Gabapentin in the Management of Meal-time Anxiety in Restrictive Eating Disorders

Gabapentin in the Management of Meal-time Anxiety in Restrictive Eating Disorders | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Gabapentin in the Management of Meal-time Anxiety in Restrictive Eating Disorders View ORCID Profile Nikhil Rao , Alexandra Wadford doi: https://doi.org/10.1101/2025.08.06.25332917 Nikhil Rao 1 Kartini Clinic , Portland, Oregon 2 Legacy Health System , Portland, Oregon MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Nikhil Rao For correspondence: nikhilraomd{at}gmail.com Alexandra Wadford 2 Legacy Health System , Portland, Oregon MSN Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Objectives Few psychotropic medications have shown efficacy in treating eating disorders during the acute weight restoration phase, with olanzapine being the primary option despite its side effect profile. This study is the first to show that gabapentin may aid in eating disorder management, demonstrating objective improvements in meal completion and weight gain, as well as subjective relief of pre-meal anxiety and post-meal gastrointestinal distress. Methods Youth (N=14) enrolled in partial hospital treatment from 2020 to 2025 who received gabapentin for mealtime anxiety and poor meal completion were identified via chart review. Extracted data included demographics, comorbidities, and subjective/objective treatment response measures (e.g., meal completion rates). As mealtime anxiety was not universally documented, a control group was not feasible. Meal completion was assessed at three time points: two weeks prior, the day of initiation, and two weeks post-initiation. Analyses included paired t-tests, Hedges’ G for effect size, and the sign test for subjective response data. Results Gabapentin was most commonly dosed (n=8) at 300mg scheduled before meals. There were statistically significant subjective responses for preprandial anxiety (86%), postprandial abdominal discomfort (57%), and early satiety (50%). Meal completion improved by an average of 36% two weeks after initiation, compared to 2.5% in the two weeks prior (p =.002, g = 1.14). Among the nine youth who were nasogastric tube–dependent, the improvement was even greater at 52.5% (p =.003, G = 1.5). Both of these effect sizes were large. Conclusions Despite limitations in methodology and sample size, this case series strongly suggests that gabapentin may be a promising option for managing mealtime anxiety and improving intake in youth with eating disorders. With the particularly notable effects in NGT-dependent youth and those with poor response to olanzapine in this study, gabapentin’s potential in eating disorder management warrants further exploration. Introduction Despite decades of research, few pharmacologic interventions have proven successful in the management of restrictive eating disorder symptoms, especially in the acute treatment period (Muratore & Attia, 2020). Medications with negative trials include anxiolytics, first and second generation antidepressants, first generation antipsychotics, and most second generation antipsychotics (SGAs). One notable exception to this has been the SGA olanzapine (OLZ), which has shown efficacy in Anorexia Nervosa (AN) and Avoidant Restrictive Food Intake Disorder (ARFID) in multiple treatment settings ( Çöpür & Çöpür, 2020 ; Brewerton & D’Agostino, 2017 ). Although effective, olanzapine is associated with significant risks and limitations. In the short term, the most common side effect is oversedation. However, acute hypertriglyceridemia (with attendant pancreatitis risk) and liver function abnormalities are also common with rates of 1-10%. Notably, these risks may be greater in adolescents compared to adults ( Woods et al, 2002 ). Of specific concern for eating disorders, olanzapine, like many antipsychotics, may cause or exacerbate orthostatic hypotension through alpha-1 antagonism ( Jana et al, 2015 ). Finally, although considered lower in risk compared to most antipsychotics, olanzapine nevertheless confers risk of extrapyramidal symptoms including tremor, spasticity, and neuroleptic malignant syndrome, the latter of which can be fatal ( Leucht et al, 1999 ). For youth who may need long-term pharmacologic treatment for restrictive eating disorder, olanzapine is problematic, given the high risk of obesity, dyslipidemia, and impaired glucose metabolism, and secondarily due to risk of neurologic side effects including tardive dyskinesia, which may be permanent even after discontinuation ( Woods, et al. 2002 ). As in acute treatment, there is no evidence of benefit for any class of medication in long-term treatment of restrictive eating disorders, although some benefit has been noted in SSRI therapy specifically in the treatment of Bulimia Nervosa ( Sanil, 2025 ). Specific targeting of pre- and post-meal anxiety with anxiolytics has been sparsely studied, despite anxiety being known to contribute substantially to outcome variability and course of treatment (Lloyd et al, 2021). A small RCT of alprazolam for pre-meal anxiety