Psychosomatics 2014:55:692–697
& 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Case Reports SSRI Discontinuation Syndrome Following Bariatric Surgery: A Case Report and Focused Literature Review Kathleen Bingham, M.D., Raed Hawa, M.D., F.R.C.P.C., Sanjeev Sockalingam, M.D., F.R.C.P.C.
Introduction Bariatric surgery is a durable and successful treatment for severely obese patients for whom dietary or medical weight loss interventions have failed. Despite the emergence of new bariatric surgery procedures, the most common surgery performed currently is the Roux-en-Y gastric bypass.1 Patients undergoing bariatric surgery have a high degree of psychiatric co-morbidity, with lifetime rates of an affective and anxiety disorder approximating 44% and 32%, respectively,2 and depression and obesity seemingly reciprocally related.3 Consequently, many bariatric surgery candidates take antidepressant medication. In a recent multisite study, it was reported that 35% of a large cohort (n ¼ 2148) of patients presenting for bariatric surgery were taking at least 1 antidepressant on baseline assessment.4 Given the established effect of gastric bypass surgery on drug absorption in general5, it is imperative that physicians managing bariatric surgery patients are aware of possible complications associated with impaired psychiatric medication absorption and are comfortable addressing these complications. This report provides an example of the potential psychiatric complications associated with impaired medication absorption in the post–bariatric surgery period and discusses the etiology, differential diagnosis, and management strategies.
Case Report Ms. J, a 42-year-old woman, presented to our bariatric surgery psychosocial clinic as part of our routine 692
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multidisciplinary assessment process for gastric bypass candidates. Her body mass index on initial presentation was 37.7 kg/m2 and she had obesity-related medical co-morbidities, including gastroesophageal reflux disease, musculoskeletal pain, stress incontinence, dyslipidemia, and hypertension. She had attempted to lose weight 6 times using a commercial diet program but had always regained the weight. Despite her medical co-morbidities, her only medication at the time of initial assessment was 30 mg of paroxetine taken daily. On psychiatric assessment, Ms. J reported a history of panic disorder, starting at the age of 16 years and in remission for 10 years on paroxetine. She had no additional psychiatric history except subclinical binge-eating symptoms. Following her assessment, her formal psychiatric diagnoses (the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision6 criteria) were panic disorder with agoraphobia (in remission) and eating disorder not otherwise specified (subthreshold binge-eating disorder). Based on the clinical history, paroxetine did not seem to have contributed to her weight gain. Ms. J underwent an uncomplicated laparoscopic Roux-en-Y gastric bypass procedure and was discharged from hospital 2 days postoperatively. She
Received June 3, 2014; revised July 10, 2014; accepted July 10, 2014. From Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Bariatric Surgery Program, Toronto Western Hospital, Department of Psychiatry, University Health Network, Toronto, Ontario, Canada. Send correspondence and reprint requests to Kathleen Bingham, M.D., Toronto General Hospital, 200 Elizabeth Street8EN-218, Toronto, Ontario, Canada M5G 2C4; e-mail: kathleen. [email protected] & 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Psychosomatics 55:6, November/December 2014
Bingham et al. resumed taking 30 mg of paroxetine immediately postoperatively (she did not miss a dose). At 2 days after surgery, she started to experience irritability and flulike symptoms. Her irritability was such that she struck her husband during an argument. This behavior was quite out of character for her and was disconcerting to her and to her husband. When asked about her symptoms systematically during a subsequent interview, she also described experiencing dizziness, shocklike sensations, nervousness, mood swings, agitation, vivid dreams, insomnia, restless legs, unsteady gait, and nausea. She recalled having similar (but less severe) symptoms in the past after missing a dose of paroxetine. She did not typically have any of these symptoms at baseline. On assessment, Ms. J scored 17 on 43 on the Discontinuation-Emergent Signs and Symptoms checklist, a clinician-rated scale that measures signs and symptoms associated with antidepressant termination.7 Higher scores indicate more severe discontinuation symptoms. In clinical studies, patients are typically defined as experiencing a discontinuation syndrome if their Discontinuation-Emergent Signs and Symptoms score increases by 4 points or more from baseline7. Ms. J's symptoms resolved within 10 days. However, approximately 4 weeks after surgery, she developed a recurrence of panic attacks. At 8 weeks after surgery and