Depression Its a Family Affair Angela M Hill

Depression, It’s a “Family Affair” Angela M. Hill, Pharm. D. , BCPP Professor and Chair of Pharmacy Practice University of South Florida 2011 Diamondback Alumni Council Convention

Learning Objectives • Describe the prevalence of depressive disorders. • Discuss the presentation of depressive symptoms across the lifespan. • Describe treatment considerations based on the age of patients with depression. • Describe the clinical workup for depressive disorders. • Discuss treatment considerations for treatmentresistant patients with depressive disorders.

Major Depression q Affects 14. 8 million adults q Lifetime prevalence rate of 17% q Affects 1 of 4 females (10 -24%) q Affects 1 of 8 males (5 -12%) q Most common between ages 25 -44 National Institute of Mental Health. The Numbers Count: Mental Disorders in America. NIH. Reviewed February 2011. [Accessed February 26 th, 2011]. http: //www. nimh. nih. gov/health/publications/thenumbers-count-mental-disorders-in-america/index. shtml

Depression • Mental illness characterized by sadness, general apathy, a loss of self-esteem, feelings of guilt, and, at times, suicidal tendencies. • Without treatment, symptoms can persists for weeks, months, or years • The biological cause of depression is often a deficiency in neurotransmitters, particularly serotonin, norepinephrine, and dopamine. • Antidepressant medications treat depression by restoring the normal levels of these neurotransmitters.

Who does it affect? Epidemiology: • Women • Men • Elderly • Children • Adolescents Causes: • Genetic • Pregnancy (hormonal changes) • Weather • Medical illness • An Emotional Loss of Something/Someone • Changes in stress levels • Drugs

How is Depression Diagnosed? • Subjectively • Use of Guidelines • Assessment scales

Types of Depression • Major • Atypical • Bipolar • Melancholic • Post Partum • Psychotic • Dysthymia • Premenstrual Dysphoric Disorder • Grief • Seasonal Affective

What Happens if Depression is left Untreated? • • • Anxiety Unemployment Self-abuse Suicide Substance Abuse ▫ nicotine, alcohol, and/or illicit drugs

Treatment Considerations

Pharmacological Therapy • Monoamine Oxidase Inhibitors (MAOIs) ▫ Risk of hypertensive crisis • Tricyclic Antidepressants (TCAs) ▫ Causes sedation and cardiovascular changes, and exacerbates BPH, glaucoma. • Selective Serotonin Reuptake Inhibitors (SSRIs) ▫ May cause drug interactions, bruising/bleeding, and sodium imbalance (SIADH)

Other Antidepressants • Effexor ▫ Like TCAs but lacks muscarinic, alpha adrenergic, and histaminic activity. May elevate cholesterol and blood pressure (at higher doses) • Cymbalta ▫ Similar to Effexor but, does not increase blood pressure as much as Effexor. • Pristiq ▫ Metabolite of Effexor but, does not increase blood pressure as much as Effexor. • Remeron ▫ Helpful with insomnia and increases appetite. (Dose specific) • Trazodone ▫ Helpful with insomnia. Hypotension and priaprism may occur. • Serzone ▫ Monitor liver function. Only the generic is available. • Wellbutrin ▫ Least sexual dysfunction. Lowers seizure threshhold. • Amoxapine ▫ Proconvulsant; chemically similar to clozapine and loxapine • Ludiomil ▫ Proconvulsant

Selegiline (Emsam®) • Applied daily to upper chest, between neck and waist, upper thigh, or outer area of upper arm • May continue normal diet with use of 6 mg/day patch; must moderate dietary tyramine at higher doses • Do not cut the patches • Rotate sites of adminsitration

Things to Remember about Using Antidepressants • The onset of action may vary between 2 and 6 weeks • Selection of therapy should be based on individual symptoms • Antidepressants can cause drug interactions • Patients should be treated until symptoms are resolved • Augmentation may be necessary. • There is a need to respect the boxed warnings.