in AN was negative ( Steinglass et al, 2014 ), while a cohort study in which hydroxyzine was administered before meals alongside an SSRI in ARFID showed equivocal results ( Mahr et al, 2022 ). Although not studied in eating disorders, gabapentinoids have emerged as promising treatments for a variety of anxiety manifestations, but perhaps most relevant to this study is clear and consistent finding of benefit in treatment of situational anxiety ( Hong, et al. 2021 ). An additional feature of gabapentinoids not common to more typical psychotropics is its known benefits in hyperesthesia ( Rose & Kam, 2002 ). Given the frequent occurrence of nonspecific and/or functional gastrointestinal symptoms in eating disorders, we postulate that they may provide benefit here as well ( Sato & Fukudo, 2015 ). Other potential benefits of gabapentinoids over other agents include lower risk of constipation than antipsychotics, serotonergics, and antihistaminergic agents, lower risk of dependence or altered mental status than benzodiazepines, and that they are generally hemodynamically neutral ( Quintero, 2017 ). In this retrospective chart review study of youth admitted for restrictive eating disorders to a partial hospital program, we investigate the effects of pre-prandial gabapentin administration on mealtime anxiety, early satiety, and postprandial discomfort. Using a within-group pre- and post-intervention comparison, we demonstrate clinically and statistically significant improvements in both subjective and objective measures across a variety of subgroups, including in youth already receiving olanzapine. To our knowledge, this is the first report of the therapeutic benefit of gabapentinoid use in eating disorder management. Methods Participants We conducted a retrospective chart review of all adolescents admitted to a partial hospital program for eating disorders who received psychiatric consultation between 11/1/2020 and 1/13/2025. These included youth diagnosed with ARFID, Anorexia Nervosa, Restrictive subtype (AN-R), and Anorexia Nervosa, Binge-Purge (AN-BP) subtype who were prescribed gabapentin for pre-meal anxiety during the treatment period. Youth were excluded if they did not complete at least 2 weeks of treatment both before and after gabapentin initiation. A control group could not be established as clinicians did not consistently rate or document pre-meal anxiety across all youth in treatment. Cases were further stratified by diagnosis (AN-R, AN-BP, ARFID), nasogastric tube (NGT) dependence, and concomitant/prior olanzapine treatment. Ethical Considerations IRB approval was obtained from Legacy Research Institute on Feb 14, 2024, #2092, with waiver of consent as a low risk retrospective chart review and as obtaining consent for prior patients was not practicable. This study was performed in accordance with the ethical standards of the 1964 Helsinki Declaration. Data Demographic and Medical Collected data included demographic information, body weight and height at admission, goal weight, and weight measured at multiple time points throughout treatment. Psychiatric and Eating Disorder All participants and their parents completed a comprehensive, DSM-5-based semi-structured clinical interview as well as other diagnostic tools as indicated. Standardized screening and diagnostic tools included the Revised Eating Disorder Scale – Concise (REDS-C), Center for Epidemiologic Studies Depression Scale – Child (CES-DC), Screen for Child Anxiety Related Emotional Disorders (SCARED), Child Yale-Brown Obsessive Compulsive Scale (CYBOCS), Child Stress Disorder Checklist (CSDC), Vanderbilt ADHD Diagnostic Rating Scale, McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) All comorbid diagnoses required evidence that symptoms preceded the onset of eating disorder. Intervention In the course of routine clinical care, youth with severe pre-meal anxiety were identified by staff and pharmacologic approaches were discussed with youth and family. Gabapentin was dosed flexibly with initial dosing of 100mg as needed 30-60 minutes before meals and as high as 600mg scheduled before meals, with additional as-needed doses as indicated. Tolerability and symptom response were monitored throughout treatment. Outcome Measures Primary outcomes included treatment response (e.g., meal completion, rate of weight gain, and completion of treatment). Secondary outcomes included patient report and clinician-rated CGI-I for anxiety, early satiety, and post-prandial abdominal discomfort. Statistical Methods Means and standard deviations are reported for continuous variables and frequencies for categorial responses. Pre and post intervention comparisons were performed using one-tailed paired t-tests while subgroup comparisons used two-tailed unpaired t-tests. Symptom response outcomes were assessed with the sign test and one-sample t -test for patient report and clinician-rated CGI-I, respectively. Effect sizes were calculated using Hedges’ g where applicable. Results Descriptive Statistics Ultimately, 14 cases were identified for inclusion in this study, including 7 with