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Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder

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Title: Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder
Language: English
Authors: Riley A. Argonis, Ernest V. Pedapati, Kelli C. Dominick, Katherine Harris, Martine Lamy, Cara Fosdick, Lauren Schmitt, Rebecca C. Shaffer, Elizabeth Smith, Meredith Will, Christopher J. McDougle, Craig A. Erickson (ORCID 0000-0003-4512-398X)
Source: Journal of Autism and Developmental Disorders. 2025 55(6):1969-1975.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 7
Publication Date: 2025
Document Type: Journal Articles
Reports - Research
Descriptors: Drug Therapy, Depression (Psychology), Autism Spectrum Disorders, Patients, Symptoms (Individual Disorders), Comorbidity, Program Termination, Program Effectiveness, Intervention
DOI: 10.1007/s10803-023-06126-z
ISSN: 0162-3257
1573-3432
Abstract: Introduction: Depression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. Purpose: The purpose of this study is to discover prescribing patterns for individuals with MDD and ASD during this time period (2004-2012) to inform current and future prescribing practices with historical data. Methods: Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 166 individuals with ASD (mean age 14.5 ± 8.3 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Results: Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 241 drug starts, 123 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ± 0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. Conclusion: This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1470844
Database: ERIC
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  Value: <anid>AN0185099698;aut01jun.25;2025May14.02:48;v2.2.500</anid> <title id="AN0185099698-1">Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder </title> <p>Introduction: Depression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. Purpose: The purpose of this study is to discover prescribing patterns for individuals with MDD and ASD during this time period (2004–2012) to inform current and future prescribing practices with historical data. Method: Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 166 individuals with ASD (mean age 14.5 ± 8.3 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Results: Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 241 drug starts, 123 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ± 0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. Conclusion: This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.</p> <p>Keywords: Autism; Psychopharmacology; Pharmacotherapy; Depression; Medical and Health Sciences Clinical Sciences Public Health and Health Services</p> <p>Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10803-023-06126-z.</p> <hd id="AN0185099698-2">Introduction</hd> <p>Mental illness is a growing concern among adolescents and adults alike, with 21% of adults and 49.5% of adolescents aged 13–17 years in the United States experiencing any mental disorder in the past year (U.S. Department of Health and Human Services, [<reflink idref="bib8" id="ref1">8</reflink>]). Autistic individuals may be at particular risk for mental health concerns, with over 2 in 3 autistic adults (Fombonne et al., [<reflink idref="bib12" id="ref2">12</reflink>]) and up to 80% of autistic adolescents (Buck et al., [<reflink idref="bib3" id="ref3">3</reflink>]) diagnosed with at least one comorbid psychiatric disorder (Fombonne et al., [<reflink idref="bib12" id="ref4">12</reflink>]). Depression disproportionately affects individuals with autism spectrum disorder (ASD) and contributes to functional disability, including educational and vocational impairment, social withdrawal, and suicide (Cassidy et al., [<reflink idref="bib5" id="ref5">5</reflink>]). The risk of developing major depressive disorder (MDD) is nearly four times greater in individuals with ASD than in their neurotypical peers (Hudson et al., [<reflink idref="bib14" id="ref6">14</reflink>]). Other studies have found rates of depression in autistic patients higher than rates in the general population, including rates of depression of 23% of autistic adults (Hollacks et al., [<reflink idref="bib13" id="ref7">13</reflink>]) and 30% of autistic adolescents (Matson & Nebel-Schwalm, [<reflink idref="bib18" id="ref8">18</reflink>]) compared to rates of 8% and 17% of adults and adolescents respectively of depression (U.S. Department of Health and Human Services, [<reflink idref="bib7" id="ref9">7</reflink>]) in the general population. Understanding the true prevalence rates of depression in the autistic population is difficult due in part to a lack of validated instruments and measures to identify atypical presentations of comorbid depression in individuals with ASD (DeFilippis, [<reflink idref="bib6" id="ref10">6</reflink>]). The presence or absence of intellectual disability (ID) in the context of ASD may also impact rates of depression noted among autistic individuals. Individuals