Augmentation Strategies 1. Counseling 2. Maximize tolerable dose of one antidepressant 3. Add antidepressant with different pharmacology 4. Thyroid Supplementation 5. Antipsychotics 6. ECT 7. Mood Stabilizer 8. Stimulants 9. Vagus Nerve Stimulation

Use of Atypical Antipsychotics in Depression Risperidone (Risperdal®) • 3 studies • Duration of trials: 4 -8 weeks • Augmentation to various antidepressants Olanzapine (Zyprexa® ) • 5 studies • Duration of trials: 8 -12 weeks • Augmentation to fluoxetine

Use of Atypical Antipsychotics in Depression Aripripazole (Abilify® ) Quetiapine (Seroquel ® ) • 3 studies • Duration of studies: 6 weeks • Augmentation to SSRIs/SNRIs • Onset of action: 1 -2 weeks • 6 studies • Duration of studies: 4 -8 weeks • Augmentation to SSRIs, SNRIs, bupropion, TCAs, • Onset of Action: 1 -2 weeks

Non-Pharmacological Treatments • • Psychotherapy and Behavioral Therapy ECT Light therapy Acupuncture Alternative Medicines Transcranial Magnetic Stimulation Vagus Nerve Stimulation

Psychotherapy Behavioral Therapy • Talk sessions with therapist • Used to alter a person’s selfdefeating thoughts • Helps people to operate in a more positive approach to life and to increase communication skills with friends, family, and co-workers

Light therapy • One theory as to how this therapy works is that the suprachiasmatic nucleus responds to visual light by signaling the suppression of melatonin

Acupuncture • The Chinese practice of inserting needles into the body at specific points manipulates the body's flow of energy to balance the endocrine system. • This manipulation regulates functions such as heart rate, body temperature, and respiration, as well as sleep patterns and emotional changes.

Vagus Nerve Stimulation • Used adjunctively in treatment-resistant patients • May cause hoarseness, cough, shortness of breath • Requires surgery • Expensive • May interfere with mammograms • May be damaged by defibrillators and ultrasounds

Transcranial Magnetic Stimulation • May be used as monotherapy for treatment resistant patients • Device delivers MRI-strength magnetic pulses to the brain • Administered daily for 4 -6 weeks in 40 minute sessions • Done on an outpatient basis • Side effects may include headache or scalp pain at the site of application

Alternative Medicines • St. John’s wort (Hypericum perfortum) ▫ Blocks secretion of cortisol, increases serotonin, mild MAO-inhibition ▫ 300 mg three times daily ▫ P 450 inducer • SAMe (S-adenosylmethionine) ▫ A substance found naturally in the body that is believed to fuel dozens of biochemical reactions ▫ 400 -1600 mg/day ▫ Has been reported to block platelet aggregation. • 5 -HTP (5 -Hydroxytryptophan) ▫ 50 -100 mg 1 -3 times daily ▫ Immediate precursor for serotonin ▫ Comparable to TCAs and fluvoxamine

Alternative Medicines • Evening primrose oil ▫ ▫ Contain unsaturated fatty acids Provide precursor for prostaglandin synthesis Benefits breast tenderness 500 mg/day to 1000 mg three times/day • Chaste tree berry ▫ 30 to 40 mg/day ▫ Thought to have anti-androgenic effects as well as inhibit prolactin production ▫ Benefits breast tenderness *Recommended use: Days 17 -28 of menstrual cycle

Investigational Antidepressants • Vilazidone (Viibryd®) • Agomelatine (Valdoxan®, Melitor®, Thymanax®)

(Vilazodone) Viibryd® • Selective serotonin reuptake inhibitor • Partial 5 HT 1 A agonist • Side effects: diarrhea, nausea, vomiting, and insomnia, increased impulsivity, inhibition of penile erection, impairment of cognition, learning, and memory. • Scheduled for approval late summer 2011 • May interact with triptans, NSAIDs, aspirin, warfarin, tramadol, & other antidepressants

Agomelatine (Valdoxan®, Melitor®, Thymanax®) • Agonizes M 1 & M 2 receptors and antagonizes the 5 HT 2 c receptor • No discontinuation effects noted in studies. • Side effects include less GI distress, sexual, and metabolic side effects compared to the SSRIs and SNRIs • Should have a positive impact on sleep • May reset circadian rhythms

Precautions and Warnings for the Antidepressants

Boxed Warning • Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Patients of all ages started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.

Boxed Warning • Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1. 6 to 1. 7 times) of death, compared to placebo (4. 5% vs 2. 6%, respectively).

Hyperglycemia and Diabetes Mellitus • Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. • Patients starting treatment with atypical antipsychotics who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.

