Resistance is Futile: Functional Outcomes for Major Depressive Disorders

Transcription

1 Resistance is Futile: Functional Outcomes for Major Depressive Disorders Primary Care Updates July 24, 2013 New York, New York Presenter: Thomas L. Schwartz, MD Educational Partner:

2 Session 2: Resistance is Futile: Functional Outcomes for Major Depressive Disorders Learning Objectives 1. Choose initial evidence-based depression treatment that is specifically suited to the individual patient's need. 2. Monitor patients with depression over time in order to track treatment adherence, response, and side effects. 3. Make evidence-based treatment adjustments to address residual symptoms and side effects. Faculty Thomas L. Schwartz, MD Associate Professor Department of Psychiatry SUNY Upstate Medical University Syracuse, New York Thomas L. Schwartz, MD, associate professor of psychiatry, director of adult outpatient services, and assistant director for psychiatric residency training at SUNY Upstate Medical University, Syracuse, New York, completed his MD and residency at SUNY. Dr Schwartz directs the depression & anxiety disorders research program. He provides resident supervision, lectures, and directs CME events for the psychiatry department. Dr Schwartz maintains a private practice and consults for the Indian Health Service, pharmaceutical companies, and associated industries. He has been recognized with the Marc H. Hollander, MD, Psychiatry Award, Teacher of the Year, and Mentor of the Year awards from SUNY Upstate; Nancy Roeske, MD, and Irma Bland Certificates of Recognition for Excellence in Medical Student and Resident Education from the APA, and the SUNY Upstate President's Award and Chancellor's Awards for Teaching. He has served as principal investigator on clinical trials, authored Depression: Treatment Strategies and Management, 2nd ed., published articles in medical journals, and served as peer reviewer for U.S. and international journals. Faculty Financial Disclosure Statement The presenting faculty reports the following: Dr Schwartz receives research grants from Bristol-Myers Squibb Company; Cephalon, Inc.; and Cyberonics. Education Partner Financial Disclosure Statement The content collaborators at the Neuroscience Education Institute report the following: Meghan Grady, director of content development, has no financial relationships to disclose. Acronym List Acronym 5HT DA DSM HA MAOI NDRI NE NNT NOS Definition serotonin dopamine Diagnostic and Statistical Manual histamine monoamine oxidase inhibitor norepinephrine dopamine reuptake inhibitor norepinephrine number needed to treat nitric oxide synthase Acronym NRI PHQ-9 SERT SNRI SSRI TCA Definition norepinephrine reuptake inhibitor Patient Health Questionnaire serotonin transporter serotonin norepinephrine reuptake inhibitor selective serotonin reuptake inhibitor tricyclic antidepressant Session 2

3 Suggested Reading List Bostwick JM. A generalist's guide to treatment patients with depression with an emphasis on using side effects to tailor antidepressant therapy. Mayo Clin Proc. 2010;85(6): Cascade E, Kalali AH, Kennedy SH. Real-world data on SSRI antidepressant side effects. Psychiatry (Edgmont). 2009;6(2): Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antideprssants: a multiple-treatments meta-analysis. Lancet. 2009;373: Dallaspezia S, Benedetti F. Chronobiological therapy for mood disorders. Expert Rev Neurother. 2011;11(7): Rost K. Disability from depression: the public health challenge to primary care. Nord J Psychiatry. 2009;63: Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants. A meta-analysis. J Clin Psychopharmacol. 2009;29: Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71(10): Stahl SM. Stahl s Essential Psychopharmacology. 3rd ed. New York, NY: Cambridge University Press; Stahl SM. Stahl s Essential Psychopharmacology: The Prescriber s Guide. 4th ed. New York, NY: Cambridge University Press; U.S. Preventive Services Task Force. Screening for depression in adults: U.S. preventive services task force recommendation statement. Ann Intern Med. 2009;151(11): Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci Oct;342(4): Session 2

