Palliative care (PC) providers often prescribe psychotropic medications to address psychological and physical suffering of patients with serious medical illness. Consideration must be given to the significant medical comorbidities of the patient when selecting a medication. This article seeks to provide guidance on how to safely and effectively select a psychotropic agent for depression, anxiety, and other distressing symptoms for patients with serious illness. To do so, we draw upon a team of physicians and a pharmacist with training in psychiatry and PC to highlight the “Top 10” tips for selecting a psychotropic medication to provide relief for patients with serious medical illness.
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References
1.
ZhangY, PostWS, Blasco-ColmenaresE, et al.: Electrocardiographic QT interval and mortality: A meta-analysis. Epidemiology, 2011; 22:660–670.
2.
GlassmanAH, BiggerJTJr.: Antipsychotic drugs: Prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry, 2001; 158:1774–1782.
3.
IsbisterGK, PageCB: Drug induced QT prolongation: The measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacovl, 2013; 76:48–57.
4.
RectorTS, AdabagS, CunninghamF, et al.: Outcomes of citalopram dosage risk mitigation in a veteran population. Am J Psychiatry, 2016; 173:896–902.
5.
DrewBJ, AckermanMJ, FunkM, et al.: Prevention of torsade de pointes in hospital settings: A scientific statement from the American Heart Association and the American College of Cardiology Foundation endorsed by the American Association of Critical-Care Nurses and the International Society for Computerized Electrocardiology. J Am Coll Cardiol, 2010; 55:934–947.
6.
VandenberkB, VandaelE, RobynsT, et al.: Which QT correction formulae to use for QT monitoring?. J Am Heart Assoc, 2016; 5:e003264.
7.
ChanA, IsbisterGK, KirkpatrickCM, et al.: Drug-induced QT prolongation and torsades de pointes: Evaluation of a QT nomogram. QJM, 2007; 100:609–615.
8.
HasnainM, ViewegWV: QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: A comprehensive review. CNS Drugs, 2014; 28:887–920.
9.
BeachSR, CelanoCM, NoseworthyPA, et al.: QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics, 2013; 54:1–13.
10.
RochesterMP, KaneAM, LinneburSA, et al.: Evaluating the risk of QTc prolongation associated with antidepressant use in older adults: A review of the evidence. Ther Adv Drug Saf, 2018; 9:297–308.
11.
IribarrenC, RoundAD, PengJA, et al.: Validation of a population-based method to assess drug-induced alterations in the QT interval: A self-controlled crossover study. Pharmacoepidemiol Drug Saf, 2013; 22:1222–1232.
12.
BeachSR, CelanoCM, SugrueAM, et al.: QT prolongation, torsades de pointes, and psychotropic medications: A 5-year update. Psychosomatics, 2018; 59:105–122.
13.
BruggemanAR, KamalAH, LeBlancTW, et al.: Cancer cachexia: Beyond weight loss. J Oncol Pract, 2016; 12:1163–1171.
14.
Ruiz GarciaV, Lopez-BrizE, Carbonell SanchisR, et al.: Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev, 2013; 3:CD004310.
15.
BadowskiME, YanfulPK: Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther Clin Risk Manag, 2018; 14:643–651.
16.
HatanoY, MoroniM, WilcockA, et al.: Pharmacovigilance in hospice/palliative care: The net immediate and short-term effects of dexamethasone for anorexia. BMJ Support Palliat Care, 2016; 6:331–337.
17.
ZimmermannU, KrausT, HimmerichH, et al.: Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients. J Psychiatr Res, 2003; 37:193–220.
18.
RiechelmannRP, BurmanD, TannockIF, et al.: Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care, 2010; 27:106–110.
19.
BakM, FransenA, JanssenJ, et al.: Almost all antipsychotics result in weight gain: A meta-analysis. PLoS One, 2014; 9:e94112.
20.
ManuP, DimaL, ShulmanM, et al.: Weight gain and obesity in schizophrenia: Epidemiology, pathobiology, and management. Acta Psychiatr Scand, 2015; 132:97–108.
21.
DaurignacE, LeonardKE, DubovskySL: Increased lean body mass as an early indicator of olanzapine-induced weight gain in healthy men. Int Clin Psychopharmacol, 2015; 30:23–28.
22.
NavariRM, BrennerMC: Treatment of cancer-related anorexia with olanzapine and megestrol acetate: A randomized trial. Support Care Cancer, 2010; 18:951–956.
23.
GuinaJ, MerrillB: Benzodiazepines I: Upping the care on downers: The Evidence of risks, benefits and alternatives. J Clin Med, 2018; 7:17.
24.
KamellA, SmithLK: Attitudes toward use of benzodiazepines among US hospice clinicians: Survey and review of the literature. J Palliat Med, 2016; 19:516–522.
25.
BrewsterGS, RiegelB, GehrmanPR: Insomnia in the older adult. Sleep Med Clin, 2018; 13:13–19.
26.