Duration of Therapy • First Episode: 6 -9 months (50% chance of recurrence) • Second Episode: 12 months (80 -90% chance of recurrence) • Third Episode: Life

The neurotransmitter pathway Dysregulation of Serotonin (5 HT) and Norepinephrine (NE) in the brain are strongly associated with depression Dysregulation of 5 HT and NE in the spinal cord may explain an increased pain perception among depressed patients 1 -3 Imbalances of 5 HT and NE may explain the presence of both emotional and physical symptoms of depression. Descending Pathway Ascending Pathway

There at least two sides to the neurotransmitter story Functional domains of Serotonin and Norepinephrine 5 -HT Sex Appetite Aggression Anxiety Depressed Mood Aches and pain Irritability Thought process (NE) Concentration Interest Motivation • Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms

Depression, It’s a Family Affair

Major Depression • Major depression is also called clinical depression and unipolar depression • Ages: 25 -44 (but can occur at any age) • Women are 2 -3 times more likely than men to experience major depression • Causes: -dysregulation in neurotransmitters (NE & 5 HT) -neuroendocrine dysregulation - genetic predisposition -stress

DSM-IV-TR Diagnosis of Major Depression • Five or more of the following symptoms have been present for the same 2 -week period and at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure: -depressed mood -diminished interest in activities -significant weight loss or gain (5% change in 1 month) -insomnia or hypersomnia -agitation -fatigue or loss of energy -feelings of worthlessness or guilt -diminished ability to think or concentrate -recurrent thoughts of death

Acronyms for Diagnosing Depression Sadness, ↓ Socialization Interest Guilt Energy Concentration Appetite Psychomotor function Sucidiality Sadness, ↓ Socialization Apathy Depressed mood Feelings of guilt Appetite Concentration Energy Suicidaltiy

Signs and Symptoms of Depression in the Pediatric Population 3 -5 year old Decreased interest in play, feelings of worthlessness, selfdestructive 6 -8 year old Somatic complaints, outbursts of crying, shouting 9 -12 year old Boredom, low self-esteem, guilt, wanting to run away 12 -18 year old Irritability, reckless behavior, poor school performance

Signs and Symptoms in the Geriatric Population • Depression in late life is typically difficult to recognize when compared with younger adults • Clinicians and patients inappropriately attribute depressive symptoms to the aging process and minimize their significance • Older patients present with psychomotor retardation (mental slowing, cynacism, amotivation) and are less likely to acknowledge depression • Instead, they tend to dwell on somatic concerns (e. g. poor sleep, low energy, changes in bowel function bodily aches and pains) • They are also less likely to share or admit to suicidal thoughts.

Neurotransmitters • Serotonin ▫ Regulates sleep, appetite, and mood. • Norepinephrine ▫ Regulates alertness and arousal. • Dopamine ▫ Regulates appetite, pleasure and movement.

Case CS is a 30 yo female who broke up with her boyfriend of 3 years a month ago. For the past 3 weeks her friends have noticed that she no longer wants to go out with them, something she used to enjoy greatly. She has had a hard time concentrating at work and has had difficulty sleeping at night. She also feels as though she has no energy during the day. She feels excessively guilty about the demise of her relationship. Her friends are very concerned. She has lost 15 pounds in the last 3 weeks also.

How can we treat this patient?

Case Study GH is a 48 year old female who remembers that her first bout of depression occurred in early adolescence. She states that her depression gets better for a period and then worsens again. She is able to enjoy the pleasures of life during the better times. She will enjoy speaking to people, going out with her husband, and eating. She states that she especially enjoys going to good restaurants, where she will frequently overeat. GH states that one of her worst traits is being late for appointments due to oversleeping. When her depression worsens, GH will experience fatigue, shows little or no initiative, and can be overly sensitive to rejection by others.

How can we treat this patient?

Atypical Depression • Mood is dependent on negative or positive external events. ▫ Sufferers feel deeply depressed or somewhat hopeful depending on the latest situation. • Often first appears in the teenage years

Atypical Depression • Symptoms (in addition to typical symptoms of depression, the patient should have 2 out of 4) ▫ Increased appetite with weight gain of 10 lbs or more when depressed ▫ Hypersomnia of 10 hours or more per day or 2 hours more sleep than the usual amount of sleep when not depressed ▫ Heavy, leaden feelings in arms and legs ▫ Longstanding pattern of interpersonal rejection sensitivity, not limited to episodes of depression, that results in significant social or occupational impairment • Treatment ▫ SSRIs ▫ MAOIs

Case Study • AD is a 37 yo AA female who has been acting differently for the past 5 months, according to her husband. He says, “she has happy days and sad days. ” She will be very sad some days, crying a lot. However, about a month ago she went on a two day shopping spree and maxed out all of her credit cards.