after experiencing 4 panic attacks, she made an appointment with her former psychiatrist, who identified that the presentation was likely the result of decreased paroxetine absorption following gastric bypass surgery. Her psychiatrist increased the paroxetine dose to 30 mg taken in the morning and 20 mg before bedtime, with the view that increasing and dividing the dosage would result in improved gastrointestinal absorption. Following this adjustment, the panic attacks completely resolved and Ms. J returned to her baseline. She had a successful outcome 1 year after surgery, with a weight loss of 45.4 kg for a new body mass index of 25.1 kg/m2. Her medical co-morbidities and quality of life had significantly improved. This case illustrates the clinical effect of antidepressant pharmacokinetic changes following gastric bypass surgery. In Ms. J's case, she experienced both selective serotonin reuptake inhibitor (SSRI) discontinuation symptoms and a recurrence of the panic disorder, previously remitted for 10 years. Her symptoms Psychosomatics 55:6, November/December 2014
affected her emotional and physical well-being and her family relationships. Fortunately, once her condition became more apparent, it was quickly stabilized, and she experienced a very positive postsurgical outcome. Pharmacokinetic Changes Following Gastric Bypass Surgery Small, observational pharmacokinetic studies have demonstrated reduced bioavailability of sertraline,8,9 duloxetine,10 citalopram,8 and escitalopram8 in patients after gastric bypass surgery. The small sample sizes in these studies make it difficult to draw clinical conclusions, but in a study of 12 patients taking stable doses of antidepressant medication, with serum levels drawn at sequential points before and after bariatric surgery, Hamad et al. identified that in patients who experienced relapse of depression after surgery, the symptoms improved in conjunction with normalization of antidepressant bioavailability.8 Bioavailability tended to be lowest after 1 month and returned to (or increased from) baseline by 6 months in this study, although it remained lower than baseline for 1 patient at the 1-year point. The authors postulated that the increase in bioavailability at 6 months was because of the adaptive increase in the absorptive component of the intestinal mucosa that occurs postoperatively.8 Antidepressants, as with most oral medications, are maximally absorbed in the small intestine, the anatomy of which is significantly altered following gastric bypass.5 The rate and amount of drug absorption may be affected by a variety of changes postoperatively, including alterations in drug dissolution and solubility because of differences in intestinal pH, reduced intestinal surface area, and delayed gastric emptying.5,8 In addition, antidepressants are lipophilic and most are highly protein bound, qualities that make them susceptible to the changes in the volume of distribution and concentration of drug-binding proteins that accompany obesity and rapid weight loss.11,12 SSRI Discontinuation Syndrome To our knowledge, there is no literature addressing SSRI discontinuation syndrome after bariatric www.psychosomaticsjournal.org
693
Case Reports surgery, although bariatric surgery patients are theoretically at risk for this condition given the immediate and drastic change to their gastrointestinal system and the documented effects of this change on drug absorption. Although previously recognized as a complication of tricyclic discontinuation, adverse effects associated with abrupt SSRI discontinuation were first reported in the 1990s, and the first randomized controlled trial investigating this phenomenon was done in 1998.7 The symptoms include a variety of neurologic, emotional, and somatic phenomena associated with antidepressant termination or intermittent nonadherence, described in detail by the Discontinuation-Emergent Signs and Symptoms checklist.7 The common symptoms (reported in 410% of patients) include dizziness, “shocklike sensations,” gait incoordination, nausea, headache, fatigue, and insomnia.13 Antidepressants with short half-lives, such as venlafaxine and paroxetine, have been associated
TABLE.
with more severe discontinuation symptoms.14 Symptoms are typically mild and self-limiting, but they can be quite distressing.15 Differential Diagnosis in Bariatric Surgery Patients Given the deleterious effect of psychiatric co-morbidity on weight loss outcomes in bariatric surgery patients16, along with the negative effect of SSRI discontinuation syndrome on quality of life, clinicians working in bariatric surgery clinics should monitor for the emergence of these symptoms. Interestingly, the symptoms of SSRI discontinuation syndrome have some overlap in quality and temporal onset with the symptoms of at least one of the other postoperative complications of bariatric surgery: dumping syndrome—the gastrointestinal, vasomotor, and hypoglycemia-related symptom cluster associated with rapid gastric emptying17 (Table).
