A Review of Affective (Mood) Disorders

1. A Review of Affective (Mood) Disorders Ashley Owen, Ph.D. Department of Family and Preventive Medicine

2. Major Depressive Episode - Assessment A. Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning. 1. Depressed mood most of the day* 2. Markedly diminished interest or pleasure in activities most of the day, nearly every day.* 3. Significant weight loss when not dieting or weight gain or decrease or increase in appetite nearly every day.

3. Major Depressive Episode - Assessment (cont’d) 4. Insomnia or hypersomnia nearly every day. 5. Psychomotor agitation or retardation. 6. Fatigue or loss of energy nearly every day. 7. Feelings of worthlessness or excessive guilt. 8. Diminished ability to think or concentrate. 9. Recurrent thoughts of death.

4. SIGECAPS Assessment (Neurovegetative Sx) • S- Is your sleepdisturbed? • I- Have you noted a loss of libido or interest in your usual activities? • G-Are you feeling guilty or having self-deprecatory thoughts? • E-Have you noticed a decrease in your energy level? • C-Have you been having trouble concentrating? • A-Have you experienced changes in your appetite or weight? • P-Have you been physically slowed down or sped up? (psychomotor abnormalities) • S- Have you had thoughts of hurting yourself, feelings of hopelessness, preoccupation with issues related to death, or suicide?

5. Depression Screening - Assessment • Ask: • 1.During the past month, have you been often bothered by little interest or pleasure in doing things? • 2.During the past month, have you been feeling down, depressed, or hopeless? • If yes to either: further assessment SIGECAPS or administer a measure

6. Depression Screening - Assessment Measures • Beck Depression Inventory (BDI) • Edinburgh Postnatal Depression Scale (EPDS) • Geriatric Depression Scale (GDS) • Pediatric Symptom Checklist (PSC) ALWAYS PERSONALLY REVIEW THE SUICIDE ITEM AND DISCUSS WITH YOUR PATIENT!

7. Major Depressive Disorder A. Presence of a Major Depressive episode (single episode – recurrent) B. Not better accounted for by Schizoaffective Disorder C. Never been a Manic Episode Some patients become preoccupied with somatic complaints such as bowel or bowel dysfunction.

8. Specifier Highlights:With Psychotic Features • Important to assess! • Additional features of hallucinations (auditory or visual), delusions, bizarre bx, or disorganized thinking.

9. Specifier Highlights:With Postpartum onset • Onset within 4 weeks of postpartum – though studies suggest an extension of process that begins during pregnancy – affects 12-15% of women with good support/excited about being pregnant - Affects 20-25% of women who are single/young/family disocord/no support • Baby blues (70%) vs Postpartum Depression (10%-15%) - decreased participation in prenatal care and care following delivery (delayed social development) - fetal exposure to stress hormones - negative maternal outcomes - increased risk of divorce (2-3)

10. Specifier Highlights:With Atypical Features 1. Mood reactivity (mood brightens in response to actual or potential positive events) 2. Two or more of the following criteria: • Significant weight gain or increase in appetite • Hypersomnia • Leaden paralysis (heavy, laden feelings in arms or legs) • Long-standing pattern of interpersonal rejection sensitivity that results in significant social or occupational impairment

11. Specifier Highlights:With Seasonal Pattern • Hx of temporal relationship between season and onset of major depressive episode • Typically notice onset in fall or winter with progressing resolution of sxs in spring or summer • Depressive sxs generally atypical – hypersomnia, hyperphagia, and weight gain

12. Major Depressive Disorder -course and prevalence stressor  mediators  reduced depression (ex. social support, sense of control) Life stressors  Normal depressogenic reaction Multiple major life stressors  Multiple depressogenic reactions - cognitions “this is my life” – extended periods of neurons being damaged by stress/depression  depressions cycle on their own rhythm in absence of stressors  increased risk of depression for the rest of the patient’s life without intervention