Depressive Symptoms: How a Patient May Present • Chief Complaint – “I’m feeling down in the dumps” • History of Present Illness ▫ Loss of interest in usual hobbies for several weeks ▫ Feels “blue” and worthless ▫ Self-medicating with alcohol • Past History ▫ Hypomanic episode History of signs and symptoms of mania with milder intensity and shorter duration Marital conflict due to impulsive behavior ▫ ▫ ▫ Maria S. 37 -year-old working mother Treated with antidepressant that induced a manic switch while in college Mother was treated for psychiatric illness Has had frequent career changes Nonadherence due to suboptimal outcome with previous medicines Lassitude (difficulty in getting started or slowness in initiating and performing everyday activities) • Mental Status Examination ▫ Sad and tearful ▫ Depressed but not actively suicidal

Bipolar Depression • Bipolar depression is also called manic depression • Bipolar is marked by extreme changes in mood, thought, energy and behavior. • The moods range between highs and lows • The changes in moods can last for hours, days, weeks or months • Equal amounts of men and women have bipolar disorder, but women typically start in the depressed phase • Mood episodes in bipolar disorder include: -Mania -Hypomania -Major Depressive Episodes -Mixed episodes • The major depressive episode is diagnosed using the same criteria for major depressive disorder

51 Prior to Starting Treatment, Patients With Depressive Symptoms Should Be Adequately Screened to Determine If They Are at Risk for Bipolar Disorder Depressive episode symptoms Major depressive disorder No history of manic, hypomanic, or mixed episode Depressed mood Loss of interest or pleasure Physical agitation Slowed speech or movements Change in sleep Change in appetite Significant weight change Concentration difficulties Indecisiveness Fatigue Loss of energy Feelings of worthlessness Feelings of guilt Suicidal thoughts or plans Suicide attempt Bipolar disorder Diagnostic criteria for Major Depressive Episodes are identical in Major Depressive Disorder and Bipolar Disorder Adapted from Diagnostic and Statistical Manual of Mental Disorders, 4 th ed, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000. History of at least one manic, hypomanic, or mixed episode

Differential Diagnosis: MDD or Bipolar Depression? It may take up to 10 years for bipolar disorder to be accurately diagnosed. Clues that your patient may have bipolar disorder: 1. Family History: • Higher rates of psychiatric illness • Positive for bipolar disorder 5. Associated Features: • Unevenness in intimate 2. Course of Illness: • Illness onset usually before • • • relationships Frequent career changes High prevalence of comorbidities (eg, substance use disorders) Key Elements 4. Mania Symptoms: • Distractibility • Decreased need for sleep • Grandiosity / Flight of ideas / Racing thoughts • Irritability / Risky behavior / Pressured speech Diagnostic and Statistical Manual of Mental Disorders, 4 th ed. , 2000. Hirschfeld RM, et al. J Clin Psychiatry. 2003; 64: 161 -174. • • age 25 Increased overall mood episodes Postpartum onset of depression Highly recurrent depressive episodes 3. Treatment Response: • Suboptimal outcome with • antidepressants Antidepressant-induced manic switch

Treatment for Bipolar Depression Mood stabilizer + Antidepressant n Mood stabilizers: - Lithium - Lamictal - Valproex - Carbamazepine Products • Antidepressants - SSRI - Wellbutrin XR

