The American Journal of Psychiatry Residents’ Journal July 2015 Volume 10 Issue 7 Inside In This Issue 2 New Formats and New Opportunities: The Time to Get Involved is “Now”! Rajiv Radhakrishnan, M.B.B.S., M.D. 3 Prevention of Posttraumatic Stress Disorder: Predicting Response to Trauma Jennifer H. Harris, M.D. 7 Weight Gain in Patients With Schizophrenia: A Recipe For Timely Intervention Ammar El Sara, M.B.Ch.B. 10 Hyperprolactinemia and Antipsychotics: Update for the Training Psychiatrist Stephanie Pope, M.D. 13 A Clinical Case Conference on Spiritual Growth and Healing Elizabeth S. Stevens, D.O. This issue of the Residents’ Journal features a variety of topics. Jennifer H. Har- ris, M.D., discusses prevention of posttraumatic stress disorder, with an overview 15 Priapism: A Rare but Serious of various responses to trauma. Ammar El Sara, M.B.Ch.B., presents a review of Side Effect of Trazodone clinically applicable evidence-based interventions targeting obesity in schizophre- Kamalika Roy, M.D. nia patients. Stephanie Pope, M.D., examines antipsychotic-induced hyperprolac- 17 Classifying Psychopathology: tinemia, including variables affecting prolactin and clinical implications. Elizabeth Mental Kinds and Natural Kinds S. Stevens, D.O., discusses several psychological, social, and spiritual developmen- Reviewed by Aaron J. Hauptman, tal frameworks in a clinical case conference. Kamalika Roy, M.D., presents a case M.D. of priapism as a side effect of trazodone in a middle-aged patient. Lastly, Aaron J. Hauptman, M.D., offers his review of the book Classifying Psychopathology: Mental 18 Residents’ Resources Kinds and Natural Kinds.

Editor-in-Chief Associate Editors Editors Emeriti Rajiv Radhakrishnan, M.B.B.S., M.D. Rafik Sidaros, M.B.B.Ch. Sarah B. Johnson, M.D. Janet Charoensook, M.D. Senior Deputy Editor Molly McVoy, M.D. Katherine Pier, M.D. Staff Editor Joseph M. Cerimele, M.D. Deputy Editor Angela Moore Sarah M. Fayad, M.D. Hun Millard, M.D., M.A. Monifa Seawell, M.D. Misty Richards, M.D., M.S.

Editorial New Formats and New Opportunities: The Time to Get Involved is “Now”!

Rajiv Radhakrishnan, M.B.B.S., M.D., Editor-in-Chief

It is an exciting time at the American We have seen volved with the journal. Once you have Journal of Psychiatry Residents’ Journal successfully published in the journal, Editorial Board as we plan ahead for the remarkable growth we offer additional opportunities to new academic year. This is also a special serve as a Guest Section Editor, receive year, since it marks the 10th year of the in the journal over a free book for writing a book review, journal since its inception in 2006. the past year. and join the Editorial Board. This year, We have seen remarkable growth in we had 14 applicants who competed to the journal over the past year, with ap- secure a place on the Editorial Board. proximately three-fold greater engage- cal students, residents, and fellows will I’m very happy to introduce our fab- ment by residents and fellows. Many have an opportunity to submit reviews ulous new Editorial Board for this aca- of our Guest Section Editors and Edi- of pharmacological medications in the demic year: Senior Deputy Editor, Kath- torial Board members of the past year new manuscript type called “Drug Re- erine Pier, M.D., from the Icahn School of have gone on to obtain fellowship posi- view,” as well as articles in another new Medicine at Mount Sinai; Deputy Editor, tions and many academic awards at the manuscript type called “History of Psy- Hun Millard, M.D., M.A., from Yale Uni- national level. Hearty congratulations chiatry.” These new formats, along with versity School of Medicine; and Associ- to them on their outstanding achieve- our existing formats on “Treatment in ate Editors, Rafik Sidaros, M.B.B.Ch., ments and a heartfelt thank you for their Psychiatry” and “Clinical Case Confer- from SUNY Downstate Medical Cen- contributions to the journal! The above ence,” will allow us to cover topics on ter, and Janet Charoensook, M.D., from facts speak to not only the educational psychopharmacology, clinical treat- the University of California, Riverside. content of the journal but also to the im- ment, neuroscience, and DSM-5. Soon, We look forward to working with you mense academic opportunities that par- each article will be accompanied by to transform the Residents’ Journal into ticipation with the journal provides. a table that lists “Key Points/Clinical a leading educational resource for resi- At the beginning of the year, we Pearls” to enable readers to peruse key dents and fellows. asked ourselves, “What can we do to teaching points despite their busy sched- The time to get involved is now! further improve the educational content ules. Readers will also have an opportu- of the journal and improve participa- nity to answer quiz questions related Dr. Radhakrishnan is a fourth-year psy- tion by medical students, residents, and to an issue. Additionally, authors will chiatry resident in the Department of fellows?” To answer these questions, have an opportunity to create podcasts Psychiatry, Yale University School of we conducted a nation-wide survey of for their articles that would be featured Medicine. He is the past Senior Deputy- medical students, residents, and fellows on our Facebook page (https://www. Editor (2014–2015), and new Editor-in- and received an impressive number of facebook.com/AJPResidentsJournal). Chief (2015–2016) of the American Jour- nal of Psychiatry Residents’ Journal. responses. The majority of respondents We also have a new landing page that indicated that they would like to see lists the article titles of an issue. The Dr. Radhakrishnan is supported by an more articles on psychopharmacology, titles are hot-linked and take the reader NIMH-R25 IMPORT grant (R25 MH071584) and the Thomas P. Detre Research clinical treatment, neuroscience, and directly to the article when clicked. Fellowship. DSM-5. (Check it out here: http://ajp.psychiatry- In response to the survey, we are online.org/residents_journal). in the process of implementing some This is indeed an exciting time for changes to the format of articles in the the American Journal of Psychiatry Resi- journal. In the coming months, medi- dents’ Journal and a great time to get in-

The American Journal of Psychiatry Residents’ Journal 2 Article Prevention of Posttraumatic Stress Disorder: Predicting Response to Trauma

Jennifer H. Harris, M.D.

“Although the world is full of suffer- symptoms (5). The presence of avoid- Yet a resilient response is in fact more ing, it is full also of the overcoming ance (group C) symptoms in particular common (35%–65%), suggesting that of it.” has been strongly associated with meet- the majority of the population possesses —Helen Keller ing the full diagnostic criteria for PTSD the capacities to adapt quickly to stress- (5). This suggests that intrusion and ful events (8). Most people in their lifetime will expe- hyperarousal are normal responses to rience a traumatic event. In one study, trauma and that avoidance may actually Pathophysiology of PTSD 69% of people experienced “a violent comprise the pathological part of PTSD. encounter marked by sudden or extreme Several studies have consistently Sensory input is appraised as stressful force and involving an external agent of shown that PTSD develops in about one- by the limbic brain structures, which in- nature, technology, or humankind” (1). third of those exposed to trauma (1, 6, 7). clude the amygdala, hippocampus, and But what determines why people re- spond so differently to trauma? Why FIGURE 1. Hypothesized Trajectories of the Course of Stress Responses With are some people able to maintain nor- Posttraumatic Stress Disorder Symptoms on the Y-Axisa mal functioning, while others respond Resistance Relapsing/remitting pathologically with posttraumatic 12 12 stress disorder (PTSD)? 10 10 8 8 6 6 Responses to Trauma 4 4 Researchers continue to debate about 2 2 the exact nature of resilience, but most 0 0 Pre- Post- Post- Post- Pre- Post- Post- Post- definitions include a concept of healthy, disaster T1 T2 T3 disaster T1 T2 T3 adaptive, or integrated positive func- Resilience Delayed dysfunction tioning over time in the aftermath of ad- 12 12 versity (2). Resilience is not simply “lack 10 10 of psychopathology.” Resilience is one of 8 8 several possible trajectories in response 6 6 to traumatic events characterized by 4 4 a brief period of disequilibrium after 2 2 trauma followed by continued health 0 0 (Figure 1) (2). Pre- Post- Post- Post- Pre- Post- Post- Post- The ideal response to stress is resis- disaster T1 T2 T3 disaster T1 T2 T3 tance, a trajectory in which adaptive ca- Recovery Chronic dysfunction pacities have absorbed the impact of the 12 12 stressor and there is no dysfunction at 10 10 all (3). In reality, some level of distress is 8 8 universal immediately after the trauma. 6 6 A total of 96% of individuals directly ex- 4 4 posed to the Oklahoma City bombing re- 2 2 ported at least one posttraumatic symp- 0 0 tom (4, 5). Immediately after trauma Pre- Post- Post- Post- Pre- Post- Post- Post- disaster T1 T2 T3 disaster T1 T2 T3 exposure, most individuals meet DSM a Reprinted with permission from Norris FH, Tracy M, Galeo S: “Looking for Resilience: Understanding the criteria for intrusive (group B) symp- Longitudinal Trajectories in Response to Stress.” Soc Sci Med 2009; 68:2190–2198. Copyright © Social toms and cognitive and mood (group D) Science and Medicine 2009.

