Jolene R. Bostwick, PharmD, BCPS, BCPP Clinical Associate Professor Associate Chair, Department of Clinical Pharmacy University of Michigan College

Transcription

1 Jolene R. Bostwick, PharmD, BCPS, BCPP Clinical Associate Professor Associate Chair, Department of Clinical Pharmacy University of Michigan College of Pharmacy Clinical Pharmacist in Psychiatry University of Michigan Health System

2 Disclosure I have NO actual or potential conflict of interest in relation to this educational activity or presentation.

3 Objectives 1. Identify key adverse drug events associated with psychotropic medications used to treat anxiety, depression, and ADHD 2. Describe potential strategies to mitigate adverse events associated with psychotropic medication use

4 BACKGROUND

5 ACHA Survey Findings Within the last 12 months, diagnosed or treated by a professional for the following: Female Male 5 0 Attention deficit and hyperactivity disorder Anxiety Depression Obsessive compulsive disorder Panic attacks American College Health Association. American College Health Association-National College Health Assessment II: Reference Group Executive Summary Fall Hanover, MD: American College Health Association; 2016.Available at: II%20FALL%202015%20REFERENCE%20GROUP%20EXECUTIVE%20SUMMARY.pdf

6 College Students Speak: a survey report on mental health (NAMI) % of respondents N= Adapted from: College Students Speak: a survey report on mental health. Speak_A-Survey-Report-on-Mental-Health-NAMI-2012.pdf

7 College Students Speak: a survey report on mental health (NAMI) Are you no longer attending college because of a mental health related reason?" 36% 64% Yes No

8 College Students Speak: a survey report on mental health (NAMI) When respondents were asked, what might have helped you stay in school?, managing side effects of medications. what triggered your crisis?, medications stopped working. College Students Speak: a survey report on mental health. NAMI/Publications-Reports/Survey-Reports/College-Students-Speak_A-Survey-Report-on-Mental-Health-NAMI pdf

9 ACHA Survey Findings % reporting using prescription drugs that were NOT prescribed to them within the last 12 months: Female Male American College Health Association. American College Health Association-National College Health Assessment II: Reference Group Executive Summary Fall Hanover, MD: American College Health Association; 2016.Available at: II%20FALL%202015%20REFERENCE%20GROUP%20EXECUTIVE%20SUMMARY.pdf

10 Within the last 12 months, students reported the following top four factors affecting individual academic performance 35 Percentage Stress Anxiety Sleep difficulties Depression American College Health Association. American College Health Association-National College Health Assessment II: Reference Group Executive Summary Fall Hanover, MD: American College Health Association; 2016.Available at: II%20FALL%202015%20REFERENCE%20GROUP%20EXECUTIVE%20SUMMARY.pdf

11 Impact of Mental Illness on Performance and Cost Poorer Academic Performance 64% of students with a mental health condition quit school for mental health related reasons Increased Healthcare Costs Annual mental health expenditures in the United States are in the billions People with an anxiety disorder are more likely to utilize health care resources National Alliance on Mental Illness (NAMI) 2012

12 Trends in Prescription Drug Use Available at: Accessed 4/25/16.

13 Trends in Prescription Drug Use Available at: Accessed 4/25/16.

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15 Objectives 1. Identify key adverse drug events associated with psychotropic medications used to treat anxiety, depression, and ADHD 2. Describe potential strategies to mitigate adverse events associated with psychotropic medication use

16 Potential Adverse Events Associated with Psychotropic Medications Weight gain Sexual dysfunction Risk of seizures with bupropion + alcohol Serotonin syndrome Antidepressant discontinuation syndrome Prescription drug misuse

17 Patient Case Joe is a 18 year old male with a history of severe and recurrent treatment resistant depression. He presents to the university clinic with suicidal ideation and is hospitalized for his current depressive episode. While hospitalized, his antidepressant regimen is changed.

18 Patient Case Past medication trials include various antidepressants, one of which included mirtazapine and was associated with a significant amount of weight gain. Patient is no longer obese, as he has worked hard to reduce his weight. BMI=27.3.

19 Weight Gain Implications for college students Body image and the freshman 15 Meta-analysis of 5549 students found that 60.9% gained an average of 7.5lbs during freshman year Students continue to gain weight sophomore year Vadeboncoeur C, et al. BMC Obes. 2015;2:22. Lloyd-Richardson EE, et al. Prev Med. 2009;48(3):

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21 Antidepressants and Weight Gain Obesity is up to 3 times more common in psychiatric patients Medication induced or notable improvement in depressive symptoms? Short-term use of SSRI antidepressants (2-3 months) typically associated with little or no weight change Risk with mirtazapine paroxetine >>> fluoxetine > bupropion Serretti A, et al. J Clin Psychiatry 2010;71(10):

22 Antidepressants and Weight Gain Loss Modest Gain Gain Neutral Bupropion Fluoxetine Citalopram Duloxetine Escitalopram Sertraline Trazodone Venlafaxine Amitriptyline Imipramine Mirtazapine Paroxetine Phenelzine Fluvoxamine Nefazodone Nortriptyline? Schwartz TL, et al. Current Psychiatry 2007;6(5).