4 SESSION 2 9:30 AM 10:45 AM Resistance is Futile: Functional Outcomes for Major Depressive Disorder SPEAKER Thomas L. Schwartz, MD Presenter Disclosure Information The following relationships exist related to this presentation: Dr Schwartz receives research grants from Bristol-Myers Squibb Company; Cephalon, Inc.; and Cyberonics. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Generic Trade agomelatine Not in U.S. amitriptyline Elavil amoxapine Asendin aripiprazole Abilify armodafinil Nuvigil bupropion Wellbutrin buspirone * Buspar carbamazepine* Tegretol, others citalopram Celexa clomipramine Anafranil desipramine Norpramin desvenlafaxine Pristiq doxepin Sinequan duloxetine Cymbalta escitalopram Lexapro eszopiclone Lunesta fluoxetine Prozac fluvoxamine* Luvox* gabapentin Neurontin imipramine Tofranil isocarboxazid Marplan lamotrigine* Lamictal lithium various l-methylfolate Deplin Drug List Generic Trade maprotiline Ludiomil melatonin melatonin milnacipran Savella mirtazapine Remeron modafinil Provigil nefazodone Serzone nortriptyline Pamelor paroxetine Paxil phenelzine Nardil pramipexole* Mirapex pregabalin Lyrica protriptyline Triptil quetiapine Seroquel reboxetine Not in U.S. ropinirole* Requip SAMe* selegiline EMSAM sertraline Zoloft topiramate* Topamax tranylcypromine Parnate trazodone Desyrel trimipramine Surmontil venlafaxine Effexor vilazodone Viibryd *Off-label Learning Objectives Choose initial evidence-based treatment that is specifically suited to the individual patient s need Monitor patients with depression over time in order to track treatment adherence, response, and side effects Make evidence-based treatment adjustments to address residual symptoms and side effects Demographic ARS Outcomes Question 1 How many patients do you see each week who may require treatment for major depression? 1. None 2. 1 to to to to to to > 60 A 31-year-old man presents complaining of insomnia, constant fatigue, lack of appetite, psychomotor retardation, depressed mood, and feelings of helplessness. He completes the Patient Health Questionnaire with a score of 16, indicating moderate depression. Which of his symptoms might be a particular warning sign for suicidality, warranting further assessment? 1. Insomnia 2. Fatigue 3. Helplessness 4. 1 and and 3 1

5 Outcomes Question 2 Outcomes Question 3 A 44-year-old woman has been taking an SSRI for 3 months. At her follow-up visit, she informs you that although her mood has improved with treatment, she is having problems engaging in sexual activity with her husband. What treatment option might be appropriate to address her sexual dysfunction? 1. Serotonin 2 partial agonist or serotonin 1A partial agonist 2. Serotonin 1A partial agonist or serotonin 2 antagonist 3. Serotonin 2 antagonist or serotonin 1A antagonist 4. Serotonin 1A antagonist or serotonin 2 partial agonist A 29-year-old woman has just been diagnosed with major depressive disorder and is being prescribed a selective serotonin reuptake inhibitor (SSRI). In addition to depressed mood, lack of interest in her work or friends, and difficulty sleeping, she has been experiencing aches and pains in her arms, shoulders, and torso. She asks if the SSRI is likely to alleviate her painful physical symptoms as well as her emotional ones. Which of the following statements is true? 1.SSRIs may have inconsistent effects on pain because serotonin can both inhibit and facilitate ascending nociceptive signals 2.SSRIs may worsen pain because serotonin can facilitate but not inhibit ascending nociceptive signals 3.SSRIs generally alleviate pain because serotonin can inhibit but not facilitate ascending nociceptive signals 4.SSRIs generally have no effect on pain because serotonin neither facilitates nor inhibits nociceptive signals Patient Health Questionnaire-9 (PHQ-9) 1. Over the last two weeks have you been bothered by the following problems? a. Little interest or pleasure in doing things More than Nearly Not Several half the every at all days days day Treating Depression in Adults b. Feeling down, depressed, or hopeless c. Trouble falling or staying asleep, or sleeping too much d. Feeling tired or having little energy e. Poor appetite or overeating Guidelines and Monitoring Patients f. Feeling bad about yourself, or that you are a failure... g. Trouble concentrating on things, such as reading... h. Moving or speaking so slowly... i. Thoughts that you would be better off dead how difficult have these problems made it for you to do your work, take care of things Subtotals: at home, or get along with other people? TOTAL: Not difficult at all Somewhat Difficult Very Difficult Extremely Difficult Copyright 2012 Neuroscience Education Institute. All rights reserved. Apps for Mood Monitoring and/or Adherence Use Apps that track mood to save time, engage the patient, and monitor mood between visits T2 Mood tracker vas&hl=en MoodTracker.com MyMoodTracker.com Depression Treatment Guidelines Severity / Impairment PHQ-9 Score Initial Strategy Mild Monotherapy psychotherapy or antidepressant Moderate Antidepressant, psychotherapy, or combination Severe 20 May start with antidepressant or psychotherapy but prefer combination Psychoeducation and self-management should be provided at all severity levels Follow-up (2 weeks): Symptoms improving (PHQ-9) Treatment well-tolerated Adherent yes Continue current treatment Reassess by 4 6 weeks yes Full remission? Continue to prevent relapse Possible long-term maintenance no no Adjust treatment Weihs K, Wert JM. Am J Med Sci 2011; 342(4): APA. Practice Guideline... 3 rd ed. APA;

