Antidepressant Selection in Primary Care Rebecca D. Lewis, DO OOA Summer CME Oklahoma City, OK 6 August 2017 Objectives Understand the epidemiology of depression. Recognize factors to help choose antidepressants. Identify side effect profile of common antidepressants. Identify patient populations that have unique antidepressant needs. 1
Disclosures None Epidemiology 1 in 11 patients meet criteria for depression Antidepressants are 3 rd most common med class in US Depression is 2 nd leading cause of disability in US Can contribute to conditions such as IBS, chronic pain, and others 2
Definition DSM-V: 5+ of the following symptoms for 2-week period and a change from previous functioning; AND at least one of the symptoms is either depressed mood or loss of interest or pleasure. The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning. Sx not due to effects of a substance or a general medical condition. Rule out anemia, hypothyroid, electrolyte d/o, etc. Depression Symptoms Sleep Interest Guilt Energy Concentration Attention Psychomotor Suicide 3
Depression Symptoms Positive On Edge Agitation Anxiety Insomnia Negative - Blah Flat affect Hypersomnolence Fatigue Somatic Symptoms Abdominal Pain Back Pain Constipation Fatigue Headache Insomnia/Hypersomnia Joint Pain Neck Pain Weakness 4
Depression Risk Factors Chronic Medical Illness Chronic Pain High Daily Stress Levels Personal or Family Hx of Depression Female Low SES Single/Divorced/Widowed TBI Depression Screening USPSTF Grade B Recommendation Screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and followup. 5
Depression Assessment PHQ-2 PHQ-9 Geriatric Depression Scale (5 and 15 item) Edinburgh Postpartum Depression Scale Tools are great for screening and follow up Side Effects 2/3 of pts will have a side effect Education on side effects is key to compliance Most Common Diarrhea N/V Sexual Dysfunction Somnolence Weight Gain 6
Common Prescribing Errors One size fits all medicine Treating all meds in one class the same Giving up after one med Under dosing Choosing a med you are not comfortable with starting or stopping Choosing An Antidepressant Things to consider: Predominating symptoms Cost Side Effect Profile Any desired side effects? Coexisting conditions Patient Preference 7
Antidepressant Classes Selective Serotonin Reuptake Inhibitor (SSRI) Sertraline, Citalopram, Escitalopram, Paroxetine, Fluoxetine, Vortioxetine Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Venlafaxine, Desvenlafaxine, Duloxetine Serotonin Modulators Trazodone, Nefazodone, Vilazodone Tricyclic Antidepressants (TCA) Amitriptyline, Nortriptyline, Imipramine, Doxepin Monoamine Oxidase Inhibitors (MAOI) Phenelzine Atypicals Bupropion, Mirtazapine SSRIs One of 1 st line meds Easy to switch from one to another Easy to wean off Longer Half-lives, especially Fluoxetine Lowest side effect profile Side Effects: N/V/D, headaches, weight gain, libido decrease, diaphoresis, bruxism Titrate up to therapeutic dose to decrease side effects Effectiveness at 2-4 weeks Time of day to take: AM or PM 8
SNRIs Another 1 st line med Harder to wean off and switch Lower side effect profile Side Effects: N/V/D, headaches, libido decrease, HTN, dry mouth, significant w/d sx with dose decrease, diaphoresis Titrate up to therapeutic dose to decrease side effects Effectiveness at 2-4 weeks Time of day to take: AM or PM tends toward AM Bupropion Another 1 st line med Lower side effect profile Contraindications: Eating disorders, seizure disorder, caution with alcohol abuse Side Effects: N/V/D, headaches, HTN, dry mouth, seizures Titrate up to therapeutic dose to decrease side effects Effectiveness at 2-4 weeks Time of day to take: AM or PM tends toward AM 9
Mirtazapine Another 1 st line med Higher side effect profile More effective for sleep at lower doses Side Effects: Weight gain, increased cholesterol, drowsiness, appetite increase Fastest effectiveness of all antidepressants at 24-48 hours Time of day to take: PM Serotonin Modulators 2 nd line Side Effects: Orthostatic hypotension, priapism (trazodone), hepatotoxicity (nefazodone), sedation More effective as antidepressant at higher doses, sedative at lower doses Effectiveness at 2-4 weeks, sedation effects immediate Time of day to take: PM 10
TCAs 2 nd line High side effect profile, easy OD Side Effects: arrhythmia, constipation, dry mouth, sedation, delirium, sexual side effects, bladder retention, diaphoresis, weight gain Titrate up to therapeutic dose to decrease side effects Effectiveness at 2-4 weeks, sedation immediate Time of day to take: PM MAOIs Last line med Require a 2-6 week washout period before starting or stopping MAOI Dietary restrictions Side Effects: Orthostatic hypotension, anorgasmia, HTN crisis, severe serotonin syndrome Effectiveness at 2-12 weeks Time of day to take: AM or PM tends toward PM 11
