Antidepressant Use in Patients with Carcinoid / Neuroendocrine Tumors: Results of A Systematic Review

Elie Isenberg-Grzeda MD CM FRCPC1, Meredith MacGregor MD2, Konstanna Matsoukas MLIS2, Diane Reidy-Lagunes MD2, Yesne Alici MD2 (1) University of Toronto / Sunnybrook Health Sciences Center (2) Memorial Sloan Keering Cancer Center

Learning Objectives Results Conclusion Andepressant, (1) Define the core theorecal problem that may make andepressant use unsafe in paents Age, • Over 42 cases reported Arcle Year dose (mg) if Notes with carcinoid tumors Gender • Nearly all did not report adverse reacons reported (2) List the studies that have been published to date arguing for and against the safe use of Bariani et al 2013 64 M Sertraline 12-month progression-free survival on octreode and mTOR • One paent hospitalized due to dehydraon andepressants in carcinoid tumor paents. inhibitor • One paent with worsening CS symptoms following (3) Weigh the risks and benefits of andepressant use in paents with carcinoid tumor. Bajwah et al. 2005 67,F Venlafaxine Only took 1 dose due to nausea/voming overdose • Furse et al 2008 55 M Fluoxene 10 mg “sudden deterioraon in symptoms” following fluoxene. Based on the available evidence, it appears premature to eliminate andepressants in paents with carcinoid/ NET Introduction Methods Symptoms rapidly improved aer disconnuaon. Larsson et al 2001 “several” Unspecified “only a few paents suffered from depression, and those • Paents should be advised about potenal side-effects who developed symptoms of depression were successfully including the possibility of worsening of CS symptoms • Paents with neuroendocrine tumors 577 records iden*fied through bibliographic 1 addi*onal records iden*fied database searching (November 2015) through other sources treated with andepressants. “ • Future studies should examine whether somatostan (NET) have high rates of depression. Noyer et al 1997 56 F Sertraline Carcinoid tumor “unmasked” following overdose of sertraline PubMed – 325 Bibliography Searching – 1 analogs protect against andepressant-related side- • NETs may secrete vasoacve substances, Embase – 242 (500 mg) in suicide aempt. Previously tolerated sertraline Cochrane CENTRAL – 1 effects in paents with carcinoid / NET including serotonin. CINAHL – 2 for 3 months. Iden%fica%on • Future studies should examine the role of non- • Tryptophan is a precursor of serotonin, PsycINFO – 7 Oberg et al 1986 Unspec. Tricyclics Paent developed “mental depression aer 3 months of serotonergic andepressants in NET and NETs may effecvely deplete interferon which resolved on treatment with tricyclic andepressants”… References serotonin in the brain by shunng it 558 records eligible for screening Patel et al 2009 51 F Unspecified aBer duplicates removed 1. Bariani GM, Carvalheira JB, Riechelmann RP. Antumor effect of everolimus in a paent with type 3 gastric towards the tumor. Neuroendocrine Tumor. Onkologie(Czech Republic). 2013;36:502-504.