FDA-approved Indications of Agents Used in the Treatment of Adults with Bipolar Disorder* Bipolar Depression Acute Treatment Agents Bipolar Mania Mixed State Maintenance Treatment Acute Treatment Maintenance Treatment ✔ ✔ ✔† ✔ ✔ ✔ ✔† ATYPICALS Aripiprazole (Abilify ) Olanzapine (Zyprexa ) Quetiapine (SEROQUEL ) ✔ Risperidone (Risperdal ) Ziprasidone (Geodon ) ✔ ✔ OTHER ✔ ✔ ✔ Carbamazepine ER (Equetro. TM) Divalproex DR (Depakote ) Divalproex ER (Depakote ER) Lamotrigine Lithium (Lithobid , ✔ Eskalith ) Olanzapine/fluoxetine (Symbyax ) ✔ ‡ ✔ (Lamictal ) ✔ ✔ ✔ This chart does not imply comparable efficacy or safety profiles. All brand names and product names used in this slide are trade names, service marks, trademarks, or registered trademarks of their respective owners. *Based on FDA-approved labeling and index episode of responding patients enrolled in bipolar maintenance trials. †SEROQUEL is approved for maintenance only as adjunct therapy to lithium or divalproex. ‡Maintenance indication for lamotrigine (Lamictal®) also includes hypomania. Data on File, DA-SER-51. As of 5/08

How can we treat this patient?

Melancholic Depression • Melancholic features occur in 16 -53% of patients with Major Depressive Disorder • Equal Incidence in Males and Females • More Frequent in Older Patients

Melancholic Depression: Diagnosis • Either of the following, at the most severe period of the episode (1) loss of pleasure in all, or almost all, activities (2) lack of reactivity to usually pleasurable stimuli • Three (or more) of the following (1) distinct quality of depressed mood (distinctly different from the feeling of loss of a loved one) (2) depression worse in the morning (3) early morning awakening (2 hours before usual time of awakening) (4) marked psychomotor retardation or agitation (5) significant anorexia or weight loss (6) excessive or inappropriate guilt

Melancholic Depression: Treatment • SSRIs (first line) • TCAs

Case Study • CM is a new mother of a 3 week old boy. Her husband’s job transferred them to a new city and CM hasn’t made friends yet. Her husband works long hours, leaving her a alone with the new baby. She has found herself sad and crying uncontrollably for no apparent reason. One day as she was changing her son on his changing table, an intrusive thought started running through her head, “What if I push him off the table? ”

Post Partum Depression • PPD includes all the symptoms of depression but occurs only following childbirth. ▫ It can begin any time after delivery and can last up to a year. Typically, PPD is diagnosed if mood does not lift within two weeks after delivery. ▫ PPD is estimated to occur in approximately 10 to 20 percent of new mothers. • Possible causes ▫ Hormonal theories During pregnancy the levels of estrogen and progesterone increase up to tenfold. After delivery these hormone levels decline rapidly to prepregnancy levels in about 72 hours. Stress of a new baby may increase levels of cortisol.

Post Partum Depression • Symptoms include: ▫ ▫ ▫ Confusion Sluggishness Uncontrollable crying Fatigue Lack of interest in the baby Exhaustion Fear of harming the baby or Feelings of hopelessness or oneself depression Disturbances with appetite Mood swings: highs and lows and sleep • Treatment ▫ SSRI (Zoloft) + Emotional support ▫ TCAs

What if this patient was pregnant?

Pregnancy and Depression • 14 to 23% of pregnant women experience depression • Depression usually goes untreated in pregnant females • Depressed women are more prone to poor prenatal care & pregnancy complications (N/V, preeclampsia) and to use drugs, alcohol, & nicotine

Treatment Considerations for Depression in Pregnant Women • Weigh teratogenic risks against benefits of therapy • Consider psychotherapy • Respect stage of gestation • Consider history of depression and symptoms

Pregnancy Considerations • SSRIs are considered 1 st line agents • Some studies indicate increased short-term neonatal SE after exposure to SSRI and TCAs in third trimester • Little to no major risk for major malformations when SSRIs or TCAs are used in pregnancy • Neonatal toxicity reported in women taking TCAs up through delivery. • Antidepressant used during late pregnancy increases risks for preterm birth and adverse short-term neonatal effects with TCAs having the greater risk

Pregnancy Considerations • Desipramine is the preferred TCA because of less anticholinergic effects and orthostasis • Avoid the use of MAOIs • Bupropion is a class B, but limited data exists on its use in pregnancy

Lactation Considerations SSRIs • Paroxetine • Fluoxetine TCAs • Widely used in lactation • Nortriptyline • Avoid Doxepin