with ASD without an ID are more likely to be diagnosed with comorbid depression (Buck et al., [<reflink idref="bib3" id="ref11">3</reflink>]; Hudson et al., [<reflink idref="bib14" id="ref12">14</reflink>]). This may be related to a tendency to exhibit canonical signs and symptoms of MDD, including sadness, anhedonia, cognitive changes, suicidality, and neurovegetative symptoms among the subgroup of persons with ASD and higher cognitive ability. Moreover, depressive symptoms can also present atypically in ASD and have overlapping features with ASD (e.g., social withdrawal and flat affect). These symptoms may include increased irritability (including self-injury), loss of special interests, engagement in repetitive behavior, and decreases in adaptive function and self-care (Pezzimenti et al., [<reflink idref="bib21" id="ref13">21</reflink>]). Higher rates of the diagnosis of MDD in autistic individuals without ID may also be due to their relative language ability, with these individuals more able to communicate thoughts and feelings, given that diagnosing depression often relies on patient self-report (Buck et al., [<reflink idref="bib3" id="ref14">3</reflink>]). Therefore, MDD may be underdiagnosed in autistic individuals with ID and/or significant expressive language deficits (Cassidy et al., [<reflink idref="bib5" id="ref15">5</reflink>]; Cassidy & Rogers, [<reflink idref="bib4" id="ref16">4</reflink>]; Magnuson & Constantino, [<reflink idref="bib16" id="ref17">16</reflink>]). Though new tools and validation measures to better identify and diagnose MDD in autistic individuals are being developed and beginning to enter clinical practice (Angel et al., [<reflink idref="bib2" id="ref18">2</reflink>]), it remains a challenge in both present and past literature to accurately identify the condition in this unique context.</p> <p>Not surprisingly, given high rates of comorbid mental illness in autistic patients, reports have noted high psychiatric medication use in this population with a high rate of polypharmacy. In a large registry of autistic children, Rosenberg et al. ([<reflink idref="bib22" id="ref19">22</reflink>]) noted that 35% of youth received at least one psychotropic drug targeting mental illness and 10% received at least three different classes of psychiatric drugs at one time (Rosenberg et al., [<reflink idref="bib22" id="ref20">22</reflink>]). A second report noted 40% of autistic youth took at least one psychiatric drug targeting comorbid mental illness, and up to 31% received at least two psychiatric medications (Feroe et al., [<reflink idref="bib11" id="ref21">11</reflink>]). Specific to depression in autistic adults, Zheng et al., [<reflink idref="bib28" id="ref22">28</reflink>] noted among all patients receiving medication, psychotherapy, or both, 85% received a psychotropic medication targeting symptoms of depression (Zheng et al., [<reflink idref="bib28" id="ref23">28</reflink>]). Despite the frequency of psychiatric medication use targeting comorbid mental illness in autistic patients, little information is available describing specific drug use, dosing, and tolerability to inform this prescribing practice. This is particularly true regarding the medication management of depression in autistic patients.</p> <p>In this study, we aim to extract historical information on specific prescribing patterns targeting symptoms of depression in autistic patients from a large clinical medication management database focused on this population in order to help inform current prescription practices and overall understanding of treating MDD in autistic individuals. We will review specific medications utilized, medication dosing, duration of treatment, and aspects of drug tolerability, including whether specific drug trials were maintained long-term.</p> <hd id="AN0185099698-3">Methods</hd> <p></p> <hd id="AN0185099698-4">Procedure</hd> <p>Data for this report was gathered from a well-established patient research database (Wink et al., [<reflink idref="bib25" id="ref24">25</reflink>], [<reflink idref="bib26" id="ref25">26</reflink>]; Dominick et al., [<reflink idref="bib9" id="ref26">9</reflink>]; Adler et al., [<reflink idref="bib1" id="ref27">1</reflink>]) describing clinical medication management in 1100 autistic patients treated at an academic medical center from July 2004 to April 2012. The database was queried for autistic patients who received one or more medications targeting symptoms of depression associated with an established diagnosis of MDD.</p> <p>Descriptive statistics of demographic information and medication usage patterns were generated using the statistical software JASP (version 0.16; Amsterdam, Netherlands) to summarize the sample. Demographic variables include age, sex assigned at birth, and race. Additional variables included the presence or absence of ID, the presence or absence of Fragile X syndrome, and the specific ASD-associated diagnosis using DSM-IV-TR classification: namely, Autistic Disorder, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), or Asperger's Disorder. We elected to use data from all participants aged 6 years and older in order to better capture prescribing and medication trends during the time when autistic people most often begin treatment for their condition and comorbidities.