Educational Objectives:

Transcription

1 Managing Depression in Primary Care Controversies in Women's Health December 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) Describe current guidelines for management of depression in pregnancy 4) Understand risks of Osteoporosis, GI bleeding, QTc prolongation, and Suicide with antidepressants Relevant Disclosures none 1

2 Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc, and Suicide Questions and Summary Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc, and Suicide Questions and Summary The Crazy State of Psychiatry, by Marcia Angell 2

3 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 In Defense of Antidepressants American Psychiatric Association Practice Guidelines for Depression Agency for Health Care Policy and Research, Clinical Practice Guidelines Cochrane Review ab html In Defense of Antidepressants, by Peter Kramer (The New York Times, July 9, 2011) Bottom Line: The milder the depression, the more difficult it is for treatments to separate from placebo. 3

4 Other options Psychotherapy Bibliotherapy Self-help organizations Exercise Light therapy Complementary/alternative medications Bibliotherapy Feeling Good, by David Burns Mind Over Mood, by Greenberger and Padefsky Self Help organizat ions 4

5 Outline Current Controversies Overview of Antidepressants SSRIs Other Antidepressants TCAs MAOIs Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc and Suicide Questions and 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) SSRI: Side Effects Categories Early and frequently transient Early and persist: sexual dysfunction Gradually and accrue: weight gain 5

6 Early and Transient Examples: Nausea or dull headache Jitteriness Gi upset Early and Transient Strategies: 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 6

7 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: Second Generation Antidepressants Mirtazapine (Remeron): sedation and weight gain Second Generation Antidepressants Nefazodone (Serzone): 5-HT2 blocker,?for anxious depression black box for liver failure (1/250K pt-yrs) low rate of sexual se s 7

8 Second Generation Antidepressants Trazodone (Desyrel): usually prescribed as a hypnotic Warn about priapism Second Generation Antidepressants Venlafaxine (Effexor): Mixed NE and 5HT activity increases BP similar side effect profile to ssri s significant withdrawal syndrome Note: Duloxetine, a newer dual action antidepressant, has more equal 5HT and NE effects across its dosage range. 8

9 Tricyclic Antidepressants (TCA s ) NE reuptake inhibitors anticholinergic side effects, orthostatic hypotension, tremor, weight gain, sexual side effects, cardiac conduction delay (quinidine like effect) 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: ,

10 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! 10

11 SSRI s SGA ( Other ) Tricyclics MAOI s Antidepressants Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Sedation Sexual Dysfunction Weight Gain Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc and Suicide Questions and 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):

12 Case Vignette Depressed for 2 months, No medical problems, No comorbidities Which ONE of the following is the best medication intervention? 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 How to pick antidepressant? Current evidence does not warrant the choice of one antidepressant over another on the basis of differences in efficacy and effectiveness. 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:

13 Choosing an Antidepressant is Not Based on Efficacy? Clinically important differences exist for both efficacy and acceptability in favour of escitalopram and sertraline. 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 SSRI s and SGA s Safer than: Tricyclics MAOI s How to pick antidepressant? Patient preference Patient or Family history of response Clinician familiarity Comorbidities--Side effect profile 13

14 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%) 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),

15 Choosing an Antidepressant Side Effects Sedation/activation Sexual dysfunction Weight gain (Cost) 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),

16 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) Case Vignette No medical problems Depressed for 2 months Fears loss of libido 16

17 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 DEPRESSION DECREASED LIBIDO ANTIDEPRESSANT AROUSAL DISORDER ORGASM DYSFUNCTION Segraves. J Clin Psychiatry Monogr Effect on sexual functioning Increased? Neutral or mixed Common Psychostimulants Bupropion Nefazadone Mirtazapine Duloxetine Tricyclics Maoi s Ssri s,venlafaxine Kelly, K, Posternak, M, & Alpert, J E. (2008). Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues in clinical neuroscience, 10(4),

18 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) 18

19 Case Vignette No medical problems Depressed for 2 months Obesity Weight loss Impact on weight Weight loss (?) Neutral or mixed mild to moderate Significant psychostimulants Bupropion Nefazadone Ssri s (fluoxetine < paroxetine) Maoi s Tricyclics 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), Weight Management strategies 19

20 Sample Year End Diary Entry Alcohol units 3836 (poor) Cigarettes 5277 Calories 11,090,265 (repulsive) 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] Weight Management strategies (Off-Label) 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 20

21 Choosing an Antidepressant Side Effects 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! 21

22 Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc and Suicide Questions and Summary Antidepressants in Pregnancy 2.3% (ca. 100K) out of 4 million infants born in the U.S. are exposed to SSRIs 30% of these discontinue ssri before second month of pregnancy 14.6% of pregnant women have diagnosis of substance abuse disorder Half of pregnancies in US are unplanned Antidepressants in Pregnancy Baseline risk for birth defects is around 3% No randomized, controlled studies Not able to control for effects of depression during pregnancy Most studies indicate that SSRIs are associated with a small absolute risk, if any, for major defects 22

