Selective Serotonin Reuptake Inhibitor (SSRI) Step Therapy Program

Transcription

1 Selective Serotonin Reuptake Inhibitor (SSRI) Step Therapy Program Policy Number: Last Review: 7/2018 Origination: 7/2014 Next Review: 7/2019 LoB: ACA Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for brand name SSRI medications when the following criteria are met. The brand name medications affected are: Brisdelle (paroxetine 7.5 mg capsules Noven Therapeutics) Celexa (citalopram tablets and oral solution Forest, Fluoxetine 60 mg tablets (branded product) Edgemont fluvoxamine tablets ( Lexapro (escitalopram tablets and oral solution Forest, Luvox CR (fluvoxamine extended-release capsules Jazz, Paxil (paroxetine hydrochloride tablets and oral suspension GlaxoSmithKline, Paxil CR (paroxetine hydrochloride controlled-release tablets GlaxoSmithKline, Pexeva (paroxetine mesylate tablets JDS Pharmaceuticals) Prozac (fluoxetine capsules, tablets, and oral solution Lilly, Prozac Weekly (fluoxetine delayed-release capsules Lilly, Sarafem (fluoxetine capsules generics only) Sarafem (fluoxetine tablets Warner Chilcott) Trintellix (formerly Brintellix ) [vortioxetine tablets Takeda] Viibryd (vilazodone hydrochloride tablets Forest) Zoloft (sertraline tablets and oral solution Pfizer, When Policy Topic is covered A step therapy program has been developed to encourage the use of one generic Step 1 product prior to the use of a Step 2 product If the step therapy rule is not met for a Step 2 agent at the point of service, coverage will be determined by the step therapy criteria below. All approvals are provided for 1 year in duration. Automation: Patients > 18 years of age will be targeted in this step therapy program. Patients with a history of one Step 1 drug within the 130-day look-back period are excluded from step therapy. Step 1 SSRIs: generic citalopram tablets, generic citalopram oral solution, generic escitalopram tablets, generic escitalopram oral solution, generic fluoxetine immediate-release capsules and tablets, generic fluoxetine oral solution, generic fluvoxamine immediaterelease tablets, generic fluvoxamine extended-release capsules, generic paroxetine HCl immediate-release tablets, generic paroxetine HCl oral suspension, generic paroxetine HCl controlled-release tablets, generic sertraline tablets, generic sertraline oral solution, generic fluoxetine delayed-release 90 mg capsule

2 Step 2 SSRIs: Fluoxetine 60 mg tablets (branded product), Lexapro, Paxil, Paxil CR, Pexeva, Prozac, Prozac Weekly, Sarafem, Celexa, Zoloft, Luvox CR, Viibryd, Trintellix (formerly Brintellix), Brisdelle Standard Criteria 1. If a patient has tried one generic SSRI, then authorization for a Step 2 product may be given. 2. Patients who are currently taking or who have taken Pexeva, Viibryd, or Trintellix (formerly Brintellix) at any time in the past and discontinued their use may receive authorization for the SSRI that they have used. 3. Exceptions for Pexeva, Viibryd, and Trintellix (formerly Brintellix) can be made for patients with suicidal ideation. When Policy Topic is not covered The use of Selective Serotonin Reuptake Inhibitors is considered investigational for all other indications Considerations Selective Serotonin Reuptake Inhibitors require prior authorization through the Clinical Pharmacy Department. This Blue Cross and Blue Shield of Kansas City policy Statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers Description of Procedure or Service The selective serotonin reuptake inhibitors (SSRIs) are a pharmacologic class of agents with antidepressant action and efficacy in the treatment of a wide range of mood and anxiety disorders (see Table 1) In addition to being an SSRI, Viibryd is also a partial agonist at serotonergic 5-HT 1A receptors; however, the net result of this action on serotonergic transmission and its role in Viibryd s antidepressant effect are unknown. 11 Similarly, the antidepressant effect of Trintellix is thought to be related to its enhancement of serotonergic activity in the central nervous system (CNS) through inhibition of the reuptake of serontonin. 13 Trintellix also antagonizes 5-HT 3 receptors and has an agonist effect on 5-HT 1A receptors; however, the contribution of these activities to the antidepressant effect of Trintellix has not been established. Of note, a fluoxetine 60 mg tablet is available as a branded product. 12 This formulation carries the same indications as the other fluoxetine products (Prozac,. The capsule, tablet, and oral solution dosage forms of fluoxetine are bioequivalent. The exposure (maximum concentration [C max ], area-under-the-concentration-time-curve [AUC]) to fluoxetine was similar after administration of either one 60 mg fluoxetine tablet or three 20 mg fluoxetine tablets. Table 1. FDA-Approved Indications Brand (generic) MDD OCD Panic Disorder Trintellix (vortioxetine tablets) Brisdelle (paroxetine mesylate 7.5 mg capsules) Celexa (citalopram tablets and oral solution, Fluvoxamine (generics only) Lexapro (escitalopram tablets α and oral solution, Bulimia Nervosa PTSD Social Anxiety Disorder GAD PMDD VMS