23 Patient Case The patient inquires whether an antipsychotic would be a good option, as he has recently seen advertisements touting the benefits. How should you respond? A. No B. Yes C. Maybe - Let s discuss the risks and benefits

24 Antipsychotics and Weight Gain Antipsychotic Weight gain Diabetes Dyslipidemia Aripiprazole Asenapine -/+ - - Clozapine Iloperidone Lurasidone Olanzapine Paliperidone -/+ - - Quetiapine Risperidone Ziprasidone (-)low;(+)moderate; (++)high Adapted from: PL Detail-Document, Comparison of Atypical Antipsychotics. Pharmacist s Letter/Prescriber s Letter. July 2015.

25 Recommended Metabolic Monitoring Parameters for Second Generation Antipsychotics Parameters Baseline 4 & 8 weeks 12 weeks Quarterly Annually Personal/ Family History x Weight (BMI) x x x x Waist Circumference x x x Blood Pressure Fasting Plasma Glucose or HbA1c Fasting Lipid Panel x x x x x x x x Every 5 years if wnl Adapted from Diabetes Care 2004;27(2)

26 Patient Case Assuming each of the following would be appropriate from a symptom management as well as past medication trial perspective, which of the of the following would be the most appropriate agent to consider next in Joe? A. Olanzapine B. Paroxetine + aripiprazole C. Fluoxetine and/or bupropion D. Mirtazapine

27 Antidepressants and Antipsychotics: Minimizing Weight Gain Mitigation Strategies Inform patients that their appetite may be increased Use weight neutral agents when possible Monitor changes in weight at follow-up visits and document these changes Encourage diet and exercise engage patient in self-management Discuss risks and benefits of treatment Consider cognitive behavioral therapy Place for weight-loss agents?? Schwartz TL, et al. Current Psychiatry 2007;6(5). Bickerdike HJ et al. Diabetes Obes Metab 1999;1:

28 Potential Adverse Events Associated with Psychotropic Medications Weight gain Sexual dysfunction Risk of seizures with bupropion + alcohol Serotonin syndrome Antidepressant discontinuation syndrome Prescription drug misuse

29 Patient Case Briana is a 23 year old female on multiple medications, including escitalopram 20 mg daily to manage her anxiety. It is working well to target her anxiety symptoms, however, she is concerned about her lack of interest in sexual activity. What are some potential management strategies?

30 Antidepressants and Sexual Dysfunction: Risk Factors Male Increasing age Lower academic achievement Employment status other than full time Poor physical health Polypharmacy Poor interpersonal relationships CYP2D6 poor metabolizer status + treatment with paroxetine Others Baldwin DS, et al. CNS Drugs 2015;29:

31 Sexual Dysfunction Common reason for non-adherence May be due to: Side effect of psychotropic agent (impacts relapse rates by limiting dose/duration of treatment) Primary sexual disorder Symptom of illness (medical or psychiatric) Substance abuse Psychosocial stressors Other causes Clayton AH, et al. J Sex Med 2009;6:

32 Types of Sexual Dysfunction Altered sexual desire/reduced libido Orgasmic and ejaculatory dysfunction Anorgasmia Hyperorgasmia Painful orgasm and inhibited ejaculation Erectile problems Erectile dysfunction Priapism Painful erection Reduced sexual satisfaction, issues with sexual arousal, lubrication, vaginismus, and dyspareunia Taylor MJ et al. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD DOI: / CD pub3. Baldwin DS, Foong T. Br J Psychiatry 2013;202:396-7

33 Risk of Sexual Dysfunction by Antidepressant Risk Level Antidepressants Comments Highest Risk High Risk Lowest Risk Citalopram, fluoxetine, paroxetine, sertraline, venlafaxine Fluvoxamine, escitalopram, duloxetine, phenelzine, imipramine Bupropion, mirtazapine, nefazodone Rates approximately 65-80% of treated patients Significantly higher rates compared to placebo, but significantly less than the highest risk group, rates ranging from roughly 25-44% Rates are lower or comparable to placebo (14.2%) Serretti et al. J Clin Psychopharmacol 2009;29:

34 Minimizing Sexual Dysfunction Watchful waiting Modifying sexual technique Individual and couple psychotherapy Altering antidepressant use Reducing dose Switching agents Delaying use until after sexual activity Drug holiday Taylor MJ et al. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD DOI: / CD pub3.