13. Major Depressive Disorder -course and prevalence (contd.) Evidence of biological effects of depression… Glucocorticoids (highly elevated) – damage nervous system - hippocampuses atrophy (poor synaptic activity; disrupting neuronal connections; neuronal atrophy) - exercise/psychotropics/psychotherapy (or both) may impede this process and even initiate neurogenesis Similar in anxiety – amygdala (arousal, fear conditioning) networks strengthened – more connections, more resilient pathways Depression is a biological disorder that is very sensitive to the environment

14. Major Depressive Disorder -course and prevalence (contd.) • • Lifetime prevalence in women 1 in 4 (highest in >44) • men 1 in 8 • •Age of onset often in mid-20s (possibly earlier and undetected) • •2/3 complete remission of sxs, 1/3 partial remission and increased likelihood of future episodes • Single episode – 50% have a future episode • 70% of those who have 2 episodes have a third • 90% of those with 3 episodes have a fourth • •Possible increased fx of episodes with age - relapse prevention.

15. Dysthymic Disorder • Depressed mood for most of the day, for at least two years. • Presence, while depressed, of two or more of the following: • Poor appetite or overeating • Insomnia or hypersomnia • Low energy or fatigue • Low self-esteem • Poor concentration or difficulty making decisions • Feelings of hopelessness

16. Dysthymic Disorder (contd.) • Sxs are less severe than those of MDD and neurovegetative sxs are fewer. • Common clinical feature – generalized anhedonia or anergia • Also, social withdrawal, feelings of guilt or inadequacy, poor work or academic performance • Can be frustrating to treat because of chronic dysphoria, self-pity, and seemingly irrational patterns of negative thinking “things always go wrong for me” – negative filter

17. Adjustment Disorder • Develops within 3 months of a significant life stressor • Symptoms are clinically significant as evidenced by either – marked distress in excess of what would be expected given the nature of the stressor Or • Significant impairment in social or occupational functioning

18. Adjustment Disorder (contd.) • Symptoms don’t represent Bereavement. • Presentation typically depressed mood, anxiety, helplessness, and worthlessness. Thoughts often predominated by activities that precipitated the event. • If criteria are met for MDD, this diagnosis supersedes Adjustment Disorder • Or when condition represents an exacerbation of a preexisting psych disorder • Remember to evaluate criteria regardless of event because evaluating need for intervention could be essential to patient in need of treatment.

19. Manic Episode • A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week.

20. Manic Episode, cont’d. • During the period of mood disturbance, at least three of the following symptoms have persisted (four if only irritable): • Inflated self-esteem or grandiosity • Decreased need for sleep • Flight of ideas or subjective experience that thoughts are racing • More talkative than usual • Distractibility • Increase in goal directed activity • Excessive involvement in pleasurable activities

21. Bipolar Disorder, Type 1 • Essential feature is occurrence of one or more Manic Episodes or Mixed Episodes (both Depressive and Manic episodes within 1-week period). • Often individuals have also had one or more Major Depressive Episodes • Episodes of Substance-Induced Mood Disorder or of Mood Disorder Due to a General Medical Condition do not count toward a diagnosis of Bipolar I Disorder.

22. Bipolar Disorder-Type II • Essential feature - occurrence of one or more Major Depressive Episodes and at least one Hypomanic Episode* (not euthymia that follows remission of a Depressive Episode). • Episodes of Substance-Induced Mood Disorder or of Mood Disorder Due to a General Medical Condition do not count toward this diagnosis *(sxs consistent with manic sxs, but only have to last 4 days)

23. Cyclothymic Disorder • The presence of numerous periods with hypomanic symptoms • Numerous periods with depressive symptoms that do not meet criteria for a major depressive episode lasting for at least 2 years. • No major depressive episode, manic episode, or mixed episode.