AN-R, 5 with AN-BP, and 2 with ARFID. Average age was 15.7 (SD=1.6) years old at admission, with an average BMI of 18.6 (SD=2) at admission. The most common comorbidities included Cannabis Use Disorder (n=5), OCPD traits (n=4), BPD traits (n=3), and Obsessive Compulsive and Related Disorders (5). Eleven of these youth were on other psychotropic medications at the time of gabapentin initiation, including seven on olanzapine, five on SSRI, and two on mirtazapine. Gabapentin administration started on average 31.8 (SD=14.8) days into treatment, not including prior medical hospitalization or outpatient treatment. The modal dose (n=8) was 300mg three times daily 1 hour before meals on a scheduled basis. There were no discontinuations during the study period. Main Outcome Measures Baseline rate of weight gain was 1.5lbs (SD=1.4) per week, which increased to 3.1lbs (SD=1.4) per week after gabapentin was initiated.This result was statistically significant (p=.002, t(13)=3.6) and the effect size was large (Hedges’ g =1.14). Meal completion rate increased from 31.4% (SD=35.7) at baseline to 67.9% (SD=35.6%) after gabapentin treatment, which was again both statistically significant (p=.002, t(13)=4.501) and large in effect ( g =1.02). Download figure Open in new tab Figure 1. Weight Gain Before and After Addition of Gabapentin Notes: Oral = Eating all meals orally. NGT = Requiring either bolus or continuous feeds via nasogastric tube. All differences in weight gain between pre-treatment and post-treatment were statistically significant. The change in weight gain and meal completion (%) were not statistically different between oral and NGT fed youth. Symptom Response Rates All 14 participants reported significant preprendial anxiety prior to gabapentin. Twelve reported a positive response, which was statistically significant (t=3.45, p=.0003). Mean CGI-I was 2.4 (SD=1), which was clinically and statistically significant (t=-6, p<.001). Half of the six youth with early satiety reported improvement (p=.042, z=1.73), while CGI-I was 2.8 (SD = 1.4) (t=-2.1, p=.045). Five of seven youth with postprandial abdominal discomfort reported a positive response (p=0.023, z=2.24), with a CGI-I of 2.3 (SD=1.3) (t=-3.46, p=.007). Subgroup Analyses Youth who had previously or were concomitantly prescribed olanzapine was a pre-specified subgroup of interest, while two others emerged due to over-representation in our sample: Youth with comorbid cannabis use disorder (35.8% of sample vs 11.7% of clinic population) and NGT-dependent youth (64.2% of sample vs 12% of clinic population). Gabapentin and Olanzapine Half of the youth (n=7) in our sample had been prescribed olanzapine, which they had been taking on average 31.4 days prior to initiation of gabapentin. Of these seven, six were also NGT-dependent for feeds at the time of initiation, compared to three of the seven youth who were not receiving olanzapine. The addition of gabapentin to olanzapine resulted in an increase in weight gain of 1.2lb/wk (SD=0.9) compared to baseline (p=.005, t(13)=3.7) which was a large effect (g=1.07) whereas the group receiving only gabapentin saw increases of 2.1(2.0) lb/wk (p=.028, t=3.7) with a similarly large effect size of g=1.4. The difference in response between subgroups was not statistically significant (p=.31,t=1.08). Download figure Open in new tab Figure 2. Weight Gain and Meal Completion with addition of Gabapentin to Olanzapine Notes: This graph demonstrates the change in both rate of weight gain and meal completion in youth with and without olanzapine. OLZ=olanzapine. GBP = gabapentin. Within-group improvements in meal completion and weight gain were all statistically significant. Between group (OLZ+GBP vs GBP only) differences were statistically significant for meal completion but not weight gain. In terms of meal completion, the olanzapine+gabapentin subgroup demonstrated substantial improvement, improving from 14.3% (SD=29.9) to 67.1% SD=35.9) (p=.002, t=4.2) for a 52.9% increase in meal completion percentage with a very large effect size ( g =1.6, p=.002, t=4.2). The gabapentin-only group improved from 48.6% (SD = 34.4%) to 68.6% (SD = 38%), a 20% increase that approached statistical significance (p =.088, t = 3.24) and represented a moderate effect size (g = 0.56). The overall improvement in meal completion was significantly greater in the combined olanzapine-gabapentin group (p =.036, t = 2.36, g = 1.26), although both finished with roughly equal meal completion rates. Gabapentin and Cannabis Use Five participants reported clinically significant cannabis use at admission. The weight gain response to gabapentin did not differ significantly between cannabis users and non-users, with users improving by an average of 1.6 lbs/week (SD = 1.8) and non-users improving by 1.7 lbs/week (SD = 1.5) (p =.87, t = 0.16). However, meal completion improvement was significantly lower among cannabis users, who showed a 16% increase (SD = 8.9%) to a final completion rate of 60% (SD = 47%), compared to a 47.8% increase (SD = 32.3%) and a final rate of 72% (SD = 29.9%) in