Educational Objectives: Outline. Relevant Disclosures. Managing Depression in Primary Care Lake Tahoe, August 2011

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1 Managing Depression in Primary Care Lake Tahoe, August 2011 Descartes Li, M.D. Clinical Professor University of California, San Francisco Educational Objectives: By the end of the presentation, a participant will be able to: 1) Choose antidepressant based on side effect profile 2) Manage common antidepressant related side effects 3) Understand risks of suicide, osteoporosis, and bleeding with antidepressants Outline Relevant Disclosures none Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Non-pharmacological treatments Questions Summary 1

2 Outline The Crazy State of Psychiatry, by Marcia Angell Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Non-pharmacological treatments Questions Summary How generalizable are study findings? In one study of psychiatric outpatients, only 41 (12%) of 346 patients would have been eligible for typical research studies. Zimmerman M et al. Are subjects in pharmacological treatment trials of depression representative of patients in routine clinic practice? Am J Psychiatry. 2002;159(3): Turner E et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM (3):252 2

3 In Defense of Antidepressants American Psychiatric Association Practice Guidelines for Depression Agency for Health Care Policy and Research, Clinical Practice Guidelines Cochrane Review 54.html In Defense of Antidepressants, by Peter Kramer (The New York Times, July 9, 2011) Bottom Line: For mild depression, watchful waiting is a reasonable option Outline Current Controversies Overview of Antidepressants SSRIs Other Ads TCAs MAOIs Antidepressants: Selection and Side Effect Management Non-pharmacological treatments Questions Summary SSRI s (selective serotonin reuptake inhibitors) First line Fairly safe in OD 9m minimum duration of treatment Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro) Categories SSRI: Side Effects Early and frequently transient Early and persist: sexual dysfunction Gradually and accrue: weight gain 3

4 Early and Transient Examples: Nausea or dull headache Jitteriness Gi upset Strategies: Early and Transient Start low and go slow Reassurance For anxiety/nervousness: add lowdose benzodiazepines For sedation: see later Furukawa, T A, Streiner, D L, & Young, L T. (2001). Is antidepressant-benzodiazepine combination therapy clinically more useful? A meta-analytic study. Journal of affective disorders, 65(2), Second Generation Antidepressants Buproprion (Wellbutrin): Low rate of sexual side effects or wt gain, Assoc. w/ increased rate of seizures, not for pts w/ eating d/o or prior sz d/o Second Generation Antidepressants Duloxetine (Cymbalta): mixed NE and 5HT activity, Alleviates pain of diabetic neuropathy and fibromyalgia Kajdasz DK et al, Clin Ther 2007;29 Suppl:

5 Second Generation Antidepressants Second Generation Antidepressants Mirtazapine (Remeron): sedation and weight gain Nefazodone (Serzone): 5-HT2 blocker,?for anxious depression black box for liver failure (1/250K pt-yrs) low rate of sexual se s Second Generation Antidepressants Second Generation Antidepressants Trazodone (Desyrel): usually prescribed as a hypnotic Warn about priapism Venlafaxine (Effexor): Mixed NE and 5HT activity increases BP similar side effect profile to ssri s significant withdrawal syndrome 5

6 Tricyclic Antidepressants (TCA s ) NE reuptake inhibitors anticholinergic side effects, orthostatic hypotension, tremor, weight gain, sexual side effects, cardiac conduction delay (quinidine like effect) Note: Duloxetine, a newer dual action antidepressant, has more equal 5HT and NE effects across its dosage range. Examples [not a complete list]: amitriptyline (Elavil), doxepin (Sinequan), imipramine (Tofranil), desipramine (Norpramin), nortriptyline (Pamelor, Aventyl), maprotiline (Ludiomil) Monoamine-oxidase inhibitors (MAOIs) Who was Libby Zion? Prevalence of MAOI usage Psychiatrists who had prescribed MAOIs Never 12 Not for at least three years 27 Between one to three years ago 17 Between three and 12 months ago Percentage (N=573) 14 Within last 3 months 30 Balon R et al. A Survey of Prescribing Practices for Monoamine Oxidase Inhibitors. Psychiatric Services 50: ,

