Scz spectrum & oter related d/o Anxiety d/o Substance-use d/o ADHD Personality d/o Bipolar I

42. Bipolar Disorder Treatment Lifestyle eat well, exercise, socialize, SLEEP!!! Meds Mood Stabilizers Antipsychotics Lamotrigine – for depression only + SSRIs (usually with a mood stabilizer or anti-psychotic) Psychotherapy Case Management, Mental Health Teams ECT

43. Mood Stabilizers  Lithium, Valproic Acid, Carbamazepine  Drugs of choice for bipolar disorder, schizoaffective disorder and cyclothymia  Acute mania and prophylaxis of mania and depression in bipolar disorders  Less effective for bipolar disorder depression  Sometimes used for impulse control disorders, aggressive behaviour and mood management in personality d/o

44. Lithium Used in Bipolar mania, but also popular as an antidepressant augmenter (especially resistant) Forms: regular, slow release, liquid 300-1200mg total daily dose (OD or BID dosing) Start with 300mg OD/BID Dose increased over 7 to 10 days until plasma level 0.8 to 1.2 mEq/L (0.8 to 1.2 mMol/L) for acute mania Lower in elderly (0.4 –1.0) 0.6 to 0.8 mEq/L for maintenance Usual dose range: 900 mg/day to 2100 mg/day Make sure to measure levels 12 hrs after the preceding dose

45. Lithium Baseline Labs: BUN, Creat, lytes, FBG, TSH, fT4, ECG>40yrs or cardiac disease Effects: 2 weeks, need 4-8 weeks for trial (7-14 days for acute mania) Levels: drawn on day 5, usually weekly for first 1-2 month, then q2-4wks. Watch TSH and Creat q6months For side effects relief always think sustained release or spreading the dose around For tremor consider beta blocker

46. Predictors of Lithium Response Previous or family history of response Few previous manic episodes “Classic mania” (not mixed) Lack of rapid cycling Less effective than Valproic Acid in rapid cycling

47. Lithium: SEs Acute SE GI (nausea, diarrhea) Neuro (drowsiness, cognitive dulling, fine hand tremor) Metabolic (wt gain) Derm (rash, worsening of psoriasis, acne) GU (polydipsia/polyuria, DI) Hematologic (mild leukocytosis common) Long-term SE Hypothyroidism (20%) GU: impaired concentration of urine, DI, renal parenchymal changes, rare kidney failure

48. Lithium: Toxicity/Overdose Symptoms: Mental status changes Nausea/Vomiting Incontinence Course hand tremor Dysarthria Gait ataxia Cardiac: depressed ST segments, T wave inversions, arrhythmias CAN BE FATAL Causes: Dehydration, NSAIDs, ACEi, diuretics can increase Li levels Management: Stop lithium Supportive medical care Draw lithium levels Dialysis if serum level > 4 or if clinically indicated

49. Valproic Acid Effective for bipolar disorder, schizoaffective disorder, cyclothymia More effective than lithium for rapid cycling and mixed state episode bipolar disorder Can also be used for impulse control disorders, aggression and Cluster B personality disorders  May take up to 14 days to see antimanic effect  Trial of 4 to 6 weeks should be completed

50. Valproic Acid - Dosing  Starting dose: 20 mcg/kg for rapid stabilization of mania Approx: 500 mg TID or 750 mg BID  Titrate up to serum level of 50 to 125mg/mL (350 – 700) = Avg maintenance dose: 1500 to 3000mg/day Available in once daily or divided doses  Elderly require approximately half that of younger adults

51. Valproic Acid Labs Baseline: CBC, LFTs Serum levels, CBC, platelet count, and PT/PTT should be done weekly during first month Serum levels, CBC, LFTs Q3-6months SEs Favourable SE profile and lower toxicity compared to Lithium Nausea, diarrhea, headache, sedation, fine tremor, weight gain, alopecia, leukopenia, neutropenia, thrombocytopenia, elevated LFT’s – in rare cases liver failure and/or pancreatitis

52. Lamotrigine  Anticonvulsant  Indicated for bipolar depression  More effective in the treatment of bipolar depression compared to other mood stabilizers  Also used in treatment resistant unipolar depression  Used as monotherapy or adjuncive tx to other mood stabilizers and/or antidepressants