35 Minimizing Sexual Dysfunction Become skilled and comfortable discussing topic Patient education when treatment initiated Encourage reporting inquire about concerns Take patient concerns seriously, which may include problems with desire, excitement, or orgasm Add an agent to manage symptoms Clayton AH, et al. J Sex Med 2009;6: Prabhakar D, et al. Current Psychiatry 2010;9(12):30-4. Nurnberg AG, et al. JAMA. 2008;300(4): Baldwin DS, Foong T. Br J Psychiatry. 2013;202:396-7

36 Pharmacologic Management Strategies In men Sildenafil (3 studies, 255 participants) and tadalafil (1 study, 54 participants) better than placebo; treatment effect similar to those reported for erectile dysfunction due to other causes Higher dose bupropion (150 mg twice daily) beneficial (1 study, 234 participants) In women Bupropion 150 mg twice daily better than placebo (3 studies, 482 participants) Additional published studies needed with sildenafil Taylor MJ et al. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD DOI: / CD pub3.

37 Patient Case As previously described, what is likely the best strategy to try first to minimize sexual dysfunction that may be induced by escitalopram in Briana? A. Discontinue escitalopram and initiate bupropion B. Consider a dose reduction C. Take a wait and see approach D. Add on sildenafil

38 Potential Adverse Events Associated with Psychotropic Medications Weight gain Sexual dysfunction Risk of seizures with bupropion + alcohol Serotonin syndrome Antidepressant discontinuation syndrome Prescription drug misuse

39 Patient Case Message from prescriber: I treat a fair number of students and this question has come up several times for me. Regarding the use of bupropion, I wonder about this with students who drink alcohol. Some of them seem to binge drink on the weekends. Should I tell them not to take the bupropion if they are planning to drink or would it be better not to prescribe it for them at all? I am concerned about the fact that bupropion and alcohol use together could increase their risk for seizures.

40 Bupropion and Seizure Risk Recommend Avoid use in specific patients with predisposing risk factors: Titrate up slowly History or current excessive alcohol use When possible, avoid high total daily doses (<400mg) and do NOT exceed recommended maximum daily dose Unless taking the XL formulation, avoid doses >200mg at one time Use lower doses if using as part of combination antidepressant regimen Abrupt alcohol cessation Taking other medications that lower seizure threshold (e.g. amphetamines) History of head trauma Bulimia nervosa Tai M, et al. Current Psychiatry 2015;14(8):29-31, 43-46; Bupropion product labeling.

41 Patient Case What would you recommend to this prescriber or do in this case? Tell them: A. The warning for risk of seizures is overstated, you can prescribe without concerns B. Avoid bupropion only if the patient has a history of an eating disorder C. Do not use bupropion in a patient at risk for binge drinking D. Evaluate on an individual basis; discuss risks with patient; may avoid if high risk for binge drinking

42 Pain Relievers Acetaminophen Commonly used OTC pain medication in the United States Found in several products Knowledge gaps are common in the general population Risk of adverse events is high Concerns among college students Accidental and intentional overdose Risk of liver damage with alcohol abuse

43 Pain Relievers NSAIDs Found in many OTC and Rx products lithium levels and renal lithium clearance Even when one dose is used or when used PRN, NSAIDs can significantly alter lithium levels Recommend: If possible, avoid newly starting NSAID therapy, even PRN use For patients that are receiving concurrent NSAID and lithium therapy, monitor lithium levels every 4-5 days. Dose of lithium may need to be reduced if NSAID use is chronic/long term Educate patients on NSAID containing OTC products and signs/symptoms of lithium toxicity BMJ 1991;302: Clin Pharmacokinet Sep;29(3): J Clin Psychiatry 1987 Apr;48(4):161-3.

44 Potential Adverse Events Associated with Psychotropic Medications Weight gain Sexual dysfunction Risk of seizures with bupropion + alcohol Serotonin syndrome Antidepressant discontinuation syndrome Prescription drug misuse

45 Patient Case Emily is a 20 year old female university student presenting to the university health clinic today with complaints of a migraine. She reports throbbing pain, sensitivity to light, nausea, vomiting, and lightheadedness. Her migraines have been occurring about twice per month, each lasting 1 day. Her past medical history includes depression, and she is currently treated with sertraline 100 mg daily. She inquires about being prescribed a triptan, which has been helpful in the past, prior to her treatment with sertraline.

46 Triptans and Serotonin Syndrome FDA alert in 2006 warned about the possibility for serotonin syndrome when triptans are used concomitantly with SSRIs or SNRIs American Headache Society 2010: Position paper citing conflicting and insufficient data to support the FDA warning Sclar DA, et al. Headache 2012;52:

47 Medications associated with Serotonin Syndrome Antidepressants Valproic acid Analgesics: meperidine, fentanyl, tramadol, pentazocine Antiemetics: ondansetron, granisetron, metoclopramide Antibiotics: linezolid, ritonavir Dextromethorphan Drugs of Abuse: MDMA/ecstasy, LSD Dietary/Herbal Supplements: tryptophan, St. John s Wort, Panax ginseng, Garcinia? Lithium Boyer EW, Shannon M. N Engl J Med. 2005;352:

48 MDMA Structurally related to both amphetamine and the hallucinogen mescaline Produces large increases in serotonin release mood elevation, feeling a sense of closeness to others, greater sociability, sharpened sensory perception, and extraversion Adverse effects related to excessive CNS and cardiovascular stimulation Pharmacist 2006;25(9):684-9.