Vol 13, No 2 (2019)
Review paper
Published online: 2019-06-05

open access

Page views 1518
Article views/downloads 1207
Get Citation

Connect on Social Media

Connect on Social Media

Pharmacotherapy of depression in patients with advanced diseases

Jakub Grabowski1, Mateusz Przybylak1
Palliat Med Pract 2019;13(2):82-89.

Abstract

Sadness and anxiety are natural reactions to approaching death. However, sometimes these symptoms reach the significant intensity and are associated with the development of a depressive episode in people at the end of life. Diagnosis of depression may mean that somatic symptoms of advanced disease are subject to exacerbation due to the mental condition (reduced pain threshold, fatigue, sleep disorders, reduced appetite). Depressive patients will be less likely to cooperate in treatment, which may lead to deterioration of overall health, worse prognosis and higher mortality. It seems, therefore, that pharmacotherapy of depression in end-of-life patients should not be marginalized. However, due to antidepressants’ delayed onset of action most patients probably fail to achieve satisfactory improvement on time. We propose as the first target for the treatment of depression in palliative care a fast and safe reduction of symptoms. Without giving up the basic antidepressant treatment, expected risk and benefits should be carefully and individually considered before the inclusion of standard medications, especially in terms of remaining life expectancy. We also believe that, if started, such pharmacotherapy should often be accompanied by medications that can quickly alleviate at least some depression symptoms making it easier for the patient to wait for the beneficial effect of the drug. Focusing on the rapid improvement of mental state, mianserin, mirtazapine, pregabalin, quetiapine, trazodone and vortioxetine seem to be beneficial for use in palliative care.