SateiaMJ, BuysseDJ, KrystalAD, et al.: Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med, 2017; 13:307–349.
27.
GlassJ, LanctotKL, HerrmannN, et al.: Sedative hypnotics in older people with insomnia: Meta-analysis of risks and benefits. BMJ, 2005; 331:1169.
28.
SherY, Miller CramerAC, AmentA, et al.: Valproic acid for treatment of hyperactive or mixed delirium: Rationale and literature review. Psychosomatics, 2015; 56:615–625.
29.
NeufeldKJ, YueJ, RobinsonTN, et al.: Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: A systematic review and meta-analysis. J Am Geriatr Soc, 2016; 64:705–714.
30.
AgarMR, LawlorPG, QuinnS, et al.: Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: A randomized clinical trial. JAMA Intern Med, 2017; 177:34.
31.
KishiT, HirotaT, MatsunagaS, et al.: Antipsychotic medications for the treatment of delirium: A systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry, 2016; 87:767–774.
32.
Van Den BoogaardM, SlooterAJ, BrüggemannRJ, et al.: Effect of haloperidol on survival among critically ill adults with a high risk of delirium: The REDUCE randomized clinical trial. JAMA, 2018; 319:680–690.
33.
HirstJM, VaughanCL, IrwinSA: Delirium: Use antipsychotics when appropriate and appropriately. J Palliat Med, 2017; 20:799.
34.
LimCJ, TrevinoC, TampiRR: Can olanzapine cause delirium in the elderly?. Ann Pharmacother, 2006; 40:135–138.
35.
GuggerJJ: Antipsychotic pharmacotherapy and orthostatic hypotension: Identification and management. CNS Drugs, 2011; 25:659–671.
36.
CiprianiA, FurukawaTA, SalantiG, et al.: Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet, 2018; 391:1357–1366.
37.
RaynerL, PriceA, EvansA, et al.: Antidepressants for the treatment of depression in palliative care: Systematic review and meta-analysis. Palliat Med, 2011; 25:36–51.
38.
ValerioMP, SzmulewiczAG, MartinoDJ: A quantitative review on outcome-to-antidepressants in melancholic unipolar depression. Psychiatry Res, 2018; 265:100–110.
39.
O'ConnorCM, JiangW, KuchibhatlaM, et al.: Safety and efficacy of sertraline for depression in patients with heart failure: Results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol, 2010; 56:692–699.
40.
FinnerupNB, AttalN, HaroutounianS, et al.: Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol, 2015; 14:162–173.
RiordanP, BriscoeJ, KamalAH, et al.: Top ten tips palliative care clinicians should know about mental health and serious illness. J Palliat Med, 2018; 21:1171–1176.
43.
SleeA, NazarethI, BondaronekP, et al.: Pharmacological treatments for generalised anxiety disorder: A systematic review and network meta-analysis. Lancet, 2019; 393:768–777.
44.
MartinottiG, LupiM, SarchioneF, et al.: The potential of pregabalin in neurology, psychiatry and addiction: A qualitative overview. Curr Pharm Des, 2013; 19:6367–6374.
45.
ChessickCA, AllenMH, ThaseM, et al.: Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev, 2006:CD006115.
46.
PottieK, ThompsonW, DaviesS, et al.: Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline. Can Fam Physician, 2018; 64:339–351.
47.
KonopkaA, Pełka-WysieckaJ, GrzywaczA, SamochowiecJ: Psychosocial characteristics of benzodiazepine addicts compared to not addicted benzodiazepine users. Prog Neuropsychopharmacol Biol Psychiatry, 2013; 40:229–235.
48.
GuinaJ, NahhasRW, GoldbergAJ, et al.: PTSD symptom severities, interpersonal traumas, and benzodiazepines are associated with substance-related problems in trauma patients. J Clin Med, 2016; 5:70.
49.
GuinaJ, RossetterSR, DeRB, et al.: Benzodiazepines for PTSD: A systematic review and meta-analysis. J Psychiatr Pract, 2015; 21:281–303.
50.
WangPS, BohnRL, GlynnRJ, et al.: Hazardous benzodiazepine regimens in the elderly: Effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry, 2001; 158:892–898.
51.
HaiderA, AzharA, NaqviS, et al.: Concurrent use of opioids and benzodiazepines or non-benzodiazepines sedative hypnotics among cancer patients referred to outpatient palliative care clinic of a comprehensive cancer care center (S762). J Pain Symptom Manag, 2018; 55:690–691.
52.
TradounskyG: Seizures in palliative care. Can Fam Physician, 2013; 59:951–955, e401–e955.
53.
EkströmMP, Bornefalk-HermanssonA, AbernethyAP, et al.: Safety of benzodiazepines and opioids in very severe respiratory disease: National prospective study. BMJ, 2014; 348:g445.
54.
AbernethyAP, CurrowDC, FrithP, et al.: Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ, 2003; 327:523–528.
55.
SimonST, HigginsonIJ, BoothS, et al.: Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev, 2016; 10:CD007354.
56.