24. Differential Diagnosis • Lyme disease • Fibromyalgia • Chronic Fatigue Syndrome • Rheumatoid disease • Endocrinopathies • Intimate Partner Violence • Other Psychiatric Disorders

25. Suicidality • About 15% of depressed patients take their life • Assess for • Thoughts (ideas, wishes, motives) • Intent (degree to which pt intends to act on those thoughts) - 1013 • Plans (for self-harm) • Assess and document suicidality in all patients who report depressed mood, hopelessness, helplessness, or suffering – asking does not put ideas into their heads “Do you ever feel so badly that you would prefer not to go on living?”

26. Psychotherapy Treatment • Psychodynamic approach • Cognitive-Behavioral approach • Interpersonal approach • Psychoanalytic therapy • Family therapy

27. Drug Classes • Selective Serotonin Reuptake Inhibitors (SSRIs) • Atypical Antidepressants • Tricyclic antidepressants (TCAs) • Others (MAOIs-monoamine oxidase inhibitors, ECT, Bright Light)

28. General Information • Antidepressants show similar efficacy. • Seventy percent of patients will respond after 4-6 weeks of therapy. • Approximately 7000 deaths per year from Tricyclic Antidepressant overdose.

29. SSRIs: Class Side Effects • Nausea, diarrhea • decreased libido (especially in women) • Decreased appetite (especially Prozac) • Headache • Delayed orgasm

30. SSRIs: Class Side Effects • If activation/ Insomnia (15%) ----> take in morning. • If sedation(15%) ----> take at bedtime. • Reduce GI side effects by taking medication with meals. • Don’t use SSRIs in combination with MAOIs. Must wean SSRI before starting MAOI. • Lowest potential for toxicity from an overdose

31. SSRIs: Prozac/fluoxetine • Long half-life • Reduced risk ofSSRI Discontinuation Syndrome • Dose range is 10 - 80 mg/day

32. SSRIs: Prozac/fluoxetine • Prozac has several interesting features: • Tends to be activating (stimulation/restlessness). Consider another antidepressant for angry, irritable, depressed patients. • Weight loss a more dominant side effect than weight gain. • Secondary to its effect on delayed ejaculation, it may be useful in treating premature ejaculation.

33. SSRIs: Zoloft/sertraline • Shown efficacy for • Depression • Obsessive compulsive disorder (OCD) • Panic Disorder • Posttraumatic stress disorder (PTSD) • Dose range is 50-200 mg/day – start at 25mg first week • Stimulating/GI and sexual side effects

34. SSRIs: Paxil/paroxetine • Possibly more sedating than activating, but fairly neutral. • Efficacy shown in studies for - major depressive disorder (MDD) - obsessive compulsive disorder (OCD) - panic disorder (PD) • Decreases seizure threshold • Dose range is 10-50 mg/day

35. SSRIs: Celexa/citalopram • Side effect profile similar to other SSRIs – though stimulation/restlessness may be less than other SSRIs • Dose range is 20-80 mg/day • LEXAPRO - derived by isolating the Celexa (citalopram HBr) molecule – improved efficacy and side effects • Dose range is 10-20 mg/day

36. SSRIs: Serotonin Syndrome • A syndrome involving: - Mental status changes - High fever - Muscular rigidity - If not treated, potential coma and death - Occurs in setting of multiple drugs which block serotonin metabolism

37. SSRIs: SSRI Discontinuation Syndrome • Flu-like (fatigue, myalgia, loose stools, and nausea) • Lightheadedness/dizziness • Uneasiness/restlessness • Sleep and sensory disturbance • Headache

38. Atypical Antidepressants • Desyrel/trazodone • Major side effect of note are sedation (most sedating of antidepressants), GI, and priapism • Starting dose is 50mg bid – max dose 400mg • Most commonly used as a sedative in patients who may be depressed.

39. Atypical Antidepressants • Serzone/nefazodone - similar to trazodone • However, priapism not a side effect. Consider choosing this in men over trazodone. • Potential hepatic consequences – requires hepatic monitoring • Should not be taken with antihistamines • Does not have sexual dysfunction as a common side effect, as do the SSRIs. • Major side effect is somnolence, though not as sedating as trazodone. • Starting dose – 100mg bid. May give up to 300-600 mg divided bid.

