Depressin Management Case February 2017 Patient Case NW is an 80-year-ld female admitted t hspice yesterday with a primary diagnsis f cngestive heart failure. Her c-mrbidities include hypertensin and crnary artery disease. She has allergies t penicillin, which caused a rash, and lrazepam with reprted cnfusin. She was recently started n dulxetine by her family dctr t manage cnstant wrry, irritability and sadness. NW lives with her daughter wh als reprts that her mther has truble sleeping due t these recent symptms. Current medicatins include: Amldipine (Nrvasc ) 5mg; 1 tab p daily fr bld pressure Carvedill (Creg ) 3.125mg; 1 tab p BID fr heart failure Clpidgrel (Plavix ) 75mg; 1 tab p daily fr clt preventin Digxin (Lanxin ) 0.125mg; 1 tab p daily fr heart failure Dulxetine (Cymbalta ) 30mg; 1 cap p daily fr md Fursemide (Lasix ) 40mg; 1 tab p BID fr fluid retentin Mrphine (Rxanl ) 20mg/ml; 25ml p/sl every 3 hurs PRN pain r shrtness f breath Spirnlactne (Aldactne ) 25mg; 1 tab p daily fr fluid retentin Albuterl (Ventlin ) inhaler; Inhale 2 puffs p q4h PRN shrtness f breath NW s bld pressure is currently cntrlled and lwer extremity edema that has been a prblem in the past, is being managed well with her diuretics. Her family reprts that she frequently gets up t use the bathrm at night. She experiences shrtness f breath with activity and uses an albuterl inhaler as needed. She uses mrphine 1-2 times per day fr pain with gd respnse. She has a histry f becming cnfused with lrazepam, hwever, her family states that she has tlerated ther benzdiazepines in the past. The dulxetine that was started tw weeks ag by her family dctr has already imprved NW s md, hwever, she cntinues t have prblems sleeping. Dulxetine is nt n the hspice pharmacy s frmulary, but the frmulary includes a number f SSRIs. WHAT ARE SYMPTOMS OF DEPRESSION AT END-OF-LIFE? Depressin is a medical illness that invlves bth the mind and bdy. Hspice patients may face a greater likelihd f develping r wrsening a clinical diagnsis f depressin due t the awareness f their limited lifespan. Cmmn symptms include feelings f sadness/unhappiness, irritability, lss f interest/pleasure in nrmal activities, insmnia r excessive sleeping, changes in appetite r an increased craving fr fd, and agitatin. Other symptms include slwed thinking r bdy mvements (psychmtr slwing), decreased cncentratin, fatigue, lss f energy, feelings f wrthlessness r guilt, frequent thughts f death, crying spells and unexplained physical prblems. Due t its symptms, depressin has a negative impact n quality f life and untreated depressin leads t significant mrbidity and mrtality als negatively affects caregivers. In sme peple, depressin is als assciated with an increased desire fr hastened death. 2017 Enclara Pharmacia. All rights reserved. 1
WHAT MUST BE ASSESSED BEFORE INITIATING AN ANTIDEPRESSANT? Befre initiating drug therapy, it is imprtant t rule ut ther factrs such as medicatins r cmrbidities that may be causing r wrsening depressin. Review the medicatin list and try t relate changes in medicatin t the nset f the symptms and rule ut ther secndary causes such as: C-mrbidities: Anemia, cancer, cardiac disease, endcrine disrders, infectins, metablic disrders, neurlgical disrders Medicatins: Baclfen, barbiturates, benzdiazepines, beta-blckers, clnidine, crticsterids, diuretics, piids Other: Alchlism, psychscial issues, pain, insmnia Evaluate patient with DSM-IV criteria r utilize anther depressin screening assessment tl r simply ask the patient, Are yu depressed? Cnsider the fllwing as a part f a differential diagnsis and recgnize that prgnsis will affect treatment appraches: 1 Majr depressive disrder: Treat with drug therapy plus psychtherapy Unspecified depressive disrder: Cntinually assess; May treat with drug therapy plus psychtherapy Adjustment disrder with depressed md: Treat with supprtive cunseling aimed at cping skills and prblem slving aimed at reslving r remving stressr Grief: Treat with supprtive cunseling r psychtherapy Demralizatin: Treat with supprtive cunseling r psychtherapy HOW DO I CHOSE THE RIGHT ANTIDEPRESSANT? 