CurrowDC, McDonaldC, OatenS, et al.: Once-daily opioids for chronic dyspnea: A dose increment and pharmacovigilance study. J Pain Symptom Manage, 2011; 42:388–399.
57.
BreitbartW, MarottaR, PlattMM, et al.: A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Focus, 2005; 153:231–340.
58.
HuiD, Frisbee-HumeS, WilsonA, et al.: Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: A randomized clinical trial. JAMA, 2017; 318:1047–1056.
59.
Murray-BrownF, DormanS: Haloperidol for the treatment of nausea and vomiting in palliative care patients. Cochrane Database Syst Rev, 2015:CD006271.
60.
UritskyTJ, AtayeeRS, HerndonCM, et al.: Ten tips palliative care pharmacists want the palliative care team to know when caring for patients. J Palliat Med, 2018; 21:1017–1023.
61.
SutherlandA, NaessensK, PluggeE, et al.: Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. Cochrane Database Syst Rev, 2018; 9:CD012555.
62.
FriedgoodCE, RipsteinCB: Chlorpromazine (thorazine) in the treatment of intractable hiccups. J Am Med Assoc, 1955; 157:309–310.
63.
DavignonA, LemieuxG, GenestJ: Chlorpromazine in the treatment of stubborn hiccup. Union Med Can, 1955; 84:282–284.
64.
PolitoNB, FellowsSE: Pharmacologic interventions for intractable and persistent hiccups: A systematic review. J Emerg Med, 2017; 53:540–549.
65.
DeppingAM, KomossaK, KisslingW, et al.: Second-generation antipsychotics for anxiety disorders. Cochrane Database Syst Rev, 2010:CD008120.
66.
HershenbergR, GrosDF, Brawman-MintzerO: Role of atypical antipsychotics in the treatment of generalized anxiety disorder. CNS Drugs, 2014; 28:519–533.
67.
PignonB, Tezenas du MontcelC, CartonL, et al.: The place of antipsychotics in the therapy of anxiety disorders and obsessive-compulsive disorders. Curr Psychiatry Rep, 2017; 19:103.
68.
AlbertU, CarmassiC, CosciF, et al.: Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: A systematized review. Int Clin Psychopharmacol, 2016; 31:249–258.
69.
PuetzTW, YoungstedtSD, HerringMP: Effects of pharmacotherapy on combat-related PTSD, anxiety, and depression: A systematic review and meta-regression analysis. PLoS One, 2015; 10:e0126529.
70.
SteinDJ, IpserJC, SeedatS: Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev, 2006:CD002795.
71.
HetrickSE, PurcellR, GarnerB, et al.: Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev, 2010; 7:CD007316.
72.
MarksDM, ParkMH, HamBJ, et al.: Paroxetine: Safety and tolerability issues. Expert Opin Drug Saf, 2008; 7:783–794.
73.
VillarrealG, HamnerMB, CaniveJM, et al.: Efficacy of quetiapine monotherapy in posttraumatic stress disorder: A randomized, placebo-controlled trial. Am J Psychiatry, 2016; 173:1205–1212.
74.
BritnellSR, JacksonAD, BrownJN, et al.: Aripiprazole for post-traumatic stress disorder: A systematic review. Clin Neuropharmacol, 2017; 40:273–278.
75.
RaskindMA, PeskindER, ChowB, et al.: Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med, 2018; 378:507–517.
76.
PrommerEE: Ketamine for pain: An update of uses in palliative care. J Palliat Med, 2012; 15:474–483.
77.
ShillingburgA, KanateAS, HamadaniM, et al.: Treatment of severe mucositis pain with oral ketamine mouthwash. Support Care Cancer, 2017; 25:2215–2219.
78.
SlatkinNE, RhinerM: Topical ketamine in the treatment of mucositis pain. Pain Med, 2003; 4:298–303.
79.
McGirrA, BerlimMT, BondDJ, et al.: A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med, 2015; 45:693–704.
80.
MurroughJW, IosifescuDV, ChangLC, et al.: Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. Am J Psychiatry, 2013; 170:1134–1142.
81.
PriceRB, NockMK, CharneyDS, et al.: Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry, 2009; 66:522–526.
82.
IrwinSA, IglewiczA: Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. J Palliat Med, 2010; 13:903–908.
83.
IglewiczA, MorrisonK, NelesenRA, et al.: Ketamine for the treatment of depression in patients receiving hospice care: A retrospective medical record review of thirty-one cases. Psychosomatics, 2015; 56:329–337.
84.
IrwinSA, IglewiczA, NelesenRA, et al.: Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: A 28-day open-label proof-of-concept trial. J Palliat Med, 2013; 16:958–965.
85.
LapidusKA, LevitchCF, PerezAM, et al.: A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry, 2014; 76:970–976.
86.
aan het RotM, CollinsKA, MurroughJW, et al.: Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry, 2010; 67:139–145.
87.
StahlSM: Stahl's Essential Psychopharmacology: Prescriber's Guide: Cambridge University Press, 2014.