The American Journal of Psychiatry Residents’ Journal 3 TABLE 1. Predictors of Response to Trauma Pathological Trajectory/ Risk Factors Posttraumatic Stress Disorder (PTSD) Resilient Response Trajectory Sympathetic nervous system Increased activation after event Decreased activation after event hypothalamus-pituitary-adrenal axis Neuropeptide Y Lower neuropeptide Y Higher neuropeptide Y Early life Uncontrollable stress during infancy and childhood Good maternal care; exposure to manageable stressors Psychiatric comorbidities Anxiety disorder; Illicit drug use; previous PTSD Trauma type Assault; sexual trauma Disaster (if previously resilient) Gender Female Male Age Older age Younger age Education Lower education Higher education Personality High perceived control; trait self- enhancement; cognitive reappraisal Social Strong social/emotional support prefrontal cortex. The stress response opment of fear conditioning and pro- in life (9, 11). Good maternal care has is chiefly mediated by the sympathetic motes the extinction of stress responses. been shown to protect against future nervous system and hypothalamus-pi- These findings correlate with studies in stressors. Studies of rat pups found that tuitary-adrenal (HPA) axis. Resilient humans showing that combat veterans those who experienced higher maternal individuals can restrict the activation without PTSD have higher levels of neu- care (as measured by licking and groom- of the stress response to the stressful ropeptide Y than those who have devel- ing) showed decreased stress activation event; individuals with PTSD exhibit oped PTSD (11). and decreased anxiety behavior that continued overactivation after the event Brain-derived neurotrophic factor persisted through adulthood compared has passed (9). This overactivation is is an important nerve growth factor with pups who received less maternal mediated by corticosteroids, which re- whose levels are affected by antidepres- care (12). duce the branching and length of den- sants. Chronic stress decreases brain- drites and the number of synaptic con- derived neurotrophic factor levels in the Epidemiological Risk Factors tacts, suppress cell proliferation, and hippocampus but increases levels in the increase cell death. Timing is crucial, nucleus accumbens. Mice with an allele The presence of an anxiety disorder as corticosteroids produce effects only associated with decreased brain-derived and illicit substance abuse predicts the when cells are concurrently excited by neurotrophic factor function show in- occurrence of trauma (13). Preexisting noradrenaline (10). creased anxiety and impaired hippo- anxiety disorder has been associated Genetic polymorphisms have been campus learning but are in fact more re- with an increased risk of trauma, ap- identified in the sympathetic nervous silient to chronic stress (11). parently due to an increased tendency system, HPA axis, neuropeptide Y, and Many of these neurotransmitter sys- to report events as being horrific. On serotonin systems that predispose in- tems exert opposite and region-specific the other hand, presence of illicit drug dividuals toward pathological response effects, suggesting that there are un- use likely increases the risk of assaultive to trauma. Variations in the corticotro- likely to be simple pharmacological and sexual traumatic exposures. pin-releasing hormone type 1 receptor therapies to prevent pathological stress After the traumatic event, the sub- genes, as well as brain mineralcorticoid responses. sequent development of PTSD is most and glucocorticoid receptor genes, set strongly predicted by female gender and the threshold and regulate the termina- assault or sexual trauma (Table 1) (5, 13). Early-Life Conditioning tion of the HPA response to stress and Resilient outcomes have been associated have been shown to predict the develop- Early-life conditioning shapes the devel- with male gender, older age, and higher ment of PTSD (10, 11). opment and responsiveness of these sys- levels of education (8). Previous devel- Neuropeptide Y, a neurotransmit- tems, likely through epigenetic changes. opment of PTSD in response to trauma ter in the brain and autonomic nervous Uncontrollable stress during the key also tends to predict future develop- system, counteracts the anxiogenic ef- developmental periods of infancy and ment of PTSD. However, previous resil- fects of corticotropin-releasing hormone childhood can lead to learned helpless- ient responses predict future resilience in the limbic areas of the brain. Rodent ness and chronically high levels of cor- only in particular types of trauma, such studies have shown that administering ticotropin releasing hormone and cause as disaster (8). neuropeptide Y both inhibits the devel- exaggerated responses to stress later on

The American Journal of Psychiatry Residents’ Journal 4 Personality Factors However, a 2014 Cochrane review of count for, at best, only 27% of the vari- published studies found no evidence to ance in response to traumatic events Whether a person considers a stressor to support the efficacy of propranolol, esci- (20). No single factor accounts for resil- be a threat or a challenge to be mastered talopram, temazepam, and gabapentin ience; responses to stress are a result of reflects beliefs about his or her own in preventing PTSD onset. Only hydro- subtle genetic polymorphisms and the helplessness or agency. Individuals with cortisone has demonstrated significant accumulation of external events that traits of high perceived control, who uti- efficacy in preventing the development produce vulnerable phenotypes (8, 10). lize active rather than passive responses of PTSD (16). One theory is that a con- However, as we continue to gain a bet- to threats, show lower glucocorticoid stant level of corticosteroid blocks the ter understanding of the human stress responses and are less likely to develop effect of the HPA axis activation and response, there is hope that we can de- PTSD (8, 11). therefore reduces the emotional re- velop a more effective multipronged One of the personality traits most sponse and disrupts the over-consolida- strategy for preventing PTSD and pro- strongly associated with resilient re- tion of traumatic memories (10). moting positive adaptation. sponses is trait self-enhancement. Trait self-enhancers are individuals who ha- Psychological Interventions Dr. Harris is a second-year resident in bitually engage in overly positive and Psychological interventions to prevent the Department of Psychiatry, University self-serving biases, and although these the development of PTSD have been of Texas Southwestern Medical Center, traits may evoke negative reactions studied more extensively than pharma- Dallas. from other people, they also tend to en- cological interventions, but the results The author thanks Carol North, M.D., for able resilient responses to trauma (8). to date have been similarly disappoint- her feedback and suggestions. These biases have been correlated with ing. Initial efforts have focused on sin- higher activation of the mesolimbic do- gle-session early psychological debrief- pamine reward circuitry to facilitate ing. Results have consistently shown References fear extinction (11). that single-session interventions are not 1. Norris F: Epidemiology of trauma: fre- Another predictor of resilience is helpful and may actually be harmful. In quency and impact of different potentially cognitive reappraisal, the ability to some studies, the intervention group re- traumatic events on different demographic positively reframe and draw meaning, groups. J Consult Clin Psychol 1992; ported more PTSD symptoms compared purpose, and strength from negative 60:409–418 with the comparison group (8, 17). events. Cognitive reappraisal reflects 2. Southwick SM, Bonanno GA, Masten AS, et Recent efforts have focused on mul- the strength of the prefrontal cortex al: Resilience definitions, theory, and chal- tiple-session cognitive-behavioral ther- lenges: interdisciplinary perspectives. Eur and its ability to regulate the limbic sys- apy (CBT) for postexposure PTSD pre- J Psychotraumatol 2014; doi:10.3402/ejpt. tem (2, 9). vention. CBT generally falls under three v5.25338 In addition, the presence of a strong 3. Norris F, Stevens SP, Pfefferbaum B, et al: subtypes: 1) exposure therapies, such as social and emotional support system is Community resilience as a metaphor, the- systematic desensitization and flooding, associated with resilient responses to ory, set of capacities, and strategy for disas- 2) anxiety management, which includes ter readiness. Am J Community Psychol trauma. A strong social support system relaxation and self-distraction, and 3) 2008; 41:127–150 reflects an individual’s psychosocial cognitive therapy, which seeks to cor- 4. Norris FH, Stevens SP: Community resil- health and buffers responses to trauma rect harmful cognitions. ience and the principles of mass trauma in- (14). High levels of social support have tervention. Psychiatry 2007; 70:320–328 Reviewing all the data on psycho- been positively associated with active 5. North CS, Nixon SJ, Shariat S, et al: Psychi- logical interventions for prevention of problem-focused coping, a sense of con- atric disorders among survivors of the PTSD up to 2007, a Cochrane analysis Oklahoma City bombing. JAMA 1999; trol and predictability in life, and damp- found no significant difference in the 282:755–262 ened neuroendocrine and cardiovascu- development of PTSD between psycho- 6. Bonanno GA, Wortman CB, Nesse RM: lar responses to stress (9). logical intervention and comparison Prospective patterns of resilience and mal- adjustment during widowhood. Psychool groups (18). Treatment programs that Aging 2004; 19:260–271 Interventions involve a screening mechanism to iden- 7. North CS, Pollio DE, Smith RP, et al: tify individuals at high risk for devel- Trauma exposure and posttraumatic stress Pharmacological Interventions oping PTSD or individuals manifesting disorder among employees of New York Pharmacologic treatment of PTSD after acute stress disorder have shown better City companies affected by the September symptoms have become manifest has 11th attacks. Disaster Med Public Health results (8, 18, 19). been extensively studied. Of recent inter- Prep 2011; 5(suppl 2)S205–213 est is whether interventions prior to the 8. Bonanno GA, Westphal M, Mancini AD: development of symptoms can prevent Conclusions Resilience to loss and potential trauma. Ann Rev Clin Psychol 2011; 7:511–535 psychopathology. Theoretically, several Can resilience be learned or fostered? 9. Southwick SM, Charney DS: The science of classes of drugs show promise for pre- One difficulty with developing general resilience: implications for the prevention venting PTSD, such as antidepressants and treatment of depression. Science 2012; PTSD prevention programs is that the and antiadrenergic agents (9, 15). 338:6179–6182 known predictors of PTSD together ac-