40. Atypical Antidepressants • Effexor/venlafaxine and Effexor XR • Shown efficacy in • depression, • generalized anxiety disorder (GAD) • social anxiety disorder • GI and sexual side effects – less sedation than many atypicals • Starting dosage is 37.5mg bid – maximum total daily dose is 375mg.

41. Atypical Antidepressants • Mirtazapine/Remeron • Dose range is 15-30mg qHS (bedtime) – max dose 45mg, secondary to sedation. • Side Effects • Somnolence in 50% of patients. • No increase in sexual dysfunction. • Agranulocytosis (low white cell count) in 1:1000 (actually same statistic as other antidepressants, but noted on most side effect profiles). • Increased appetite and weight gain can use in depressed patients who are malnourished

42. Atypical Antidepressants Wellbutrin/bupropion-Zyban (smoking cessation) • Is an activating antidepressant - makes people energetic vs sleepy. • Can also cause insomnia ----> take in the morning • Contraindicated in patients with seizure disorder or eating disorder • Starting dose 100mg - don’t give greater than 200mg in one dose or greater than 450mg per day • Zyban – 150mg 1st 3 days; then 150am and 150pm-8hrs apart • Some GI side effects • Inducing mania in bipolar less common than other antidepressants • Not associated with weight gain or disturbance in sexual fx

43. Atypical Antidepressants Cymbalta/duloxetine 20-30 mg BID – depression Diabetic peripheral neuropathic pain and depression-related pain sxs in elderly– 60 mg once/day Side Effects -associated with slight increases in blood pressure -not indicated for patients with… renal impairment hepatic insufficiency/substantial alcohol use

44. Elavil/amitriptyline Tofranil/imipramine Sinequan/doxepin Pamelor/nortriptyline Norpramin/desipramine Tricyclic Antidepressants

45. TCAs - Complex Side Effect and Drug Interaction Potential • Anticholinergic - dry mouth, blurred vision, constipation, urinary retention, increased pulse – monitor use of other anticholinergic treatments. • Cardiotoxicity - (contraindicated in pts w/hx of coronary event and recommended to obtain EKG prior to initiation) • Greatest risk of inducing mania in bipolar • Only class of antidepressants in which you can draw blood levels to document use • If prescribing in suicidal patient, no more than a 1-week supply should be dispensed at a time.

46. MAOIs Nardil/phenelzine, Parnate/tranylcypromine • Major side effect is hypertensive crisis • Must be on a tyramine free diet (fermented cheese, yogurt, caffeine, chocolate, beer, and red wine) • At least two week washout before changing from SSRI to an MAOI or MAOI to SSRI • Drug and dietary interactions complex – rarely needed in primary care

47. Others • Electroconvulsive therapy • Severe depression/ schizophrenia/bipolar (induce seizures) • Retrograde amnesia • Can improve neuronal activity and initiate neurogenesis • 50-80% of patients relapse within 6 -9 months (lithium and nortriptyline combo significantly reduces risk) • Bright Light used in seasonal affective disorder – Alaska, Canada, in the winter

48. When do you refer a patient to a psychiatrist? • Severe/recurrent depression • Suicidal patient • Depression with psychotic features (delusions, hallucinations, loss of contact with reality) • Bipolar disorder (Manic depression) • Monitor with frequent visits until consistently under referring doctor’s care

49. Special Cases • Pregnancy/Lactation • Consider SSRIs or buproprion (category B) • Weigh exposure risk –tx vs consequences of depression • Elderly Consider SSRIs - beneficial side effect profile. E.g., no orthostatic hypotension, no urinary retention in men. Start at low doses.

50. . • Discuss side effects and determine what’s acceptable to patient. • Typically, no recipe determined a priori to be best for a patient – an interactive process. • The secret of patient care is caring for the patient, making sure, once that initial treatment is chosen, that it is an interactive tailored process over time. • Patient will not respond if he or she stops the medication prematurely – communication is key.