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INITIATION OF ANTIDEPRESSANTS IN PRIMARY CARE Avoiding Potentially Dangerous Treatment Delays OBJECTIVES Define Depressive Disorders Identify Useful Screening Tools Identify When to Initiate Antidepressants Distinguish Between Types of Antidepressants to Predict & Evaluate Efficacy Strive to be a healer, not a technician. Allan Peterkin, MD DEPRESSIVE DISORDERS DSM IV-TR (2000) Major Depressive Disorder Single Episode (296.2x) Recurrent (296.3x) Mild, Moderate, Severe without & with psychotic features, Partial & Full Remission Coded 296.x1-6 MAJOR DEPRESSIVE DISORDER 5 or more symptoms present in same 2 -week period, a change in previous functioning, at least 1 is depressed mood or loss of interest/pleasure Not mixed with manic symptoms Cause clinically significant distress/impaired functioning Not due to substances, general medical condition, grief Marked preoccupation with worthlessness, suicidal ideation, psychotic symptoms, psychomotor retardation SPECIFIC DEPRESSIVE SYMPTOMS Depressed mood most days: sad, empty, irritable Marked loss of interest or pleasure Weight loss when not dieting, e.g. >5% in a month Insomnia or Hypersomnia Psychomotor retardation or agitation, observable by others Fatigue or loss of energy Feelings of worthlessness or guilt Dif ficulty concentrating, or indecisiveness Recurrent thoughts of death, suicidal ideation With or without plan WE MUST ASK DEPRESSIVE DISORDERS DSM IV-TR Dysthymic Disorder (300.4) Chronic, less severe depressive symptoms Present for many years DEPRESSIVE DISORDERS DSM IV-TR Substance-Induced Mood Disorder (292.84) Mood Disorder NOS (296.90) Mood Disorder Due to General Medical Condition (293.83) INCREASES RISK OF SUICIDE SUICIDE & GENERAL MEDICAL CONDITIONS Rates vary depending on specific condition Chronic, incurable, painful conditions carry the greatest risk WE MUST ASK DEPRESSIVE DISORDERS DSM 5 (2013 – due out in May) Disruptive Mood Dysregulation Disorder (previously described as Pediatric Bipolar D/O Premenstrual Dysphoric Disorder >5 of 12 months, 1 week before menses Mixed Anxiety/Depression At least 3 symptoms of MDD or GAD Major correlate to suicidal thoughts DSM 5 DEPRESSIVE DISORDERS Dystonic: Patient is aware & in pain Severe impairment in functioning Correlation to drug use, especially EtOH, amphetamines, cocaine Powerful correlate to suicide SCREENING TOOLS Wide Variety Clinician vs Client/Self Rating Time Involved: 2-30 minutes Public Domain vs Copyrighted Realistic Application: Valid & Brief SCREENING TOOLS Choosing a Rating Scale Consider your Population Scale Validity & Reliability Assessing what it’s designed to assess Ability to provide consistent, reproducible info Available Staff Resources, Time, Training Scale Standardization Ease of Participation by Patient SCREENING TOOLS Hamilton Rating Scale for Depression (HAM -D, 1960) 17-31 items, public, 30 minutes Beck Depression Inventory (BDI, 1961; BDI -II, 1993) 21 items, copyright, 5-10 minutes Montgomery - Asberg Depression Rating Scale (MADRS, 1979) 10 items, public, 20 minutes Raskin-Covi Scales (1969, 1981) 6 items, public, several minutes Mood Disorder Questionnaire (MDQ, 2000) 13 items, public, 5-10 minutes, screens for Bipolar Disorder SCREENING TOOLS Examples Included Raskin-Covi Scales Observer Rated Severity score used in pharmacologic study outcome MADRS Observer Rated Does not cover somatic or psychomotor symptoms as fully as HAM-D Make even your first assessment a therapeutic experience for the patient. One encounter may actually be enough or all the patient can afford right now. Allan Peterkin, MD WHEN MIGHT IT BE NECESSARY TO INITIATE ANTIDEPRESSANTS ? You may be the First & Only Provider (Un)Availability or (Un)Desirability of Psychiatric Providers Severity of symptoms vs Time delay WHEN MIGHT IT BE NECESSARY TO INITIATE ANTIDEPRESSANTS? Important Considerations Patient has significant distress/impaired function Patient has no capacity to cope with problem Patient is motivated for treatment Patient has thoughts or intentions of suicide Consider in-patient referral WHEN MIGHT IT BE NECESSARY TO INITIATE ANTIDEPRESSANTS? Additional Important Considerations Less risk than long-term Benzodiazepine use Discuss Black Box Warnings Discuss risk of mania if Bipolar D/O is possible Serotonin Syndrome potential Consider non-psychiatric drugs patient takes T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Why are there so many different antidepressant drugs? Why is the efficacy so unpredictable? Consider: There are 3 known Serotonin receptor genes T YPES OF ANTIDEPRESSANT DRUGS – PREDICTING & EVALUATING EFFICACY Monoamine Oxidase Inhibitors Example: Parnate (Tranylcypromine) Indications: Refractory Depression Dosing: 30 mg/day, divided; max 60 mg/day Concerns: Numerous Hypertensive Crisis w/ sympathomimetics, levodopa, high-tyramine foods e.g. cheese, chocolate, yogurt, wine, beer Must stop other drugs 1-5 weeks before use Less problematic with transdermal EMSAM T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Tricyclics Example: Elavil (Amitriptyline) Indications: Depression, especially endogenous; also used in pain management Dosing: 10-75 mg/day; max 