Retrospective Chart Review of Antidepressant Use in Patients with Carcinoid Tumors EAPM Annual Meeting - Barcelona, Spain
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1 Retrospective Chart Review of Antidepressant Use in Patients with Carcinoid Tumors EAPM Annual Meeting - Barcelona, Spain Elie Isenberg-Grzeda MD CM FRCPC Co-Authors: Meredith MacGregor MD Afton Bergel MD Stacy Eagle MD Fernando Espi Forcen MD Reema Mehta MD Konstantina Matsoukas MLIS Jonathan Wills BA Diane Reidy-Lagunes MD Yesne Alici MD
2 Disclosure: Elie Isenberg-Grzeda MD CM FRCPC With respect to the following presentation, there has been no relevant (direct or indirect) financial relationship between the party listed above (and/or spouse/partner) and any for-profit company in the past 24 months which could be considered a conflict of interest.
3 Learning Objectives At the end of this talk, the attendee will be able to: 1. Describe the theoretical concerns for using antidepressants in carcinoid tumor 2. Compare the evidence for/against antidepressant safety in patients with carcinoid tumor
4 Clinical Vignette 54 year old man with secreting carcinoid tumor of the small intestine with metastasis to liver. Diagnosed 4 years ago. No past psychiatric history, progressively worsening mood. Paroxetine 20 mg daily started by oncologist.
5 Carcinoid Tumors Well-differentiated, low-grade neuroendocrine tumor Incidence: < 5 /100,000 Median age of onset = 64 yrs Jejunum, Ileum, Appendix, Cecum Functional (secretory) Serotonin Others Mawe, G. M. & Hoffman, J. M. (2013) Serotonin signalling in the gut functions, dysfunctions and therapeutic targets Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro
6 Carcinoid Syndrome Diarrhea Flushing Sweating Wheezing Valvular disease Serotonin excess (maybe histamine and tachykinins too)
7 No se puede mostrar la imagen en este momento. Serotonin Metabolism L-Tryptophan 5-Hydroxy- Tryptophan (5-HTP) 5-Hydroxy- Tryptamine (5-HT) mons/thumb/1/1c/serotonin_biosynthesis.s vg/2000px-serotonin_biosynthesis.svg.png 5-Hydroxyindole acetic acid (5-HIAA)
8 Serotonin Metabolism Gut Blood CNS L-Tryptophan L-Tryptophan 5-Hydroxy- Tryptophan (5-HTP) 5-Hydroxy- Tryptophan (5-HTP) 5-Hydroxy- Tryptamine (5-HT) 5-Hydroxy- Tryptamine (5-HT) 5-Hydroxy-indole acetic acid (5-HIAA) 5-Hydroxy-indole acetic acid (5-HIAA)
9 Serotonin Metabolism Gut Blood CNS L-Tryptophan L-Tryptophan 5-HTP 5-HTP 5-HT 5-HT 5-HIAA 5-HIAA
10 Depression in Carcinoid/NETs Major et al. (1973): N=22 50% depression, clinical impression Soliday et al. (2004): N=182 22% depression, HADS
11 Depression in Carcinoid/NETs Major et al. (1973): N=22 50% depression, clinical impression Soliday et al. (2004): N=182 22% depression, HADS Antidepressants may have a role in treating Carcinoid/NET
12 Antidepressants in Carcinoid/NET: The Problem Noyer 1997
13 Antidepressants in Carcinoid/NET: The Problem Noyer 1997
14 Antidepressants in Carcinoid/NET: The Problem Simbera 2005
15 Antidepressants in Carcinoid/NET: The Problem Simbera 2005
16 Antidepressants in Carcinoid/NET: The Problem Furse 2008
17 Antidepressants in Carcinoid/NET: The Problem Furse 2008
18 Antidepressants in Carcinoid/NET: The Problem Simbera 2005 Noyer 1997 Furse 2008
19 Antidepressants in Carcinoid/NET: The Problem Murphy, 1998 Warner 2001 Soliday 2005b Soliday 2005a Simbera 2005 Macpherson 2009 Lapi 2012 Noyer 1997 Russo 2005 Williams 2005 Moran 2012 Vybornykh 2005 Furse 2008 Dolenc 2005 Kurklinsky 2011 Moretti 2013