non-users. This difference in improvement was statistically significant (p =.033, t = 2.4), although final completion rates did not differ significantly between groups (p =.35, t = 0.98). Gabapentin and NGT Dependence Over half of our sample (n=9) was NGT-dependent for nutrition at the time of addition of gabapentin, with six also receiving olanzapine treatment. Gabapentin was initiated on average 32.3 (SD=16.9) days into program entry. Download figure Open in new tab Figure 3. Meal Completion Before and After Addition of Gabapentin Notes: NGT = Nasogastric-tube dependent. Meal completion rates before and after treatment were statistically significant both within and between all groups. Weight gain rates increased from 1.3 lbs/week (SD = 1.1) to 3.1 lbs/week (SD = 1.4), a significant improvement (p =.007, t = 3.17) with a large effect size (g = 0.93). This change was similar to the 1.5 (SD=1.5) lbs/wk improvement over the baseline rate seen in orally fed youth (p=.78, t=-.311). Meal completion in NGT-dependent youth rose from 8.9% (SD = 20.3%) to 52.5% (SD = 35.3%), a statistically significant improvement (p =.003, t = 3.61) with a very large effect size (g = 1.5). However, the magnitude of improvement (43.3%, SD = 36.1%) was not significantly different from the change seen in orally fed youth (24%, SD = 8.9%) (p =.11). Discussion Gabapentin was well tolerated, with no discontinuations due to side effects. In addition to strong objective improvements in weight gain and meal completion, both clinicians and youth rated gabapentin as effective for both anxiolysis and reduction in hyperesthesia. Subjective improvement rates ranged from 50% for postprandial discomfort to 86% for preprandial anxiety. Clinically meaningful improvements were also observed in objective treatment outcomes, including weight gain and meal completion. Prior to treatment, just three of fourteen youth were completing greater than 80% of meals, with none completing 100%. Following treatment, this rose to eight and six of fourteen, respectively. The response to gabapentin in NGT-dependent youth was perhaps the most striking. By an average of 30 days into treatment, only two out of the nine were completing any amount of oral intake. Within two weeks of receiving gabapentin, seven of nine had measurable oral intake, and five of nine were completing 50% of meals or more. Importantly, gabapentin appears to confer benefit even in youth already receiving olanzapine, providing options for youth with incomplete or inadequate response to this medication. Despite constraints, this small case series offers preliminary evidence across subjective and objective domains that gabapentin may have a therapeutic role in management of eating disorders. Primary limitations include the small sample size and over-representation of certain subgroups. Additionally, the retrospective chart review design, lack of a comparator group, and subgroup confounds between OLZ and NGT, limits the precision of data on dosing and symptom response measures. However, the consistency and strength of observed responses to gabapentin suggest a robust treatment effect. Future research is needed to more rigorously evaluate the role of gabapentin in eating disorder recovery. In the meantime, given its favorable safety profile and tolerability, gabapentin should be considered in individuals whose preprandial anxiety and postprandial physical discomfort contributes to stagnation in eating disorder treatment. Conclusions Gabapentin appears to be a promising adjunctive treatment for restrictive eating disorders and may have unique efficacy in youth dependent on nasogastric tubes due to their eating disorders. Gabapentin appears to aid in both objective measures of treatment including weight gain and meal completion, as well as subjective measures of preprandial anxiety and post-prandial discomfort. It is likely that both anxiolysis and reduction in hyperesthesia contribute to its clinical effects. Clinical Significance Few options other than olanzapine are currently available for the management of acute or chronic eating disorders. Gabapentin appears to be well-tolerated and efficacious providing benefit for meal completion, weight gain, anxiety, and gastrointestinal discomfort and may be suitable for both acute and chronic management of restrictive eating disorders. Disclosures and Conflicts of Interest None Author Contributions Conceptualization: Rao, Wadford Data Analysis: Rao Interpretation: Rao, Wadford Writing - Original Draft: Rao Writing - Review and Editing: Wadford Data Availability Data is available upon reasonable request. Acknowledgements We thank Naghmeh Moshtael, MD, MPH, for her clinical perspective, as well as Margarita Stepanyan, BA, Alisha Steigerwald, BS, and Morgan Metcalfe, BS for their assistance in data collection. References 1. Bacaltchuk J , Hay P and Mari JJ . Antidepressants Versus Placebo for the Treatment of Bulimia Nervosa: A Systematic Review . Aust N Z J Psychiatry 2000 ; 34 ( 2 ): 310 – 317 ; doi: 10.1080/j.1440-1614.2000.00709.x . 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