Patient journey of civilian adults diagnosed with posttraumatic stress disorder—A chart review study

Abstract

Objective

To assess the journey of individuals from experiencing a traumatic event through onset of symptoms, diagnosis, and treatment of posttraumatic stress disorder (PTSD).

Methods

Patient- and psychiatrist-level data was collected (02/2022–05/2022) from psychiatrists who treated ≥1 civilian adult diagnosed with PTSD. Eligible charts covered civilian adults diagnosed with PTSD (2016–2020), receiving ≥1 PTSD-related treatment (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical antipsychotics [AAs]), and having ≥1 medical visit in the last 12 months. Collected information included clinical and treatment characteristics surrounding the PTSD diagnosis.

Results

A total of 273 psychiatrists contributed data on 687 patients with PTSD (average age 36.1; 60.4% female). On average, the traumatic event and symptom onset occurred 8.7 years and 6.5 years prior to PTSD diagnosis, respectively. In the 6 months before diagnosis, 88.9% of patients had received a PTSD-related treatment. At time of diagnosis, 87.8% of patients had intrusion symptoms and 78.9% had alterations in cognition/mood; 41.2% had depressive disorder and 38.7% had anxiety. Diagnosis prompted treatment changes for 79.3% of patients, receiving treatment within 1.9 months on average, often with a first-line SSRI as either monotherapy (52.8%) or combination (24.9%). At the end of the 24-month study period, 34.4% of patients achieved psychiatrist-recorded remission. A total of 23.0% of psychiatrists expressed dissatisfaction with approved PTSD treatments, with 88.3% at least somewhat likely to prescribe AAs despite lack of FDA approval.

Conclusion

PTSD presents heterogeneously, with an extensive journey from trauma to diagnosis with low remission rates and limited treatment options.

Keywords:

• Adults
• posttraumatic stress disorder
• psychiatrist
• symptoms
• treatment

1. Introduction

Posttraumatic stress disorder (PTSD) is a complex and debilitating neuropsychiatric disorder that can occur in individuals following personal or indirect exposure to traumatic events, such as actual or threatened death, physical or sexual abuse, combat, serious accidents, and natural disasters¹. Manifestation of PTSD is heterogeneous and includes four core symptom clusters: intrusion symptoms such as recurring unwanted traumatic memories, persistent avoidance of stimuli associated with the traumatic event, negative alterations in cognition and mood, and alterations in arousal and reactivity^1,2. Posttraumatic reactions of individuals vary widely and may range from resilient to those that are major and chronic³.

PTSD inflicts a substantial humanistic and economic burden. The condition is associated with frequent psychiatric and somatic comorbidities (e.g. depression, anxiety, suicidality, substance use disorder, pain, sleep disturbances), marked functional disability, psychosocial dysfunction, premature death, and increased medical and mental health service use^4,5. The annual excess economic burden associated with PTSD among adults in the United States (U.S.) has been estimated at $232 billion in 2018, with over 80% of the burden borne by civilian adults, primarily in direct healthcare and unemployment costs⁶.

In the U.S. general population, the lifetime prevalence of PTSD is estimated at 6.1%, with higher prevalence rates among women, younger adults, and those with lower education and income⁷. Nonetheless, it has been recognized that PTSD is frequently undiagnosed or misdiagnosed in both primary^8,9 and secondary care settings¹⁰ for patient-driven reasons (e.g. hesitation to disclose trauma and seek care, fear of repercussions) or physician-driven reasons (e.g. lack of recognition of PTSD symptoms that overlap with other psychiatric comorbidities, reluctance to ask patients about trauma) ^11–13. Importantly, a prior study has shown that undiagnosed individuals may experience comorbidities and use healthcare services (e.g. inpatient admissions) at levels that are similar to that of patients with diagnosed PTSD¹⁴, suggesting that improved detection of PTSD to prompt a formal diagnosis of PTSD may be important to facilitate the initiation of proper PTSD-targeted treatment.

For patients with diagnosed PTSD, most evidence-based guidelines recommend psychotherapy, including both general cognitive behavioral therapy and trauma-focused psychotherapies, as the cornerstone treatment^15–17. Pharmacological treatments are also recommended¹⁶, and real-world studies have suggested that pharmacological treatments may be used to manage more severe PTSD symptoms and PTSD-related comorbidities in clinical practice^18,19; but with limited approved options, symptoms can be difficult to manage. The American Psychological Association recommends four agents for the treatment of PTSD, including three selective serotonin reuptake inhibitors (SSRIs), namely fluoxetine, paroxetine, and sertraline, and one serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine³. Of these therapies, only paroxetine and sertraline are currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of PTSD; however, response rates to SSRIs rarely exceeds 60%²⁰. The National Institute for Health and Care Excellence (NICE) and International Society for Traumatic Stress Studies (ISTSS) guidelines further recommend off-label use of antipsychotic medication, particularly quetiapine²¹, as a second-line treatment. Prior studies have also noted some evidence of the effectiveness of agents such as prazosin and risperidone when added to an SSRI or SNRI^22–24.

The diagnosis and management of PTSD may be more challenging among civilians compared to veterans, given less access to dedicated screening and care programs compared to those provided by the Veterans Health Administration^25,26. To date, research on general civilian adults with PTSD remains more limited compared to other commonly identified subgroups of individuals with PTSD such as veterans or children^27–29, and there is scarce literature characterizing the journey of adult civilians with PTSD in the U.S., particularly of patients with more severe symptoms who may require pharmacological treatment.