20 Conversely Psychosomatics (4):
21 Conversely Psychosomatics (4):
22 Research Questions: Are they safe? Do they precipitate / unmask CS? Do they worsen CS or cause catastrophic events?
23 Methods Design: Chart Review All patients diagnosed with carcinoid tumor AND prescribed antidepressant (Jan 2008 April 2015) Outcomes: Duration of use Was antidepressant stopped (yes/no) Reason for stopping Any serious events (carcinoid crisis, death)
24 Results: Demographics CS+ N (%) CS- N (%) Total 16 (17.4%) 76 (82.6%) P-value Age (years), Mean(SD) 61.8 yr (14.9) 60.1 yr (10.9) Gender: Female 7 (43.8%) 50 (65.8) Tumor Location: Lung 41 (53.9%) Pancreas 9 (11.8%) Ileum 10 (62.5%) 8(10.5%) Duodenum 1 (6.3%) 5 (6.6%) Appendix 5 (6.6%) Unknown 4 (25%) 2 (2.6%) Jejunum 1 (6.3%) 1 (1.3%) Other 5 (6.6%) Metastatses 16 (100%) 34 (44.7%)
25 Results: Antidepressant Variables CS+ N (%) CS- N (%) Any Antidepressant 16 (100%) 72 (100%) P-value Serotonergic Antidepressant 15 (93.8%) 68 (89.5%).511 Multiple Antidepressants 4 (25%) 12 (15.8%).289 Reason for Starting: Depression/Anxiety 13 (81.3%) 53 (69.7%) Sleep 3 (18.8%) 6 (7.9%) Other psychiatric symptom 4 (5.3%) Somatic Symptoms 3 (3.9%) Smoking Cessation 5 (6.6%) Unspecified 8 (10.5%)
26 Results: Duration of Use Duration of Use (months), MD (range) CS+ N (%) 11.6 mo (0-121) CS- N (%) 14.3 mo (0-172) Stopped for Any Reason 4 (25%) 27 (35.5%).308 Stopped within 1 month 3 (18.8%) 10 (13.2%) P-value.641 Reason for Stopping: Unspecified 1 (25%) 17 (63%) Symptoms Resolved 2 (50%) 5 (18.5%) Ineffective 2 (7.4%) Delirium 2 (7.4%) Side-Effects 1 (25%)* 1 (3.7%)** *Unspecified side-effect **Dizziness
27 Results: Serious Events Serious Adverse Events CS+ N (%) CS- N (%) P-value Carcinoid Crisis 0 (0%) 0 (0%) n/a Conversion from CS- to CS+ n/a 0 (0%) n/a
28 Results: Antidepressants
29 Discussion Long duration of antidepressant use in 92 patients with NET/carcinoid tumors No documented carcinoid crisis No conversion of CS- patients to CS+ patients (i.e., no unmasking) No serious adverse effects
30 Cancer, March 2017 (Published online Month 00, 2017) DOI: /cncr.30633
31 Limitations Retrospective design Recall bias Adequate documentation of symptoms Lost to follow up Nomenclature changes Endpoints Serious adverse events Quality of Life
32 Conclusions Did not find evidence to support the claims that antidepressants must be avoided in carcinoid/net Future research Prospective Design Tolerability Efficacy
33 Questions
34
35 Carcinoid Tumors
36 First described in 1907 Slow growing tumor carcinoid = cancer-like (benign) Carcinoid Tumors Malignant potential discovered in 1938
37 Carcinoid NET Neuroendocrine Tumors Epithelial tumors Endocrine / Neuroendocrine Secretory / 100,000 person-years
38 No se puede mostrar la imagen en este momento. Carcinoid NET Neuroendocrine Tumors Epithelial tumors Endocrine / Neuroendocrine Secretory / 100,000 person-years Anatomical Locations Gastroenteropancreatic Pulmonary Other
39 Functional = Secretory Non-Functional = Non-Secretory Functional Status Secretory Products (amines/peptides) Serotonin Histamine Kinins Prostaglandins VIP ACTH
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