</p> <p>For each medication associated with targeting depression, we captured the generic medication name, duration of treatment across visits, reported side effects, and CGI-I information when attributed to a specific medication. We assigned each medication to one of five drug class categories including selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), antipsychotic (AP), other serotonin modulator (OSM), and other class (OC). Patients who received more than one medication for depression at the same time were also noted. If prescription of a drug was recorded through the patient's final visit in the database, this was counted as a continued medication. If a medication was discontinued, the reason for discontinuation (if available) was noted. The mean and standard deviation for drug dosing at the last recorded visit was calculated. Infrequently prescribed medications (less than five times) are summarized in Supplementary Tables.</p> <p>Finally, we located CGI-I results as reported in the database and recorded them when associated with a medication of interest. We specifically captured the last CGI-I result mentioned for a particular medication for each patient, if applicable. Not all medications we recorded had an associated CGI-I report, which we would record as 'none.' After recording the associated CGI-I report for each patient regarding each medication of interest, we further narrowed the results down to specifically show the percentage of time a medication was associated with a CGI-I report of much or very much improved. When calculating this figure, we omitted instances where no CGI-I results were provided.</p> <hd id="AN0185099698-5">Results</hd> <p></p> <hd id="AN0185099698-6">Patient Demographics</hd> <p>Of all the patients within the 1,100-person database, One hundred and sixty six patients (15.1% of the total database sample) were prescribed at least one medication listed within the database as treating symptoms of depression. Patients were considered eligible for the study if they were prescribed medication targeting symptoms of depression at least once at any point while they were being seen at the treatment center for the duration of time that data was collected (07/2004–04/2012). The duration of time all data was collected is when psychiatrists CAE and CJM were practicing at the clinic. This group of patients served as our population of interest for this study. Our sample of 166 autistic patients had a mean age of 14.5 years (SD = 8.3 years) with an age range of 3.61–53.53 years from when they were first seen at the clinic. Patients who received medication under six years old did not have that medication information reported in order to narrow the range investigated in the analysis. However, patients who remained at the clinic after six years had all subsequent medication records retained and analyzed. We decided that for these patients, their age at the time of entering the clinic was retained for consistency across each record. Consistent with prevalence estimates of ASD, males outnumbered females in our sample at a ratio of 4.9 to 1. The sample was overwhelmingly white, with 4.4% of the patient sample being black. Sixteen (9.6%) of the patients had Fragile X syndrome-associated autism. Among specific autism-associated diagnoses made at the time using DSM-IV-TR, 71 (42.8%) were diagnosed with autistic disorder, 63 (38.0%) with PDD-NOS; and 32 (19.3%) with Asperger's disorder. Eighty (48.2%) of the patients had a comorbid diagnosis of ID. See Table 1 for summary of demographic and clinical details.</p> <p>Table 1 Characteristics of Study Sample (<emph>N</emph> = 166)</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Variable</p></th><th align="left" /><th align="left" /></tr></thead><tbody><tr><td align="left"><p>Mean Age, years ± SD</p></td><td align="left" /><td align="left"><p>14.5 ± 8.3</p></td></tr><tr><td align="left"><p>Sex (M/F)</p></td><td align="left" /><td align="left"><p>138 (83.1%) /28 (16.9%)</p></td></tr><tr><td align="left"><p>Race (% Black)</p></td><td align="left" /><td align="left"><p>7/159 (4.4%)</p></td></tr><tr><td align="left"><p>DSM-IV-TR diagnoses <italic>n</italic> (% of sample)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Autistic Disorder</p></td><td align="left" /><td align="left"><p>71 (42.8%)</p></td></tr><tr><td align="left"><p> Pervasive Developmental Disorder Not Otherwise Specified</p></td><td align="left" /><td align="left"><p>63 (38.0%)</p></td></tr><tr><td align="left"><p> Asperger's disorder</p></td><td align="left" /><td align="left"><p>32 (19.3%)</p></td></tr><tr><td align="left"><p> Any Intellectual disability</p></td><td align="left" /><td align="left"><p>80 (48.2%)</p></td></tr><tr><td align="left"><p> Fragile X syndrome-associated ASD</p></td><td align="left" /><td align="left"><p>16 (9.6%)</p></td></tr></tbody></table> </ephtml> </p> <hd id="AN0185099698-7">Medication Use Details</hd> <p>In total, 23 different medications were utilized to treat depression in our patient cohort. The use of two drugs (L-methylfolate and fluvoxamine) did not have valid data for dosage or duration of use, and therefore these medications were excluded from our final data analysis. The remaining 21 medications accounted for over 241 medication starts within the cohort. Of these, 11 medications were prescribed more than five times (see Table 2) and served as the main focus of this analysis. Among these 11 medications, five are SSRIs, two are SNRIs, one is an antipsychotic, two are OSMs, and one is from another class. Medications that were prescribed fewer than five times are summarized in supplementary tables. Twenty-six patients (15.7%) received two or more medications at one time to treat depression.</p> <p>Table 2 Details of Medication Use</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Medication</p></th><th align="left"><p>Mean final daily dose, ± SD (mg)</p></th><th align="left"><p>Mean age of drug initiation (years)</p></th><th align="left"><p>Mean duration of treatment (years)</p></th></tr></thead><tbody><tr><td align="left"><p>Sertraline (n = 70)</p></td><td char="?" align="char"><p>91.2 ± 58.3</p></td><td char="." align="char"><p>15.1</p></td><td char="." align="char"><p>1.2</p></td></tr><tr><td align="left"><p>Fluoxetine (n = 29)</p></td><td char="?" align="char"><p>27.5 ± 20.4</p></td><td char="." align="char"><p>13.8</p></td><td char="." align="char"><p>1.1</p></td></tr><tr><td align="left"><p>Mirtazapine (n = 27)</p></td><td char="?" align="char"><p>21.7 ± 13.4</p></td><td char="." align="char"><p>15.4</p></td><td char="." align="char"><p>0.7</p></td></tr><tr><td align="left"><p>Bupropion (n = 21)</p></td><td char="?" align="char"><p>241.8 ± 95.2</p></td><td char="." align="char"><p>18.3</p></td><td char="." align="char"><p>0.6</p></td></tr><tr><td align="left"><p>Citalopram (n = 19)</p></td><td char="?" align="char"><p>31.1 ± 20.0</p></td><td char="." align="char"><p>15.0</p></td><td char="." align="char"><p>1.1</p></td></tr><tr><td align="left"><p>Escitalopram (n = 14)</p></td><td char="?" align="char"><p>15.1 ± 7.8</p></td><td char="." align="char"><p>17.8</p></td><td char="." align="char"><p>0.9</p></td></tr><tr><td align="left"><p>Duloxetine (n = 14)</p></td><td char="?" align="char"><p>61.3 ± 35.7</p></td><td char="." align="char"><p>22.1</p></td><td char="." align="char"><p>0.6</p></td></tr><tr><td align="left"><p>Paroxetine (n = 13)</p></td><td char="?" align="char"><p>23.5 ± 15.1</p></td><td char="." align="char"><p>15.6</p></td><td char="." align="char"><p>0.7</p></td></tr><tr><td align="left"><p>Aripiprazole (n = 7)</p></td><td char="?" align="char"><p>10.4 ± 6.7</p></td><td char="." align="char"><p>16.2</p></td><td char="." align="char"><p>0.7</p></td></tr><tr><td align="left"><p>Venlafaxine (n = 6)</p></td><td char="?" align="char"><p>112.5 ± 99.7</p></td><td char="." align="char"><p>24.0</p></td><td char="." align="char"><p>0.8</p></td></tr><tr><td align="left"><p>Trazodone (n = 5)</p></td><td char="?" align="char"><p>170 ± 125.5</p></td><td char="." align="char"><p>18.3</p></td><td char="." align="char"><p>0.2</p></td></tr></tbody></table> </ephtml> </p> <p>The three most prescribed drugs were sertraline, fluoxetine, and mirtazapine. Sertraline was the most prescribed drug to patients (n = 70 patients receiving sertraline at some point) representing 29% of all medication uses in this sample. Patients were, on average, 15.1 years old when first prescribed sertraline, and the average final dose was 91.2 mg per day (<emph>SD</emph> = 58.3 mg). Thirty three patients continued on sertraline at the last visit (47.1% continuation rate). Fluoxetine was prescribed 29 times, the second-most prescribed drug (12% of all medication uses). The average age at start of fluoxetine treatment was 13.8 years old, and the average final recorded daily dose was 27.5 mg (<emph>SD</emph> = 20.4 mg). Sixteen patients continued on fluoxetine at the last visit (55.2% continuation rate). Mirtazapine was the third-most prescribed medication to treat depression with 27 prescription starts (nearly 11.2% of all medication uses). Patients were, on average, 15.4 years old at the beginning of their treatment with mirtazapine, and the average final dose prescribed was 21.7 mg per day (<emph>SD</emph> = 13.4 mg). Ten patients continued using mirtazapine at the final available visit (37% continuation rate).</p> <hd id="AN0185099698-8">Medication Discontinuation Details</hd> <p>Reasons for discontinuation of the 11 most commonly prescribed medications are tabulated in Table 3. Overall, "loss of effectiveness" was by far the most common reason for medication discontinuation. Other reasons for the discontinuation of a drug across the 11 drugs of interest were "aggression," "weight gain," and "sedation/tiredness." At times, no reason was given in the data for discontinuation. Among all 241 medication trials reviewed in this analysis, 119 drug treatments were continued at the final visit (49% overall drug continuation rate). For those drug trials discontinued, the average duration prior to discontinuation was 0.89 years.