Psychotic Depression • MM is a 32 year old female. Her marriage fell apart 2 years ago and since then she has been angry all the time. She is tired, but can't afford to be as she has a 5 year old son to support, the rent to pay, and the housework to do, etc. She stated “I am prone to bursting into tears. My tiredness was treated with comments like, 'it's probably stress, you need to relax more, or do yoga'. " • One day at work, one of her bosses made a comment about her son. He meant nothing by it, just a tease. But she started to cry. “I couldn't stop. I was still crying at 2. 00 pm at the end of lunch hour, so I went home. I sat in the middle of my living room floor and continued to cry. " • "As the days passed, I started to believe that the people at work were after me and were going to take my son away. When I watched the newscasts on TV, the reporters were whispering special messages warning me of impending doom and telling me what to do. "

Psychotic Depression • Characterized by depressive symptoms accompanied by hallucinations and/or delusions. ▫ Occurs in over 20% of patients hospitalized with depressive disorder. • Possible causes ▫ Thought to be genetically linked. ▫ May be associated with stress (high levels of cortisol)

Psychotic Depression • Symptoms that occur more commonly in psychotically depressed patients include: ▫ ▫ ▫ ▫ Anxiety Agitation Hypochondria Insomnia Physical immobility Constipation Cognitive impairment

Psychotic Depression • Treatment Options ▫ Combinations of tricyclic or SSRI antidepressants plus an antipsychotic medications. Amitriptyline + Perphenazine Fluoxetine + Olanzapine ▫ Electroconvulsive therapy is very effective for this condition, but it is generally a second line treatment. • Recovery usually takes a year, but continual medical follow-up may be necessary. ▫ High rate of recurrence.

Case Study • DW is a 42 year old female who never really remembers feeling happy. Although, some times were better than others, she doesn’t remember getting any joy out of her life. DW doesn’t have many friends nor does she laugh much, though she attributes this to her not having much of a sense of humor. She feels like she carries the weight of the world on her shoulders. She always agonizes over what for others would be simple decisions. Others accuse her of spending half the day debating with herself.

Dysthymia • Long lasting depression with milder symptoms • Patients seem to think “They have always felt this way” • Preferred Agents: Paroxetine and Fluoxetine • Dysthymia in children usually presents as more irritable than depressed. • Children w/ dysthymia are at high risk of developing Major Depressive Disorder

Dysthymia: Diagnostic Criteria • • Chronic depressed mood throughout most of the day on most day for > 2 yrs (>1 yr for adolescents) Depression plus > 2 symptoms are present: a. b. c. d. e. f. • • • Poor appetite/overeating Insomnia/hypersomnia Low energy or fatigue Low self-esteem Poor concentration/difficulty making decisions Feelings of hopelessness During the 2 year period, symptom free intervals are < 2 months Symptoms should not occur or be caused by a chronic disorder or drugs Symptoms must impair functional daily living

Case Presentation DD, a 29 year old kindergarten teacher, ordinarily loves her students to no extreme. But ever since she can remember, she has had cramps, bloating, nausea, depression, and irritability a week before her menses begins. Over the past 5 or 6 years she has noticed, these symptoms become increasingly worse with every cycle. During that week, she feels easily fatigued after just 3 minutes of interacting with her students and has even found her self to have sudden crying spells triggered by her students’ statements. She feels overwhelmed dealing with her class and questions if she is capable of continuing in this career because she feels inadequate. Yet, after her menses begins, she feels inferior to the world with endless limits of her capability.

Premenstrual Dysphoric Disorder (PMDD) • Dysphoria: greek term meaning “distress” or “hard to bear” • Women with a history of depression are at increased risk of developing PMDD • PMDD women have an intensified response to stress • Symptoms worsen with age • Usually develops in late teens to late 20 s, however treatment is not sought until the 30 s • Ovulation is the trigger for PMDD; Cessation of ovulation is necessary in extreme cases • Associated with Serotonin deficiency

PMDD: Diagnostic Criteria • In the past year during most menstrual cycles, > 5 symptoms are present ▫ for most of last week of luteal phase ▫ begins to remit within a few days after onset of follicular phase ▫ absent in postmenses week *Luteal phase: period between ovulation & onset of menses (lasts about 10 -14 days) *Follicular phase: begins with menses • Symptoms should include at least 1 of first four bulleted symptoms listed