6 Antidepressants and Risk of Suicidality Efficacy, tolerability, and safety of antidepressants have been studied mostly in individuals between the ages of 19 to 64 Limited data in children and adolescents suggest increased risk of suicidality Efficacy not well studied, particularly in younger children Data show reduced risk of suicidality with antidepressant treatment (vs. without) for adults ages 65 years and older Stone M, et al. BMJ 2009;339:b2880. Suicide Risk Assessment Identify risk factors and/or warning signs Identify possible protective factors Assess level of risk Document Suicide Prevention Resource Center. Immutable Patient s history (experience of trauma/loss, previous attempt, psychiatric illness) Family history Demographics (male, unmarried, early 20s) Cultural/religious belief about suicide Personality traits (impulsive, aggressive) Risk Factors for Suicide Circumstantial Unemployment Financial difficulties Relationship difficulties Physical injury/illness, chronic physical pain Life transitions Access to lethal means Modifiable Drinking/drug use Nicotine use Unstructured time Perceived stress Current psychiatric illness (depression, alcohol abuse) Hopelessness, helplessness Anxiety, panic attacks, agitation, insomnia* Delusions *Often precede suicide within hours/days/weeks. McDowell AK, et al. Mayo Clin Proc 2011;86(8): Warning Signs: Are Some Symptoms Precursors to Suicidality? Anxiety Agitation Panic attacks Insomnia Irritability Hostility Aggressiveness Impulsivity Restlessness Hypomania and mania McDowell AK, et al. Mayo Clin Proc 2011;86(8): Suicide Risk is Highest When: The person sees no way out and fears things may get worse The predominant emotions are hopelessness and helplessness The person is anxious, agitated, has insomnia Thinking is constricted with a tendency to perceive his or her situation as all bad Judgment is impaired by use of alcohol or other substances Asking About Suicidality Be direct but non-confrontational Start with general and move on to more specific Thoughts of death Suicidal ideation Suicide plan Means available Suicidal intent Also ask about family history of suicide and previous suicide attempts McDowell AK, et al. Mayo Clin Proc 2011;86(8): McDowell AK, et al. Mayo Clin Proc 2011;86(8):

7 Collaboration With a Psychiatrist For patients who do not initially respond For patients who have intolerable side effects When to refer Severe depression with significant impairment in functioning Psychotic or manic features, or history of psychotic/manic symptoms Comorbid psychiatric disorders Suicidal ideation, plan, or intent; family history of suicide Other complicating factors or concerns Side Effects Options to Avoid or Address the Most Troublesome Side Effects Prager LM. Ped Rev 2009;30(6): Weihs K, Wert JM. Am J Med Sci 2011; Epub ahead of print. Most Troubling Antidepressant Side Effects Mechanisms Associated With Troubling Short-Term Side Effects receptor sensitivity amount of neurotransmitter therapeutic effect antidepressant introduced nausea headache activation sedation sexual dysfunction weight gain Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. New York, NY: CUP; 2013; Bostwick JM. Mayo Clin Proc 2010;85(6):538-50; Cascade E, et al. Psychiatry (Edgmont) 2009;6(2):16-8. Nausea Headache Activation 5HT reuptake inhibition X X X NE reuptake inhibition X X DA reuptake inhibition Psychomotor 5HT: serotonin. NE: norepinephrine. DA: dopamine. Morehouse R, et al. J Affective Disord 2011;132:S14-20; Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. New York, NY: CUP; 2013 Management of Short-Term Side Effects Headaches Slower dose titration Use non-ssri/snri Use OTC analgesics Avoid migraine serotonergic meds and tramadol Nausea Slower titration Use OTC symptomatic treatments Add serotonin 3 blockers SSRI: selective serotonin reuptake inhibitor. SNRI: serotonin norepinephrine reuptake inhibitor. OTC: over-the-counter. Kelly K, et al. Dialogues Clin Neurosci 2008;10(4): Management of Activation Propensity for SSRIs to induce activation fluoxetine > sertraline > citalopram/escitalopram/paroxetine SNRIs activate too Activation usually subsides in the first few weeks of treatment First consider a temporary dose reduction or a more gradual uptitration Can consider adding a benzodiazepine short term Can consider adding trazodone or mirtazapine Kelly K, et al. Dialogues Clin Neurosci 2008;10(4):