</p> <p>Table 3 Details of Drug Discontinuation</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Medication</p></th><th align="left"><p>Total medication starts</p></th><th align="left"><p>Continuations at last recorded follow-up visit (% of starts)</p></th><th align="left"><p>Most common reasons for drug discontinuation</p></th><th align="left"><p>n = X, (% of starts)</p></th></tr></thead><tbody><tr><td align="left"><p>Sertraline</p></td><td char="." align="char"><p>70</p></td><td align="left"><p>33 (47.1%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>6 (8.6%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Aggression</p></td><td align="left"><p>3 (4.3%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Study</p></td><td align="left"><p>2 (2.9%)</p></td></tr><tr><td align="left"><p>Fluoxetine</p></td><td char="." align="char"><p>29</p></td><td align="left"><p>16 (55.2%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>8 (27.6%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Sedation/tiredness</p></td><td align="left"><p>1 (3.43%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Tics</p></td><td align="left"><p>1 (3.43%)</p></td></tr><tr><td align="left"><p>Mirtazapine</p></td><td char="." align="char"><p>27</p></td><td align="left"><p>10 (37%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>4 (14.8%)</p></td></tr><tr><td align="left"><p>Bupropion</p></td><td char="." align="char"><p>21</p></td><td align="left"><p>14 (66.7%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>1 (4.8%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Suicidality</p></td><td align="left"><p>1 (4.8%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Weight gain</p></td><td align="left"><p>1 (4.8%)</p></td></tr><tr><td align="left"><p>Citalopram</p></td><td char="." align="char"><p>19</p></td><td align="left"><p>10 (52.6%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>3 (15.8%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Sedation/tiredness</p></td><td align="left"><p>2 (10.5%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Confusion/disorientation</p></td><td align="left"><p>1 (5.3%)</p></td></tr><tr><td align="left"><p>Escitalopram</p></td><td char="." align="char"><p>14</p></td><td align="left"><p>6 (42.9%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>5 (35.7%)</p></td></tr><tr><td align="left"><p>Duloxetine</p></td><td char="." align="char"><p>14</p></td><td align="left"><p>7 (50%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>5 (35.7%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Increased repetitive behavior</p></td><td align="left"><p>1 (7.1%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Weight gain</p></td><td align="left"><p>1 (7.1%)</p></td></tr><tr><td align="left"><p>Paroxetine</p></td><td char="." align="char"><p>13</p></td><td align="left"><p>8 (61.5%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>1 (7.7%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Study</p></td><td align="left"><p>1 (7.7%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Weight gain</p></td><td align="left"><p>1 (7.7%)</p></td></tr><tr><td align="left"><p>Aripiprazole</p></td><td char="." align="char"><p>7</p></td><td align="left"><p>3 (42.9%)</p></td><td align="left"><p>Loss of effectiveness</p></td><td align="left"><p>1 (14.3%)</p></td></tr><tr><td align="left" /><td align="left" /><td align="left" /><td align="left"><p>Sedation/tiredness</p></td><td align="left"><p>1 (14.3%)</p></td></tr><tr><td align="left"><p>Venlafaxine</p></td><td char="." align="char"><p>6</p></td><td align="left"><p>3 (50%)</p></td><td align="left"><p>Discontinued by primary care physician</p></td><td align="left"><p>1 (16.7%)</p></td></tr><tr><td align="left"><p>Trazodone</p></td><td char="." align="char"><p>5</p></td><td align="left"><p>4 (80%)</p></td><td align="left"><p>Difficulty swallowing</p></td><td align="left"><p>1 (20%)</p></td></tr></tbody></table> </ephtml> </p> <hd id="AN0185099698-9">CGI-I Details</hd> <p>CGI-I ratings across all medication entries were detailed in Table 4. Omitting cases where there was no CGI-I rating reported (indicated in the table as 'none'), "much improved" was most often reported across the cohort with 41 instances of such report. A more specific breakdown of CGI-I reports for the 11 most commonly prescribed medications can be found in Table 5. When excluding instances where no CGI-I report was provided, mirtazapine was found to have the highest overall rate of much improved and very much improved CGI-I reports. This process was repeated for the remaining medications, illustrated in Supplemental Table 3.