3 Luvox CR (fluvoxamine extended-release capsules, Paxil (paroxetine HCl tablets and oral suspension, Paxil CR (paroxetine HCl controlled-release tablets, Pexeva (paroxetine mesylate tablets) Prozac (fluoxetine capsules, tablets, and oral solution, Prozac Weekly (fluoxetine delayed-release capsules, Sarafem (fluoxetine capsules and tablets, Viibryd (vilazodone tablets) Zoloft (sertraline tablets and * oral suspension, FDA Food and Drug Administration; MDD - Major Depressive Disorder; OCD - Obsessive compulsive disorder; PTSD - Posttraumatic stress disorder; GAD - Generalized anxiety disorder; PMDD - Premenstrual dysphoric disorder; VMS Vasomotor symptoms; - FDA-approved indication includes children and adolescents; α - FDA-approved indication includes adolescents 12 to 17 years of age; CR Controlled release; HCl - Hydrochloride; * - Approved for the prevention of relapse during the continuation treatment phase of depression. Rationale Vasomotor Symptoms For vasomotor symptoms (VMS) associated with menopause, hormone therapy is considered to be very effective for the management of VMS due to menopause; however, it may not be appropriate for all women (e.g., women with a history of breast cancer or other estrogen-dependent neoplasia). 15 In women who have contraindications, cannot tolerate, or do not want to take hormone therapy, other non-fda approved alternatives have been used. The pharmacologic alternatives include SSRIs (e.g., paroxetine, fluoxetine), serotonin norepinephrine reuptake inhibitors (SNRIs) [venlafaxine has the most data for this use], clonidine, and gabapentin. Generic paroxetine hydrochloride is available as 10, 20, 30, and 40 mg immediate-release (IR) tablets and as 12.5, 25, and 37.5 mg extended-release (ER)/controlled-release (CR) tablets. Among these doses, paroxetine 12.5 mg and 25 mg ER/CR tablets have some efficacy data for the treatment of hot flashes due to menopause. 16 A systematic review and meta-analysis of randomized controlled trials analyzed the evidence of impact of different SSRIs on perimenopausal hot flashes in healthy women. 17 Data from pivotal studies for Brisdelle were also included in this meta-analysis. The conclusion based on 11 randomized controlled trials was that SSRI use was associated with a modest improvement in the severity and frequency of hot flashes. Other Indications The SSRIs have been used for a wide variety of psychiatric and nonpsychiatric conditions. There are insufficient comparative data for the SSRIs in the treatment of these conditions. Other Considerations Adverse Events (AEs) Overall, the SSRIs have comparable tolerability; however, specific medications differ somewhat in their AE profile. 18 SSRIs commonly cause nausea, vomiting, and diarrhea, which are generally dose dependent and dissipate over the first few weeks of treatment (diarrhea may persist). SSRIs can precipitate or exacerbate restlessness, agitation, and sleep disturbances. Sexual dysfunction has been reported with all of the SSRIs. Of note, rates of sexual AEs were minimal in the Viibryd pivotal studies. 11 Similar findings related to safety were observed in a 52-week, open-label study. 20 Weight gain, at times substantial, occurs in some patients taking SSRIs. 18 Patients who take paroxetine have a higher incidence of weight gain than those who take other SSRIs. Fluoxetine causes an initial reduction in weight, which tends to normalize with continued treatment. Viibryd had no effect on weight