The American Journal of Psychiatry Residents’ Journal 5 10. de Kloet ER, Joels M, Holsboer F: Stress 15. Nemeroff CB, Bremner JD, Foa EB, et al: 19. Forneris CA, Gartlehner G, Brownley KA, and the brain: from adaptation to disease. Posttraumatic stress disorder: a state-of- et al: Interventions to prevent post-trau- Nat Rev Neurosci 2005; 6:463–475 the-science review. J Psychiatr Res 2006; matic stress disorder: a systematic review. 11. Feder A, Nestler EJ, Charney DS: Psychobi- 40:41–21 Am J Prev Med 2013; 44:635–650 ology and molecular genetics of resilience. 16. Amos T, Stein DJ, Ipser JC: Pharmacological 20. North CS, Oliver J, Pandya A: Examining a Nat Rev Neurosci 2009; 10:446–457 interventions for preventing post-traumatic comprehensive model of disaster-related 12. Levine S: Infantile experience and resis- stress disorder (PTSD). Cochrane Database PTSD in systematically studied survivors tance to physiological stress. Science 1957; Syst Rev 2014; 7:CD006239 of ten disasters. Am J Public Health 2012; 126:405 17. Rose S, Bisson J, Churchill R, et al: Psycho- 102:e140–e148 13. Stein MB, Höfler M, Perkonigg A, et al: Pat- logical debriefing for preventing post trau- terns of incidence and psychiatric risk fac- matic stress disorder (PTSD). Cochrane tors for traumatic events. Int J Methods Database Syst Rev 2002; (2)CD000560 Psychiatr Res 2002; 11:143–153 18. Roberts NP, Kitchiner NJ, Kenardy J, et al: 14. North C: Epidemiology of disaster mental Multiple session early psychological inter- health, in Textbook of Disaster Psychiatry. ventions for the prevention of post-trau- New York, Cambridge University Press, matic stress disorder. Cochrane Database 2011, pp 29–47 Syst Rev 2009; (3):CD006869

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The American Journal of Psychiatry Residents’ Journal 6 Article Weight Gain in Patients With Schizophrenia: A Recipe For Timely Intervention

Ammar El Sara, M.B.Ch.B.

Obesity is a key feature of the metabolic The interventions included cognitive- studies (two randomized controlled tri- syndrome, with significant implications behavioral, psycho-educational, and nu- als, two retrospective trials). This high- for long-term morbidity and mortal- tritional- and physical activity-based lights the significant gap in our knowl- ity (1). Obesity is more prevalent among interventions. Four studies evaluated in- edge regarding the customization of individuals with serious mental illness dividually delivered interventions, while standard diabetes-management inter- than in the general population (2). the other nine evaluated group interven- ventions for people with mental illness. Alarmingly, and despite improve- tions. Interventions lasted for a mean of Participants were inpatients in two ments in health services worldwide, 18 weeks, with follow-up periods of up studies, with ages ranging between 44 standardized mortality ratios in schizo- to 3 months. Participants were mostly and 53. Both inpatient and outpatient in- phrenia, especially cardiovascular mor- outpatients, along with stable long- terventions were built on diabetes self- tality, appear to be increasing (3, 4). In term inpatients and supported housing management principles, with emphasis addition, the long-term influence of sec- residents. on simplification of instructions, grad- ond-generation antipsychotic drugs on Overall, nonpharmacological inter- ual introduction of new concepts and adverse metabolic outcomes is a major ventions resulted in a 0.98-kg/m2 reduc- skills, incorporating memory aids, and reason for concern. tion in body mass index (BMI) (or a loss continuous motivational enhancement. The aim of the present review is of 3.12% of the initial weight), which is In one intervention, patients were pro- to propose an outline of clinically ap- well below the 5%–10% proposed by the vided with exercise facilities. The length plicable evidence-based interventions National Institutes of Health/National of interventions in these four studies that target obesity in individuals with Heart, Lung, and Blood Institute. This was significantly longer than those in schizophrenia, from both primary and could be explained in part by the short the nondiabetic population, ranging be- secondary preventative points of view. duration of intervention/follow-up. In- tween 6 months and 1 year. Overall, both terestingly, there was no difference in in- and outpatient interventions had the dropout rates between experimen- a positive impact on weight, BMI, and Screening tal and control groups, suggesting that blood glucose measurements. A problem cannot be remedied if it is interventions were feasible and well ac- not recognized. All patients should have cepted by patients. “ACHIEVE”ing Weight Loss their metabolic profiles routinely moni- The interventions with the highest The ACHIEVE trial (9) is a rigorously tored, with more frequent monitoring impact were those of a preventive na- designed, large trial, in which 291 obese for patients with significant weight gain ture (as opposed to weight loss inter- patients with severe mental illness at- or those taking specific antipsychotics ventions), along with individual inter- tending a community outpatient psy- (5). Despite being a low-cost/high-yield ventions that included diet and physical chiatric rehabilitation program were intervention, there is strong evidence activity. randomly assigned to an 18-month long that metabolic monitoring is alarmingly behavioral weight-loss intervention or a low in individuals prescribed antipsy- Addressing Diabetes control intervention. Ninety percent of chotics (6). Designing and implementing a life- these patients were taking an antipsy- style intervention for individuals with chotic. The intervention consisted of schizophrenia becomes inherently individual and group weight-manage- Lifestyle Interventions more complicated when diabetes is a ment sessions, as well as group exercise Overview comorbidity. sessions. The educational component In a systematic meta-analysis, Bonfioli Cimo et al. (8) systematically re- was tailored to the population’s learn- et al. (7) examined 13 randomized con- viewed the literature on nonpharmaco- ing capabilities, with small incentives trolled trials of nonpharmacologic in- logical interventions targeting the co- to encourage attendance. Patients in the terventions for weight management in morbidity of schizophrenia and type 2 intervention arm lost significantly and patients with psychosis. diabetes. Despite an extensive literature progressively more weight (average of search, they only identified four original 3.2 kg at 18 months). In addition, 37.8%

The American Journal of Psychiatry Residents’ Journal 7 lost 5% or more of their body weight, TABLE 1. STRIDE Core Intervention Components compared with 22.7% in the control Component arm. This study represents strong evi- Increasing awareness through monitoring: diet, physical activity, and sleep dence for the utility of long-term, inten- sive, tailored lifestyle interventions in Creating personalized diet and physical activity plans overweight and obese adults with seri- Reducing calories ous mental illness. Reducing portion sizes, identifying and choosing alternative foods, modifying meals Increasing consumption of fruits, vegetables, fiber, and low-fat dairy products A “STRIDE” in The Right Direction Another landmark study is a recently Increasing physical activity published randomized controlled trial Developing action plans for high-risk eating situations of weight loss and lifestyle intervention Graphing progress and making adjustments for individuals taking antipsychotics Addressing mental health effects on lifestyle-change efforts (10). The STRIDE study recruited 200 overweight patients, 91% of whom re- ceived second-generation antipsychot- medication, with suggested mecha- reboxetine (selective norepinephrine ics. The first 6 months of the year-long nisms including 5-HT2c antagonism, reuptake inhibitor), reboxetine-betahis- intervention consisted of weekly stand- H1 antagonism, peripheral M3 musca- tine combination (betahistine is an H1 alone group meetings, followed by 6 rinic receptor antagonism, hyperprolac- agonist, H3 antagonist), rosiglitazone, monthly group meetings focusing on tinemia, and leptin desensitization (14). sibutramine (norepinephrine and 5-HT weight maintenance and motivational Antipsychotics differ significantly in reuptake inhibitor), metformin-sibutra- enhancement. their capacity to induce weight gain (15). mine combination, topiramate, and The STRIDE intervention was based Antipsychotics most associated with zonisamide (exact mechanism of action on the PREMIER lifestyle interven- weight gain are clozapine and olanzap- is not known). tion with the DASH diet (11, 12) and on ine, while chlorpormazine, iloperidone, It is important to note that some of guidelines for obesity treatment for in- quetiapine, and risperidone fall under these medications are no longer avail- dividuals at risk for cardiovascular dis- the moderate weight gain category. The able in U.S. markets, including D-fenflu- ease (13). Components of the STRIDE antipsychotics associated with the least ramine (withdrawn in 1997 after reports intervention protocol are presented in weight gain include ziprazidone, halo- of heart valve disease) and sibutramine Table 1. peridole, aripiprazole, asenapine, and (withdrawn in 2010 after being associ- At 12 months, patients in the inter- lurasidone. ated with a higher risk of nonfatal myo- vention arm lost 2.6 kg more than the When clinically feasible, carefully cardial infarction and nonfatal stroke). control group, along with a reduction in switching one antipsychotic to another While widely available, amantadine mean fasting glucose from 106.3 mg/dl with lesser potential for causing weight may (theoretically at least) exacerbate to 100.4 mg/dl. Moreover, 6.7% of inter- gain could be an effective strategy (16). psychosis, and the use of orlistat while vention patients compared with 18.8% not adhering to a low-fat diet will result of control subjects required medical Add-On Medications in fatty diarrhea and malabsorption of hospitalization during that year. In the most recent and extensive sys- orally administered medications. In addition to being the first ran- tematic meta-analysis of pharmaco- Metformin was the most extensively domized controlled trial to show re- logical interventions for antipsychotic- studied medication, with a –3.17-kg ductions in glucose levels and in the induced weight gain, Mizuno et al. (17) mean difference in body weight. Dosage number of medical hospitalizations, the have identified and analyzed data from range was 500 mg/day–2,550 mg/day. SRIDE study lends itself to implemen- 40 randomized controlled trials be- Despite the common side effects of diar- tation in most outpatient settings. The tween 1950 and November 2013. Con- rhea, nausea, and flatulence, metformin materials and instructions needed to clusions from this meta-analysis are dis- was generally well tolerated. It should run a STRIDE-based group (including cussed below. not be prescribed for individuals with a detailed “Facilitator Guide,” a “Food With change in weight as the pri- impaired creatinine clearance. and Fitness Diary,” and a “Participant mary outcome, data on 19 unique in- Patients who received both adjunc- Workbook”) are available online free of terventions were pooled, including: tive metformin and lifestyle changes did charge (www.kpchr.org/stridepublic). amantadine, aripiprazole, atomoxetine, better in terms of weight loss and over- D-fenfluramine (nonselective 5-HT all metabolic profiles than those receiv- agonist), dextroamphetamine, famoti- ing lifestyle changes plus placebo or pla- Pharmacological dine, fluoxetine, intranasal insulin, cebo alone (18). Interventions metformin, nizatidine (H2 competitive Topiramate, sibutramine, aripipra- Switching Antipsychotics inhibitor), orlistat (reversible inhibi- zole, and reboxetine were also separated Weight gain has long been considered tor of gastric and pancreatic lipases), from placebo in the meta-analysis. Ar- an intrinsic side effect of antipsychotic phenylpropanolamine (alpha1 agonist), ipiprazole was associated with modest