1-3 Depressin may be mediated by the depletin f several neurtransmitters including nrepinephrine, sertnin, and dpamine. Antidepressants affect hw these neurtransmitters behave, but hw they imprve symptms is nt well understd. All antidepressants have similar efficacy, s chse an agent based n patient histry and cmrbidities, prgnsis, side effects and tlerability, ptential drug interactins and cst. All agents prvide sme symptm imprvement in the initial weeks f therapy, hwever, it may take 1-2 mnths f dse titratin and system acclimatin fr patients t experience the full extent f benefits. Reserve antidepressants fr patients with terminal cnditins that have lnger prgnses. Cmmn undesired effects (r desirable effects in sme cases) that may help t distinguish the best agent fr yur patient include sexual dysfunctin, weight gain, sleep, energy, anxiety and pain. Nte that the mnamine xidase inhibitr (MAOI) class f antidepressants (phenelzine (Nardil ), (tranylcyprmine (Parnate ) is typically nt used as initial therapy in the general ppulatin nr initiated in hspice. Please cnsult yur pharmacist fr guidance if yur patient is taking an MAOI. Selective Sertnin Reuptake Inhibitrs (SSRIs) Agents: Citalpram (Celexa ), Escitalpram (Lexapr ), Fluxetine (Przac ), Fluvxamine (Luvx ), Parxetine (Paxil ), Sertraline (Zlft ) 2017 Enclara Pharmacia. All rights reserved. 2
Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Cncmitant anxiety, psychmtr slwing Avid/Cautin in: Cncmitant agitatin, insmnia (particularly fluxetine and sertraline), sexual dysfunctin cncerns Ntes: Citalpram and sertraline have lwer ptential fr drug-drug interactins. Fluxetine and Parxetine have a higher ptential fr drug-drug interactins. Other Agents similar t SSRIs Agent: Vrtixetine (Trintellix ) Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Cncmitant psychmtr slwing Avid/Cautin in: Nausea cncerns Ntes: Cmbinatin sertnin reuptake inhibitr and sertnin receptr antagnist Agent: Vilazdne (Viibryd ) Indicated fr: Prgnsis ~ 6 mnths Ntes: Cmbinatin sertnin reuptake inhibitr and sertnin receptr partial agnist Selective Nrepinephrine Reuptake Inhibitrs (SNRIs) Agents: Dulxetine (Cymbalta ), Venlafaxine (Effexr ), Desvenlafaxine (Pristiq ), Levmilnacipran (Fetzima ) Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Cncmitant neurpathic pain, psychmtr slwing, anxiety Avid/Cautin in: Hypertensin, agitatin r insmnia, sexual dysfunctin cncerns Hetercyclic Antidepressants Agents: Mirtazapine (Remern ), Trazdne (Desyrel ) Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Cncmitant insmnia (mirtazapine, trazdne), appetite lss (mirtazapine), agitatin (mirtazapine), sexual dysfunctin cncerns Avid/Cautin in: Overweight cncerns Ntes: Nt cnsidered first-line therapy withut cncmitant indicatins fr use. Tricyclic Antidepressants (TCAs) Agent: Amitriptyline (Elavil ), Desipramine (Nrpramin ), Dxepin (Sinequan ), Imipramine (Tfranil ), Nrtriptyline (Pamelr ) Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Cncmitant insmnia and/r neurpathic pain 2017 Enclara Pharmacia. All rights reserved. 3