Knowledge on the patient journey from trauma exposure to pre-diagnosis disease and treatment history and to post-diagnosis clinical trajectory may help identify unmet needs and areas for interventions to reduce PTSD burden, which could be particularly crucial for patients with more severe symptoms requiring pharmacological treatment. Therefore, the current study aimed to add to the scarce literature on PTSD in civilian adults and provide a comprehensive description of characteristics and treatment patterns of U.S. civilian adults diagnosed with, and pharmacologically treated for, PTSD by a psychiatrist. Medical charts were abstracted by psychiatrists, whose clinical practices and perspectives on civilian PTSD management, including potential reasons for not documenting a PTSD diagnosis, were described. Furthermore, this study sought to understand the civilian adult patient journey before and after receiving a PTSD diagnosis to identify the timing of key clinical milestones as well as potential diagnosis and treatment delays, treatment patterns, and their impact on patients’ clinical trajectories.

2. Methods

2.1. Participants and procedure

This descriptive retrospective panel-based chart review study analyzed anonymized data obtained through an online medical chart abstraction conducted from February to May 2022. Psychiatrists in the U.S. who treat patients with PTSD were recruited among one of the largest panels of healthcare providers in the U.S., M3 Global Research, which is representative of the American Medical Association Masterfile. An email invitation was sent to eligible psychiatrists who met the following eligibility criteria: (1) practicing psychiatry in the U.S.; (2) had diagnosed and treated at least one adult patient with PTSD; (3) had access to detailed patient medical charts, including the traumatic event(s), diagnosis, treatments received, treatment patterns, and reasons for treatment changes for at least 24 months following the PTSD diagnosis; and (4) were willing to provide information from at least one patient’s medical chart. Eligible psychiatrists who were willing to participate provided their written informed consent. Participating psychiatrists were asked to provide patient-level clinical information on 1–5 patients with PTSD via an electronic case report form (eCRF) designed specifically for this study. To minimize selection bias, psychiatrists were asked to compile a list of patients who met the selection criteria and enter information for an individual patient whose last name began with a letter randomly generated by the survey.

The collected data did not include any patient-identifying information. This study was conducted in accordance with the applicable ethical regulations; it was exempt from full review and approved through an expedited review by the Western Copernicus Group Institutional Review Board (work order: 1-1485181-1).

To capture a population of treated patients with PTSD with the goal of assessing treatment patterns, patients meeting the following eligibility criteria were included in the study: (1) at least 18 years of age at the time of the PTSD diagnosis; (2) not an active military member or a veteran, and without military healthcare coverage (i.e. civilian); (3) treated with at least one PTSD-related therapeutic agent (i.e. SSRI, SNRI, atypical antipsychotic [AA]) on or following the PTSD diagnosis; and (4) had at least one recorded visit with the participating psychiatrist in the 24 months following the PTSD diagnosis. SSRIs, SNRIs, and AAs were selected to determine whether patients were treated, as these categories broadly capture commonly used therapies for PTSD, in accordance with treatment guidelines. Information on augmenting agents, such as benzodiazepines and anti-hypertensive agents, was also collected^3,22–24.

The study index date was the date of the formal PTSD diagnosis, the pre-diagnosis period was the 6-month period prior to the index date, and the post-diagnosis period was the 24-month period following the index date.

2.2. Measures

Psychiatrist characteristics, including demographics (e.g. age, gender), clinical practice characteristics (e.g. practice type, size, region), and reasons for documenting and not documenting a PTSD diagnosis were summarized.

Data collected from the patient chart review included demographics on the index date, information about the traumatic event(s), and clinical and disease characteristics (e.g. comorbidities, symptoms, physician-reported PTSD severity). Treatment characteristics were captured as nonpharmacological treatments (e.g. trauma-focused psychotherapies, non-trauma-focused psychotherapies), PTSD-related therapeutic agents (SSRIs, SNRIs, AAs), and PTSD-related augmenting agents that may be used to treat symptoms of PTSD (e.g. benzodiazepines, antihypertensives). Psychiatrists were asked to report reasons for initiating treatments, the direct treatment changes occurring following the PTSD diagnosis, and whether remission from PTSD (i.e. patients no longer met the clinical criteria for PTSD) had occurred by the end of the 24-month post-diagnosis period. Patient journey was assessed by capturing the timing of the traumatic event(s), PTSD symptom presentation, PTSD diagnosis, treatment initiation, and remission, as available.

2.3. Data analysis

Means, medians, interquartile ranges, and standard deviations were reported for continuous variables. Counts and percentages were reported for categorical variables.

All statistical analyses were performed using the Statistical Analysis System (SAS) Enterprise Guide, Version 7.1 (SAS, Cary, North Carolina, U.S.) and R 4.1.0 (R Core Team, 2021). Sankey plots were generated to visualize treatment sequences: the nodes represent treatment regimens during the 6-month pre-diagnosis period, as of the index date, and up to 3 lines of therapy in the 24-month post-diagnosis period; the links represent the proportion of patients receiving the line of therapy at each node.

3. Results

3.1. Psychiatrist characteristics

A total of 273 psychiatrists treating adults with PTSD participated in the study (Table 1). The majority were 35–64 years old (75.8%), male (60.1%), practiced general psychiatry (93.0%), and were in private/community practice (67.8%). Participating psychiatrists followed an average of 396 civilian adult patients annually, 25% of which were estimated to have PTSD. Over half of participating psychiatrists (51.6%) reported that 50–100% of their civilian adult patients with PTSD had chronic PTSD (defined as PTSD symptoms persisting for at least 2 years). The average number of patient reviews contributed per psychiatrist was 2.5, with 41.8% of psychiatrists contributing data from a single patient chart.