The American Journal of Psychiatry Residents’ Journal 8 but significant effects on weight gain. For additional information on the topic of 10. Green CA, Yarborough BJH, Leo MC, et al: These results, however, should be in- weight gain and schizophrenia, see the The STRIDE weight loss and lifestyle in- tervention for individuals taking antipsy- terpreted in the context of the risks and seminal study on metformin for treatment chotic medications: a randomized trial. Am benefits of antipsychotic polypharmacy. of antipsychotic-induced weight gain by Ren-Rong Wu, M.D., Ph.D., et al., in the J Psychiatry 2015; 172:71–81 When secondary outcomes were ana- American Journal of Psychiatry. 11. Funk KL, Elmer PJ, Stevens VJ, et al: PRE- lyzed (including fasting glucose, HbA1c, MIER: a trial of lifestyle interventions for fasting insulin, insulin resistance, cho- blood pressure control: intervention design lesterol, and triglycerides), metformin and rationale. Health Promot Pract 2008; References 9:271–280 and rosiglitazone improved insulin re- 12. Svetkey LP, Harsha DW, Vollmer WM, et sistance, while aripiprazole, metformin, 1. Isomaa B, Almgren P, Tuomi T, et al: Car- diovascular morbidity and mortality asso- al: PREMIER: a clinical trial of compre- and sibutramine decreased blood lipids. ciated with the metabolic syndrome. hensive lifestyle modification for blood First-episode patients seemed to de- Diabetes Care 2001; 24:683–689 pressure control: rationale, design and rive the most benefit from all effective 2. Dickerson FB, Brown CH, Kreyenbuhl JA, baseline characteristics. Ann Epidemiol 2003; 13:462–471 interventions, highlighting the role of et al: Obesity among individuals with seri- 13. Jensen MD, Ryan DH, Apovian CM, et al: metformin in primary (starting metfor- ous mental illness. Acta Psychiatr Scand 2006; 113:306–313 2013 Guideline for the Management of min and antipsychotics concurrently), 3. Ösby U, Correia N, Brandt L, et al: Time Overweight and Obesity in adults: a report as well as secondary, prevention of anti- trends in schizophrenia mortality in Stock- of the American College of Cardiology/ psychotic-related weight gain. holm County, Sweden: cohort study. BMJ American Heart Association Task Force on 2000; 321:483–484 Practice Guidelines and the Obesity Soci- ety. J Am Coll Cardiol 2014; 63:2985–3023 4. Saha S, Chant D, McGrath J: A systematic Summary review of mortality in schizophrenia: Is the 14. Reynolds GP, Kirk SL: Metabolic side ef- differential mortality gap worsening over fects of antipsychotic drug treatment: Prescribers should be cognizant of the time? Arch Gen Psychiatry 2007; pharmacological mechanisms. Pharmacol long-term morbidity and mortality im- 64:1123–1131 Ther 2010; 125:169–179 plications of weight gain on individuals 5. American Diabetes Association, American 15. Rummel-Kluge C, Komossa K, Schwarz S, with schizophrenia. All such patients Psychiatric Association, American Associ- et al: Head-to-head comparisons of meta- ation of Clinical Endocrinologists, North bolic side effects of second generation anti- should have their metabolic profiles psychotics in the treatment of routinely screened. American Association for the Study of Obe- sity: Consensus development conference on schizophrenia: a systematic review and The body of evidence supporting antipsychotic drugs and obesity and diabe- meta-analysis. Schizophr Res 2010; the utility of early, long-term, tailored, tes. Diabetes Care 2004; 27:596–601 123:225–233 multipronged lifestyle interventions 6. Mitchell AJ, Delaffon V, Vancampfort D, et 16. Mukundan A, Faulkner G, Cohn T, et al: Antipsychotic switching for people with is constantly growing. Such interven- al: Guideline concordant monitoring of schizophrenia who have neuroleptic-in- tions need to be widely disseminated metabolic risk in people treated with anti- psychotic medication: systematic review duced weight or metabolic problems. Co- and integrated with other modalities of and meta-analysis of screening practices. chrane Database Syst Rev 2010; interventions. Psychol Med 2012; 42:125–147 (12):CD006629 When lifestyle interventions alone 7. Bonfioli E, Berti L, Goss C, et al: Health 17. Mizuno Y, Suzuki T, Nakagawa A, et al: are insufficient, and switching anti- promotion lifestyle interventions for Pharmacological strategies to counteract weight management in psychosis: a system- antipsychotic-induced weight gain and psychotics to relatively weight-neutral metabolic adverse effects in schizophrenia: agents is not possible, adjuvant metfor- atic review and meta-analysis of ran- domised controlled trials. BMC Psychiatry a systematic review and meta-analysis. min is the first choice among multiple 2012; 12:78 Schizophr Bull 2014; 40:1385–1403 possible pharmacological interventions. 8. Cimo A, Stergiopoulos E, Cheng C, et al: Ef- 18. Wu R, Zhao J, Jin H, et al: Lifestyle inter- A combination of adjuvant metformin fective lifestyle interventions to improve vention and metformin for treatment of an- and a lifestyle intervention is feasible type II diabetes self-management for those tipsychotic-induced weight gain: a randomized controlled trial. JAMA 2008; and effective. with schizophrenia or schizoaffective dis- order: a systematic review. BMC Psychiatry 299:185–193 2012; 12:24 Dr. El Sara is a third-year resident in the 9. Daumit GL, Dickerson FB, Wang N-Y, et al: Department of Psychiatry and Behavioral A behavioral weight-loss intervention in Sciences, State University of New York, persons with serious mental illness. N Engl Downstate Medical Center, Brooklyn, N.Y. J Med 2013; 368:1594–1602

The American Journal of Psychiatry Residents’ Journal 9 Article Hyperprolactinemia and Antipsychotics: Update for the Training Psychiatrist

Stephanie Pope, M.D.

Antipsychotic-induced hyperprolactin­ way, such as in the case for postpartum peridone remains for at least 1 year (2). emia has become a larger concern in women, or as a side effect of antipsy- The association between age and anti- psychiatry given the growing number chotic medications. With the presence psychotic-induced hyperprolactinemia of antipsychotics, larger focus on the of antipsychotics blocking dopamine is also compounded by the patient’s sex, short- and long-term impacts of such receptors in this pathway, prolactin lev- since estrogen is a risk factor. medications, and recent litigation. One els increase and can cause galactorrhea, study found that in patients treated with amenorrhea, infertility issues, demin- Estrogen antipsychotics for severe mental illness, eralization of bone, sexual dysfunction, It is now known that endogenous and 18% of men and 47% of women were and weight gain (3). Dopamine blockade exogenous estrogens are associated asymptomatic but had elevated serum is an important component of antipsy- with a higher increase in prolactin from prolactin levels (1). In another study chotic-induced hyperprolactinemia. antipsychotics. One study examined examining those with schizophrenia serum prolactin levels in healthy men treated with antipsychotics, 42% of men Dopamine­ Blockade and women who were given haloperi- and 75% of women suffered hyperpro- The more dopamine blockade an anti- dol, reserpine, aripiprazole, or placebo. lactinemia (2). psychotic offers, the stronger the associ- In the haloperidol and reserpine groups, Recent research has expanded our ation with hyperprolactinemia. Agents serum prolactin levels were elevated in understanding of antipsychotic-induced such as first-generation antipsychotics contrast to the aripiprazole and placebo hyperprolactinemia beyond blockade and risperidone are known offenders, groups. Meanwhile, the increase in the in the tuberoinfundibular tract. Other but any antipsychotic medication with haloperidol and reserpine groups was variables affecting serum prolactin lev- dopaminergic blockage could theoreti- significantly higher in women com- els, along with dopamine antagonism, cally cause hyperprolactinemia (4). In a pared with men. Lastly, women taking include D2 receptor polymorphisms, en- study using the data set from the Clini- hormonal contraception had a higher dogenous and exogenous estrogens, and cal Antipsychotic Trials of Intervention increase than women not taking hor- smoking status. In patients treated with Effectiveness, the relationship between monal contraception. This study also antipsychotics, recent literature suggests hyperprolactinemia and the D2 occu- supports findings from the literature regularly monitoring serum prolactin pancy of risperidone, olanzapine, and that aripiprazole, a partial dopamine and assessing for hyperprolactinemia ziprasidone was demonstrated. In that agonist, is a protective against antipsy- symptoms, as well as making pharmaco- study, the threshold of D2 occupants was chotic-induced hyperprolactinemia (6). logical changes to a less offending agent if slightly below the therapeutic window Use of aripiprazole in antipsychotic-in- symptoms or levels become problematic. for these antipsychotics. This suggests duced hyperprolactinemia is an impor- that therapeutic effect encompasses D2 tant concept that may warrant further blockade. Therefore, when using an an- investigation. Variables Affecting Prolactin tipsychotic for therapeutic effect, con- Tuberoinfundibular Pathway sideration should be made for prolactin Addition of Aripiprazole and Physiologic Prolactin elevation (5). Considering the idea that aripiprazole Because antipsychotics cause dopamine maintains prolactin levels, a study as- blockade in the mesocortical and me- Age sayed the prolactin serum levels of fe- solimbic dopaminergic pathways, they Along with the dopamine blockade male patients with schizophrenia with also cause blockage in the tuberoin- properties of a pharmacologic treat- risperidone-induced hyperprolactine­ fundibular pathway. This pathway, as it ment, age is also an important com- mia who were then given aripiprazole. projects from the hypothalamus to the ponent of changes in serum prolactin. The dosages were increased every 2 to anterior pituitary, regulates the release Younger patients seem to be more sus- 4 weeks, from 3 mg/day to 12 mg/day. of prolactin. Prolactin is released and re- ceptible to antipsychotic-induced pro- Serum prolactin levels were obtained sponsible for galactorrhea and amenor- lactin changes (4). In adults, it seems at baseline and then every 2 to 4 weeks. rhea either in a physiological functional that the elevation of prolactin from ris- Serum prolactin levels after receiving