Article available in PDF format

View PDF Download PDF file

References

  1. Signer M. Depression in palliative care. Ther Umsch. 2012; 69(2): 99–106.
  2. Hotopf M, Chidgey J, Addington-Hall J, et al. Depression in advanced disease: a systematic review Part 1. Prevalence and case finding. Palliat Med. 2002; 16(2): 81–97.
  3. Warmenhoven F, van Rijswijk E, Engels Y, et al. The Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in Dutch advanced cancer patients. Support Care Cancer. 2012; 20(2): 319–324.
  4. Cohen-Cole SA, Stoudemire A. Major depression and physical illness. Special considerations in diagnosis and biologic treatment. Psychiatr Clin North Am. 1987; 10(1): 1–17.
  5. Simon GE, VonKorff M, Piccinelli M, et al. An international study of the relation between somatic symptoms and depression. N Engl J Med. 1999; 341(18): 1329–1335.
  6. Cameron C, Habert J, Anand L, et al. Optimizing the management of depression: primary care experience. Psychiatry Res. 2014; 220 Suppl 1: S45–S57.
  7. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010; 363(8): 733–742.
  8. Machado-Vieira R, Baumann J, Wheeler-Castillo C, et al. The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and Somatic Treatments. Pharmaceuticals (Basel). 2010; 3(1): 19–41.
  9. Nierenberg AA, Wright EC. Evolution of remission as the new standard in the treatment of depression. J Clin Psychiatry. 1999; 60 Suppl 22: 7–11.
  10. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 1905–1917.
  11. Vitetta L, Kenner D, Kissane D, et al. Clinical outcomes in terminally ill patients admitted to hospice care: diagnostic and therapeutic interventions. J Palliat Care. 2001; 17(2): 69–77.
  12. Volkers AC, Nuyen J, Verhaak PFM, et al. The problem of diagnosing major depression in elderly primary care patients. J Affect Disord. 2004; 82(2): 259–263.
  13. Jarema M. Standardy leczenia farmakologicznego niektórych zaburzeń psychicznych. Via Medica, Gdańsk 2015.
  14. Weng LC, Huang HL, Wilkie DJ, et al. Predicting survival with the Palliative Performance Scale in a minority-serving hospice and palliative care program. J Pain Symptom Manage. 2009; 37(4): 642–648.
  15. Lloyd-Williams M, Friedman T, Rudd N. A survey of antidepressant prescribing in the terminally ill. Palliat Med. 1999; 13(3): 243–248.
  16. Quitkin FM, McGrath PJ, Rabkin JG, et al. Different types of placebo response in patients receiving antidepressants. Am J Psychiatry. 1991; 148(2): 197–203.
  17. Ferguson JM. SSRI Antidepressant Medications: Adverse Effects and Tolerability. Prim Care Companion J Clin Psychiatry. 2001; 3(1): 22–27.
  18. Rayner L, Price A, Evans A, et al. Antidepressants for the treatment of depression in palliative care: systematic review and meta-analysis. Palliat Med. 2011; 25(1): 36–51.
  19. David DJ, Gourion D. Antidépresseurs et tolérance : déterminants et prise en charge des principaux effets indésirables. L'Encéphale. 2016; 42(6): 553–561.
  20. Rayner L, Higginson IJ, Price AHM. The Management of Depression in Palliative Care: European Clinical Guidelines. In London: Department of Palliative Care, Policy & Rehabilitation (www.kcl.ac. uk/schools/medicine/depts/palliative)/ European Palliative Care Research Collaborative. (www.epcrc.org): 2010.
  21. Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015; 18(4): 395–400.
  22. Andersen AB, Frydenberg M. Long-term use of zopiclone, zolpidem and zaleplon among Danish elderly and the association with sociodemographic factors and use of other drugs. Pharmacoepidemiol Drug Saf. 2011; 20(4): 378–385.
  23. Valenstein M, Taylor KK, Austin K, et al. Benzodiazepine use among depressed patients treated in mental health settings. Am J Psychiatry. 2004; 161(4): 654–661.
  24. Hajak G, Müller WE, Wittchen HU, et al. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction. 2003; 98(10): 1371–1378.
  25. Vgontzas AN, Kales A, Bixler EO. Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics. Pharmacology. 1995; 51(4): 205–223.
  26. Wagner J, Wagner ML. Non-benzodiazepines for the treatment of insomnia. Sleep Med Rev. 2000; 4(6): 551–581.
  27. Rayner L, Price A, Hotopf M, et al. Expert opinion on detecting and treating depression in palliative care: A Delphi study. BMC Palliat Care. 2011; 10: 10.
  28. Uzun S, Kozumplik O. Management of side effects of antidepressants - brief review of recommendations from guidelines for treatment of major depressive disorder. Psychiatr Danub. 2009; 21(1): 91–94.