4 in the short-term (8-week) pivotal studies. 11 Trintellix had no significant effect on body weight in shortterm placebo-controlled studies. 13 Drug Interactions Most of the SSRIs have drug-drug interaction warnings or contraindications regarding concomitant use with alcohol, use of other central nervous system (CNS)-active drugs, monoamine oxidase inhibitors (MAOIs), drugs that interfere with hemostasis (nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, warfarin), lithium, pimozide, triptans, and tryptophan Cytochrome P450 (CYP) inhibition and, to a much lesser extent, protein binding competition account for other SSRI interactions. Given their spectrum of inhibitory effects on the CYP system, fluvoxamine and fluoxetine have the most potential interactions. Also, co-administration of paroxetine with CYP2D6 substrates may result in clinically significant interactions. Citalopram, escitalopram, and sertraline have the least potential for drug interactions. Table 2 is a summary of the CYP inhibitory potential of SSRIs as noted in the APA guidelines for the treatment of MDD (published in 2010, prior to availability of Viibryd and Trintellix). 18 The dose of Viibryd should be reduced to 20 mg if co-administered with a strong inhibitor of CYP3A4 and also if patients experience intolerable AEs while on a moderate inhibitor of CYP3A4 (e.g., erythromycin). 11 The dose of Trintellix should be reduced by one-half when a strong CYP2D6 inhibitor is co-administered and increased when a strong CYP inducer is co-administered. 13 Table 2. Cytochrome P450 (CYP) Enzyme Inhibition. 18 CYP Enzyme Drug 1A2 2A6 2B6 2C8 2C9 2C19 2D6 2E1 3A4 Citalopram Escitalopram ++ Fluoxetine Norfluoxetine* Paroxetine Sertraline Desmethylsertraline* * Active metabolite of the parent compound; + Weak inhibitor; ++ Moderate inhibitor; +++ Strong inhibitor. Pregnancy/Lactation Paroxetine is in pregnancy category D, whereas the other SSRIs are rated as pregnancy category C All of the SSRIs appear to be excreted into breast milk to some extent. 21 Because there are limitations to the data available on SSRIs and nursing, more studies are needed to clearly deduce which agent is the agent of choice for breastfeeding mothers requiring an SSRI antidepressant. At this time, if a woman is suffering from her first lifetime episode, sertraline or paroxetine are recommended as first-line agents during lactation. Pediatric Patients Prescribing information for the SSRIs includes a Boxed warning that antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24, and there was a trend toward reduced risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Trintellix, Viibryd, Sarafem, Pexeva, paroxetine IR and R, and citalopram are not approved for use in pediatric patients. Fluoxetine immediate-release formulations (excluding Sarafem) are indicated for treatment of MDD in children and adolescents 8 to 18 years of age 1, and escitalopram is indicated for treatment of MDD in adolescents 12 to 17 years of age. 6 Fluoxetine immediate-release (excluding Sarafem), fluvoxamine immediate- and controlled-release formulations, and sertraline are approved in children and adolescents with OCD. 1,3,8,10

5 References: 1. Prozac capsules, tablet, oral solution, Prozac Weekly capsules [prescribing information]. Indianapolis, IN: Eli Lilly and Company; July Paxil tablets and oral suspension [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; December Zoloft tablets, oral concentrate [prescribing information]. New York, NY: Pfizer Laboratories; December Celexa tablets and oral solution [prescribing information]. St Louis, MO: Forest Pharmaceuticals, Inc.; December Paxil CR controlled-release tablets [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January Lexapro tablets/oral solution [prescribing information]. St Louis, MO: Forest Pharmaceuticals, Inc.; December Pexeva paroxetine mesylate tablets [prescribing information]. Miami, FL: Noven Therapeutics, LLC.; December Fluvoxamine maleate tablets [prescribing information]. Weston, FL: Apotex Corp: September Sarafem tablets [prescribing information]. Hunt Valley, MD: Pharmaceutics International, Inc.; July Luvox CR extended-release capsules [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; December Viibryd tablets [prescribing information]. St. Louis, MO: Forest Pharmaceuticals, Inc.; December Fluoxetine tablets [prescribing information]. Austin, T: Edgemone Pharmaceuticals; October Trintellix tablets [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc and Lundbeck; September Brisdelle capsules [prescribing information]. Miami, FL: Noven Therapeutics LLC; June Kalantaridou SN, Dang DK, Davis SR, et al. Hormone therapy in women. In: Dipiro JT, Talbert RL, Yee GC, et al, (Eds). Pharmacotherapy - A Pathophysiologic Approach. 8 th Ed., New York, NY: McGraw-Hill Companies, Inc. 2008: Stearns V, Beebe KL, Iyengar M, et al. Paroxetine controlled release in the treatment of menopausal hot flashes. A randomized controlled trial. JAMA. 2003;289: Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J Gen Intern Med July 26 [Epub ahead of print]. 18. Gelenberg A, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder, third edition. American Psychiatric Association, November Available at: Accessed on: February 26, American Medical Association. Report 10 of the council on scientific affairs (A-05). Safety and efficacy of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents. April 18, Robinson D, Kajdasz D, Gallipoli S, et al. A 1-year open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder [abstract NR4-22]. Presented at: the 163 rd Annual Meeting of the American Psychiatric Association; New Orleans, LA; May 22 to 26, Halberg P, Sjoblom V. The use of selective serotonin reuptake inhibitors during pregnancy and breastfeeding: a review and clinical aspects. J Clin Psychopharmacol. 2005;25: Billing Coding/Physician Documentation Information N/A The Selective Serotonin Reuptake Inhibitors are considered a pharmacy benefit. Additional Policy Key Words Policy Number:

6 Policy Implementation/Update Information 07/2014 New Policy titled Selective Serotonin Reuptake Inhibitor (SSRI) Step Therapy Program 07/2015 Annual Revision no changes made 06/2016 Changed titled to Trintellix when the manufacturer changed the drug name from Brintellix 07/2016 Annual Revision- no changes made to policy statement 07/2017 Annual Revision- no changes made to policy statement 07/2018 Annual Review no changes made State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.