Symptom Comparison Between SSRI Discontinuation Syndrome and Dumping Syndrome SSRI discontinuation syndrome*
Onset Within 3-d postoperatively Characteristics Resolves with re-initiation of antidepressant Symptoms Anxiety Dizziness/light-headedness/vertigo Fatigue Diarrhea Nausea/emesis Impaired concentration Chills Irritability Vivid dreams Depersonalization/detachment Suicidal thoughts/behaviors Agitation Visual disturbances Gait instability Paresthesia Headache Shocklike sensations Myalgia – – – – –
Dumping syndrome† Immediately postoperatively once patient resumes oral intake Occurs 15 min (GI and vasomotor symptoms) to 3 h (hypoglycemic symptoms) after eating17 Palpitations, tachycardia, perspiration, tremor Hypotension, syncope Weakness Diarrhea Nausea Confusion – – – – – – – – – – – – Abdominal cramping Bloating Borborygmi Flushing Hunger
GI ¼ gastrointestinal; SSRI ¼ selective serotonin reuptake inhibitor. n
†
694
Symptoms compiled from Rosenbaum et al.7 and literature review by Black et al.13 Symptoms compiled from Tack et al.17
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Bingham et al. Discontinuation symptoms may also mimic relapse of the original psychiatric condition or the emergence of a new psychiatric disorder. Additional differential diagnoses include upper respiratory infection, benign paroxysmal positional vertigo, radiculopathy, and substance intoxication/withdrawal.18 These phenomena demonstrate the importance of maintaining a differential diagnosis when presented with neuropsychiatric symptoms in these complex patients.
Management of SSRI Discontinuation Syndrome After Bariatric Surgery All bariatric surgery patients taking antidepressant medication should be monitored postoperatively for changes in mental status, particularly in the first month, and patients should be counseled to selfmonitor for worsening psychiatric symptoms in the postoperative period.8 Clinicians should have a high index of suspicion for SSRI discontinuation syndrome in patients exhibiting psychiatric symptoms within the first week postoperatively, particularly when combined with neurologic and somatic symptoms. Patients taking antidepressants with short halflives, such as paroxetine and venlafaxine, may be at particular risk, and we suggest that these patients be counseled to this effect and educated about SSRI discontinuation symptoms. Presumably, patients like Ms. J who have previously experienced discontinuation symptoms on missing doses would also be at an elevated risk. Primary care providers, bariatric surgery clinicians, and community psychiatrists may also benefit from education about this issue for select patients so that they can assist in postoperative management. Surgeons, primary care providers, and allied health team members may be the clinicians most likely to identify SSRI discontinuation symptoms, as psychiatrists do not typically follow-up bariatric patients in the immediate postoperative period. By contrast, patients experiencing a recurrence of their primary psychiatric illness are more likely to experience symptoms within weeks to months. In the case of Ms. J, her discontinuation symptoms were not identified originally, and it was not until she developed panic attacks and followed up with her community psychiatrist that her medication dose was adjusted. Psychosomatics 55:6, November/December 2014
This case illustrates that SSRI discontinuation symptoms may represent a harbinger of recurrence of a primary psychiatric disorder, a phenomenon that makes intuitive sense given that these symptoms represent decreased antidepressant bioavailability. If Ms. J's discontinuation symptoms had been identified and the paroxetine dose been increased in the initial postoperative period, we may have been able to avoid a recurrence of the panic attacks. It is evident that identifying discontinuation symptoms early alleviates patient suffering and may prevent recurrence of psychiatric illness, highlighting the benefit of systematic inquiry into this condition in select patients. The Discontinuation-Emergent Signs and Symptoms checklist (described earlier) has not been validated for use in the bariatric population, but clinicians may consider using this scale as a guide to screen for SSRI discontinuation symptoms in patients whom they suspect may have or are at risk for the condition, even possibly administering it preoperatively to obtain a baseline in select high-risk patients. The literature considers an increase of 4 points or greater over the past 7 days (or from the beginning of the treatment interruption period) to be indicative of discontinuation syndrome, and generally, the higher the score, the more severe the condition