53. Lamotrigine – Dosing Initial dose: 25 mg OD, increased weekly by 25 mg/week until you reach 200 mg/day Up to 400 mg may be required to treat depression Once or twice daily dosing usually qhs Therapeutic effect may be seen in 2 to 4 weeks

54. Lamotrigine Labs Baseline: renal and hepatic fx (both involved in excretion) Serum levels not useful as therapeutic window not yet determined SEs Very well tolerated by most patients HA, somnolence, nausea, diarrhea, dizziness, ataxia, diplopia, blurred vision RASH (10%): limbs Steven – Johnson (0.3%): chest, neck, face, oral mucosa If rash of any sort advise pt to DC and see MD immediately

55. Carbamazepine Anticonvulsant Used in pts who do not respond to lithium Starting dose: 200 mg BID Maintenance dose: 800 to 1600 mg/day Divided BID or TID to minimize SE Serum level 25 to 60 mM

56. Carbamazepine – SEs Agranulocytosis and aplastic anemia (1 in 20 000) Induction of liver enzymes: effects most psych meds, decreased effectiveness of OCP, auto–induction (half life and serum level decrease with time) SJS reported (rare)

57. Second Generation Antipsychotics:  Evidence for efficacy as monotherapy and add-on mood stabilizers for: Risperidone, Olanzapine, Quetiapine Same doses as treating psychotic d/o Risperidone 4-8mg/d Olanzapine 15-35mg/d Quetiapine 600-900mg/d More info about antipsychotics with Psychosis lecture

58. Other Treatments Psychotherapy Re: medication compliance ECT For prolonged or severe mania Bipolar depression

59. Persistent Depressive Disorder (Dysthymia) Depressed Mood most of the day, for more days than not, for > 2 yrs Children: mood can be irritable & > 1 year Not without symptoms for > 2 months at a time > 2 of 6 following (CHASES): Concentration, poor or difficulty making decisions Hopelessness Appetite, poor or increased Sleep, decreased or increased Energy low Self-esteem low

60. The Dysthymia Dog CHASES its Tail

61. Cyclothymia Numerous periods of Hypomanic symptoms and Numerous periods of depressive symptoms for 2 years. No full manic, hypomanic or major depressive episode Not symptom-free for > 2 months

62. Adjustment Disorder Emotional or behavioural symptoms in response to an identifiable stressor Occurs within 3 months of onset of stressor Marked and excessive distress Sig impairment in important areas of functioning Symptoms don’t persist > 6 months after stressor or its consequences have ended

63. Adjustment Disorder Specifiers With depressed mood With anxiety With mixed anxiety and depressed mood With disturbance of conduct* With mixed disturbance of emotions and conduct Unspecified *abnormal conduct violating the rights of others or going against societal norms. Ie. truancy, vandalism, reckless driving, fighting, or defaulting on legal responsibilities.

64. Summary Depression: Bereavement exclusion gone, but use clin judgement MAOi/TCAs rarely used Anti-depressants equally efficacious  S/E profile Watch for serotonin syndrome Bipolar disorder: New criteria: mood PLUS energy/ goal-directed activity Watch for lithium toxicity

65. Thank-you! QUESTIONS? :):

66. Hypertensive Crisis: “the cheese reaction” Tyramine causes a potent release of NE In the absence of an MAO-I, tyramine is broken down by MAO-A in the gut, liver and any NE released is broken down in the synaptic cleft Normally a person can ingest 400mg of tyramine with no increase in BP (a high tyramine meal only has 40mg) Drug-drug interactions can also lead to hypertensive crises (decongestants, stimulants, SNRIs)

67. TCA Overdose Most symptoms related to anticholinergic load: delirium, tachycardia, dilated pupils, ileus Seizures and coma (mechanism poorly understood) Cardiotoxicity mediated via the Na channel blockade Arrhythmias ECG changes: QT prolongation, widening of the QRS, AV blockade, V tach Severe hypotension (a-adrenergic blockade)

68. TCA Overdose Management Hospitalization, cardiac monitoring (continue for 24 hours after signs of toxicity have resolved) Charcoal IV fluid resuscitation Bicarb infusion to treat acidosis Psychiatric consult