Table 1. Psychiatrist and practice setting characteristics.

	Overall N = 273
Demographics and medical experience^a
Age (years), n (%)
≤34	45 (16.5%)
35–44	99 (36.3%)
45–54	62 (22.7%)
55–64	46 (16.8%)
≥65	21 (7.7%)
Gender, n (%)
Male	164 (60.1%)
Female	100 (36.6%)
Prefer not to answer	9 (3.3%)
Specialty^b,c, n (%)
General psychiatry	254 (93.0%)
Addiction psychiatry	16 (5.9%)
Sleep medicine	1 (0.4%)
Other	2 (0.7%)
Number of years in practice, n (%)
0–5	60 (22.0%)
6–10	53 (19.4%)
11–15	63 (23.1%)
16–20	35 (12.8%)
21–25	31 (11.4%)
≥26	31 (11.4%)
Practice setting
Practice type, n (%)
Private/community practice	185 (67.8%)
Institutional	64 (23.4%)
Institutional non-academic	18 (6.6%)
Other	6 (2.2%)
Number of civilian adult patients followed on an annual basis, mean ± SD [median]	395.7 ± 197.8 [400.0]
Number of civilian adult patients with PTSD followed annually, mean ± SD [median]	100.3 ± 94.2 [75.0]
Proportion of civilian adult patients with PTSD followed with chronic PTSD^d, n (%)
0%–24%	34 (12.5%)
25%–49%	98 (35.9%)
50%–74%	95 (34.8%)
75%–100%	46 (16.8%)
Number of patient charts contributed per physician, mean ± SD [median]	2.5 ± 1.6 [2.0]
1, n (%)	114 (41.8%)
2, n (%)	47 (17.2%)
≥3, n (%)	112 (41.0%)

Abbreviations. N, number; PTSD, posttraumatic stress disorder; SD, standard deviation.

^a Psychiatrist and practice setting characteristics were measured at the time of data collection.

^b More than one option could be selected (i.e. not mutually exclusive).

^c Source: American Board of Medical Specialties, https://www.abms.org/board/american-board-of-psychiatry-neurology/.

^d Chronic PTSD was defined as patients with PTSD symptoms persisting for at least 2 years for alignment with the data collection period that required psychiatrists to enter data on patients for 2 years following diagnosis (i.e. patients who still had symptoms 2 years following the diagnosis at the end of the data collection period would be considered to have chronic PTSD).

3.2. Psychiatrists’ reasons on documenting a diagnosis of PTSD

The most common reasons for not documenting a diagnosis of PTSD were symptoms remained sub-threshold (45.8%), at least partial symptom management by treatment of a comorbid condition (21.6%), and social or legal concerns (19.0%). The most frequent reasons given for documenting a diagnosis of PTSD were to facilitate targeted PTSD symptom management (92.7%), patient acceptance of their condition (58.2%), and PTSD-specific treatment access (56.0%; Table 2).

Table 2. Psychiatrists’ reasons on documenting a diagnosis of PTSD^a.

	N = 273
Reasons to document a diagnosis of PTSD in addition to completing standard diagnostic practices^b, n (%)
Facilitate targeted PTSD symptom management	253 (92.7%)
Facilitate patient acceptance of their condition	159 (58.2%)
Facilitate PTSD-specific treatment access (e.g. reimbursement)	153 (56.0%)
Facilitate access to disability programs (e.g. social security payments, short/long-term disability)	92 (33.7%)
Reduce social stigma/raise awareness of the condition	92 (33.7%)
Facilitate family/friend/employer acceptance of patient condition	76 (27.8%)
Other^c	5 (1.8%)
None of the above	5 (1.8%)
Potential reasons to not document a diagnosis of PTSD^b, n (%)
Symptoms are sub-threshold	125 (45.8%)
At least partial symptom management by treatment of a comorbid condition	59 (21.6%)
Social/legal concerns (e.g. custody arrangements, secondary gain)	52 (19.0%)
Sufficient treatment access without a diagnosis	38 (13.9%)
Request by patient/family	38 (13.9%)
Concern of social stigma	31 (11.4%)
Financial/employment concerns	28 (10.3%)
Other^c	2 (0.7%)
None of the above	83 (30.4%)

Abbreviations. N, number; PTSD, posttraumatic stress disorder; SD, standard deviation.

^a Measured at the time of data collection.

^b More than one option could be selected (i.e. not mutually exclusive).

^c Other responses were collected as free-text entry but were not analyzed.

3.3. Patient characteristics at time of PTSD diagnosis

A total of 687 civilian adults with PTSD were included in the study (Table 3). As of the index date, patients were on average 36.1 years old, and the majority of patients were female (60.4%), white (64.5%), and had commercial/private insurance (58.8%). Almost half of patients with PTSD (43.8%) experienced a single traumatic event. The vast majority of patients (84.7%) experienced the traumatic event directly, 10.6% witnessed an event, and 2.5% learned that it had happened to a close family member or friend. The most frequently reported traumatic event(s) included interpersonal violence (48.3%), sexual relationship violence (39.4%), and interpersonal-network traumatic experience (14.0%).

Table 3. Patient demographic and clinical characteristics.