is.7 However, any patient presenting with discontinuation symptoms warrants close attention. Certain symptoms, such as vivid dreams and shocklike sensations, are fairly specific to SSRI discontinuation syndrome (as opposed to other sequelae of bariatric surgery) and their presence should guide clinicians to strongly consider the diagnosis. For patients experiencing either discontinuation symptoms or recurrence of a primary psychiatric disorder after bariatric surgery, physicians should consider a medication dose increase or a change in formulation (e.g., to a liquid, if available) or both. Based on the literature to date, we suggest that all patients taking controlled-release medications switch to an immediate-release formulation before surgery, if available.19 When this is not an option, we suggest consulting with the pharmacist regarding other potential modifications to controlled-release medications that may improve dissolution/disintegration (e.g., opening and sprinkling capsules). If it is not possible to adjust controlled-release formulations, a clinical decision must be made to switch to a different medication or to continue the same medication (possibly at a higher dose) with close monitoring. www.psychosomaticsjournal.org
695
Case Reports It is noteworthy that Hamad et al. found that SSRI bioavailability tended to normalize or even increase in their small sample of patients by 6 months after surgery.8 Based on this evidence, one should consider closer monitoring for an emergence of antidepressant adverse effects starting at approximately 6 months postoperatively, particularly if patients' antidepressant doses were increased in the shortterm to combat initial lower bioavailability. Clinicians may wish to use rating scales to monitor symptoms on a regular basis in perioperative patients with a history of anxiety or depression. This strategy provides longitudinal data and allows for early identification of symptom recurrence. The Patient Health Questionnaire-920 has been validated as a depressionscreening tool in the bariatric population.21 Given the evidence of potential reduced bioavailability for 6–12 months postoperatively, patients taking antidepressant medication require monitoring for complications of pharmacokinetic changes, including SSRI discontinuation syndrome, worsening of their primary psychiatric disorder, and antidepressant adverse effects, for at least the first postoperative year.8 Conclusion This case illustrates the need for close monitoring of bariatric surgery patients who are taking
antidepressant medications in the postoperative period. The risk of SSRI discontinuation syndrome is individually based and depends on patient, medication, and surgical factors. A theoretical high-risk patient is one who is taking an antidepressant medication with a short half-life, has experienced discontinuation symptoms in the past with missed doses, and undergoes a procedure, such as gastric bypass, with malabsorpitve effects (as opposed to a procedure that is predominately restrictive, such as a sleeve gastrectomy). This case underlines the importance of psychiatric involvement in bariatric surgery clinics for direct patient care and education purposes. Bariatric surgery patients tend to be complex, with medical and psychiatric co-morbidities, and the surgery poses unique challenges concerning medication management. The need for collaboration will only become more apparent as bariatric surgery reaches more patients, including those living with severe mental illness. The authors thank Ms. J for participating in this process. They would also like to thank the Toronto Western Hospital Bariatric Interdisciplinary team for their support. Disclosure: The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Buchwald H, Oien DM: Metabolic/bariatric surgery worldwide 2011. Obes Surg 2013; 23(4):427–436 2. Mitchell JE, Selzer F, Kalarchian MA, et al: Psychopathology before surgery in the longitudinal assessment of bariatric surgery-3 (LABS-3) psychosocial study. Surg Obes Relat Dis 2012; 8(5):533–541 3. Luppino FS, de Wit LM, Bouvy PF, et al: Overweight, obesity, and depression: a systematic review and metaanalysis of longitudinal studies. Arch Gen Psychiatry 2010; 67(3):220–229 4. Mitchell JE, King WC, Chen JY, et al: Course of depressive symptoms and treatment in the longitudinal assessment of bariatric surgery (LABS-2) study. Obesity 2014. http://dx. doi.org/10.1002/oby.20738 [Epub ahead of print] 5. Padwal R, Brocks D, Sharma AM: A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev 2010; 11(1):41–50 6. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision;
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7.
8.
9.
10.