The American Journal of Psychiatry Residents’ Journal 10 aripiprazole were lower than levels at efiting from risperidone therapy and Pharmacologic Treatment Options baseline but without significant change experiencing mild hyperprolactinemia The question about which antipsychot- in serum concentration or reduction symptoms, it is reasonable to continue ics are less associated with hyperpro- ratios among the 6, 9, and 12 mg/day treatment for 6–12 months. This recom- lactinemia has been studied in various dosages. This study suggests that ad- mendation is based on noted evidence ways. If a patient is experiencing hy- junctive use of aripiprazole reduces pro- that serum levels peak 1–2 months after perprolactinemia symptoms with noted lactin in risperidone-induced hyperpro- starting risperidone but then return serum elevation, it is recommended to lactinemia (7). close to normal within 3–5 months (10). discontinue the medication for 3 days Another study found a similar increase or substitute another medication and at around 2 months but an eventual re- recheck serum prolactin. If the medi- Clinical Implications turn close to normal near 22 months (12). cation cannot be stopped, it is recom- Clinical Manifestations Other studies have found that elevations mended to obtain imaging to differenti- Clinical sequelae of hyperprolactinemia of serum prolactin can be detected at 6 ate between a pituitary or hypothalamic are either from distortions in the hy- months, and patients have been symp- mass and antipsychotic-induced etiol- pothalamic-pituitary axis or direct ef- tomatic within weeks of increases in an- ogy (9). fects on specific tissues. Symptoms of tipsychotic dosage (13). Once hyperpro- A meta-analysis of the efficacy and hyperprolactinemia can include amen- lactinemia is suspected, the differential tolerability of antipsychotics in schizo- orrhea, breast enlargement or engorge- diagnosis should be considered. phrenia found that aripiprazole was ment, galactorrhea, decreased libido or the least associated with an increase in erectile dysfunction, or disruptions in Differential Diagnosis prolactin levels, while paliperidone was pubertal changes. Those with hyperp- Hyperprolactinemia can come from a the worst offender (14). A recent litera- rolactinemia are at higher risk of benign variety of endocrine or nonendocrine ture review addressed such concerns in breast tumors and disruption in bone pathologies. Endocrine pathologies in- relationship to the newest antipsychot- density. In adolescents, this bone loss clude craniopharyngoima, sellar or ics (15). This review suggests that ami- can persist for up to 2 years after anti- parasellar masses, granulomatous in- sulpride, risperidone, and paliperidone psychotics have been discontinued. Pre- filtration of the hypothalamus, head have the strongest association, while ar- menopausal women with schizophre- trauma, and pituitary adenomas. Non- ipiprazole and quetiapine have the low- nia treated with antipsychotics known endocrine pathologies associated with est. This review also suggests that ase- to increase prolactin have higher rates increased serum prolactin levels in- napine and iloperidone are comparable of osteoporosis compared with those clude chronic renal failure, chronic he- to clozapine, while lurasidone is compa- treated with olanzapine (8). patic failure, and pregnancy polycystic rable to ziprasidone and olanzapine (15). ovarian syndrome. Interestingly, hypo- Overall, these associations are dose- Monitoring Serum Prolactin thyroidism is known to elevate serum dependent, and the profiles are simi- Laboratory serum testing for prolactin prolactin in some cases, but the mech- lar for children and adults (15). Anti- levels is an appropriate monitoring tool anism is unclear. Other nonpathologic psychotics known to be less offending and should be considered annually (9). It causes of elevated prolactin include than risperidone include, in no specific has been suggested that a baseline pro- pregnancy, exercise, eating, stress, sex- order, aripiprazole (16), ziprasidone (17), lactin level be considered for all pediat- ual intercourse, and chest wall stimu- quetiapine (18), and paliperidone (19). ric patients starting risperidone therapy, lation. Medications, other than anti- Switching from risperidone to aripip- especially in those who have reached psychotics, known to elevate prolactin razole in adolescents with autism spec- sexual maturity. Serum prolactin lev- levels include antidepressants (such as trum disorder requiring pharmacother- els should be checked every 2 months tricyclic antidepressants, monoamine apy has been shown to be well tolerated after initiation, along with screening oxidase inhibitors, and selective sero- (20). questions for symptoms of hyperprolac- tonin reuptake inhibitors), opiates, anti­ tinemia. If any level is above 100 ng/mL, hypertensives, metoclopramine, and Conclusions imaging is recommended to evaluate domperidone, as well as the stimulant for a tumor (10). It is important to note cocaine. Medications thought to pos- Hyperprolactinemia associated with that the estimated prevalence of asymp- sibly increase serum prolactin include antipsychotics, specifically risperidone tomatic pituitary tumors is common, H2 blockers, protease inhibitors, and es- and paliperidone, should be considered. and any lesions found could be misin- trogens. Lastly, idiopathic hyperprolac- Baseline and periodic serum prolactin terpreted as being related to an antipsy- tinemia should also be considered in the levels should be obtained, along with chotic treatment (11). differential for hyperprolactinemia (9). monitoring for symptoms associated Others suggest that if the serum level If hyperprolactinemia is due to an anti- with hyperprolactinemia. If such a con- is elevated without reported symptoms, psychotic and does not remit with time, cern arises, and it does not improve with it is recommended to repeat the level in a different pharmacologic treatment time or is too severe, a switch to another another 2 months. If the patient is ben- regimen should be considered.