23 Depression Relapse in Pregnancy: Cohen et al. 2006: 43% of the women experienced relapse during pregnancy 26% who maintained medication relapsed 68% who discontinued medication relapsed Cohen L, Altshuler L, Harlow B et al. Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment. JAMA Vol 295 (5),: , 2006.?pregnancy + currently on ADs Yonkers KA et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. General Hospital Psychiatry 2009; 31: Considering pregnancy, taking ADs -Consider delay conceiving until stable -If in full remission, but h/o both recurrence and non-response to psychotherapy, continue meds -If in full remission with no h/o recurrence and/or non-response to psychotherapy, consider taper off medication and refer for therapy Yonkers KA et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. General Hospital Psychiatry 2009; 31:

24 Pregnant, depressed, not taking ADs -If depression is severe, start meds -If depression is not severe, and: -If pt has never failed a course of therapy, do therapy -If pt has failed therapy, start meds Yonkers KA et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. General Hospital Psychiatry 2009; 31: Pregnant, depressed, taking ADs -If depression is severe or therapy has been ineffective, continue and optimize meds -If depression is not severe, and pt has either responded to therapy before or has never had therapy, start therapy either in combination with meds or (if symptoms are relatively mild) with a med taper Yonkers KA et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. General Hospital Psychiatry 2009; 31: Which antidepressant is best in pregnancy? 24

25 Antidepressants in Pregnancy Beware of using newer or less well studied ADs just because of lack of data Recommend monotherapy with lowest possible dose Consultations can be very useful See also Wisner, K. L. (2010), SSRI treatment during pregnancy: are we asking the right questions?. Depression and Anxiety, 27: doi: /da Outline Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc and Suicide Questions and Summary GI Bleeding 25

26 SSRIs and GI bleeding Two potential mechanisms: platelet aggregation, gastric acidity Overall risk is low: 1 per 8000 SSRI prescriptions Associated also with increased blood loss during surgical procedures. TCAs, mirtazapine, and bupropion NOT associated with bleeding What s the bottom line? You should mention this risk in the following situations: history of stomach ulcers or bleeding disorders. about to have surgery (consider stopping SSRI a few days in advance). taking NSAIDs, aspirin, warfarin, or antiplatelet drugs (clopidogrel). Osteoporosis 26

27 SSRIs and osteoporosis Two observational studies in Archives of Internal Medicine: Women on SSRIs lost double the bone density of those either on tricyclics or on no antidepressants (2-year) Men on SSRIs had 4-6% lower bone density than men on no antidepressants (crosssectional) Diem SJ et al., 2007;167(12): Haney EM et al. 2007;167(12): SSRIs and osteoporosis More recent study, with longer followup, found association with: wrist fracture (HR = 1.30, 95% CI ), but not with first hip fracture (HR = 1.01, 95% CI ) Diem SJ et al. Use of Antidepressant Medications and Risk of Fracture in Older Women. Calcif Tissue Int (2011) 88: The bottom line Warn your elderly patients about osteoporosis, even though the findings are still preliminary. 27

28 QTc and Citalopram QTc and Citalopram trial of 119 adults showed that QTc is increased in a dose-dependent fashion with citalopram Dosage QT prolongation CI (msec) 20mg 8.5msec mg 18.5msec mg 12.6msec inferred Bottom Line Check EKG before you go higher than 40mg, then again after they have been on a higher dose If they're already on a higher dose, just check the EKG If QTc in men over 450 and women over 500, consider decreasing dosage or switching to escitalopram Review other risk factors for increased QTc 28

29 Antidepressants and Suicide Risk Suicide Risk and Antidepressants In 2004, FDA issued a black box warning for children and adolescents warning of a risk of suicidal events. In 2007, another black box warning issued for adults up to 25 years of age. (based on an odds ratio, 1.55; 95% confidence interval, 0.91 to 2.70) Friedman RA and Leon AC. Expanding the black box - depression, antidepressants, and the risk of suicide. NEJM 2007 Jun 7;356(23): Epub 2007 May 7. Suicide Risk and Antidepressants Furthermore, benefit of antidepressants in pediatric patients is controversial Bridge JA et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA 2007;297:

30 Suicide Risk and Antidepressants Increase in suicidal ideation in children up to age 18, but not actual suicide. Probably suicide neutral or slightly beneficial in yr age range Hammad et al. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006;63: Stone M et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 2009 Aug 11;339:b2880. Odds Ratios for Suicidal Behavior and Ideation among Patients Treated with Antidepressants for Psychiatric Indications, as Compared with Placebo. Data are from the Summary Comments of the December 13, 2006, meeting of the FDA's Psychopharmacologic Drugs Advisory Committee. CI denotes confidence interval. Bottom line In younger patients (<25years), suicide risk is increased Risk decreases with increasing age Warn younger patients (and their families) to monitor for increased suicidality 30

31 Summary Current Controversies Overview of Antidepressants Antidepressants: Selection and Side Effect Management Antidepressants in Pregnancy Osteoporosis, GI bleeding, QTc and Suicide Questions (and Answers?) Questions 31

32 Management of Depression in Primary Care Controversies in Women s Health, San Francisco 2011 Descartes Li, M.D. descartes.li@ucsf.edu Current Controversy Antidepressant Overview SSRI s (selective serotonin reuptake inhibitors) First line, Fairly safe in OD, Recommend 9m minimum duration of treatment Management of early and transient side effects: gi upset, jitteriness, nausea, HA Start low and go slow Reassurance For anxiety/nervousness: add low-dose benzodiazepines Other 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 Duloxetine (Cymbalta): mixed NE and 5HT activity, Alleviate pain of diabetic neuropathy and fibromyalgia? 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 Venlafaxine (Effexor): Mixed NE and 5HT activity increases BP similar side effect profile to ssri s significant withdrawal syndrome Trazodone (Desyrel): usually prescribed as a hypnotic Warn about priapism Tricyclic Antidepressants (TCA s ) NE reuptake inhibitors anticholinergic side effects, orthostatic hypotension, tremor, weight gain, sexual side effects, cardiac conduction delay (quinidine like effect) Monoamine-oxidase inhibitors (MAOIs) Important: dietary restrictions! (b/o hypertensive crisis) MAOI Diet and Multiple Drugs to Avoid with MAOI s: Remember to look it up! Choosing an Antidepressant based on Side Effects Cipriani et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: Rational Antidepressant Selection Choosing an Antidepressant History of response in pt (or family) Side Effects Patient preference Sedation/activation Clinician familiarity Weight gain Side effect profile Sexual dysfunction Co-morbidities (Cost)

33 Management of Depression in Primary Care Controversies in Women s Health, San Francisco 2011 Descartes Li, M.D. descartes.li@ucsf.edu Relative Activation of various Antidepressants Activating Neutral or mixed Mildly to Moderately Sedating Strongly sedating psychostimulants Bupropion Fluoxetine, Sertraline Venlafaxine, Escitalopram Citalopram Paroxetine, Fluvoxamine Nefazodone Tricyclics Trazadone Mirtazapine Relative Weight Gain Potential Weight loss (?) Neutral or mixed psychostimulants Bupropion Nefazodone mild to moderate Ssri s (fluoxetine < paroxetine) Significant Maoi s Tricyclics mirtazapine Effect on Sexual Functioning Drug & Strength, Unit cost (per Drugstore.com, 7/16/11) Increased? Psychostimulants Bupropion Budeprion XL 150MG Tabs Wellbutrin SR 150MG Tab $1.64 $3.62 Neutral or mixed Nefazadone Mirtazapine Duloxetine Escitalopram 10MG Tab Fluoxetine HCl 20MG Cap $3.50 $0.57 Common Tricyclics Maoi s Ssri s,venlafaxine Mirtazapine 15mg Tab, 30mg $1.67 Sertraline HCl 100MG Tab $0.33 Venlafaxine HCl 75mg Cap $1.88 Side Effect Management Summary (N.B. Medication recommendations are off-label) Sedation Sexual Dysfunction Weight Gain Review other meds Switch from am to hs dosing Reduce dosage Switch to another AD?Consider psychostimulant: methylphenidate or dextroamphetamine or modafinil Dose reduction Timing of sexual activity Drug holiday Anti-dote therapy: buspirone 45mg qd DA agonists: amantadine bupropion 300mg qd a 2 -adrenergic receptor antagonists: yohimbine psychostimulants: methylphenidate 5-20mg PDE-5 inhibitors: Sildenafil mg qd 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