DSM-IV-TR. Washington, DC and London, England: American Psychiatric Association; 2000 Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB: Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998; 44(2):77–87 Hamad GG, Helsel JC, Perel JM, et al: The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors. Am J Psychiatry 2012; 169(3):256–263 Roerig JL, Steffen K, Zimmerman C, Mitchell JE, Crosby RD, Cao L: Preliminary comparison of sertraline levels in postbariatric surgery patients versus matched nonsurgical cohort. Surg Obes Relat Dis 2012; 8(1): 62–66 Roerig JL, Steffen KJ, Zimmerman C, Mitchell JE, Crosby RD, Cao L: A comparison of duloxetine plasma levels in postbariatric surgery patients versus matched nonsurgical control subjects. J Clin Psychopharmacol 2013; 33(4): 479–484
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Bingham et al. 11. Macgregor AM, Boggs L: Drug distribution in obesity and following bariatric surgery: a literature review. Obes Surg 1996; 6(1):17–27 12. Yska JP, van der Linde S, Tapper VV, et al: Influence of bariatric surgery on the use and pharmacokinetics of some major drug classes. Obes Surg 2013; 23(6):819–825 13. Black K, Shea C, Dursun S, Kutcher S: Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25(3):255–261 14. Parker G, Blennerhassett J: Withdrawal reactions associated with venlafaxine. Aust N Z J Psychiatry 1998; 32(2):291–294 15. Schatzberg AF, Haddad P, Kaplan EM, et al: Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation consensus panel. J Clin Psychiatry 1997; 58(7 Suppl):5–10 16. Kalarchian MA, Marcus MD, Levine MD, Soulakova JN, Courcoulas AP, Wisinski MS: Relationship of psychiatric disorders to 6-month outcomes after gastric bypass. Surg Obes Relat Dis 2008; 4(4):544–549
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17. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R: Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol 2009; 6 (10):583–590 18. Ditto KE: SSRI discontinuation syndrome. Awareness as an approach to prevention. Postgrad Med 2003; 114(2): 79–84 19. Malone M: Altered drug disposition in obesity and after bariatric surgery. Nutr Clin Pract 2003; 18(2):131– 135 20. Spitzer RL, Kroenke K, Williams JB: Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. J Am Med Assoc 1999; 282 (18):1737–1744 21. Cassin S, Sockalingam S, Hawa R, et al: Psychometric properties of the Patient Health Questionnaire (PHQ-9) as a depression screening tool for bariatric surgery candidates. Psychosomatics 2013; 54(4):352–358
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& 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Case Reports SSRI Discontinuation Syndrome Following Bariatric Surgery: A Case Report and Focused Literature Review Kathleen Bingham, M.D., Raed Hawa, M.D., F.R.C.P.C., Sanjeev Sockalingam, M.D., F.R.C.P.C.
Introduction Bariatric surgery is a durable and successful treatment for severely obese patients for whom dietary or medical weight loss interventions have failed. Despite the emergence of new bariatric surgery procedures, the most common surgery performed currently is the Roux-en-Y gastric bypass.1 Patients undergoing bariatric surgery have a high degree of psychiatric co-morbidity, with lifetime rates of an affective and anxiety disorder approximating 44% and 32%, respectively,2 and depression and obesity seemingly reciprocally related.3 Consequently, many bariatric surgery candidates take antidepressant medication. In a recent multisite study, it was reported that 35% of a large cohort (n ¼ 2148) of patients presenting for bariatric surgery were taking at least 1 antidepressant on baseline assessment.4 Given the established effect of gastric bypass surgery on drug absorption in general5, it is imperative that physicians managing bariatric surgery patients are aware of possible complications associated with impaired psychiatric medication absorption and are comfortable addressing these complications. This report provides an example of the potential psychiatric complications associated with impaired medication absorption in the post–bariatric surgery period and discusses the etiology, differential diagnosis, and management strategies.