</p> <p>Table 4 CGI-I Ratings Across all Medication Entries</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>CGI-I Rating</p></th><th align="left"><p>Number of reports</p></th></tr></thead><tbody><tr><td align="left"><p>Much Worse</p></td><td char="." align="char"><p>8</p></td></tr><tr><td align="left"><p>Minimum Worse</p></td><td char="." align="char"><p>17</p></td></tr><tr><td align="left"><p>No change</p></td><td char="." align="char"><p>27</p></td></tr><tr><td align="left"><p>Minimum</p></td><td char="." align="char"><p>35</p></td></tr><tr><td align="left"><p>Much</p></td><td char="." align="char"><p>41</p></td></tr><tr><td align="left"><p>Very much</p></td><td char="." align="char"><p>7</p></td></tr><tr><td align="left"><p>None (no score)</p></td><td char="." align="char"><p>106</p></td></tr><tr><td align="left"><p>Total</p></td><td char="." align="char"><p>241</p></td></tr></tbody></table> </ephtml> </p> <p>Table 5 CGI-I Information for Each Medication</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Medication</p></th><th align="left"><p>Much and very much improved / all CGI-I entries (excluding none) (%)</p></th></tr></thead><tbody><tr><td align="left"><p>Sertraline</p></td><td align="left"><p>13/41 (31.7%)</p></td></tr><tr><td align="left"><p>Fluoxetine</p></td><td align="left"><p>7/18 (38.9%)</p></td></tr><tr><td align="left"><p>Mirtazapine</p></td><td align="left"><p>8/19 (42.1%)</p></td></tr><tr><td align="left"><p>Bupropion</p></td><td align="left"><p>5/13 (38.5%)</p></td></tr><tr><td align="left"><p>Citalopram</p></td><td align="left"><p>2/11 (18.2%)</p></td></tr><tr><td align="left"><p>Escitalopram</p></td><td align="left"><p>2/8 (25%)</p></td></tr><tr><td align="left"><p>Duloxetine</p></td><td align="left"><p>3/6 (50%)</p></td></tr><tr><td align="left"><p>Paroxetine</p></td><td align="left"><p>3/4 (75%)</p></td></tr><tr><td align="left"><p>Aripiprazole</p></td><td align="left"><p>3/6 (50%)</p></td></tr><tr><td align="left"><p>Venlafaxine</p></td><td align="left"><p>0/2 (0%)</p></td></tr><tr><td align="left"><p>Trazodone</p></td><td align="left"><p>0/1 (0%)</p></td></tr></tbody></table> </ephtml> </p> <hd id="AN0185099698-10">Discussion</hd> <p>Here we summarize patterns of medication use for depression in a large clinical cohort of individuals with ASD. Given that no randomized controlled medication trials focused on treating depression in ASD have been published, we expected prescribing patterns to vary and likely be based on evidence-based practices in non-ASD populations (Kim & Lecavalier, [<reflink idref="bib15" id="ref28">15</reflink>]; McCracken et al., [<reflink idref="bib19" id="ref29">19</reflink>]; Pezzimenti et al., [<reflink idref="bib21" id="ref30">21</reflink>]). In our sample, we found that medications targeting depression were discontinued around half the time, usually based on perceived lack of effectiveness. This is consistent with the growing observations that treatment response to standard-of-care medications for mood disorders may be unpredictable or they may be poorly tolerated in individuals with ASD (Masi et al., [<reflink idref="bib17" id="ref31">17</reflink>]).</p> <p>Our data, like others, found a high rate of prescribing SSRIs (Esbensen et al., [<reflink idref="bib10" id="ref32">10</reflink>]). This is not unexpected, as SSRIs are commonly used to treat MDD in neurotypical populations. However, in ASD, SSRIs have been extensively studied outside of depression for core and non-core symptoms such as self-injury. A Cochrane review did not find any evidence of benefit (and potential emerging evidence of harm) for SSRI use in ASD (Williams et al., 2013). Our dataset precludes any objective analysis of clinical outcomes and does not support any clear consensus on effectiveness of any particular medication. Selective serotonin reuptake inhibitors were used for the longest duration of time in our study, with sertraline, fluoxetine, and citalopram being the only medications to be taken on average for a year or longer. On average, SSRI use in our dataset was initiated during adolescence. This pattern of use differed from that of SNRIs in our dataset, where venlafaxine, desvenlafaxine, and duloxetine were most often initially prescribed to individuals in young adulthood (range of mean ages for SNRI initiation = 19.0–24.0 years).</p> <p>Despite the pressing need, limited results from intervention research specifically targeting depression and suicidality in ASD is available. Thus, there is great interest in developing effective interventions for MDD specifically tailored to the needs of individuals with ASD.</p> <p>In our analysis, one in two drug starts to treat depression resulted in drug discontinuation, which was most often due to lack of drug effectiveness. The reasons for this are likely multifactorial and will require alternative study designs to probe further. For example, lack of effectiveness may be associated with disease severity including severity of underlying ASD or depressive symptoms. Given higher prevalence rates for depression, suicidality, and polypharmacy in ASD, the rate of treatment-resistant MDD (following the failure of standard-of-care) in ASD may exceed that of the general population (Zhdanava et al., [<reflink idref="bib27" id="ref33">27</reflink>]). Our results may also ultimately underreport the rate of drug discontinuation, given the finite time frame and assumption that medications were continued if found on the final recorded visit in our dataset.