7 Monoamine-oxidase inhibitors (MAOIs) Important: dietary restrictions! (b/o hypertensive crisis) Also drug-drug interactions Side effects: sedation, sexual side effects, weight gain phenelzine (Nardil), trancylopramine (Parnate), [selegiline (Eldepryl) for Parkinson s] MAOI Diet Avoid: aged cheese aged or cured meats (e.g., air-dried sausage); any potentially spoiled meat, poultry, or fish; broad (fava) bean pods; Marmite concentrated yeast extract; sauerkraut; soy sauce and soy bean condiments; and tap beer. Wine and domestic bottled or canned beer are considered safe when consumed in moderation. Refer to article and give handout to patient J Clin Psychiatry 1996 Mar;57(3): The making of a user friendly MAOI diet. MAOI Summary Make sure you look up dietary restrictions! SSRI s SGA ( Other ) Tricyclics MAOI s Antidepressants 7

8 Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Sedation Sexual Dysfunction Weight Gain Non-pharmacological treatments Questions Summary As you write that Rx Patients told to stay on ADs for at least 6 months were three times more likely to continue their meds Discussing side effects was also associated with staying the course longer Bull SA et al. Discontinuation of use and switching of antidepressants: influence of patient-physician communication. JAMA 2002;288 (11): Case Vignette Depressed for 2 months, No medical problems, No comorbidities Which ONE of the following is the best medication intervention? How to pick antidepressant? a. Bupropion 150mg twice daily b. Duloxetine 40mg daily c. Fluoxetine 20mg daily d. Imipramine titrated up to 100mg at bedtime e. Venlafaxine 300mg daily B u p r o p i o n m... 15% D u l o x e t i n e 4 0 m... 8% F l u o x e t i n e 2 0 m... 75% I m i p r a m i n e t i t... 2% 0% V e n l a f a x i n e

9 Current evidence does not warrant the choice of one antidepressant over another on the basis of differences in efficacy and effectiveness. Choosing an Antidepressant is Not Based on Efficacy? Clinically important differences exist for both efficacy and acceptability in favour of escitalopram and sertraline. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication. Gartlehner et al. Comparative Benefits and Harms of Second-Generation Antidepressants. Ann Intern Med. 2008;149: Sertraline might be the best choice Cipriani et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: Do No Harm How to pick antidepressant? SSRI s and SGA s Safer than: Tricyclics MAOI s Patient preference Patient or Family history of response Clinician familiarity Comorbidities--Side effect profile 9

10 The person who takes medicine must recover twice, once from the disease and once from the medicine. Attributed to William Osler, MD The Maze of Mood Medications How do you choose? Food Fast Good Cheap Meds Sedation Sexual dysfunction Weight gain (Cheap) Of 401 out- patients taking SSRIs: Most Common drowsiness (38%) dry mouth (34%) sexual dysfunction (34%) Most Bothersome drowsiness (17%) sexual dysfunction (17%) weight gain (11%) N.B. Good side effect management means good follow-up! Hu, X H, Bull, S A, Hunkeler, E M, et al. (2004). Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry, 65(7), Choosing an Antidepressant Side Effects Sedation/activation Sexual dysfunction Weight gain (Cost) 10

11 Case Vignette No medical problems Depressed for 2 months Hypersomnia Insomnia or anxious Activating Neutral or mixed Mildly to Moderately Sedating Strongly sedating Relative activation vs. Sedation modern antidepressants psychostimulants Bupropion Fluoxetine, Sertraline Venlafaxine, Escitalopram Citalopram Paroxetine, Fluvoxamine Nefazodone Tricyclics Trazadone Mirtazapine Kelly, K, Posternak, M, & Alpert, J E. (2008). Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues in clinical neuroscience, 10(4), Sedation Management Strategies Review other meds Switch from am to hs dosing Reduce dosage Switch to another AD?Consider psychostimulant: methylphenidate or dextroamphetamine or modafinil (this is off-label) Fava M et al, Ann Clin Psychiatry 2007;19(3): Choosing an Antidepressant Side Effects Sedation/activation Sexual dysfunction Weight gain (Cost) 11

12 Case Vignette No medical problems Depressed for 2 months Fears loss of libido Sexual dysfunction is common Women: 43% total, 22% low libido, 14% sexual arousal problems, 7% pain Men: 31% total, 21% premature ejaculation, 5% erectile dysfunction, 5% low libido Remember to ask about sexual functioning beforehand Laumann EO et al, JAMA 1999;281(6): SEXUAL DYSFUNCTION Effect on sexual functioning Increased? Psychostimulants Bupropion DEPRESSION DECREASED LIBIDO ANTIDEPRESSANT Neutral or mixed Nefazadone Mirtazapine Duloxetine AROUSAL DISORDER ORGASM DYSFUNCTION Common Tricyclics Maoi s Ssri s,venlafaxine Segraves. J Clin Psychiatry Monogr Kelly, K, Posternak, M, & Alpert, J E. (2008). Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues in clinical neuroscience, 10(4),