The American Journal of Psychiatry Residents’ Journal 11 antipsychotic, such as aripiprazole, is of prolactin secretion. J Clin Psychophar- 14. Leucht S, Cipriani A, Spineli L, et al: Com- warranted. macol 2011; 31:214–220 parative efficacy and tolerability of 15 anti- 7. Yasui-Furukori N, Furukori H, Sugawara psychotic drugs in schizophrenia: a N, et al: Dose-dependent effects of adjunc- multiple-treatments meta-analysis. Lancet Dr. Pope is a fifth-year child and ado- tive treatment with aripiprazole on hyper- 2013; 14:951–962 lescent psychiatry fellow in the Depart- prolactinemia induced by risperidone in 15. Peuskens J, Pani L, Detraux J, et al: The ef- ment of Psychiatry, University Hospitals, female patient with schizophrenia. J Clin fects of novel and newly approved antipsy- Cleveland. Psychopharmacol 2010; 30:596–599 chotics on serum prolactin levels: a 8. O’Keane V, Meaney AM: Antipsychotic comprehensive review. CNS Drugs 2014; drugs: a new risk factor for osteoporosis in 28:421–453 References young women with schizophrenia? J Clin 16. Ziadi Trives M, Bonete Llacer JM, Garcia Psychopharmacol 2005; 25:26–31 Escudero MA, et al: Effect of the addition of 1. Besnard I, Ausclair V, Callery G, et al: Anti- 9. Casanueva F, Molitch ME, Schlechte JA, et aripiprazole on hyperprolactinemia associ- psychotic drug-induced hyperprolac- al: Guidelines of the Pituitary Society for ated with risperidone long-acting injection. tinemia: physiopathology clinical features the diagnosis and management of prolacti- J Clin Psychopharmacol 2013: 33:538–541 and guidance. Encephale 2014; 40:86–94 nomas. Clin Endocrinol 2006; 65:265–273 17. Arcari GT, Mendes AK, Sothern RB: A ris- 2. Carvalho MM, Gois C: Hyperprolactinemia 10. Findling RL, Kusumakar V, Daneman D, et peridone-induced prolactnioma resolved in mentally ill patients. Acte Med Port 2011; al: Prolactin levels during long-term risper- when a woman with schizoaffective disor- 24:1005–1112 idone treatment in children and adoles- der switched to ziprasidone: a case report. 3. Nordstrom AL, Farde L: Plasma prolactin cents. J Clin Psychiatry 2003; Innov Clin Neurosci 2012: 9:21–24 and central D2 receptor occupancy in anti- 64:1362–1369 18. Ben Amor L: Antipsychotics in pediatric psychotic drug-treated patients. J Clin Psy- 11. Gianfrancesco F, Pandina G, Mahmoud R, and adolescent patients: a review of com- chopharmacol 1998; 18:305–310 et al: Potential bias in testing for hyperpro- parative safety data. J Affect Disord 2012; 4. Aboraya A, Fullen JE, Ponieman BL, et al: lactinemia and pituitary tumors in risperi- 138:S22–S30 Hyperprolactinemia associated with ris- done-treated patients: a claims-based 19. Montalvo I, Ortega L, Lopez X, et al: peridone: a case report and review of litera- study. Ann Gen Psychiatry 2009; 8:5 Changes in prolactin levels and sexual ture. Psychiatry 2004; 3:29–31 12. Anderson GM, Scahill L, McCracken JT, et function in young psychotic patients after 5. Tsuboi T, Bies RR, Suzuki T, et al: Hyperp- al: Effects of short-and long-term risperi- switching from long-acting injectable ris- rolactinemia and estimated dopamine D2 done treatment on prolactin levels in chil- peridone to paliperidone palmitate. Int receptor occupancy in patients with dren with autism. Biol Psychiatry 2007; Clin Psychopharmacol 2013; 28:46–49 schizophrenia: analysis of the CATIE data. 15:545–550 20. Ishitobi M, Kosaka H, Takahashi T, et al: Prog Neuropsychopharmacol Biol Psychia- 13. Melmed S, Casaneuva FF, Hoffman AR, et Effectiveness and tolerability of switching try 2013; 1:178–182 al: Diagnosis and treatment of hyperpro- to aripiprazole from risperidone in subjects 6. Veselinovic T, Schorn H, Vernaleken IB, et lactinemia: an endocrine society clinical with autism spectrum disorders: a pro- al: Impact of different antidopaminergic practice guideline. J Clin Endocrinol spective open-level study. Clin Neurophar- mechanisms on the dopaminergic control Metab 2011; 96:273–288 macol 2013; 36:151–156

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The American Journal of Psychiatry Residents’ Journal 12 Case Report A Clinical Case Conference on Spiritual Growth and Healing

Elizabeth S. Stevens, D.O.

Spiritual growth, along with cognitive our initiatives and responses, as well as system. In “universalizing faith,” one’s and psychosocial development, often our relationships and aspirations in life faith overcomes division, oppression, occurs during developmental transi- by enabling us to see them against the and violence (2). tions. The onus for spiritual growth backdrop of a comprehensive image of This case report illustrates key points may be life crises, disruptions, intrapsy- what constitutes true power, true value, of Fowler’s theory, using a psychologi- chic conflict, or environmental changes. and the meaning of life” (2). In what cal, social, and spiritual developmental Developmental crises can either shake Fowler describes as initial stage, “un- framework (3). one’s worldview or mature one’s faith differentiated faith,” infants develop a to become a coping mechanism during rudimentary foundational faith with a Case life’s transitions. basic trust and hope built upon secure In the present clinical case confer- attachments. In “intuitive-projective A 40-year-old divorced, Caucasian man ence involving psychiatry faculty and faith,” one’s faith is magical, illogical, with no previous psychiatric history residents examining the development and fantastical as one acquires lan- presented to an emergency department of spiritual growth and healing, sev- guage, moral emotions, and a sense of with depressed mood and neurovegeta- eral developmental theories illuminate the sacred. Representations of God cor- tive symptoms of depression, reporting the discussion: James Fowler’s work on relate with one’s experiences of attach- feelings of “failure as a father and as a stages of faith, which utilizes Jean Piag- ment figures. “Mythic-literal faith” is a Christian.” et’s theory on cognitive development logical, literal, and realistic faith per- The patient reported 2 months of in- and Erik Erikson’s theory on psycho- spective. “Synthetic-conventional faith” somnia, depressed mood, decreased in- social development. Fowler posits that is an emotional investment in one’s faith terest, decreased energy, and worsened faith develops through a series of prede- without critical, independent evaluation concentration. He reported psychoso- termined stages, leading to either suc- of it. Relational stressors can produce cial and spiritual stressors, including cessful or impoverished relationships lasting negative effects on one’s spiritu- his 14-year-old daughter’s suicidal be- and self-perception (1). Key points of ality, value, and intimacy with God (2). havior. This same daughter had stated the three theories of Fowler, Piaget, and In “individuative-reflective faith,” one to him, “You are dead to me.” He perse- Erikson are presented in Table 1. Faith claims an autonomy and responsibility verated on his divorce, his wife’s abor- interacts with cognitive and emotional for one’s faith without relying on an ex- tion, spiritual decisions he had made regulatory systems at each developmen- ternal authority. In “conjunctive faith,” that adversely affected his faith, and tal transition. In Stages of Faith, Fowler one embraces and integrates polarities separation from his daughters. Over the asserts that “faith affects the shaping of of life, beyond the explicit ideological last 2 months, he was prescribed clon-

TABLE 1. Developmental Models on Spiritual Growth and Healing From James Fowler, Jean Piaget, and Erik Erikson Theoretical Model Life Stage Erikson Piaget Fowler Infancy (ages 0–2) Basic trust versus mistrust (hope) Sensorimotor Primal faith Early childhood (ages 2–6) Autonomy versus shame and doubt (will) Preoperational or intuitive Intuitive-projective faith Initiative versus guilt (purpose) Preoperational or intuitive Intuitive-projective faith Childhood (ages 7–12) Industry versus inferiority (competence) Concrete operational Mythic-literal faith Adolescence (ages 13–21) Identity versus role confusion (fidelity) Formal operational Synthetic-conventional faith Young adulthood (ages 21–35) Intimacy versus isolation (love) Formal operational Individuative-reflective faith Adulthood (ages 35–60) Generativity versus stagnation (care) Formal operational Conjunctive faith Maturity (ages 60 and older) Integrity versus despair (wisdom) Formal operational Universalizing faith

The American Journal of Psychiatry Residents’ Journal 13 azepam and citalopram for anxiety and forgiveness and redemption. He then re- Conclusions depressed mood and zolpidem for in- quested therapy, specifically to address This case presentation highlighted the somnia. He reported that his medica- his spiritual and psychosocial stressors. importance of empathy, which may re- tions were ineffective. He endorsed sui- Initially, the patient reported that he quire encouragement for our patients to cidal ideation with a plan to overdose felt “stuck in the adolescence of Chris- grow in their faith in God. In a Baylor on his medications the night prior to tianity.” He was haunted by feelings College of Medicine clinical case con- his emergency department visit. He de- of “abandonment of God.” Therapy fo- ference on sacred experiences in psy- nied having medical problems, alcohol cused on the patient’s ambivalence and chotherapy, Lomax et al. (5) agreed that or illicit substance misuse, or any other indecision regarding his faith and re- spiritual integration, or a therapeutic prominent psychiatric symptoms. He lationships, which produced his per- rapport built on affirmation, respect, was medically cleared and admitted to ceived stagnation as a father, Christian, and interest in the patient’s spiritual- the inpatient psychiatric unit. and friend. Additional foci included in- ity, can allow for growth and strengthen The patient never knew his biological congruence of his Christian beliefs and the patient’s trust and commitment to father, and his mother was rarely pres- self-worth, specifically treating his per- the therapist and healing. In the above ent because of her own “depression” and ceived disintegration of his faith and case, the patient realized how to use his busy schedule as a single mother. His its impact on his identity. His mistrust faith to break self-destructive patterns. step-father forced him and his mother in himself and others led to a fear of After assessing a patient’s spiritual and out of their home and told him, “I don’t judgment as a “hypocrite,” which per- psychosocial development, the thera- love your mother anymore.” During petuated his isolation and impoverished peutic goal is to establish an empathetic childhood, he endorsed low self-esteem sense of spiritual community. Through relationship that cultivates trust and and difficulty relating emotionally to therapy, he began to make healthier de- motivates decisions that strengthen the others, which resulted in few long-term cisions in his relationships. He recon- patient’s relationships. The patient can girlfriends. His lack of belonging, pur- nected with his spiritual community then revisit incomplete developmental pose, and fear that he would be com- and became more involved in his daugh- stages to begin healing psychological pelled to marry his girlfriend and re- ters’ lives. wounds. main trapped in the same town led him to join the military. Discussion Dr. Stevens is a child and adolescent psy- Regarding his spiritual growth, he chiatry fellow in the Department of Child reported a lack of faith or relationship This case conference raised questions and Adolescent Psychiatry, University of to a higher power. At his first military regarding what precludes residents Colorado School of Medicine, Aurora, base assignment, he met Christian men from talking about spirituality with pa- Colo. who modeled lifestyles consistent with tients and provided insight into how to their beliefs. He met weekly with these help formulate aspects of spiritual de- men, and he began to heal in the sense velopment and cognitive and psychoso- References that his depression, shame, and low self- cial development. This case conference 1. Fowler JW: Stages in faith consciousness, worth were replaced by acceptance, also showed how understanding our in Religious Development in Childhood love, and significance. own spiritual development is valuable and Adolescence: New Directions for Child At the same time, he became sexu- in understanding our patients’ current Development. Edited by Oser FK, Scarlett ally intimate with his new girlfriend, functioning and in identifying the focus G. San Francisco, Jossey-Bass, 1991, pp 27–45 which he felt was inappropriate for his of therapy. 2. Fowler JW: Stages of Faith: The Psychol- new moral standards. Despite this spiri- This patient’s presentation is con- ogy of Human Development and Quest for tual conflict, they married. He chose to sistent with Erikson’s generativity ver- Meaning. San Francisco, Harper Collins, desert his male friends and God. After sus stagnation stage (4), with his ini- 1981 12 years, little religious fellowship, two tial presentation being one of idleness 3. Josephson AM, Peteet JR: Handbook of daughters, and an abortion, the mar- and “failure” as a father and Christian. Spirituality and Worldview in Clinical Practice. Washington, DC, American Psy- riage ended in divorce. His struggle to make independent deci- chiatric Publishing, 2004, p 25 The patient discontinued sertraline, sions demonstrates an immature cogni- 4. Kaplan BJ, Kaplan V: Kaplan and Sadock’s reporting that this medication caused tive ego and thus is partially situated in Synopsis of Psychiatry: Behavioral Sci- him to feel “out of it.” He was started Piaget’s formal operational stage (2). ences/Clinical Psychiatry, 10th ed. Phila- on trazodone for insomnia. His hospital His faith development is situated in delphia, Lippincott Williams and Wilkins, stay was 3 days, and he was discharged Fowler’s synthetic-conventional stage. 2007, pp 207–213 5. Lomax JW, Kripal JJ, Pargament KI: Per- to an intensive outpatient program. He He was unable to critically evaluate his spectives on “sacred moments” in psycho- met consistently with the chaplain to faith. Shame and guilt from his “aban- therapy. Am J Psychiatry 2011: 168:12–18 discuss his excessive shame and guilt donment” of God during this stage left a and the inconsistencies with his faith of lasting feeling of inadequacy.