</p> <p>Our results also indicate that when recorded, the majority of participants saw CGI-I ratings of 'minimum,' 'much,' or 'very much.' This indicates a slight to significant positive clinical result for many participants being treated with medication targeting anti-depression by the end of their time on the medication or in treatment. These results suggest that it is more likely to see clinical improvement for those receiving anti-depression medications in this population. However, the lack of recorded CGI-I results for 104 participants also indicate that further research on this subject area should be conducted to verify that this pattern of CGI-I results is retained in a larger sample size, or between multiple samples.</p> <p>There are several limitations to our report in addition to those commonly associated with retrospective studies. First, we did not attempt to focus on treatment indications beyond depression within our cohort. For example, participants may have suffered from co-occurring anxiety disorders (reported to occur in 40% of autistic youth; White et al., [<reflink idref="bib24" id="ref34">24</reflink>]), which would confound the interpretation of medication use. We may infer, for example, that the high frequency use of the antidepressant mirtazapine may reflect prescribing patterns to target specific use for anxiety in ASD (McDougle et al., [<reflink idref="bib20" id="ref35">20</reflink>]). It is also possible that mirtazapine use could have been preferred in subjects with depressive symptoms and associated insomnia given the potential benefits of this drug for sleep disturbance.</p> <p>As mentioned earlier, the dataset does not link drug discontinuation with clinical outcomes. Thus, we are unable to assess if medication use led to a remission of symptoms of depression. Though lack of effectiveness was clearly stated as a reason for discontinuation, our data set did not allow us to determine if symptom remission was a reason for treatment discontinuation. While the dataset was collected at a research-oriented tertiary care autism center, the diagnoses of ASD represent clinical opinions of the prescribers based upon DSM-IV-TR criteria. These DSM-IV-TR diagnoses have not been reevaluated to account for changes made to diagnostic criteria for ASD in the updated DSM-V-TR. It is unknown if diagnoses were externally validated with diagnostic instruments such as the Autism Diagnostic Observation Schedule (ADOS).</p> <p>There is a clear need for more rigorous studies of depression in this patient population. While this may include prospective drug trials with rigorous patient characterization and use of validated outcome measures, it is also important to evaluate non-drug therapies for this indication including various psychotherapies and neuromodulation, among other modalities. Given our report, it appears that half of the time a medication is started targeting depression in autistic patients, the drug will be discontinued, most often due to lack of effectiveness. Due to the substantial burden depression places on the individual, family, and community, the need to establish more effective and well-studied treatments for depression in this population are required.</p> <hd id="AN0185099698-11">Funding</hd> <p>No external funding was utilized for this study.</p> <hd id="AN0185099698-12">Declarations</hd> <p></p> <hd id="AN0185099698-13">Conflicts of Interest</hd> <p>All authors report no conflicts of interest specifically related to this work.</p> <hd id="AN0185099698-14">Electronic Supplementary Material</hd> <p>Below is the link to the electronic supplementary material.</p> <p>Graph: Supplementary Material 1</p> <p>Graph: Supplementary Material 2</p> <p>Graph: Supplementary Material 3</p> <hd id="AN0185099698-15">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0185099698-16"> <title> References </title> <blist> <bibl id="bib1" idref="ref27" type="bt">1</bibl> <bibtext> Adler BA, Wink LK, Early M, Shaffer R, Minshawi N, McDougle CJ, Erickson CA. 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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Riley+A%2E+Argonis%22">Riley A. Argonis</searchLink><br /><searchLink fieldCode="AR" term="%22Ernest+V%2E+Pedapati%22">Ernest V. Pedapati</searchLink><br /><searchLink fieldCode="AR" term="%22Kelli+C%2E+Dominick%22">Kelli C. Dominick</searchLink><br /><searchLink fieldCode="AR" term="%22Katherine+Harris%22">Katherine Harris</searchLink><br /><searchLink fieldCode="AR" term="%22Martine+Lamy%22">Martine Lamy</searchLink><br /><searchLink fieldCode="AR" term="%22Cara+Fosdick%22">Cara Fosdick</searchLink><br /><searchLink fieldCode="AR" term="%22Lauren+Schmitt%22">Lauren Schmitt</searchLink><br /><searchLink fieldCode="AR" term="%22Rebecca+C%2E+Shaffer%22">Rebecca C. Shaffer</searchLink><br /><searchLink fieldCode="AR" term="%22Elizabeth+Smith%22">Elizabeth Smith</searchLink><br /><searchLink fieldCode="AR" term="%22Meredith+Will%22">Meredith Will</searchLink><br /><searchLink fieldCode="AR" term="%22Christopher+J%2E+McDougle%22">Christopher J. McDougle</searchLink><br /><searchLink fieldCode="AR" term="%22Craig+A%2E+Erickson%22">Craig A. Erickson</searchLink> (ORCID <externalLink term="http://orcid.org/0000-0003-4512-398X">0000-0003-4512-398X</externalLink>)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="SO" term="%22Journal+of+Autism+and+Developmental+Disorders%22"><i>Journal of Autism and Developmental Disorders</i></searchLink>. 2025 55(6):1969-1975.