Case Report Ms. J, a 42-year-old woman, presented to our bariatric surgery psychosocial clinic as part of our routine 692
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multidisciplinary assessment process for gastric bypass candidates. Her body mass index on initial presentation was 37.7 kg/m2 and she had obesity-related medical co-morbidities, including gastroesophageal reflux disease, musculoskeletal pain, stress incontinence, dyslipidemia, and hypertension. She had attempted to lose weight 6 times using a commercial diet program but had always regained the weight. Despite her medical co-morbidities, her only medication at the time of initial assessment was 30 mg of paroxetine taken daily. On psychiatric assessment, Ms. J reported a history of panic disorder, starting at the age of 16 years and in remission for 10 years on paroxetine. She had no additional psychiatric history except subclinical binge-eating symptoms. Following her assessment, her formal psychiatric diagnoses (the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision6 criteria) were panic disorder with agoraphobia (in remission) and eating disorder not otherwise specified (subthreshold binge-eating disorder). Based on the clinical history, paroxetine did not seem to have contributed to her weight gain. Ms. J underwent an uncomplicated laparoscopic Roux-en-Y gastric bypass procedure and was discharged from hospital 2 days postoperatively. She
Received June 3, 2014; revised July 10, 2014; accepted July 10, 2014. From Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Bariatric Surgery Program, Toronto Western Hospital, Department of Psychiatry, University Health Network, Toronto, Ontario, Canada. Send correspondence and reprint requests to Kathleen Bingham, M.D., Toronto General Hospital, 200 Elizabeth Street8EN-218, Toronto, Ontario, Canada M5G 2C4; e-mail: kathleen. [email protected] & 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Psychosomatics 55:6, November/December 2014
Bingham et al. resumed taking 30 mg of paroxetine immediately postoperatively (she did not miss a dose). At 2 days after surgery, she started to experience irritability and flulike symptoms. Her irritability was such that she struck her husband during an argument. This behavior was quite out of character for her and was disconcerting to her and to her husband. When asked about her symptoms systematically during a subsequent interview, she also described experiencing dizziness, shocklike sensations, nervousness, mood swings, agitation, vivid dreams, insomnia, restless legs, unsteady gait, and nausea. She recalled having similar (but less severe) symptoms in the past after missing a dose of paroxetine. She did not typically have any of these symptoms at baseline. On assessment, Ms. J scored 17 on 43 on the Discontinuation-Emergent Signs and Symptoms checklist, a clinician-rated scale that measures signs and symptoms associated with antidepressant termination.7 Higher scores indicate more severe discontinuation symptoms. In clinical studies, patients are typically defined as experiencing a discontinuation syndrome if their Discontinuation-Emergent Signs and Symptoms score increases by 4 points or more from baseline7. Ms. J's symptoms resolved within 10 days. However, approximately 4 weeks after surgery, she developed a recurrence of panic attacks. At 8 weeks after surgery and after experiencing 4 panic attacks, she made an appointment with her former psychiatrist, who identified that the presentation was likely the result of decreased paroxetine absorption following gastric bypass surgery. Her psychiatrist increased the paroxetine dose to 30 mg taken in the morning and 20 mg before bedtime, with the view that increasing and dividing the dosage would result in improved gastrointestinal absorption. Following this adjustment, the panic attacks completely resolved and Ms. J returned to her baseline. She had a successful outcome 1 year after surgery, with a weight loss of 45.4 kg for a new body mass index of 25.1 kg/m2. Her medical co-morbidities and quality of life had significantly improved. This case illustrates the clinical effect of antidepressant pharmacokinetic changes following gastric bypass surgery. In Ms. J's case, she experienced both selective serotonin reuptake inhibitor (SSRI) discontinuation symptoms and a recurrence of the panic disorder, previously remitted for 10 years. Her symptoms Psychosomatics 55:6, November/December 2014
affected her emotional and physical well-being and her family relationships. Fortunately, once her condition became more apparent, it was quickly stabilized, and she experienced a very positive postsurgical outcome. Pharmacokinetic Changes Following Gastric Bypass Surgery Small, observational pharmacokinetic studies have demonstrated reduced bioavailability of sertraline,8,9 duloxetine,10 citalopram,8 and escitalopram8 in patients after gastric bypass surgery. The small sample sizes in these studies make it difficult to draw clinical conclusions, but in a study of 12 patients taking stable doses of antidepressant medication, with serum levels drawn at sequential points before and after bariatric surgery, Hamad et al. identified that in patients who experienced relapse of depression after surgery, the symptoms improved in conjunction with normalization of antidepressant bioavailability.8 Bioavailability tended to be lowest after 1 month and returned to (or increased from) baseline by 6 months in this study, although it remained lower than baseline for 1 patient at the 1-year point. The authors postulated that the increase in bioavailability at 6 months was because of the adaptive increase in the absorptive component of the intestinal mucosa that occurs postoperatively.8 Antidepressants, as with most oral medications, are maximally absorbed in the small intestine, the anatomy of which is significantly altered following gastric bypass.5 The rate and amount of drug absorption may be affected by a variety of changes postoperatively, including alterations in drug dissolution and solubility because of differences in intestinal pH, reduced intestinal surface area, and delayed gastric emptying.5,8 In addition, antidepressants are lipophilic and most are highly protein bound, qualities that make them susceptible to the changes in the volume of distribution and concentration of drug-binding proteins that accompany obesity and rapid weight loss.11,12 SSRI Discontinuation Syndrome To our knowledge, there is no literature addressing SSRI discontinuation syndrome after bariatric www.psychosomaticsjournal.org
693
Case Reports surgery, although bariatric surgery patients are theoretically at risk for this condition given the immediate and drastic change to their gastrointestinal system and the documented effects of this change on drug absorption. Although previously recognized as a complication of tricyclic discontinuation, adverse effects associated with abrupt SSRI discontinuation were first reported in the 1990s, and the first randomized controlled trial investigating this phenomenon was done in 1998.7 The symptoms include a variety of neurologic, emotional, and somatic phenomena associated with antidepressant termination or intermittent nonadherence, described in detail by the Discontinuation-Emergent Signs and Symptoms checklist.7 The common symptoms (reported in 410% of patients) include dizziness, “shocklike sensations,” gait incoordination, nausea, headache, fatigue, and insomnia.13 Antidepressants with short half-lives, such as venlafaxine and paroxetine, have been associated
TABLE.