  29. de Boer TH, Nefkens F, van Helvoirt A, et al. Differences in modulation of noradrenergic and serotonergic transmission by the alpha-2 adrenoceptor antagonists, mirtazapine, mianserin and idazoxan. J Pharmacol Exp Ther. 1996; 277(2): 852–860.
  30. Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001; 7(3): 249–264.
  31. Sobańska A, Wichniak A, Wierzbicka A, et al. Mianserin for treatment of primary insomnia. Sen. 2006; 6(2): 58–63.
  32. Stahl SM, Kremer C, Pinder RM. P.1.071 Tolerability of mirtazapine used in high or low initial dose. European Neuropsychopharmacology. 1997; 7: S157–S158.
  33. Stunkard AJ, Faith MS, Allison KC. Depression and obesity. Biol Psychiatry. 2003; 54(3): 330–337.
  34. Kim SW, Shin IS, Kim JM, et al. Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression. Psychiatry Clin Neurosci. 2008; 62(1): 75–83.
  35. Rojo JE, Ros S, Agüera L, et al. Combined antidepressants: clinical experience. Acta Psychiatr Scand Suppl. 2005(428): 25–31, 36.
  36. Khawam EA, Laurencic G, Malone DA. Side effects of antidepressants: an overview. Cleve Clin J Med. 2006; 73(4): 351–3, 356.
  37. Bahk WM, Pae CU, Chae JH, et al. Mirtazapine may have the propensity for developing a restless legs syndrome? A case report. Psychiatry Clin Neurosci. 2002; 56(2): 209–210.
  38. Bonne O, Shalev AY, Bloch M. Delirium associated with mianserin. Eur Neuropsychopharmacol. 1995; 5(2): 147–149.
  39. Stimmel GL, Dopheide JA, Stahl SM. Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. Pharmacotherapy. 1997; 17(1): 10–21.
  40. Lai FY, Shankar K, Ritz S. Mirtazapine-associated peripheral oedema. Aust N Z J Psychiatry. 2016; 50(11): 1108.
  41. Bottlender R, Erfurth A, Hoff P, et al. [Mianserin-induced hypertension 2 weeks after discontinuation of tranylcypromine]. Nervenarzt. 1997; 68(7): 591–592.
  42. Na KS, Jung HY, Cho SJ, et al. Can we recommend mirtazapine and bupropion for patients at risk for bleeding?: A systematic review and meta-analysis. J Affect Disord. 2018; 225: 221–226.
  43. Hernández JL, Ramos FJ, Infante J, et al. Severe serotonin syndrome induced by mirtazapine monotherapy. Ann Pharmacother. 2002; 36(4): 641–643.
  44. Gardner ME, Malone DC, Sey M, et al. Mirtazapine is associated with less anxiolytic use among elderly depressed patients in long-term care facilities. J Am Med Dir Assoc. 2004; 5(2): 101–106.
  45. Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007; 73(2): 137–150.
  46. Montgomery SA, Herman BK, Schweizer E, et al. The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacol. 2009; 24(4): 214–222.
  47. Taylor CP. Mechanisms of analgesia by gabapentin and pregabalin--calcium channel alpha2-delta [Cavalpha2-delta] ligands. Pain. 2009; 142(1-2): 13–16.
  48. Hall TD, Shah S, Ng B, et al. Changes in mood, depression and suicidal ideation after commencing pregabalin for neuropathic pain. Aust Fam Physician. 2014; 43(10): 705–708.
  49. Martinotti G. Pregabalin in clinical psychiatry and addiction: pros and cons. Expert Opin Investig Drugs. 2012; 21(9): 1243–1245.
  50. Schwan S, Sundström A, Stjernberg E, et al. A signal for an abuse liability for pregabalin--results from the Swedish spontaneous adverse drug reaction reporting system. Eur J Clin Pharmacol. 2010; 66(9): 947–953.
  51. Zacny JP, Paice JA, Coalson DW. Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers. Pharmacol Biochem Behav. 2012; 100(3): 560–565.
  52. Pae CU, Marks DM, Han C, et al. Pregabalin augmentation of antidepressants in patients with accident-related posttraumatic stress disorder: an open label pilot study. Int Clin Psychopharmacol. 2009; 24(1): 29–33.
  53. Stahl SM. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press, Cambridge 2014.
  54. DeVane C, Nemeroff C. Clinical Pharmacokinetics of Quetiapine. Clinical Pharmacokinetics. 2001; 40(7): 509–522.
  55. Schulz SC. Clinical use of quetiapine in disease states other than schizophrenia. J Clin Psychiatry. 2002; 63 Suppl 13: 32–38.
  56. Bauer M, El-Khalili N, Datto C, et al. A pooled analysis of two randomised, placebo-controlled studies of extended release quetiapine fumarate adjunctive to antidepressant therapy in patients with major depressive disorder. J Affect Disord. 2010; 127(1-3): 19–30.
  57. Karsten J, Hagenauw LA, Kamphuis J, et al. Low doses of mirtazapine or quetiapine for transient insomnia: A randomised, double-blind, cross-over, placebo-controlled trial. J Psychopharmacol. 2017; 31(3): 327–337.
  58. El-Saifi N, Moyle W, Jones C, et al. Quetiapine safety in older adults: a systematic literature review. J Clin Pharm Ther. 2016; 41(1): 7–18.
  59. Rock PL, Goodwin GM, Wulff K, et al. Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms. J Psychopharmacol. 2016; 30(3): 273–282.