Symptoms of PMDD • • • Depressed mood, hopelessness, self-deprecating thoughts Anxiety, tension, feeling of being “on edge” Affective lability (suddenly sad, tearful, sensitivity) Persistent anger, irritability, or interpersonal conflicts interest in usual activities Difficulty concentration Lethagy, easily fatigued, or lack of energy Change in appetite, overeating, food cravings Hypersomnia or insomnia Sense of being overwhelmed Physical symptoms ▫ Breast tenderness/swelling, headache, joint or muscle pain, bloating sensations, wt. gain)

PMDD: Diagnostic Criteria • Interferes with work, school, or social relationships • Disturbance is not a result of an exacerbation of another mental disorder • Diagnosis should be confirmed by daily ratings during at least 2 consecutive symptomatic cycles

PMDD: Treatment • SSRI: ▫ 1 st line(FDA approved): sertraline, fluoxetine ▫ 2 nd line: paroxetine, citalopram ▫ Can be given continuously, semi-intermittent ( dose in follicular phase and dose in luteal phase), intermittent (full dose during luteal phase only) • • Other Antidepressants: venlafaxine, clomipramine Alprazolam Vitamins: B 6, E, Ca 2+ Carbonate Ibuprofen, bromocriptine, and spironolactone

PMDD: Treatment • Light therapy • Reduced caffeine and sodium intake • Cessation of ovulation via: ▫ Gonadotropin-releasing hormone agonists Not very favorable because of SE profile and cost ▫ Oral Contraceptives Estrogen + progesterone combo pill ▫ Surgical removal of ovaries

Case Study • PJ, 63 years old, lost her husband of 32 years in a car accident that occurred 8 years ago. She irons his clothes and even cooks him dinner everyday. Although she cried when she found out about his death, she hasn’t shed a tear since. When PJ is questioned about her husband’s whereabouts, she responds by saying “Oh Child, he just round da’ corner at the store. He’ll be back. ” • Her children are concerned because she has stopped attending church, playing bridge, and

Grief • • Natural Depression Triggered by loss of emotionally attached person or thing If lasts > 9 months then treat Key features of complicated grief: ▫ Sense of disbelief regarding loss ▫ Anger or bitterness over loss ▫ Recurrent episodes of painful emotions (with intense yearning and longing for loss) ▫ Preoccupation with thoughts of the loss • Therapy: • Antidepressant individualized based on the patient • Cognitive-Behavioral therapy

Geriatric Considerations • The pharmacokinetic changes in elderly patients may affect therapeutic response. ▫ Typically require a lower dose than younger patients. • It may take elderly patients longer to respond to antidepressants. ▫ If no response is seen in 4 -5 weeks, consider otherapies. • Elderly patients are particularly prone to orthostatic hypotension and cholinergic blockade. ▫ fluoxetine, sertraline, and bupropion are frequently chosen rather than amitriptyline, imipramine, and doxepin.

Case Study JJ is an outgoing 23 yo “likes to have fun” kind of girl. She goes to the beach every summer and loves to spend time with her friends. BUT, every November, JJ starts feeling depressed. Just this August, she was saying how she couldn’t wait for her summer job to start because it would involve doing what she loved so much…. Veterinarian assistant. She started her new job Nov. 12, and has not enjoyed a day of employment yet. She works from 9 am-3 p at the Vet, goes straight home and doesn’t leave the house until it is time for work the next day. She takes a 3 hour nap most days and then sleeps another 9 -11 hours at night. Since she has started her new job, she has gained 15 lbs in one month. What’s wrong with JJ? ? !!!

Seasonal Affective Disorder • Patterns of major depressive episodes that occur (usually fall or winter) and remit (usually spring) with changes in season • Treat pharmacologically when: ▫ Prior positive response to antidepressants or mood stabilizers ▫ High suicide risk ▫ Impairment in daily functioning and/or interactions (occupational or social) ▫ History of recurrent moderate-to-severe depression ▫ Failure to other non-pharmacological therapies

Seasonal Affective Disorder: Diagnosis • Regular temporal relationship between the onset of major depressive episodes and a particular time of year • Full remission occurring at a characteristic time of year • 2 major depressive episodes in last 2 years without nonseasonal episodes in the same period • Seasonally depressive episodes significantly outnumber nonseasonal depressive episodes over the individual’s lifetime • Symptoms should not be linked to seasonal psychosocial stressors

Seasonal Affective Disorder: Treatment • Winter Depression (begins late fall to early winter with symptoms of atypical depression) ▫ MAOI ▫ Psychotherapy ▫ Light Therapy • Summer depression (begins late spring to early summer with symptoms such as sleep, wt. loss, poor appetite) ▫ Antidepressants used in nonseasonal depression

Case Study • AZ is a 7 y. o. who appears sad all of the time. Instead of playing with his classmates, he is always isolated away from the others. His teacher notes that he barely finishes his lunch. He does his homework, but won’t participate in class when asked. When she tries to engage him, he just holds his head down. Last week she called his mother, because he urinated on himself. After meeting with the mother, she discovered that his parents separated, and his pet dog died.