Patient characteristics	Overall
Number of patients, N	N = 687
Demographic characteristics at the time of PTSD diagnosis
Age, mean ± SD [median]	36.1 ± 13.0 [34.0]
18–24, n (%)	144 (21.0%)
25–34, n (%)	204 (29.7%)
35–44, n (%)	179 (26.1%)
45–54, n (%)	84 (12.2%)
55–64, n (%)	59 (8.6%)
≥65, n (%)	17 (2.5%)
Gender, n (%)
Female	415 (60.4%)
Male	262 (38.1%)
Other/nonbinary	9 (1.3%)
Prefer not to answer	1 (0.1%)
Race^a, n (%)
White	443 (64.5%)
Black or African American	142 (20.7%)
Asian	47 (6.8%)
American Indian or Alaskan Native	18 (2.6%)
Native Hawaiian or Other Pacific Islander	3 (0.4%)
Other	34 (4.9%)
Unknown	10 (1.5%)
U.S. Region of residence, n (%)
South	194 (28.2%)
West	189 (27.5%)
Northeast	153 (22.3%)
Midwest	147 (21.4%)
U.S. Territory	2 (0.3%)
Unknown	2 (0.3%)
Healthcare coverage type^a, n (%)
Commercial/private insurance	404 (58.8%)
Medicaid	203 (29.5%)
Medicare	55 (8.0%)
Other	3 (0.4%)
No insurance	25 (3.6%)
Unknown	21 (3.1%)
Clinical and disease characteristics
Type of traumatic event, n (%)
Single event	301 (43.8%)
Multiple events	261 (38.0%)
Continuous traumatic exposure	120 (17.5%)
Unknown	5 (0.7%)
Nature of traumatic event^a^,^b, n (%)
Interpersonal violence (e.g. childhood physical abuse, physical assault)	332 (48.3%)
Sexual relationship violence (e.g. rape, childhood sexual abuse, intimate partner violence)	271 (39.4%)
Interpersonal-network traumatic experiences (e.g. unexpected death of a loved one)	96 (14.0%)
Work-related traumatic events (e.g. paramedics or police officers)	66 (9.6%)
Combat (e.g. witnessing or causing injury, exposure to combat)	44 (6.4%)
Mass conflict and displacement (e.g. refugees and other conflict-affect individuals)	24 (3.5%)
Other^c (e.g. natural disaster, fire/explosion)	40 (5.8%)
Unknown	4 (0.6%)
Exposure to traumatic event, n (%)
Directly experienced the traumatic event	582 (84.7%)
Witnessed, in person, the traumatic event as it occurred to others	73 (10.6%)
Learned that the traumatic event occurred to a close family member or close friend	17 (2.5%)
Experienced repeated or extreme exposure to aversive details of the traumatic event	11 (1.6%)
Other^c	0 (0.0%)
Unknown	4 (0.6%)
PTSD symptom presentation^a^,d,e, n (%)
Intrusion symptoms	603 (87.8%)
Avoidance of stimuli associated with the traumatic event(s)	535 (77.9%)
Alterations in cognition and mood	542 (78.9%)
Alterations in arousal and reactivity	525 (76.4%)
PTSD disease severity^f^,^g, n (%)
Mild	35 (5.1%)
Moderate	314 (45.7%)
Severe	310 (45.1%)
Extreme	27 (3.9%)
Unknown	1 (0.1%)
Use of formal PTSD diagnostic tools^a, n (%)
General clinical interview	619 (90.1%)
Self-report measures (e.g. DTS, IES-R, PCL-5)	167 (24.3%)
Structured clinical interviews (e.g. CAPS-5, PSS-I-5)	109 (15.9%)
Measurement-based care	96 (14.0%)
Other^c	2 (0.3%)
PTSD subtype^a, n (%)
With dissociative symptoms	123 (17.9%)
With delayed expression	97 (14.1%)
No subtype identified	461 (67.1%)
Unknown	25 (3.6%)
Most frequent comorbidities^a^,^f, n (%)
Depressive disorder	283 (41.2%)
Anxiety disorder	266 (38.7%)
Insomnia	182 (26.5%)
Substance use disorder	118 (17.2%)
Suicidal ideation	87 (12.7%)
Remission from PTSD^h, n (%)
Yes	236 (34.4%)
No	438 (63.8%)
Unknown	13 (1.9%)

Abbreviations. N, number; PTSD, posttraumatic stress disorder; SD, standard deviation.

^a More than one option could be selected (i.e. not mutually exclusive).

^b Type of traumatic event was defined as the traumatic event most likely to be associated with the PTSD diagnosis as per the clinician opinion.

^c Other responses were collected as free-text entry but were not analyzed.

^d Based on American Psychiatric Pub (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

^e Due to updates in the survey, 9 patient charts did not have full symptoms information and were excluded from these counts.

^f Measured at the time of PTSD diagnosis.

^g Reported as physician-reported disease severity if formal assessment tools were not used.

^h Reported as physician-reported remission from PTSD (i.e. patient no longer met the clinical criteria for PTSD) as of the end of the 24-month period following and including the patient’s first PTSD diagnosis.

At the time of PTSD diagnosis, patients presented with a range of PTSD-related symptoms, including intrusion symptoms (87.8%), alterations in cognition and mood (78.9%), avoidance of stimuli associated with the traumatic event(s) (77.9%), and alterations in arousal and reactivity (76.4%). Over 40% of patients had psychiatric comorbidities as of the index date, the most frequent being depressive disorder (41.2%), anxiety disorder (38.7%), insomnia (26.5%), substance use disorder (17.2%), and suicidal ideation (12.7%).