– Name: Avail
  Label: Availability
  Group: Avail
  Data: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
– Name: PeerReviewed
  Label: Peer Reviewed
  Group: SrcInfo
  Data: Y
– Name: Pages
  Label: Page Count
  Group: Src
  Data: 7
– Name: DatePubCY
  Label: Publication Date
  Group: Date
  Data: 2025
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Drug+Therapy%22">Drug Therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Depression+%28Psychology%29%22">Depression (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+Spectrum+Disorders%22">Autism Spectrum Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Patients%22">Patients</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms+%28Individual+Disorders%29%22">Symptoms (Individual Disorders)</searchLink><br /><searchLink fieldCode="DE" term="%22Comorbidity%22">Comorbidity</searchLink><br /><searchLink fieldCode="DE" term="%22Program+Termination%22">Program Termination</searchLink><br /><searchLink fieldCode="DE" term="%22Program+Effectiveness%22">Program Effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Intervention%22">Intervention</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-023-06126-z
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257<br />1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction: Depression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. Purpose: The purpose of this study is to discover prescribing patterns for individuals with MDD and ASD during this time period (2004-2012) to inform current and future prescribing practices with historical data. Methods: Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 166 individuals with ASD (mean age 14.5 ± 8.3 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Results: Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 241 drug starts, 123 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ± 0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. Conclusion: This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.
– Name: AbstractInfo
  Label: Abstractor
  Group: Ab
  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2025
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ1470844
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1470844
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s10803-023-06126-z
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 7
        StartPage: 1969
    Subjects:
      – SubjectFull: Drug Therapy
        Type: general
      – SubjectFull: Depression (Psychology)
        Type: general
      – SubjectFull: Autism Spectrum Disorders
        Type: general
      – SubjectFull: Patients
        Type: general
      – SubjectFull: Symptoms (Individual Disorders)
        Type: general
      – SubjectFull: Comorbidity
        Type: general
      – SubjectFull: Program Termination
        Type: general
      – SubjectFull: Program Effectiveness
        Type: general
      – SubjectFull: Intervention
        Type: general
    Titles:
      – TitleFull: Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Riley A. Argonis
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            NameFull: Ernest V. Pedapati
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            NameFull: Kelli C. Dominick
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            NameFull: Katherine Harris
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            NameFull: Martine Lamy
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            NameFull: Cara Fosdick
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            NameFull: Lauren Schmitt
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            NameFull: Meredith Will
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            NameFull: Christopher J. McDougle
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            NameFull: Craig A. Erickson
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          Dates:
            – D: 01
              M: 06
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 0162-3257
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              Value: 1573-3432
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            – Type: volume
              Value: 55
            – Type: issue
              Value: 6
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            – TitleFull: Journal of Autism and Developmental Disorders
              Type: main
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