Screening Philip et al 2011 47 M Unspecified “He was placed on andepressants and remains stable at this 2. Bajwah S, Lee B. The case study masterclass. Case 20: symptom control in a paent with carcinoid tumour. • This may explain the higher rates of European Journal of Palliave Care. 2005;12:106-107 è me. “ 3. Furse RM, Green CJ, Mee AS. Carcinoid syndrome unmasked by fluoxene, a selecve serotonin reuptake inhibitor. depression. Clinical gastroenterology and hepatology : the official clinical pracce journal of the American Gastroenterological 558 records screened Russo et al 2004 Unspec. Amitriptyline Associaon. 2008;6:e27-28. • Excess serotonin in the periphery may 542 records excluded 4. Larsson G, Sjödén PO, Öberg K, Eriksson B, Von Essen L. Health-related quality of life, anxiety and depression in Seshamani et al 2009 47 M Citalopram 5-HIAA normal. “No flushing, diarrhea, or fainng” paents with midgut carcinoid tumours. Acta Oncologica. 2001;40:825-831. also contribute to carcinoid syndrome Pre-Clinical: 69 5. Noyer CM, Schwartz BM. Sertraline, a selecve serotonin reuptake inhibitor, unmasking carcinoid syndrome. The American journal of gastroenterology. 1997;92:1387-1388. 298 ar*cles selected for full- No An*depressant: 223 (CS). 6. Oberg K, Norheim I, Lind E. Treatment of malignant carcinoid tumors with human leukocyte interferon: Long-term text review No Carcinoid: 199 Simbera et al 2005 75 F Citalopram 20 mg, Worsening of diarrhea (from twice daily to 14 mes daily) Insufficient Info: 1 results. Cancer Treatment Reports. 1986;70:1297-1304. • Andepressants may theorecally 7. Patel S, Heetun M, Gurjar SV, Szakacs S. A rare case of intra-cardiac metastasis from an appendiceal carcinoid Eligibility Mirtazapine 15 mg with citalopram, leading to dehydraon and hospitalizaon. tumour without liver metastases. Internaonal Journal of Colorectal Disease. 2009;24:993-994. Non-English: 46 worsen CS via their serotonergic Normalizaon when citalopram switched to mirtazapine. 8. Philip T, Jacoby SH, Nissel-Horowitz S, Russ M, Mehrotra B. Severe psychopathology: An unusual manifestaon of Book: 2 248 full-text ar*cles carcinoid disease-Case reports. Journal of Clinical Oncology. 2011;29. properes obtained and reviewed Unable to Obtain: 2 Soliday et al 2004 25 cases Unspecified 13 paents taking SSRIs, 12 paents taking other 9. Russo S, Boon JC, Kema IP, Willemse PH, den Boer JA, Korf J, de Vries EG. Paents with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulaon. Psychosomac medicine. 2004;66:422-425. • Few case reports have cauoned against andepressants. 10.Seshamani M, Einhorn E, Mirza N. Atypical carcinoid of the larynx and potenal complicaons of the carcinoid Vollmayr et al 2005 67 F Unspecified Abdominal pain worsened. Upon diagnosis of NET (which syndrome: A case report. Ear, Nose and Throat Journal. 2009;88:E1. prescribing andepressants to paents 11.Simbera Z, Balon R. Carcinoid tumor, selecve serotonin reuptake inhibitors, and diarrhea. Psychosomacs. followed andepressant) and surgical resecon, symptoms 2005;46:88-89. with CS. 16 studies included in 12.Soliday E, Garofalo JP, Smith SR, Warner RR. Depression and Andepressant Use in Gastrointesnal Carcinoid qualita*ve synthesis abated. Cancer Paents. Journal of Applied Biobehavioral Research. 2004;9:80-90.

• No large studies have examined the Included Williams et al 2005 61M Sertraline 50 mg Duraon of use ranged from 10 weeks (75M) to 5 years (56F). 13.Vollmayr B, Lederbogen F, Hewer W. Small bowel tumors misdiagnosed as funconal gastrointesnal symptoms. General Hospital Psychiatry. 2005;27:78-80. safety of andepressant use in NET with 64F Paroxene 40 mg One of the paents (64F) had carcinoid syndrome. Two of the 14.Williams MD, Dolenc TJ. Selecve serotonin reuptake inhibitors and paents with carcinoid tumor. Moher D, Libera* A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Repor*ng Items for Systema*c Psychosomacs. 2005;46:370-372. Reviews and MetaAnalyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097 or without CS. 56F Paroxene 40 mg paents (64F and 68M) were treated with somatostan 15.Wya R, et al. Effects of MAO inhibitors and parachlorophenylalanine in longitudinal sleep studies. Psychophysiology. 1968;5:209-210. 68M Paroxene 20 mg analogs. None of the paents developed worsening carcinoid 16.Yazicioǧlu A, Yekeler E, Bicakcioǧlu P, Özaydin E, Karaoǧlanoǧlu N. Synchronous bilateral mulple typical 75M Fluoxene 20 mg syndrome. pulmonary carcinoid tumors: A unique case with 10 typical carcinoids. Balkan Medical Journal. 2012;29:450-452. Wya et al 1968 2 cases MAOI Contact Informaon è è è Yazicioglu et al 2012 64 F Escitalopram NET of the lung. No symptoms of carcinoid syndrome. Paent Elie Isenberg-Grzeda MD CM FRCPC è well 10 months post-resecon. Department of Psychiatry, University of Toronto, Odee Cancer Center, Sunnybrook Health Sciences Center L-Tryptophan 5-Hydroxy Tryptophan Serotonin 5-HIAA Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 [email protected]