8 Mechanisms Associated With Troubling Long-Term Side Effects Sedation Sexual dysfunction Serotonin reuptake inhibition X X X Serotonin 2 antagonism Weight gain Alpha 1 antagonism X X X Histamine 1 antagonism X X Anticholinergic X X Nitric oxide synthase inhibition Morehouse R, et al. J Affective Disord 2011;132:S14-20; Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. New York, NY: CUP; 2013 X X Management of Sedation Dose at night or take larger dose at night Increase daytime exercise If patient is responding and otherwise tolerating current treatment Augment (modafinil/armodafinil, bupropion, atomoxetine, stimulant)* If patient is not responding or if sedation is truly intolerable Switch to a non-sedating antidepressant * Not FDA approved for this indication Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 4th ed. New York, NY; CUP:2011; Zajecka JM. J Clin Psychiatry 2007;68(suppl 10):23-7. Management of Sexual Dysfunction Assess sexual function before starting medication Switch to mirtazapine or trazodone (serotonin 2A antagonism) Switch to vilazodone (serotonin 1A partial agonism serotonin reuptake inhibition) Add cyproheptadine, trazodone, or high-dose (60 mg/day) buspirone* Add amantadine, bupropion, or stimulant Add phosphodiesterase 5 (PDE-5) inhibitor Does not increase desire For women, consider estrogen creams * Not FDA approved for this indication Rizvi SJ, et al. J Psychosom Res 2011;70:99-109; Serretti A, Chiesa A. Clin Pharmacol Ther 2011;89(1): Management of Weight Gain In meta-analysis, average weight gain is small 1 A few patients may experience large weight gain due to their own genetic predispositions and other factors Large weight gain typically occurs gradually over many months 1 Monitor patients for change in weight, appetite, metabolic factors Diet and exercise If significant weight gain occurs, consider switching to an agent with less risk of weight change Can also consider augmentation (bupropion*, topiramate*, zonisamide*, metformin*, orlistat) 2 New obesity drugs: topiramate/phentermine, lorcaserin 2 * Not FDA approved for this indication 1. Serretti A, Mandelli L. J Clin Psychiatry 2010;71(10): Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 5th ed. New York, NY; CUP; In press. Partial Response Common Augmentation Strategies 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% STAR*D: Percent Response and Remission by Levels 48.6% 36.8% 30.6% 28.5% 16.8% 16.3% 13.7% 13.0% Level 1 Level 2 Level 3 Level 4 The further along treatment goes, the less change actually occurs Response Remission Rush AJ, et al. Am J Psychiatry 2006;163:

9 Patients Relapsing STAR*D: Increasing Relapse Rates With Every Treatment Failure STAR*D Relapse Rates After 1 Failure After 2 Failures After 3 Failures Lithium Augmentation*: What is the Evidence? Augmenting response (meta-analysis) 1 10 studies, various antidepressants Significant benefit vs. placebo; NNT = 4 Augmenting remission (STAR*D) 2 Benefit not confirmed Accelerating response (meta-analysis) 1 5 studies, tricyclic antidepressants (TCAs) No benefit (trend) Overall: evidence strongest for augmenting TCAs Level 1 Level 2 Level 3 Level 4 Rush AJ, et al. Am J Psychiatry 2006;163: * Not FDA approved for this indication NNT: number needed to treat. 1. Crossley NA, Bauer M. J Clin Psychiatry 2007;68(6):35-40; 2. Nierenberg AA, et al. Am J Psychiatry 2006;163: Triiodothyronine (T3) Augmentation*: What is the Evidence? Augmenting remission (STAR*D) 2 Trend favoring T3 over lithium (methodological factors?) Augmenting response (meta-analysis) 1 8 studies, TCAs Significantly increased response rate; NNT = 4.3 Augmenting response to SSRIs (various studies) 3 Mixed results; placebo-controlled study showed no benefit Overall: evidence strongest for augmenting TCAs * Not FDA approved for this indication 1. Aronson R, et al. Arch Gen Psychiatry 1996;53: Joffe RT, et al. Can J Psychiatry 2006;51: Connolly RK, Thase ME. Drugs 2011;71(1): Atypical Antipsychotic Augmentation: What is the Evidence? Studied as adjuncts to SSRIs/SNRIs Aripiprazole and quetiapine XR are approved as adjuncts; olanzapine-fluoxetine combo is approved, risperidone has data, lurasidone is being studied Most studies show a beneficial effect of combination treatment over monotherapy, but Effect sizes have been modest There is little head-to-head data with other strategies The adverse event profiles of atypical antipsychotics should put them late in a treatment algorithm None have been studied systematically for "advanced resistant depression" (>2 failure) Citrome L. Postgrad Med 2010;122(4): Nutraceutical Treatments for Depression l-methylfolate* 1 15 mg/day S-adenosyl methionine** mg twice per day N-acetyl cysteine** mg twice per day Common but Unsupported and/or Understudied Strategies Buspirone 1-4 Mechanistically makes sense The limited data are mixed/weak Stimulants 5 Limited controlled data show trend of benefit *Medical food for suboptimal folate levels in depressed patients (adjunct to antidepressant) **Not FDA approved for this indication 1. Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 5th ed. New York, NY: CUP; In press; 2. Nahas R, Sheikh O. Can Fam Physician 2011;57: Berk M, et al. BMC Med 2012;10: Connolly KR, Thase ME. Drugs 2011;71(7):43-64; 2. Landen M et al. J Clin Psychiatry 1998;59:664-8; 3. Appelberg BG et al. J Clin Psychiatry 2001;62:448-53; 4. Trivedi MH et al. N Engl J Med 2006;354: ; 5. Trivedi MH et al. Poster presented at APA

10 Common but Unsupported and/or Understudied Strategies (cont.) DA agonists Pramipexole: evidence of efficacy in unipolar and bipolar depression and for depressive symptoms in Parkinson's disease 1 Ropinirole: effective and well tolerated in a small pilot study of unipolar and bipolar depression 2 Modafinil/armodafinil: evidence of efficacy in unipolar and bipolar depression 3-4 Common but Unsupported and/or Understudied Strategies (cont.) Antidepressant combinations Limited data in poorly responding population Theoretical advantages over switching Preserves the response to the first antidepressant Adds mechanisms of action to "broaden" the neurochemical and thus clinical actions Is any response attributable to Drug B, Drug A+B, or to continued time on Drug A? 1. Aiken CB. J Clin Psychiatry 2007;68(8):1230-6; 2. Cassano P et al. Can J Psychiatry 2005;50(6):357-60; 3. Calabrese JR et al. J Clin Psychiatry 2010;71(10): ; 4. Fava M et al. J Clin Psychiatry 2005;66(1): Connolly KR, Thase ME. Drugs 2011;71(7): Symptom-Specific Strategies for Common Residual Symptoms Residual Pain anxiety concentration sleep disturbance fatigue vasomotor psychomotor depressed mood interest/ guilt/ pleasure sexual worthlessness dysfunction Symptom Pain Neurotransmitter Treatment strategy* system involved Use SNRI, TCA NE Add alpha 2 delta ligand (calcium channel blocker) or sodium channel blocker pain suicidality appetite/ weight sleepiness/ hypersomnia Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. New York, NY: CUP; 2013 *Not FDA approved for treating pain in depression Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. New York, NY: CUP; 2013 Depressed Mood Disrupts Brain Deactivation and Enhances Pain Unpleasantness 20 healthy volunteers Red/green: activation vs. rest Blue: deactivation vs. rest Significant lack of deactivation during pain in the depressed mood state Patients reporting greatest increase in pain unpleasantness after sad mood induction showed greater inferior frontal gyrus and amygdala activation Plotted on the average MNI 152 brain; Z coordinates are on the MNI system Berna C, et al. Biol Psychiatry 2010;67: back pain stomach pain muscle/ joint pain 5HT descending projections: less pivotal in pain dampening than NE because they can both inhibit and facilitate pain. Pain in Depression: The Role of Norepinephrine descending NE projections deficient NE release digestion back posture muscle/joint movement Stahl SM. Stahl's Essential Psychopharmacology. 3rd ed. New York, NY: CUP;