3.4. Patient journey

The overall patient journey depicting the mean times between key clinical milestones, both before and after PTSD diagnosis, is presented in Figure 1. On average, the time from trauma to symptom presentation was 2.2 years, a formal PTSD diagnosis was documented on average 6.5 years following symptom onset, pharmacological treatment was prescribed within an average of 1.9 months of the PTSD diagnosis, and of the 34.4% of patients who achieved remission, remission occurred within an average of 13.6 months from the diagnosis.

Figure 1. Description of patient journey among adults with PTSD^a. Abbreviations. N, number; PTSD, posttraumatic stress disorder. ^aAverage time from PTSD diagnosis to reported trauma, symptom presentation, pharmacological treatment prescription, and remission, as applicable. All average time points are out of patients with psychiatrist reported dates of events. Average age of the patient at each time point is also reported. ^bReported for charts where the exact time from traumatic event or symptom presentation to PTSD diagnosis was collected. ^cThe origin is set to the time of PTSD diagnosis. The horizontal axis is presented in years for the pre-diagnosis period and months for the post-diagnosis period.

3.5. Impact of PTSD diagnosis on treatment and disease characteristics

The treatment characteristics as of the index date and in the 6-month pre-diagnosis period are presented in Table 4. In the 6 months prior to a formal PTSD diagnosis, half of patients (50.1%) received nonpharmacological therapy, including trauma-focused psychotherapy (27.5%) and non-trauma-focused psychotherapy (28.5%). Most patients (85.6%) received treatments commonly used for PTSD (i.e. an SSRI, SNRI, and/or AA) prior to receiving a PTSD diagnosis, including 48.0% who received an SSRI in monotherapy and 23.6% who received an AA in combination with another PTSD-related agent (AA combo; Figure 2). In addition to the PTSD-related agents, 52.8% of patients had also received a PTSD-related augmenting agent prior to the diagnosis, including benzodiazepines/sedatives (29.5%), anti-hypertensive agents (18.5%), and other antidepressants (i.e. other than SSRI/SNRI; 11.8%).

Figure 2. Sankey diagram of PTSD-related pharmacological treatment sequences, with nodes representing the proportion of patients receiving each regimen at key stages from 6 months pre-PTSD diagnosis to 24 months post-PTSD^a. Abbreviations. AA, atypical antipsychotic; N, number; PTSD, posttraumatic stress disorder; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor. ^aThe analysis was conducted at the agent level, but reported at the class level (i.e. change within class is a continuation, change to another class is a switch). ^bAA combo includes all treatment regimens with an AA and ≥1 other treatment class (i.e. SSRI or SNRI). Figure can be read left to right starting with treatment received prior to the PTSD diagnosis spanning to the right for up to 3 regimens following the PTSD diagnosis, as applicable. Width of each connecting band is proportional to the quantity represented.

Table 4. Impact of PTSD diagnosis on treatment characteristics.

Patient characteristics	Overall
Number of patients, N	N = 687
Treatment characteristics during the 6-month pre-PTSD diagnosis period, n (%)
PTSD-related treatment received^a
Non-pharmacological treatment	344 (50.1%)
Trauma-focused psychotherapy	189 (27.5%)
Non-trauma-focused psychotherapy	196 (28.5%)
Pharmacological treatment
PTSD-related therapeutic agent (SSRI, AA, SNRI)	588 (85.6%)
PTSD-related augmenting agents	363 (52.8%)
Treatment characteristics during the 24-month post-PTSD diagnosis period, n (%)
Number of distinct PTSD-related agents received, n (%)
No PTSD-related agents	―
1 PTSD-related agent	283 (41.2%)
2 PTSD-related agents	277 (40.3%)
≥ 3 PTSD-related agents	127 (18.5%)
Impact of PTSD diagnosis on treatment^a, n (%)
Diagnosis led to a non-pharmacological treatment change	226 (32.9%)
Newly prescribed a non-pharmacological treatment	178 (25.9%)
Trauma-focused psychotherapy	161 (23.4%)
Non-trauma-focused psychotherapy	69 (10.0%)
Other	18 (2.6%)
Added a non-pharmacological treatment	64 (9.3%)
Trauma-focused psychotherapy	54 (7.9%)
Non-trauma-focused psychotherapy	21 (3.1%)
Other	7 (1.0%)
Switched a non-pharmacological treatment	21 (3.1%)
Trauma-focused psychotherapy	18 (2.6%)
Non-trauma-focused psychotherapy	6 (0.9%)
Other	1 (0.1%)
Discontinued/dropped a non-pharmacological treatment	3 (0.4%)
Trauma-focused psychotherapy	1 (0.1%)
Non-trauma-focused psychotherapy	1 (0.1%)
Other	1 (0.1%)
Diagnosis led to a pharmacological treatment change (physician-reported)^b	473 (68.9%)
Diagnosis led to a PTSD-related treatment change (observed)^c	306 (44.5%)
Diagnosis did not lead to a treatment change (non-pharmacological or pharmacological)	142 (20.7%)
Number of treatment regimens of PTSD-related therapeutic agents received, mean ± SD [median]	1.6 ± 1.2 [1.0]
First regimen received, n (%)
Unplanned dose modifications of PTSD-related therapeutic agents during regimen^d
Dose increases (excluding initiation titration)	346 (50.4%)
Dose decreases	41 (6.0%)
No unplanned dose modification	300 (43.7%)
In combination with other PTSD-related treatment
Augmenting agents	318 (46.3%)
Non-pharmacological therapy	198 (28.8%)
Among patients with a treatment change
Reason for treatment change following PTSD diagnosis^a, n (%)
Inadequate/suboptimal management of PTSD symptoms with prior treatment	354 (51.5%)
Initiated targeted PTSD symptom management	211 (30.7%)
Patient/patient’s family became more accepting of their condition and potential treatment	75 (10.9%)
Access to specific PTSD treatments became available (e.g. reimbursement)	68 (9.9%)
Issues with safety/tolerability with prior treatment	55 (8.0%)
Changed prior treatment for a previously misdiagnosed condition	55 (8.0%)
Patient’s financial or employment situation changed	26 (3.8%)
Some cost barriers were removed (e.g. out-of-pocket costs, insurance coverage)	21 (3.1%)
Access to disability programs became available (e.g. social security payments)	19 (2.8%)
Patient’s social/legal situation changed (e.g. custody arrangements)	16 (2.3%)
Other patient-driven reason^e	5 (0.7%)
Other psychiatrist-driven reason^e	1 (0.1%)