  60. Cohrs S, Rodenbeck A, Guan Z, et al. Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacology (Berl). 2004; 174(3): 421–429.
  61. Maneeton N, Maneeton B, Woottiluk P, et al. Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2016; 10: 259–276.
  62. Calabrese JR, Keck PE, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005; 162(7): 1351–1360.
  63. Melada A, Krčmar T, Vidović A. A dose-dependent relationship between quetiapine and QTc interval. Int J Cardiol. 2016; 222: 893–894.
  64. Romero GM, Martí JFP, Fayos JG, et al. Utilisation of atypical antipsychotic drugs in institutionalised elderly persons and prevalence of metabolic alterations. Farmacia Hospitalaria (English Edition). 2010; 34(3): 139–147.
  65. Komossa K, Depping AM, Gaudchau A, et al. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database Syst Rev. 2010(12): CD008121.
  66. McIntyre RS, Muzina DJ, Adams A, et al. Quetiapine XR efficacy and tolerability as monotherapy and as adjunctive treatment to conventional antidepressants in the acute and maintenance treatment of major depressive disorder: a review of registration trials. Expert Opin Pharmacother. 2009; 10(18): 3061–3075.
  67. Stahl S. Mechanism of Action of Trazodone: a Multifunctional Drug. CNS Spectrums. 2014; 14(10): 536–546.
  68. Boissier JR, Portmann-Cristesco E, Soubri P, et al. Pharmacological and Biochemical Features of Trazodone. Trazodone. 1974: 18–28.
  69. Wichniak A, Wierzbicka A, Jernajczyk W. Sleep and antidepressant treatment. Curr Pharm Des . 2012; 18(36): 5802–5817.
  70. Schatzberg AF. Trazodone: a 5-year review of antidepressant efficacy. Psychopathology. 1987; 20 Suppl 1: 48–56.
  71. Fagiolini A, Comandini A, Catena Dell'Osso M, et al. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012; 26(12): 1033–1049.
  72. Jacobsen FM. Low-dose trazodone as a hypnotic in patients treated with MAOIs and other psychotropics: a pilot study. J Clin Psychiatry. 1990; 51(7): 298–302.
  73. Montgomery I, Oswald I, Morgan K, et al. Trazodone enhances sleep in subjective quality but not in objective duration. Br J Clin Pharmacol. 1983; 16(2): 139–144.
  74. Bossini L, Casolaro I, Koukouna D, et al. Off-label uses of trazodone: a review. Expert Opin Pharmacother. 2012; 13(12): 1707–1717.
  75. Werneke U, Northey S, Bhugra D. Antidepressants and sexual dysfunction. Acta Psychiatr Scand. 2006; 114(6): 384–397.
  76. James SP, Mendelson WB. The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry. 2004; 65(6): 752–755.
  77. Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors). CNS Spectr. 2015; 20(2): 93–97.
  78. Sowa-Kućma M, Pańczyszyn-Trzewik P, Misztak P, et al. Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant. Pharmacol Rep. 2017; 69(4): 595–601.
  79. Pae CU, Wang SM, Han C, et al. Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis. J Psychiatr Res. 2015; 64: 88–98.
  80. Wichniak A, Wierzbicka A, Walęcka M, et al. Effects of Antidepressants on Sleep. Curr Psychiatry Rep. 2017; 19(9): 63.
  81. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014; 17(10): 1557–1567.
  82. Jacobsen PL, Mahableshwarkar AR, Chen Y, et al. Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction. J Sex Med. 2015; 12(10): 2036–2048.
  83. Cipriani A, Furukawa TA, Salanti G, 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(10128): 1357–1366.
  84. Hirota K, Lambert DG. Ketamine: its mechanism(s) of action and unusual clinical uses. Br J Anaesth. 1996; 77(4): 441–444.
  85. Abdallah CG, Adams TG, Kelmendi B, et al. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID-ACTING ANTIDEPRESSANTS. Depress Anxiety. 2016; 33(8): 689–697.
  86. Lapidus KAB, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014; 76(12): 970–976.
  87. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013; 170(10): 1134–1142.
  88. Aan Het Rot M, Zarate CA, Charney DS, et al. Ketamine for depression: where do we go from here? Biol Psychiatry. 2012; 72(7): 537–547.
  89. Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013; 74(4): 250–256.
  90. Andrade C. Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action. J Clin Psychiatry. 2017; 78(4): e415–e419.
  91. Scottish Palliative Care Guidelines. https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/depression.aspx.
  92. Guidelines for managing depression in palliative care. https://www.nwcscnsenate.nhs.uk/files/1814/3394/6189/Depression.pdf.
  93. Ostuzzi G, Matcham F, Dauchy S, et al. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev. 2015(6): CD011006.