Avid/Cautin in: Structural heart disease, cncmitant medicatins that prlng QT interval Ntes: Nt cnsidered first-line therapy. Antichlinergic prperties may be prly tlerated by geriatric patients. Aminketnes Agents: Buprprin (Wellbutrin, Wellbutrin SR, Wellbutrin XL) Indicated fr: Prgnsis ~ 6 mnths Cnsider fr: Patients with lw energy (mild stimulant effects), verweight cncerns, sexual dysfunctin cncerns Avid/Cautin in: Seizure histry (decreases seizure threshld), patients with insmnia Ntes: Adjunct therapy ONLY. Psychstimulants Agent: Methylphenidate (Ritalin ) Indicated fr: Prgnsis 6 mnths Cnsider fr: Patients with shrt prgnsis and gals cnsistent with maintaining alertness and energy level Avid/Cautin in: Cncmitant anxiety, agitatin, appetite lss Ntes: Onset within a few days & limited t several-week effectiveness with side effects increasing ver time. Mst effective fr shrt-term treatment f refractry depressin. HOW DO I MANAGE SWITCHING FROM ONE ANTIDEPRESSANT TO ANOTHER? When changing frm ne antidepressant t anther (fr example, t a medicatin included in the hspice frmulary), cnsider the patient s histry and prgnsis first. If a patient has a histry f depressin and symptms have been stabilized n their current medicatin, it may be mre beneficial fr the patient t cntinue that medicatin, especially if prgnsis is days t weeks. If symptms are new and/r the patient has been n an antidepressant fr a shrt time and prgnsis is mnths, switching agents may be mre apprpriate. Mnitr the patient and adjust the switching strategy fr symptms f withdrawal, side effects, r the return f symptms f depressin. 2,3 Guide fr switching frm ne agent t anther: 2-4 1. Cnservative switch r Mderate switch Gradually decrease and then d/c the ld agent fllwed by a washut perid befre initiating the new agent. Washut perids are drug-specific and shuld allw time fr the discntinued medicatin t be eliminated frm the patient s system. Full eliminatin is estimated by calculating 5 times the drug s t 1/2 (eliminatin half-life) (the time it takes fr the plasma cncentratin f the drug in the bdy t decrease by half) (i.e., dulxetine s t 1/2 averages 12.5 hurs s the washut perid wuld be 62.5 hurs (apprx. 3 days). This apprach is nt practical r recmmended in hspice. Discntinuatin f ne agent, leaving a gap f time befre starting anther agent, can cause discntinuatin syndrme (dizziness, 2017 Enclara Pharmacia. All rights reserved. 4
irritability, nausea, fatigue) r symptm recurrence. Discntinuatin syndrmes are f mst cncern when switching frm a sertnergic agent (i.e., SSRI, SNRI) t a nn-sertnergic agent (i.e., hetercyclic, TCA). 2. Direct r Next Day switch Apprpriate fr when the ld agent and new agent are in the same class r similar classes (i.e., SSRIs and SNRIs). Last dse f ld drug taken ne day and then new drug initiated at the same time f day the next cnsecutive day at a lw dse. Gradually increase t effect. Nte that Fluxetine has a lng half-life, s wait 4-7 days befre starting new agent if fluxetine is the ld drug. 3. Crss-taper switch Apprpriate fr when the ld drug and new drug are NOT in the same class and fr patients at high risk f symptm/illness relapse. Crss-tapering invlves gradually increasing the new drug while decreasing the ld drug s that patient is taking bth antidepressants simultaneusly. Tapering dwn ld agent example: Decrease dse by 25% every week until dse is at a lw/initial starting dse (i.e., fr Sertraline 100mg Daily - Week 1: 75mg/day, Week 2: 50mg/day, Week 3: 25mg/day, Week 4: D/C) Gradually increasing new agent example: Increase dse by 25% every week until dse is at therapeutic dse (i.e., fr Mirtazapine - Week 1: 7.5mg/day, Week 2: 15mg/day, Week 3: 30mg/day, Week 4: Cntinue 30mg/day if therapeutic r cnsider increase t 45mg/day) Drug-specific ntes: 1. Taper/gradually increase parxetine ver at least 4 weeks. 