The American Journal of Psychiatry Residents’ Journal 14 Case Report Priapism: A Rare but Serious Side Effect of Trazodone

Kamalika Roy, M.D.

Trazodone is a multifunctional drug have any history of using alcohol, co- trabecular smooth muscle and blood with variable receptor efficacy at differ- caine, marijuana, or any other elicit sub- vessels. This mechanism is described in ent dosages. It is one of the most com- stances in the past 10 years. His other Figure 1. monly used off-label drug for insomnia medications were hydrochlorothia- Intrinsic smooth muscles of arteri- when used in a range of 25 mg–200 mg zide and aspirin. During his outpatient oles and adrenergic tone maintain the daily. Potent 5HT-2a blocking effect and follow-up, he complained of persistent high resistance to blood flow in flaccid additional alpha adrenergic action and sleep difficulty despite using his contin- state. Alpha adrenergic blockers cause H-1 antihistamine action are promi- uous positive airway pressure machine smooth muscle relaxation and minimal nent in low-dose range, which makes with proper settings. Trazodone (200 resistance to blood flow during the erec- trazodone an effective hypnotic medi- mg at night) was added for his insomnia. tion phase. cine with no dependence potential and Possible rare instances of priapism were Another mechanism is through in- a short half-life (1). It is usually well tol- explained to him. He was instructed to hibition of cyclic guanosine monophos- erated with minor side effects such as report to the emergency department if phate degradation, which results in dizziness, morning drowsiness, head- he experienced an erection lasting lon- smooth muscle relaxation (vasodila- ache, and fatigue. However, there are ger than usual. After 2 months, he had tation) of arterioles. Phosphodiester- reported cases of prolonged, painful one episode of prolonged penile erection ase inhibitors produce erection by this penile erection or priapism lasting for for 4 hours, which resolved spontane- pathway, which is not dependent on more than 4 hours and resulting in uro- ously. Although it was not reported, he sympathetic control. Release of vasoac- logical emergency. The term “priapism” stopped taking trazodone for the next 2 tive intestinal peptide (4) has also been is originated from the Greek word “Pri- months. However, he resumed taking it proposed as a mechanism of erection. apus,” the Greek God with an oversized because it helped him with insomnia. At penis and protector of garden and live- that time, he reported that using trazo- Types of Priapism stock. Priapism is documented as a rare done at a dosage of 400 mg at night had a Low-flow (ischemic) priapism leads to but dramatic and potentially harmful more sedative effect. He did not consult cavernosal fibrosis and impotence in side effect affecting 0.01%–0.1% of the before increasing the dose by himself. 49%–50% of cases. Associated factors population on trazodone (2). Most of the This time, after 4 hours of taking one are sickle cell disease, leukemia, coagu- cases manifest within 1 month of start- 400-mg dose, he developed a prolonged, lopathy, fat emboli, drugs with alpha-1 ing therapy. However, there is one re- painful erection, sustained for 8 hours. blocking effect, and 5HT-1b stimulation ported case of priapism with one single He visited the emergency department, effect. dose of trazodone (100 mg) (3). and urology was consulted immediately. High-flow (nonischemic) priapism The present case is of a patient with He was not using any medications for does not lead to permanent damage. The priapism that resulted after adding tra- erectile dysfunction at that time or in underlying mechanism is arterial in- zodone; however, permanent functional the past year. He was treated with in- flow, which is more than venous outflow impairment was avoided by patient edu- tracavernosal instillation of a 300-mi- (e.g., in the straddle injury of groin). cation and prompt treatment. crogram phenylephrine injection to achieve detumescence. Subsequently, Drugs Causing Priapism the patient was followed up by urology, The overall incidence of priapism is Case and permanent erectile dysfunction was 1.5/100,000 person-years (5). The most “Mr. B” is a 52-year-old male patient avoided. common cause is documented to be id- with a history of sleep apnea and hy- iopathic, which accounts for almost 50% pertension who was initially prescribed of cases. Drug-induced priapism is the Discussion paroxetine for symptoms of persistent second most common cause, accounting depressive disorder. The dose was ti- Physiology of Erection for almost 30% of cases. trated to 40 mg daily. The patient tol- The erection or tumescence and flac- Almost all typical antipsychotics are erated the daily dose well, without any cidity of the penis are controlled by an known to cause priapism. Chlorproma- reported side effects. He was on parox- intricate balance between parasympa- zine and thioridazine have the great- etine for more than 1 year. He did not thetic and sympathetic control of both est alpha-1 adrenergic affinity, and thus

The American Journal of Psychiatry Residents’ Journal 15 FIGURE 1. Tumescence: Erection, Detumescence, and Flaccidity Often, a barrier of embarrassment and privacy concerns is present in both Sacral Sympathetic the physician’s and patient’s minds. Ed- parasympathetic adrenergic nerves ucating patients about any sexual side flow via a-1 receptors effects of drugs is important, not only to avoid adverse events but also to ensure adherence. Drug interaction should be seriously Dialatation of penile blood Contraction of penile considered in elderly male patients who vessels and relaxation of blood vessels and are already on alpha-1 blockers for pros- trabecular smooth muscle trabecular smooth muscle tatic hyperplasia and/or drugs for erec- tile dysfunction. Interaction between trazodone and other cytochrome P450 enzyme inhibitors should also be con- Tumescence Detumescence sidered, especially in higher dose. Medical attention should be sought for any erection lasting more than these are most frequently reported to be central 5HT-1b receptor, potent in- 4 hours to avoid serious permanent associated with priapism. Among the hibition of 5HT-2a, and synergistic dysfunction. atypical antipsychotics, risperidone has 5HT-1b inhibition by active metabolite the highest alpha-1 adrenergic affinity meta-chloro-phenyl-piperazine. Dr. Roy is a fourth-year resident in the and is most frequently associated with One study conducted in a small sam- Department of Psychiatry and Behavioral priapism. Clozapine (6), olanzapine (6), ple size found the relation of trazodone’s Neurosciences, Wayne State University, and quetiapine (6) are also reported to effect on penile erection activity and Detroit. be associated with priapism, probably sleep phases. Trazodone was shown to as a result of their potent 5HT- inhibi- prolong the nocturnal tumescence in 2a References tory property (1). Although trazodone nonrapid-eye-movement sleep phase in is the antidepressant most frequently this double-blind cross-over placebo- 1. Stahl SM: Mechanism of action of trazo- associated with priapism, other selec- controlled study. It was also shown that done: a multifunctional drug. CNS Spectr 2009; 14:536–546 tive serotonin reuptake inhibitors, such the interval from the REM sleep phase 2. Mendelson WB: A review of the evidence of as fluoxetine, citalopram, paroxetine, to penile detumescence was prolonged efficacy and safety of trazodone in insom- sertraline, venlafaxine, bupropion, and with 200 mg of trazodone (9). nia. J Clin Psychiatry 2005; 66:469–476 buspirone, are also reported to be re- In the above case, inhibition of cy- 3. Jayaram G, Rao P: Safety of trazodone as a lated to it. Drugs with a phosphodiester- tochrome P450 2D6 and 3A4 by parox- sleep agent for inpatients. Psychosomatics ase inhibition property, used for erec- etine could also play a role in increasing 2005; 46:367–369 tile dysfunction, can result in prolonged the level of trazodone and its metabolite, 4. Segraves RT: Effects of psychotropic drugs on human erection and ejaculation. Arch erection. Prostaglandin E1 agonists, which, in turn, might have played a role Gen Psychiatry 1989; 46:275–284 such as alprostadil, cause vasodilata- in increasing the chance of priapism. 5. Eland IA, van der Lei J, Stricker BH, et al: tion and can result in priapism if used Incidence of priapism in the general popu- in excess. Some antihypertensive (7) Recommendations for lation. Urology 2001; 57:970–972 drugs have strong alpha-1-adrenergic Clinical Practice 6. Crompton MT, Miller AH: Priapism associ- action. Prazosin, terazosin, and labeto- Trazodone is reported to be associated ated with conventional and atypical anti- psychotic medications: a review. J Clin lol can result in priapism through this with almost 80% of cases of drug-in- Psychiatry 2001; 62: 632–636 mechanism. Hydralazine has also been duced priapism. It is a rare side effect, 7. Eastham JH: Drug induced priapism (drug reported to be associated with priapism but often patients would not logically consult), in Drugdex System. Edited by by its direct vasodialatation (7) action. associate prolonged erection with their Hutchinson TA, Shahan DR. Greenwood Lastly, alcohol and illicit substances, medications. They may not report it in Village, Colo, Micromedex Healthcare such as cocaine and ecstasy (8), have all cases, as exemplified in the above 8. Dublin N, Razak AH: Priapism: ecstasy re- lated? Urology 2005; 56:1057xv-xvi also been reported to be associated with case. Considering the rarity of the side 9. Saenz de TI, Ware CJ, Blanco R, et al: priapism. effect, it is often used as off-label, at Pathophysiology of prolonged penile erec- times without any specific mention of tion associated with trazodone use. J Urol- Proposed Mechanisms of the gravity of the side effect. Before ogy 1991; 145: 60–64 Priapism With Trazodone prescribing any antidepressant, con- Proposed mechanisms of priapism sideration of its side effects and proper with trazodone include alpha adren- patient education will be very helpful to ergic blocking effect, stimulation of prevent any adverse outcome.