with more severe discontinuation symptoms.14 Symptoms are typically mild and self-limiting, but they can be quite distressing.15 Differential Diagnosis in Bariatric Surgery Patients Given the deleterious effect of psychiatric co-morbidity on weight loss outcomes in bariatric surgery patients16, along with the negative effect of SSRI discontinuation syndrome on quality of life, clinicians working in bariatric surgery clinics should monitor for the emergence of these symptoms. Interestingly, the symptoms of SSRI discontinuation syndrome have some overlap in quality and temporal onset with the symptoms of at least one of the other postoperative complications of bariatric surgery: dumping syndrome—the gastrointestinal, vasomotor, and hypoglycemia-related symptom cluster associated with rapid gastric emptying17 (Table).
Symptom Comparison Between SSRI Discontinuation Syndrome and Dumping Syndrome SSRI discontinuation syndrome*
Onset Within 3-d postoperatively Characteristics Resolves with re-initiation of antidepressant Symptoms Anxiety Dizziness/light-headedness/vertigo Fatigue Diarrhea Nausea/emesis Impaired concentration Chills Irritability Vivid dreams Depersonalization/detachment Suicidal thoughts/behaviors Agitation Visual disturbances Gait instability Paresthesia Headache Shocklike sensations Myalgia – – – – –
Dumping syndrome† Immediately postoperatively once patient resumes oral intake Occurs 15 min (GI and vasomotor symptoms) to 3 h (hypoglycemic symptoms) after eating17 Palpitations, tachycardia, perspiration, tremor Hypotension, syncope Weakness Diarrhea Nausea Confusion – – – – – – – – – – – – Abdominal cramping Bloating Borborygmi Flushing Hunger
GI ¼ gastrointestinal; SSRI ¼ selective serotonin reuptake inhibitor. n
†
694
Symptoms compiled from Rosenbaum et al.7 and literature review by Black et al.13 Symptoms compiled from Tack et al.17
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Psychosomatics 55:6, November/December 2014
Bingham et al. Discontinuation symptoms may also mimic relapse of the original psychiatric condition or the emergence of a new psychiatric disorder. Additional differential diagnoses include upper respiratory infection, benign paroxysmal positional vertigo, radiculopathy, and substance intoxication/withdrawal.18 These phenomena demonstrate the importance of maintaining a differential diagnosis when presented with neuropsychiatric symptoms in these complex patients.