13 Sexual Dysfunction Strategies Dose reduction Timing of sexual activity Drug holiday Anti-dote therapy: (off-label) Sexual Dysfunction Strategies anti-dote therapy: (off-label) buspirone 45mg qd dopamine (DA) agonists: amantadine bupropion 300mg qd α 2 -adrenergic receptor antagonists: yohimbine psychostimulants: methylphenidate 5-20mg PDE-5 inhibitors: Sildenafil mg qd Choosing an Antidepressant Side Effects Sedation/activation Sexual dysfunction Weight gain (Cost) Case Vignette No medical problems Depressed for 2 months Obesity Weight loss 13

14 Impact on weight Weight loss (?) Neutral or mixed mild to moderate Significant psychostimulants Bupropion Nefazadone Ssri s (fluoxetine < paroxetine) Maoi s Tricyclics mirtazapine Weight Management strategies Kelly, K, Posternak, M, & Alpert, J E. (2008). Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues in clinical neuroscience, 10(4), Sample Year End Diary Entry Alcohol units 3836 (poor) Cigarettes 5277 Calories 11,090,265 (repulsive) Fat units 3457 (approx.) (hideous idea in every way) Weight gained 74 lbs. Weight lost 72 lbs (excellent) Bridget Jones Diary, by Helen Fielding. Penguin Books Weight Management strategies (off label) Life style interventions : Eat healthy, exercise more Get the right amount of sleep and reduce stress* Address dry mouth Switch or add bupropion Add psychostimulants *Elder, C R, Gullion, C M, Funk, K L, et al. (2011). Impact of sleep, screen time, depression and stress on weight change in the intensive weight loss phase of the LIFE study. International journal of obesity, 2011 Mar 29. [Epub ahead of print] 14

15 Weight Management strategies (Off-Label) Choosing an Antidepressant Side Effects Sibutramine (Meridia): removed from US market b/o CV risks Orlistat (Xenical): 120mg tid w meals Bupropion + Naltrexone (Contrave): also rejected b/o increased P and BP (N16mg+B200mg BID) Metformin, studied in patients on atypical antipsychotics Topiramate mg daily Sedation/activation Sexual dysfunction Weight gain Cost Case Vignette No medical problems Depressed for 2 months No money Cost of some psychiatric meds Drug & Strength # Cost Unit cost Budeprion XL 150MG Tabs 180 $ $1.64 Wellbutrin SR 150MG Tab 180 $ $3.62 Clonazepam 2mg tab 90 $23.99 $0.27 Citalopram Hydrobromide 20mg Tab 90 $89.97 $1.00 Diazepam 5mg tab 90 $13.97 $0.16 Escitalopram 10MG Tab 90 $ $3.50 Fluoxetine HCl 20MG Cap 90 $50.97 $0.57 Mirtazapine 15mg Tab, 30mg 90 $ $1.67 Sertraline HCl 100MG Tab* 90 $29.97 $0.33 Venlafaxine HCl 75mg Cap 90 $ $1.88 Zolpidem Tartrate 10mg tab 90 $45.97 $0.51 from Drugstore.com 7/16/11, prices subject to change, about 50% cheaper than local drugstore *Descartes Li Best Buy! 15

16 Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Non-pharmacological treatments Questions Summary Case Vignette Depressed for six months No medical hx, no comorbidities Wants psychotherapy, but can t afford it Okay to prescribe meds? Yes Mergl et al. Are treatment preferences relevant in response to serotonergic antidepressants and cognitive-behavioral therapy in depressed primary care patients? Results from a randomized controlled trial including a patients' choice arm. Psychother Psychosom 2011;80: Depressed for six months No medical hx, no comorbidities Wants meds, should you recommend psychotherapy? No. Case Vignette Mergl et al. Are treatment preferences relevant in response to serotonergic antidepressants and cognitive-behavioral therapy in depressed primary care patients? Results from a randomized controlled trial including a patients' choice arm. Psychother Psychosom 2011;80: Psychotherapy Bibliotherapy Other options Self-help organizations Exercise Light therapy Complementary/alternative medications 16

17 Bibliotherapy Feeling Good, by David Burns Self Help organizations Mind Over Mood, by Greenberger and Padefsky Questions Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Non-pharmacological treatments Questions Summary (Good Side Effect Management means good follow up) 17