The American Journal of Psychiatry Residents’ Journal 16 Book Forum Classifying Psychopathology: Mental Kinds and Natural Kinds

Reviewed by Aaron J. Hauptman, M.D.

This volume is a 13-chapter collection of kind—it is, rather, a disunified collec- papers on such disparate topics as major tion of symptoms. The book argues that depression, pathological gambling, and because our diagnostic terms don’t pick oppositional defiant disorder, each of out a natural kind, we see a great deal of which explores aspects of a single, core inconsistency when it comes to etiology, philosophical question: Are mental ill- pathophysiology, and outcome. We con- nesses natural kinds? Natural kinds are flate a bunch of things and leave some categories that result from splitting re- other things out. This is not to say that ality apart at its seams: people are not depressed; this is rather to say that what we call major depres- “To say that a kind is natural is sive disorder isn’t an adequate charac- to say that it corresponds to a group- terization of the psychopathology. The ing or ordering that does not de- book argues that if we are using terms pend on humans .... The existence of that don’t pick out natural kinds, much these real and independent kinds of of our research into major depressive things is held to justify our scientific disorder is called into question. inferences and practices.” (1) So, no, this won’t change how you prescribe sertraline next week. But it In terms of psychiatry, the question is may affect how you conceptualize psy- this: Is the category of “a mental illness” chiatry and rock some of the funda- a natural one, which can be justifiably mental assumptions that you have had used in scientific inference and prac- about our field and its scientific under- tice, or is it a gerrymandered collection Edited by Harold Kincaid and Jacqueline A. pinnings. Such a shaking of the ground of mental states and behaviors that we Sullivan. Cambridge, Mass., MIT Press, 2014, can only be a good thing; though un- have deemed pathological? This book pp. 296, $40.00 (hardcover). comfortable, it brings about change and, addresses a wide range of fascinating ultimately, forces us all to build stronger questions surrounding issues that scru- that is taken for granted and that under- foundations. tinize the understructure of psychiatry. lies every aspect of psychiatric practice The question you might ask is this: and care. Why do I, a psychiatry resident, care Dr. Hauptman is a fourth-year resident in Here is an example. The text ad- the Department of Child and Adolescent about how philosophers of psychiatry dresses a central issue of concern to cli- Psychiatry at New York University. pick apart our diagnoses? The clinician nicians: the use of DSM criteria. Some always asks, “How will this affect my writers think that conditions like de- clinical practice?” In a sense, the con- pression are natural kinds but that the Reference tent of this book will have no impact on DSM doesn’t delineate this entity. On 1. Bird A, Tobin E: Natural kinds, in the Stan- what the clinician does in his or her day- this view, there is a natural kind, de- ford Encyclopedia of Philosophy, Winter,­ to-day treatment of patients, charting pression, that exists independently of 2012. (http://plato.stanford.edu/archives/ of documentation, and after-hours con- win2012/entries/natural-kinds/>) the DSM’s conceptualization of it. The siderations of the struggles of his or her category called major depressive dis- day. In another sense, though, the ideas order in the DSM, however, is not that discussed in this book challenge much

The American Journal of Psychiatry Residents’ Journal 17 Residents’ Resources Here we highlight upcoming national opportunities for medical students and trainees to be recognized for their hard work, dedication, and scholarship. *To contribute to the Residents’ Resources feature, contact Hun Millard, M.D., M.A., Deputy Editor ([email protected]).

August Deadlines

Fellowship/Award Organiza- and Deadline tion Brief Description Eligibility Contact Website Academy of Psy- APM To encourage psychosomatic Psychosomatic medi- N/A http://www.apm.org/ chosomatic Medi- medicine fellows, residents, and cine fellows, residents, awards/trainee-travel. cine (APM) Trainee medical students to join APM, and medical students. shtml#how_to_apply Travel Awards attend the annual meeting, and eventually become new leaders Deadline: of the Academy; a limited num- August 1, 2015 ber of monetary awards are given to help offset the cost of attending the annual meeting.

Webb Fellowship APM One-year appointment that PGY-3 or 4; N/A http://www.apm.org/ Program fosters the career development Psychosomatic medi- awards/webb-fship. and leadership potential of ad- cine fellow; shtml Deadline: vanced psychiatry residents and Recent graduates of August 1, 2015 psychosomatic medicine fel- psychosomatic medi- lows via mentorship, network- cine fellowship (within ing, sustained involvement, and 1 year of graduation). affirmation and consolidation of professional identity.

The PRITE (Psy- The Ameri- The PRITE Fellowship Selection PRITE: PGY-2 or 3; Kathryn@acpsych. http://www.acpsych. chiatry Resident can College Committee chooses PRITE Fel- Child PRITE: First-year org org/resident-fellow- In-Training Exami- of Psychia- lows to serve at least 1 year on child fellow ships/the-prite-fel- nation) and Child trists the PRITE Editorial Board. They lowship-program PRITE Fellowships provide a resident perspective to the exam as they participate Deadline: in the question writing process, August 15, 2015 developing an assigned number of questions, and then editing and referencing exam items.

The American Journal of Psychiatry Residents’ Journal 18 Author Information for The Residents’ Journal Submissions

Editor-in-Chief Senior Deputy Editor Deputy Editor Rajiv Radhakrishnan, M.B.B.S., M.D. Katherine Pier, M.D. Hun Millard, M.D., M.A. (Yale) (Icahn School of Medicine) (Yale)

The Residents’ Journal accepts manuscripts authored by medical students, resident physicians, and fellows; manuscripts authored by members of faculty cannot be accepted. To submit a manuscript, please visit http://mc.manuscriptcentral.com/appi-ajp, and select “Residents” in the manuscript type field. 1. Commentary: Generally includes descriptions of recent events, opinion pieces, or narratives. Limited to 500 words and five references.

2. Treatment in Psychiatry: This article type begins with a brief, common clinical vignette and involves a description of the evaluation and management of a clinical scenario that house officers frequently encounter. This article type should also include 2-4 multiple choice questions based on the article’s content. Limited to 1,500 words, 15 references, and one figure.

3. Clinical Case Conference: A presentation and discussion of an unusual clinical event. Limited to 1,250 words, 10 references, and one figure.

4. Original Research: Reports of novel observations and research. Limited to 1,250 words, 10 references, and two figures.

5. Review Article: A clinically relevant review focused on educating the resident physician. Limited to 1,500 words, 20 references, and one figure.

6. Letters to the Editor: Limited to 250 words (including 3 references) and three authors. Comments on articles published in The Residents’ Journal will be considered for publication if received within 1 month of publication of the original article.

7. Book Review: Limited to 500 words and 3 references.

Abstracts: Articles should not include an abstract. Upcoming Themes

Please note that we will consider articles outside of the theme.

Race/Ethnicity and Psychiatry Psychiatry and the Humanities Integrated Care/ If you have a submission related to this If you have a submission related to Mental Health Care Delivery theme, contact the Section Editors this theme, contact the Section Editor If you have a submission related to Jacqueline Landess, M.D., J.D. Vivek Datta, M.D. this theme, contact the Section Editor (jacqueline.landess@ ([email protected]) Connie Lee, M.D. ucdenver.edu) and ([email protected]) Aparna Atluru, M.D. ([email protected])

*If you are interested in serving as a Guest Section Editor for the Residents’ Journal, please send your CV, and include your ideas for topics, to Rajiv Radhakrishnan, M.B.B.S., M.D., Editor-in-Chief ([email protected]).

The American Journal of Psychiatry Residents’ Journal 19