Management of SSRI Discontinuation Syndrome After Bariatric Surgery All bariatric surgery patients taking antidepressant medication should be monitored postoperatively for changes in mental status, particularly in the first month, and patients should be counseled to selfmonitor for worsening psychiatric symptoms in the postoperative period.8 Clinicians should have a high index of suspicion for SSRI discontinuation syndrome in patients exhibiting psychiatric symptoms within the first week postoperatively, particularly when combined with neurologic and somatic symptoms. Patients taking antidepressants with short halflives, such as paroxetine and venlafaxine, may be at particular risk, and we suggest that these patients be counseled to this effect and educated about SSRI discontinuation symptoms. Presumably, patients like Ms. J who have previously experienced discontinuation symptoms on missing doses would also be at an elevated risk. Primary care providers, bariatric surgery clinicians, and community psychiatrists may also benefit from education about this issue for select patients so that they can assist in postoperative management. Surgeons, primary care providers, and allied health team members may be the clinicians most likely to identify SSRI discontinuation symptoms, as psychiatrists do not typically follow-up bariatric patients in the immediate postoperative period. By contrast, patients experiencing a recurrence of their primary psychiatric illness are more likely to experience symptoms within weeks to months. In the case of Ms. J, her discontinuation symptoms were not identified originally, and it was not until she developed panic attacks and followed up with her community psychiatrist that her medication dose was adjusted. Psychosomatics 55:6, November/December 2014
This case illustrates that SSRI discontinuation symptoms may represent a harbinger of recurrence of a primary psychiatric disorder, a phenomenon that makes intuitive sense given that these symptoms represent decreased antidepressant bioavailability. If Ms. J's discontinuation symptoms had been identified and the paroxetine dose been increased in the initial postoperative period, we may have been able to avoid a recurrence of the panic attacks. It is evident that identifying discontinuation symptoms early alleviates patient suffering and may prevent recurrence of psychiatric illness, highlighting the benefit of systematic inquiry into this condition in select patients. The Discontinuation-Emergent Signs and Symptoms checklist (described earlier) has not been validated for use in the bariatric population, but clinicians may consider using this scale as a guide to screen for SSRI discontinuation symptoms in patients whom they suspect may have or are at risk for the condition, even possibly administering it preoperatively to obtain a baseline in select high-risk patients. The literature considers an increase of 4 points or greater over the past 7 days (or from the beginning of the treatment interruption period) to be indicative of discontinuation syndrome, and generally, the higher the score, the more severe the condition is.7 However, any patient presenting with discontinuation symptoms warrants close attention. Certain symptoms, such as vivid dreams and shocklike sensations, are fairly specific to SSRI discontinuation syndrome (as opposed to other sequelae of bariatric surgery) and their presence should guide clinicians to strongly consider the diagnosis. For patients experiencing either discontinuation symptoms or recurrence of a primary psychiatric disorder after bariatric surgery, physicians should consider a medication dose increase or a change in formulation (e.g., to a liquid, if available) or both. Based on the literature to date, we suggest that all patients taking controlled-release medications switch to an immediate-release formulation before surgery, if available.19 When this is not an option, we suggest consulting with the pharmacist regarding other potential modifications to controlled-release medications that may improve dissolution/disintegration (e.g., opening and sprinkling capsules). If it is not possible to adjust controlled-release formulations, a clinical decision must be made to switch to a different medication or to continue the same medication (possibly at a higher dose) with close monitoring. www.psychosomaticsjournal.org
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Case Reports It is noteworthy that Hamad et al. found that SSRI bioavailability tended to normalize or even increase in their small sample of patients by 6 months after surgery.8 Based on this evidence, one should consider closer monitoring for an emergence of antidepressant adverse effects starting at approximately 6 months postoperatively, particularly if patients' antidepressant doses were increased in the shortterm to combat initial lower bioavailability. Clinicians may wish to use rating scales to monitor symptoms on a regular basis in perioperative patients with a history of anxiety or depression. This strategy provides longitudinal data and allows for early identification of symptom recurrence. The Patient Health Questionnaire-920 has been validated as a depressionscreening tool in the bariatric population.21 Given the evidence of potential reduced bioavailability for 6–12 months postoperatively, patients taking antidepressant medication require monitoring for complications of pharmacokinetic changes, including SSRI discontinuation syndrome, worsening of their primary psychiatric disorder, and antidepressant adverse effects, for at least the first postoperative year.8 Conclusion This case illustrates the need for close monitoring of bariatric surgery patients who are taking
antidepressant medications in the postoperative period. The risk of SSRI discontinuation syndrome is individually based and depends on patient, medication, and surgical factors. A theoretical high-risk patient is one who is taking an antidepressant medication with a short half-life, has experienced discontinuation symptoms in the past with missed doses, and undergoes a procedure, such as gastric bypass, with malabsorpitve effects (as opposed to a procedure that is predominately restrictive, such as a sleeve gastrectomy). This case underlines the importance of psychiatric involvement in bariatric surgery clinics for direct patient care and education purposes. Bariatric surgery patients tend to be complex, with medical and psychiatric co-morbidities, and the surgery poses unique challenges concerning medication management. The need for collaboration will only become more apparent as bariatric surgery reaches more patients, including those living with severe mental illness. The authors thank Ms. J for participating in this process. They would also like to thank the Toronto Western Hospital Bariatric Interdisciplinary team for their support. Disclosure: The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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