Pediatric Considerations • Depression is a serious illness in children and adolescents • Youth with depression are at an increased risk for suicide • Fluoxetine is the only FDA approved antidepressant in children and adolescents • SSRIs are better tolerated than TCAs and are relatively safer in an overdose

Pediatrics Considerations • The FDA issued a Public Health Advisory concerning the use of antidepressant medications in which they called attention to reports of both suicidal ideation and attempts in children taking antidepressant drugs for the treatment of major depressive disorder. • Reports of suicidality have been aimed at SSRIs; however, TCAs present equivalent risks.

Last Minute Reminders about Treatment Choices

Wash-Out Periods • MAOIs should be discontinued 2 weeks prior to starting an alternative antidepressant and vice versa. (Exception: Wait 5 weeks if switching from fluoxetine or clomipramine to a MAOI) • Venlafaxine to MAOI, wait 7 days to start. • Switching from a TCA to paroxetine can be done almost immediately. • May have to complete with use of Ensam (selegiline)

Dosage Conversions • Effexor ▫ Match the milligrams ▫ Example: Effexor 25 mg TID ↔ Effexor XR 75 mg QD • Wellbutrin ▫ Match the milligrams ▫ Example: Wellbutrin 100 mg TID ↔ Wellbutrin SR 150 mg BID ↔ Wellbutrin XL 300 mg QD

Dosage Conversions • Paxil CR appears to be 1. 25 times the dose of regular Paxil ▫ Paxil 10 mg ↔ Paxil CR 12. 5 mg ▫ Paxil 20 mg ↔ Paxil CR 25 mg ▫ Paxil 30 mg ↔ Paxil CR 37. 5 mg

Dosage Conversions • Prozac to Prozac Weekly Prozac 20 mg Prozac 90 mg weekly Prozac 40 mg Prozac 90 mg twice weekly (must wait 7 days between the last daily dose and the first weekly dose)

Choices of Antidepressant If: Insomnia Present • • Trazodone Mirtazepine Paroxetine Amitriptyline Over-Sedation Present • Sertraline • Fluoxetine

Choices of Antidepressant If Obesity Present • • Fluoxetine Bupropion Sertraline Trazodone

Choice of Antidepressant in Male Patients • Wellbutrin • Mirtazapine

Choices of Antidepressant If: Comorbid OCD Present • Fluoxetine • Paroxetine • Sertraline • Fluvoxamine • Clomipramine Comorbid Panic Disorder • Fluoxetine • Paroxetine • Sertraline

Choices of Antidepressant If Comorbid Anxiety Disorder Present • Social Anxiety ▫ Paroxetine ▫ Sertraline ▫ Venlafaxine • Generalized Anxiety ▫ Paroxetine ▫ Lexapro ▫ Venlafaxine ▫ Duloxetine ▫ Desvenlafaxine

Medication Guide Requirement • Studies have found an almost twofold increase in the odds of fatal and non-fatal suicidal attempts in users of SSRIs. • The FDA has now instructed the manufacturers of ALL antidepressants to revise the labeling for their products to include a boxed warning and expanded warning statements that alert healthcare providers to an increased risk of suicidality in children and adolescents being treated with these agents, and to include additional information about the results of pediatric studies • The FDA has mandated that a patient “Medication Guide” be given to patients receiving all antidepressants - advising them of the risk and precautions.

Conclusions • Individualize therapy based on: ▫ ▫ ▫ ▫ ▫ Pharmacology of the drug Drug interactions Co-morbid conditions Lifestyle habits (sleep and appetite) Cost of therapy Consider non-pharmacological therapy Consider population specific recommendations Consider augmentation strategies Age of patient Symptoms of depression

Questions? ? Angela M. Hill, Pharm. D. , BCPP ahill 2@health. usf. edu 813. 974. 2551