Abbreviations. AA, atypical antipsychotic; N, number; PTSD, posttraumatic stress disorder; SD, standard deviation; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

^aMore than one option could be selected (i.e. not mutually exclusive).

^bThis result was pulled directly from a question asked to physicians: whether there was there a change in treatment as a result of the PTSD diagnosis. It did not specify a change in SSRI, SNRI, or AA specifically, rather an overall change.

^cAmong charts where the psychiatrist reported a treatment change: A treatment change algorithm was used to flag changes in treatment specific to SSRI, SNRI, or AA agents as observed in the regimens provided by physicians. The algorithm was defined as follows: newly added was where a patient had no treatment at their diagnosis, and subsequently initiated at least one SSRI, SNRI, or AA agent; add/drop was where a patient was already taking at least one such agent, and either added at least one or removed at least one subsequent to diagnosis; switch was where a patient was taking at least one such agent, and swapped one or more of these agents for a different agent in any class (SSRI, SNRI, or AA).

^dNumber of unplanned dose changes of PTSD-related agents was measured as the number of dose changes of any AAs, SSRIs, or SNRIs during the post-diagnosis period, defined as the 24-month period following and including the patients first PTSD diagnosis, which were not initially planned at the start of the treatment regimen (e.g. dose ramp-up, titration).

^e Other responses were collected as free-text entry but were not analyzed.

The treatment characteristics during the 24-month post-diagnosis period are presented in Table 4. The majority of patients (58.8%) received at least 2 distinct PTSD-related agents within 24 months of diagnosis, with an average number of 1.6 distinct lines of therapy. Psychiatrists reported that the formal PTSD diagnosis led to a nonpharmacological treatment change in 32.9% of patients, most commonly to prescribe a new trauma-focused therapy (71.2%), and a pharmacological treatment change in 68.9% of patients. As first-line therapy post-PTSD diagnosis, 52.8% of patients received an SSRI in monotherapy, 9.0% received an SNRI in monotherapy, 7.7% received an AA in monotherapy, and 28.8% received an AA in combination with an SSRI and/or SNRI; as second-line therapy, 10.5% of patients received an SSRI in monotherapy, 8.3% received an AA in monotherapy, 6.7% received an SNRI in monotherapy, and 11.1% received an AA in combination with an SSRI and/or SNRI (Figure 2). In addition to the PTSD-related agents in first-line therapy, 46.3% of patients received an augmenting agent and 28.8% received nonpharmacological therapy. Within the first line of therapy, 56.3% of patients experienced a dose change outside of any planned titration (i.e. increase or decrease in the dose of SSRI, SNRI, or AA). The most frequently reported reasons for any treatment change in the 24-month period following diagnosis were inadequate/suboptimal management of PTSD symptoms with prior treatment (51.5%) and initiation of targeted PTSD symptom management (30.7%; Table 4). As of 24 months following the PTSD diagnosis, 82.7% of patients were no longer receiving a PTSD-related agent.

Psychiatrists reported that patients’ PTSD symptoms were most commonly assessed via general clinical interviews (90.5%), with just under a quarter (23.3%) assessed via self-report measures. At the time of diagnosis, almost half of patients (49.1%) presented with severe or extreme PTSD. In the 6-month period following the PTSD diagnosis, at least one symptom improved in 81.8% of patients, and at least one symptom remitted in 30.7% of patients (Figure 3).

Figure 3. Change in PTSD symptoms 6 months after PTSD diagnosis. PTSD: posttraumatic stress disorder.

4. Discussion

This retrospective chart review study of civilian adults diagnosed with PTSD and treated with PTSD-related pharmacotherapy under a psychiatrist’s care highlights that PTSD is a highly heterogeneous condition with diverse clinical trajectories. Patients often experience multiple traumatic events, present with a complex symptom and comorbidity profile, and typically go through a lengthy patient journey with long intervals between the traumatic event(s), symptom onset, formal PTSD diagnosis, and treatment initiation. In addition to the substantial lag of over 6 years between symptom onset and initiation of pharmacological treatment for PTSD, patients were often observed with multiple lines of therapy, involving different combinations of trauma-focused and other psychotherapies, PTSD-related therapeutic agents, and augmenting agents. Within the 24 months following the PTSD diagnosis, just over one-third of patients achieved remission; yet, more than 80% of patients were no longer receiving a PTSD-related agent by that time. Collectively, the findings of this study underscore several unmet needs along the journey of civilians with PTSD in the U.S. in regard to long diagnosis and treatment delays, multiple treatment changes, low remission rates, and poor persistence to pharmacological treatments.