34 Management of Depression in Primary Care Controversies in Women s Health, San Francisco 2011 Descartes Li, M.D. descartes.li@ucsf.edu Non-pharmacological options for depression Psychotherapy Bibliotherapy Feeling Good, by David Burns Mind Over Mood, by Greenberger and Padefsky Self-help organizations (NAMI.org, DBSAlliance.org) Exercise, Light therapy Complementary/alternative medications Osteoporosis, GI bleeding, QTc Prolongation, and Suicide Issue bottom line references GI bleeding and SSRIS You should mention this risk in the following situations: history of stomach ulcers or bleeding disorders. about to have surgery (consider stopping SSRI a few days in advance). taking NSAIDs, aspirin, warfarin, or antiplatelet drugs (clopidogrel). Andrade C et al, J Clin Psychiatry 2010;71(12): deabajo FJ et al, BMJ 1999;319(7217): Loke YK et al, Aliment Pharmacol Ther 2008;27(1): vanhaelst LMM et al, Anesthesiology 2010;112(3): Movig KLL et al, Arch Intern Med 2003;163: Osteoporosis and SSRIs QTc and Citalopram (Celexa) Suicide and Antidepressan ts Warn your elderly patients about osteoporosis, even though the findings are still preliminary. Check EKG before you go higher than 40mg, then again after they have been on a higher dose If they're already on a higher dose, just check the EKG If QTc in men > 450 and women > 500, consider decreasing dosage or switching to escitalopram Review other risk factors for increased QTc In younger patients (<25years) Suicide risk is increased Risk decreases with increasing age Warn younger patients (and their families) to monitor for increased suicidality Diem SJ et al., 2011 Calcif Tissue Int 88: Haney EM et al., Arch Intern Med. 2007;167(12): Diem SJ et al., Arch Intern Med 2007;167(12): m htm See also: Vieweg, W V. (2003). Primary care companion to the Journal of clinical psychiatry, 5(5), Olfson M and Marcus SC, J Clin Psychiatry 2008;69: ). Stone M et al. BMJ 2009 Aug 11;339:b2880. Bridge JA et al. JAMA 2007;297: Friedman RA and Leon AC. NEJM 2007 Jun 7;356(23): See also:

35 Management of Depression in Primary Care Controversies in Women s Health, San Francisco 2011 Descartes Li, M.D. descartes.li@ucsf.edu Pregnancy and Antidepressants For 2009 guidelines on management of depression during pregnancy, see: Yonkers KA et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. General Hospital Psychiatry 2009; 31: This paper also has more detailed algorithms (figures 1-3). Current APA/ACOG Recommendations for Managing Depression during Pregnancy in Three Scenarios 1. Considering pregnancy, taking ADs -If moderate to severe depressive symptoms, delay conceiving, continue and optimize meds until stable -If in early remission (started AD less than 6 months ago), delay conceiving, continue meds until stable -If in full remission, but history of both recurrence and non-response to psychotherapy, continue meds through pregnancy -If in full remission, no recurrent depression and/or positive prior response to therapy, taper off medication and refer for therapy 2. Pregnant, depressed, taking ADs -If depression is severe, continue and optimize meds -If depression is not severe, and: -If pt has either responded to therapy before or has never had therapy, start therapy either in combination with meds or (if symptoms are relatively mild) with a med taper -If pt has failed therapy, continue meds 3. Pregnant, depressed, not taking ADs -If depression is severe, start meds -If depression is not severe, and: -If pt has never failed a course of therapy, do therapy -If pt has failed therapy, start meds See also the Organization of Teratology Information Specialists: At This site has lots of handouts for patients and opportunities for patients to be followed in prospective, observational cohort studies.

36 Management of Depression in Primary Care Controversies in Women s Health, San Francisco 2011 Descartes Li, M.D. descartes.li@ucsf.edu Selected References: The Epidemic of Mental Illness: Why?, Illusions of Psychiatry, by Marcia Angell (The New York Review of Books, June 23, 2011 and July 14, 2011) Turner E et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM (3):252 In Defense of Antidepressants, by Peter Kramer (The New York Times, July 9, 2011) Furukawa, T A, Streiner, D L, & Young, L T. (2001). Is antidepressant-benzodiazepine combination therapy clinically more useful? A meta-analytic study. J Aff Disord, 65(2), Gartlehner et al. Comparative Benefits and Harms of Second-Generation Antidepressants. Ann Intern Med. 2008;149: Cipriani et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: 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), Kelly, K, et al. (2008). Toward achieving optimal response: understanding and managing antidepressant side effects. Dialog Clin Neurosci, 10(4), Fava M et al, Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry 2007;19(3): Nurnberg HG, Henslely PL, Gelenberg AJ, Fava M, Lauriello J, Paine S. Treatment of antidepressant-associated sexual dysfunction with sildenafil. JAMA. 2003;289: Nurnberg HG et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. JAMA. 2008;300: Rothschild AJ. Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a drug holiday. Am J Psychiatry. 1995;152: 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. Int J Obes, 2011 Mar 29. [Epub ahead of print] Orlistat: Hallander PA et al, Diabetes Care 1998;21(8): Bupropion+naltrexone: Greenway FL et al, Lancet 376(9741): Metformin: Praharaj SK et al. Br J Clin Pharmaco 2011;71(3): 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;80:39-47.