11 SNRIs for Painful Symptoms Duloxetine (approved for multiple neuropathic pain disorders) 60 mg once daily; higher doses increase side effects without increasing efficacy in pain disorders Milnacipran (approved for fibromyalgia) mg/day in 2 doses Venlafaxine XR mg once daily Desvenlafaxine 50 mg once daily Tricyclic antidepressants Cyclobenzaprine (muscle relaxant) 15 mg/day in 3 doses; mg/day in 1 dose (ER) Not recommended for long-term use Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 5th ed. New York, NY: CUP; In press. Alpha 2 Delta Ligands (Calcium Channel Blockade) for Painful Symptoms Pregabalin (approved for multiple neuropathic pain disorders) mg/day in 2 3 doses Gabapentin (approved for postherpetic neuralgia) mg/day in 3 doses Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 5th ed. New York, NY: CUP; In press. Relief of Painful Excessive Nociceptive Activity With Alpha 2 Delta Ligands = alpha 2 delta ligand Sodium Channel Blockers Antiepileptic and neuropathic pain medications may be helpful Carbamazepine Lamotrigine Topiramate neuropathic pain Stahl SM. Stahl's Essential Psychopharmacology. 3rd ed. New York, NY: CUP; Stahl SM. Stahl's Essential Psychopharmacology: The Prescriber's Guide. 5th ed. New York, NY: CUP; In press. Relief of Painful Excessive Nociceptive Activity With Sodium Channel Blockers topiramate zonisamide carbamazepine phenytoin oxcarbazepine Stahl SM. Stahl's Essential Psychopharmacology. 3rd ed. New York, NY: CUP; Non-Pharmacologic Treatments to Address Partial Response Electroconvulsive therapy (ECT) Vagus nerve stimulation (VNS) Repetitive transcranial magnetic stimulation (rtms) Deep brain stimulation (DBS) Psychotherapy Augmentation may decrease depressive symptoms as much as pharmacologic augmentation Family therapy Coping skills including assertiveness training and problem solving strategies Keitner GI, Mansfield AK. Psychiatr Clin N Am 2012;35:

12 Psychotherapy vs. Pharmacotherapy: Meta-Analysis Dx N g 95% CI I 2 95% CI Any mood to to 47 disorder MDD to to 63 Dysthymia * to to 83 Mixed mood disorder to to 88 Negative numbers favor pharmacotherapy *p<0.01 for effect of disorder, with pharmacotherapy superior to psychotherapy for dysthymia Summary Patient education and slower titration can often be sufficient to address early, short-term side effects Long-term side effects do not often spontaneously disappear and may require switching or augmentation to avoid patient discontinuation of medication Establishing markers and using rating scales can aid in the detection of troubling residual symptoms Common residual symptoms can be targeted by using augmentation strategies that apply mechanistic rationale Cuijpers P et al. World Psychiatry 2013;12: Outcomes Question 1 Outcomes Question 2 A 31-year-old man presents complaining of insomnia, constant fatigue, lack of appetite, psychomotor retardation, depressed mood, and feelings of helplessness. He completes the Patient Health Questionnaire with a score of 16, indicating moderate depression. Which of his symptoms might be a particular warning sign for suicidality, warranting further assessment? 1. Insomnia 2. Fatigue 3. Helplessness 4. 1 and and 3 A 44-year-old woman has been taking an SSRI for 3 months. At her follow-up visit, she informs you that although her mood has improved with treatment, she is having problems engaging in sexual activity with her husband. What treatment option might be appropriate to address her sexual dysfunction? 1. Serotonin 2 partial agonist or serotonin 1A partial agonist 2. Serotonin 1A partial agonist or serotonin 2 antagonist 3. Serotonin 2 antagonist or serotonin 1A antagonist 4. Serotonin 1A antagonist or serotonin 2 partial agonist Outcomes Question 3 A 29-year-old woman has just been diagnosed with major depressive disorder and is being prescribed a selective serotonin reuptake inhibitor (SSRI). In addition to depressed mood, lack of interest in her work or friends, and difficulty sleeping, she has been experiencing aches and pains in her arms, shoulders, and torso. She asks if the SSRI is likely to alleviate her painful physical symptoms as well as her emotional ones. Which of the following statements is true? 1.SSRIs may have inconsistent effects on pain because serotonin can both inhibit and facilitate ascending nociceptive signals 2.SSRIs may worsen pain because serotonin can facilitate but not inhibit ascending nociceptive signals 3.SSRIs generally alleviate pain because serotonin can inhibit but not facilitate ascending nociceptive signals 4.SSRIs generally have no effect on pain because serotonin neither facilitates nor inhibits nociceptive signals Question & Answer 9