The high rates of PTSD-related treatments prior to a PTSD diagnosis found in this study may reflect the treatment of individual PTSD-related symptoms and/or related comorbidities, while overlooking or potentially misdiagnosing the underlying PTSD condition. PTSD has diverse manifestations and symptoms are often similar to those with other common mental health conditions (e.g. depression or anxiety), which, when compounded by patients’ reluctance to disclose the traumatic event¹¹, may impede clinicians’ ability to distinguish PTSD from other conditions. A prior U.S.-based chart review of primary care patients with PTSD found that although 49% of patients had received a mental health treatment in the previous 12 months, most (71%) of those treated were diagnosed with depression, and only 18% were specifically diagnosed with PTSD⁹. Additionally, a 2018 systematic review found that undetected PTSD was common in secondary care mental health services, presented in 28.6% of patients¹⁰. The current study also found that partial symptom management by comorbidity treatment was among the top reason for a psychiatrist to not document a PTSD diagnosis, which could have contributed to the underdiagnosis of PTSD. Together, these findings suggest that future research focusing on raising awareness of PTSD among civilians and clinicians and reducing mental health stigma may help alleviate some barriers to PTSD diagnosis and treatment.

Unlike veterans in the U.S. who have access to dedicated screening and care for PTSD²⁵, most civilians need to actively seek professional help for their PTSD symptoms and disclose their potentially sensitive traumatic experience to be diagnosed. Although military personnel were excluded from this study, the pre-existing work in this population is still relevant and should be leveraged when considering policy or programming that may benefit the civilian population. Despite a lack of studies on the impact of PTSD screening on treatment outcomes, the Department of Veterans Affairs/Department of Defense PTSD guidelines¹ recommends periodic PTSD screening based partly on evidence of beneficial outcomes from screening for other psychiatric disorders, such as depression, in which primary care screening has been shown to be associated with a greater reduction and/or remission in depression symptoms³⁰. Furthermore, reducing the time between symptom onset and PTSD diagnosis through effective screening can help ensure patients obtain treatment earlier on in the disease course, which has been shown to outperform treatment as usual or no treatment among hospitalized civilian trauma survivors³¹. Further evidence to support early intervention in the context of PTSD is warranted, but the results from the current study describe a long period in which civilian patients may be struggling with PTSD symptoms without receiving targeted care, pointing to the potential benefits of developing and implementing PTSD screening tools for the wider population.

In addition to the long gap from symptom onset to PTSD diagnosis of 6.5 years, patients were also found to experience an average delay of 1.9 months between diagnosis and pharmacological treatment initiation. Overall, these diagnosis and treatment delays align with the findings of the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), a large U.S.-based national survey that found an average of 4.5 years elapsed from PTSD onset to first treatment⁷. Meanwhile, the delay in pharmacological treatment initiation is in line with a study among U.S. veterans that showed the time from PTSD diagnosis to first pharmacotherapy prescription ranged from 47 to 84 days (i.e. approximately 1.5–3 months) depending on the type of medication prescribed, which was in turn related to the type and severity of PTSD symptoms and comorbidities presented¹⁸.

Although PTSD-related treatment was frequently received prior to the PTSD diagnosis, the current analysis found that a formal PTSD diagnosis often led to a change in pharmacological treatment, followed by newly prescribed trauma-focused and non-trauma-focused psychotherapy, which may indicate residual core PTSD symptoms that were challenging to address without a formal PTSD diagnosis. Moreover, while the most frequently prescribed first-line pharmacological treatment was SSRI monotherapy, the use of AA monotherapy and combinations were also common, a finding that is consistent with previous studies^19,32. With limited approved therapies for PTSD, off-label use of AAs has been observed in clinical practice to manage specific PTSD-related symptoms and comorbidities such as psychosis, sleep disturbances, and depression^18,33,34. Notably, both comorbid psychiatric (e.g. depression, anxiety) and somatic (e.g. pain, trouble sleeping, cardiovascular disease) conditions could have a considerable impact on the overall well-being of patients with PTSD^5,35–38; thus, comorbidity management is a crucial component of PTSD care³.

In the 6 months after diagnosis, most patients experienced improvement in at least one PTSD symptom (81.8%), suggesting that targeted PTSD care prompted by a diagnosis may lead to positive improvements in the patient’s condition. However, it is important to note that despite observed improvements in symptoms associated with PTSD-targeted therapy, the symptoms persist in some form, with only 34.4% of patients achieving clinically evaluated remission after 24 months. The remission rate is in line with that reported in a systematic review, which found an average remission rate of 44% after 40 months, although the rates varied widely across studies³⁹. The current study also found that 82.7% of patients were no longer treated with a PTSD-related agent at 24 months post-diagnosis, suggesting poor persistence to pharmacological treatments despite ongoing symptoms. A meta-analytic study has suggested that untreated PTSD tends to persist over time, and PTSD is unlikely to spontaneously subside without an intervention once the initial remission period (i.e. within 3 months following a traumatic event) has passed⁴⁰. Another study has found that experience of multiple traumatic events may broaden the PTSD symptom spectrum and render the condition more difficult to treat⁴¹, highlighting the importance of timely treatment provision and long-term persistence.