Best for Negative Sx Meds with increased noradrenergic effect Better to avoid in high anxiety patients Activating medications: Some SSRIs, SNRIs, Bupropion Includes: Bupropion Venlafaxine Desvenlafaxine Fluoxetine Duloxetine Sertraline Best for Positive Sx More dopaminergic and serotonergic effect Better for high anxiety patients Calming Medications Include: Escitalopram Citalopram Paroxetine Vorioxetine 12
Weight Effects Weight Gain Mirtazapine TCAs especially Amitriptyline Paroxetine All other SSRIs mild weight gain Weight Neutral SNRIs Trazodone Weight Loss Bupropion Sexual Side Effects Marked Paroxetine SSRIs (much less with vortioxetine and escitalopram) SNRIs TCAs MAOIs Mild Trazodone Mirtazapine None Bupropion 13
Insomnia Patients Mirtazapine More sedating at lower doses Trazodone Lower doses used for sleep and higher for depression Sedating effect dose increase with increased dose TCAs (especially amitriptyline) Chronic Pain Types of Pain: Fibromyalgia Neuropathic Pain Migraines Meds that are helpful: Duloxetine Venlafaxine TCAs 14
Elderly Patients Start low and go slow Highly sensitive to meds Preferred medications include: Citalopram Caution with cardiac issues Escitalopram Sertraline Mirtazapine Appetite Stimulant, Sleep Venlafaxine Bupropion No paroxetine or fluoxetine Caution with TCAs Adolescent Patients Fluoxentine is first line tx Second line include sertraline, citalopram, escitalopram, and venlafaxine TCAs show no effect Black box warning in adolescents Paroxetine with strongest warning 15
Prenatal Patients Risk to benefit assessment Sertraline, Fluoxetine and Citalopram are preferred Increased risk of cardiac malformation and persistent pulmonary HTN of the newborn (PPHN) Level II ultrasound recommended if 1 st trimester use SSRI doses may need to increase in pregnancy Paroxetine is Category D DO NOT use in pregnancy Associated with cardiac malformations Lactating Patients Most SSRIs are safe in breastfeeding Sertraline and Paroxetine with lowest breast milk secretion Safest to use Fluoxetine and Venlafaxine with highest secretion Wellbutrin with reports of seizures in infant Effects on breastfeeding infant Agitation Poor feeding 16
Renal Impairment Decreased dose often required Bupropion Duloxetine Paroxetine Venlafaxine Hepatic Impairment Decreased dose often required Nefazodone can cause hepatotoxicity Bupropion Citalopram Duloxetine Fluoxetine Nortriptyline Sertraline Venlafaxine 17
Length of Treatment 4-12 months Reassessment of life stressors Weaning period Starting, Switching and Stopping To Start Start with half of intended dose x 1 week, then increase to intended dose Max effect in 4-6 weeks with most meds To D/C Slowly taper off of the medication over 1-2 weeks Longer taper with SNRIs To Change Cross taper when changing to/from MAOI, TCA, or mirtazapine SSRI to SSRI or SSRI to/from SNRI can change to equivalent dose without cross taper 18
Resistant Treatment Maximize dosing prior to changing med or adding a second med Addition of a second antidepressant Addition of an atypical antipsychotic 19
Adjunct Therapy Psychotherapy/Counseling Exercise Support Groups Combo with above decreases total treatment time and decreases relapse risk Take Home Points Not all antidepressants are equal Customize your therapy Consider desired and undesired side effect profiles Use side effects to your advantage Remember special populations when treating Subtherapeutic doses expose to risk but not to benefit 20
Questions? References Bonin L and Moreland CS. Overview of Treatment for Pediatric Depression. In: UpToDate, Middleman AB(Ed), UpToDate, Waltham, MA. (Accessed on July 27, 2015.) Ciechanowski P. Unipolar Major Depression in Adults: Choosing Initial Treatment. In: UpToDate, Roy-Burn P(Ed), UpToDate, Waltham, MA. (Accessed on July 27, 2015.) Clark MS, Jansen KL, and Cloy JA. Treatment of Childhood and Adolescent Depression. Am Fam Physician. 2012 Sep 1;86(5):442-448. 21
References Hirsh M and Birnbaum R. Antidepressant medication in adults: Switching and discontinuing medication. In: UpToDate, Roy-Burn PP(Ed), UpToDate, Waltham, MA. (Accessed on July 27, 2015.) Kovich H and Dejong A. Common Questions About the Pharmacologic Management of Depression in Adults. Am Fam Physician. 2015 Jul 15;92(2):94-100. Maurer D and Darnall C. Screening for Depression. Am Fam Physician. 2012 Jan 15;85(2: 139-144. Roy-Burn P. Unipolar major depression in pregnant women: Treatment. In: UpToDate, Stein MB(Ed), UpToDate, Waltham, MA. (Accessed on July 27, 2015.) 22