2. Taper/gradually increase ther SSRIs, venlafaxine, and dulxetine ver a ttal f 1-4 weeks Sertraline r venlafaxine, by 25 t 50 mg/day every 1-2 weeks Parxetine r citalpram by 5 t 10 mg/day every 1-2 weeks Escitalpram by 5 mg/day every 1-2 weeks 3. Literature is lacking fr switching t/frm vilazdne r vrtixetine t anther agent. Cnsider managing the same as SSRIs due t sertnergic mechanism. Fllw manufacturer s recmmended titratin schedule when starting vilazdne. 4. Literature is lacking fr switching t/frm desvenlafaxine r levmilnacipran t anther agent. Cnsider managing as venlafaxine due t similar mechanism f actin. PHARMACIST ASSESSMENT NW has cardiac disease in which depressin is cmmn. Her medicatin list cntains drugs that may precipitate depressin symptms (carvedill, fursemide, spirnlactne, mrphine) hwever, she has been n these medicatins fr sme time nw and her depressive symptms started recently. Her ther symptms, including pain and breathlessness, are generally well cntrlled. Based n assessment in cllabratin with the hspice medical directr, it is determined that the patient is experiencing a new nset unspecified depressive disrder. NW has been taking dulxetine fr tw weeks and her prgnsis is estimated t be several mnths. The hspice wishes t switch t a frmulary medicatin and the family agrees. 2017 Enclara Pharmacia. All rights reserved. 5
RECOMMENDATIONS 1. Assess timing f fursemide dsing t prevent nighttime waking t use bathrm. Cnsider timing 2 nd fursemide dse in the afternn t minimize nighttime disruptin f sleep. 2. NW has had a psitive initial respnse t dulxetine. T minimize discntinuatin symptms, switching t an agent with sertnergic prperties will prvide a smth transitin. 3. Direct r Next Day switch: When patient/family is ready, have NW take the last dse f dulxetine n Day 1. At the same time f day n Day 2, begin citalpram 20mg p daily. FOR ADDITIONAL INFORMATION ON THIS TOPIC, PLEASE REVIEW THESE REFERENCES: Enclara Pharmacia s On Demand Educatinal Webinar, Delirium, Depressin and Anxiety at End f Life. 1. Fairman N, Hirst JM, Irwin SA. Clinical manual f palliative care psychiatry. 1 st Arlingtn: American Psychiatric Assciatin; 2016. 2. PL Detail-Dcument, Chsing and Switching Antidepressants. Pharmacist s Letter/Prescriber s Letter. July 2014. 3. PL Detail-Dcument, Antidepressants. Pharmacist s Letter/Prescriber s Letter. July 2014. 4. Keks N, Hpe J, Kegh S. Switching and stpping antidepressants. Aust Prescr 2016;39:76 83. Available frm: https://www.ncbi.nlm.nih.gv/pmc/articles/pmc4919171/pdf/austprescr-39-076.pdf 5. Clinical Pharmaclgy [database nline]. Tampa, FL: Elsevier/Gld Standard, Inc.; 2017. Access 2017 Feb. Available frm: http://www.clinicalpharmaclgy.cm 6. GP Online. Switching and withdrawing antidepressants. http://www.mims.c.uk/news/882430/switching-antidepressants/. 7. Marangell LB. Switching antidepressants fr treatment-resistant majr depressin. J Clin Psychiatry 2001;62(Suppl 18):12-7. 8. Rsenstein DL. Depressin and end-f-life care f patients with cancer; Dialgues Clin Neursci. 2001 March;31(1): 101-108. Available frm: https://www.ncbi.nlm.nih.gv/pmc/articles/pmc3181973/ 9. Nrani NH and Mntagnini M. Recgnizing depressin in palliative care patient. Jurnal f Palliative Medicine. 2007;10(2):458-464. 10. Hirdes JP, et al. Predictrs f caregiver distress amng palliative hme care clients in Ontari: Evidence based n the interrai Palliative Care. Palliat Supprt Care. 2012;10(3):155-163. 11. Wilsn KG, et al. Diagnsis and management f depressin in palliative care, in Handbk f Psychiatry in Palliative Medicine, 2 nd New Yrk: Oxfrd University Press; 2009, pp 39-68. 12. Rsenfeld B, et al. Des desire fr hastened death change in terminally ill cancer patients? Sc Sci Med.2014;111:35-40. 13. Zhang B, et al. Factrs imprtant t patients quality f life at the end f life. Arch Intern Med. 2012;172(15):1133-1142. 2017 Enclara Pharmacia. All rights reserved. 6