Multiple levels of interventions may be possible to help patients with PTSD become resilient and attain positive outcomes⁴². Novel psychological intervention techniques and related policy programs informed by neuroscientific research such as those investigating the impact of traumatic stress on the whole brain network may help reduce the population burden of PTSD⁴². With an increased understanding on the underlying pathology of PTSD, psychotherapy may be packaged and delivered with modified protocols to emphasize on core mechanisms or prioritize the most critical symptoms that may influence other symptoms or outcomes based on neural connectivity⁴³. Prior research in veterans has also suggested that changes in the severity of PTSD symptoms over time may differ by symptom clusters, and targeting hyperarousal symptoms at early stages of PTSD may help reduce subsequent symptoms of intrusion and avoidance⁴⁴; future studies examining potential changes in various symptom clusters on the longitudinal course of PTSD among civilians may provide insight on more targeted interventions for individuals with PTSD. Meanwhile, research on more safe and effective pharmacological treatment options is also warranted to help advance PTSD care.

Historically, a majority of PTSD research has centered on combat-related PTSD in active-duty military members and veterans, who are disproportionately white and male. However, women are twice as likely to develop PTSD as men in the civilian population, and a growing body of research indicates disparities in patient and treatment characteristics linked to gender, race/ethnicity, age, cultural context, and socioeconomic status³⁵. The current study helps to fill knowledge gaps pertaining to civilians by analyzing an exclusively civilian sample of patients treated for PTSD by psychiatrists in a real-world clinical setting, with gender, age, and race distribution largely reflecting the U.S. population^7,45,46. Additional research focusing on the civilian population is needed to help raise awareness of PTSD manifestation in patients at risk and to enable treating physicians to identify and treat patients with PTSD earlier in the disease course, which may lead to improved patient outcomes.

4.1. Limitations

The findings of this study should be considered in light of limitations. Primarily, information captured by the study’s eCRF was input by the psychiatrist, and a second reporter was not required to assess inter-reporter reliability; therefore, data may be subject to miscoding. Furthermore, data collected are limited to information available in the patients’ medical record held by the psychiatrists participating in the study. Information was not available on healthcare services and treatments received outside of the psychiatrist’s care setting that were not recorded in the medical chart, and data collected was further limited to the questions asked as part of the eCRF. Therefore, complete information (e.g. comprehensive patient history and comorbidities, comprehensive treatment patterns and treatment dosing, etc.) was not available. The study included only psychiatrists accessible through the M3 panel who wished to participate in this study; accordingly, the sample may not be fully representative of the U.S. psychiatrist population treating adults with PTSD. Furthermore, although participating psychiatrists were instructed to select patients at random, selection bias may still arise (e.g. bias toward selecting patients recently seen by the treating psychiatrist, or with strongly favorable or unfavorable outcomes). Lastly, as per the design, this study focused on adult patients diagnosed with PTSD by a psychiatrist, who were treated with pharmacological agents. As such, it was not possible to compare the characteristics of treated and untreated adults with PTSD, or between adults with PTSD treated by other professionals (e.g. primary care physicians).

5. Conclusions

Findings from the present study highlight that civilian adults with PTSD represent a heterogeneous population with a range of traumatic experiences and clinical and treatment characteristics. Civilian patients with PTSD often contend with an extensive patient journey and a long delay from trauma to symptom onset, and to diagnosis. Patients had high rates of comorbidities and often received PTSD-related treatment prior to their formal PTSD diagnosis. Following diagnosis, patients commonly used concurrent psychotherapy, combination pharmacotherapy, and augmenting agents, potentially indicating the presence of residual core PTSD symptoms that are difficult to address. Taken together with the low remission rates observed, this study highlights the complex nature of PTSD that may pose challenges for psychiatrists to identify and treat appropriately, in part due to limited treatment options.

Transparency

Declaration of funding

This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck LLC. The study sponsor was involved in several aspects of the research, including the study design, interpretation of data, writing of the manuscript, and decision to submit the manuscript for publication.

Declaration of financial/other relationships

Lori Davis has previously received consulting fees from Boehringer Ingelheim, Lundbeck, Otsuka, and Signant Health and research funding and/or materials from Alkermes, Aptinyx, Tonix, Social Finance, and Westat. Annette Urganus is an employee of Lundbeck LLC. Patrick Gagnon-Sanschagrin, Jessica Maitland, Jerome Bedard, Remi Bellefleur, Martin Cloutier, and Annie Guérin are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck LLC, which funded the development and conduct of this study and manuscript. Jyoti Aggarwal is an employee of Otsuka Pharmaceutical Development & Commercialization, Inc.

Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

Patrick Gagnon-Sanschagrin, Jessica Maitland, Jerome Bedard, Remi Bellefleur, Martin Cloutier, and Annie Guérin contributed to study conception and design, collection and assembly of data, and data analysis and interpretation. Lori Davis, Jyoti Aggarwal, and Annette Urganus contributed to study conception and design, data analysis and interpretation. All authors reviewed and approved the final content of this manuscript.

Ethics statement

This study was conducted in accordance with the applicable ethical regulations; it was exempt from full review and approved through an expedited review by the Western Copernicus Group Institutional Review Board (work order: 1-1485181-1). Eligible psychiatrists who were willing to participate in the study provided their written informed consent.

Previous presentations

Part of the material in this manuscript was presented at the ASCP 2023 held May 30-June 2, 2023 in Miami Beach, FL, U.S. as a poster presentation.

Acknowledgements

Medical writing assistance was provided by professional medical writers, Eva Chanda, MSc, and Flora Chik, PhD, MWC, employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck LLC, which funded the development and conduct of this study and manuscript.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.