150 mg/day Concerns: Numerous Hyperpyretic crisis w/ MAOIs, anticholinergics, sympathomimetics Paralytic ileus w/ anticholinergics Arrhythmias Galactorrhea T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Tricyclics Example: Tofranil (Imipramine) Indications: Depression; off-label nocturnal enuresis Dosing: 10-75 mg/day; max 200 mg/day Concerns: Numerous Urinary retention Hyperpyretic crisis, convulsions, death w/ MAOIs Arrhythmias EPS T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Serotonin Specific Reuptake Inhibitors Example: Prozac (Fluoxetine) Indications: MDD, Bulimia nervosa, Panic D/O, OCD Dosing: 10-60 mg/day; max 80 mg/day Concerns: Suicidal Ideation Warning Long half-life Increased risk of bleeding with drugs that affect coagulation (menorrhagia even w/o these) Serotonin Syndrome (weakness, incoordination, hyperreflexia, tachycardia, confusion, agitation) Sexual side effects T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SSRIs Example: Paxil (Paroxetine) Indications: Depression, PMDD, Social Anx D/O, Panic D/O Dosing: 10-40 mg/day; max 50 mg/day Concerns: Suicidal Ideation Warning Highly protein bound Serotonin syndrome Abnormal bleeding Sexual side effects T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SSRIs Example: Zoloft (Sertraline) Indications: Depression, PMDD, Panic D/O, PTSD, OCD, Social Anxiety D/O Dosing: 25-100 mg/day; max 200 mg/day Concerns: Suicidal Ideation Warning Serotonin Syndrome Diaphoresis Sexual side effects T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SSRIs Example: Lexapro (Escitalopram) Indications: MDD, GAD Dosing: 5-20 mg/day; max 20 mg/day Concerns: Suicidal Ideation Warning Serotonin Syndrome Abnormal bleeding Interacts with Tramadol Sexual side effects T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SSRI + 5-HT 1A Receptor Partial Agonist Viibryd (Vilazodone) Indications: MDD Dosing: 10-40 mg/day; max 40 mg/day Concerns: Suicidal Ideation Warning Highly protein bound Abnormal bleeding Serotonin Syndrome with concomitant drugs, but less likely as partial agonist takes place of 5-HT that’s been inhibited T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Serotonin-Norepinephrine Reuptake Inhibitors Example: Effexor (Venlafaxine) Indications: MDD, GAD, Social AnxD/O, Panic D/O Dosing: 37.5-225 mg/day; max 375 mg/day Concerns: Suicidal Ideation Warning Hypertension Serotonin Syndrome Abnormal bleeding Severe discontinuation sx, e.g. paresthesia, tremor, GI, agitation (titrate extremely slowly) T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SNRIs Example: Pristiq (Desvenlafaxine) Indications: MDD; in trials for “Hot Flashes” Dosing: 50-100 mg/day; max 100 mg/day Concerns: Suicidal Ideation Warning Possible Hypertension Serotonin Syndrome Hyperhidrosis, mydriasis Can give 50mg qod in ESRD T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY SNRIs Example: Cymbalta (Duloxetine) Indications: MDD, GAD Dosing: 20-60 mg/day; max 120 mg/day Concerns: Suicidal Ideation Warning Highly protein bound Possible Hypertension Hepatotoxicity, avoid w/ excessive EtOH use T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Other Classes Example: Wellbutrin (Bupropion) Indications: Depression, Seasonal Affective D/O Dosing: 75-300 mg/day; max 450 mg/day Concerns: Suicidal Ideation Warning Increased seizure risk, especially >300mg/day If seizure occurs, D/C & do not restart If b.i.d. dosing, give 8 hrs apart & last dose by 5pm Possible Hypertension w/ nicotine replacement T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Other Classes Example: Remeron (Mirtazapine) Indications: MDD, off-label appetite & sleep aid Dosing: 7.5-45 mg/day; max 45 mg/day Concerns: Suicidal Ideation Warning Serotonin Syndrome Possible fatal reactions with MAOIs Dose at HS 7.5 mg dose-most SE increasing appetite & sleep T YPES OF ANTIDEPRESSANT DRUGSPREDICTING & EVALUATING EFFICACY Other Classes Example: Desyrel (Trazodone) Indications: Depression Dosing: 25-300 mg/day; max 600 mg/day (inpt) Concerns: May affect anticoagulants Drowsiness, dizziness, hypotension Headache Potentiates EtOH, other CNS depressants Most often used in lower doses for sleep aid ADJUNCT THERAPY Antiepileptics Examples: Depakote, Lamictal, Trileptal, Topamax Antipsychotics Examples: Abilify, Geodon, Risperdal, Seroquel, Zyprexa, Symbyax (Olanzapine/Fluoxetine) Lithium Used as Mood Stabilizers May be essential to effectively treat Bipolar D/O You are seldom helping only the patient in front of you. You are helping their partners, children, employees, and friends. Allan Peterkin, MD REFERENCES American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4 th ed.), Text Revision. Washington, DC: APA. Ernst, D. (Ed.). (2012). Mood disorders, Anxiety/OCD. Nurse Practitioners’ Prescribing Reference, 19 (4). Klott, J. (2012). Revolutionizing diagnosis & treatment using the DSM -5. Eau Claire, WI: CMI Education Institute. Mullen, J. (Ed.). (2004). Manual of rating scales for the assessment of mood disorders. Wilmington, DE: AstraZeneca Pharmaceuticals, LP. Peterkin, A. (1999). The psychiatrist’s little book of wisdom: 350 tips and reflections on clinical practice and the art of communicating. Royal Oak, MI: Physicians’ Press.