Use of SPRAVATO in Comorbid Personality Disorders

SUMMARY

• The SPRAVATO clinical program excluded patients with borderline personality disorder (BPD) or antisocial personality disorder. In addition, the treatment-resistant depression (TRD) program excluded patients with histrionic personality disorder or narcissistic personality disorder.^1-7
• A real-world, multicenter, prospective study in a cohort of adult patients with TRD, including patients with comorbid BPD, demonstrated improvements in outcomes related to depressive symptoms, anxiety, impulsivity, suicidal ideation, suicidal behavior, and deliberate self-harm after 6 months of SPRAVATO treatment. Remission outcomes were similar in patients with and without comorbid BPD (48.9% vs 57.8%).^8,9
• A retrospective study evaluating response predictors in patients treated with intravenous ketamine or SPRAVATO reported that patients without comorbidities experienced the greatest improvement in depressive symptoms while those with BPD showed minimal improvement.¹⁰
• A real-world, retrospective study in adult patients with TRD reported the influence of comorbid personality disorders on the effectiveness of SPRAVATO on depressive symptoms during the maintenance phase. The cohort with comorbid personality disorders did not significantly improve during the maintenance phase compared to the cohort without personality disorders.¹¹
• Three case reports of adult patients with comorbid BPD, who have a history of suicide attempts and achieved a response or remained stable following treatment with SPRAVATO, are summarized below.^12-14 

Real-world studies

Prospective Real-World Studies

Mazzoni et al (2026)⁸ and Raffone et al (2026)⁹ reported findings from a multicenter (Italy), prospective, real-world cohort of 90 adult outpatients with TRD treated with SPRAVATO, including 45 patients with comorbid BPD. Patients were followed for 6 months and were assessed for depressive symptoms (using the Montgomery-Åsberg Depression Rating Scale [MADRS]), anxiety (Hamilton Anxiety Rating Scale), impulsivity (Barratt Impulsiveness Scale–11 [BIS-11]), suicidality (using the Columbia-Suicide Severity Rating Scale [C-SSRS]), deliberate self-harm (using the Deliberate Self-Harm Inventory [DSHI]), and cognitive function (Montreal Cognitive Assessment [MoCA]). Patients were permitted to continue their baseline antidepressants, atypical antipsychotics, and other therapies, including psychotherapy.

Results

• Mazzoni et al (2026)⁸ reported that MADRS scores substantially decreased over time in both groups. In the group without personality disorders (PD), mean MADRS decreased from 30.56 to 10.64 at 6 months. In the group with BPD, mean MADRS decreased from 38.02 to 9.42. A significant time x BPD interaction was observed, indicating faster early improvement among patients with BPD. At 6 months, remission (MADRS ≤10) was achieved by 53.3% of patients overall, with no significant differences between patients with BPD and those without PD (48.9% vs 57.8%). The response rate was significantly higher in the BPD group (97.8% vs 77.8%; P=0.004). Anxiety and impulsivity decreased in both groups, and no evidence of cognitive worsening was reported. Impulsivity scores, based on BIS-11, are shown in Table: BIS-11 scores from baseline to month 6.

BIS-11 scores at baseline and 6 months by BPD status⁸

• Raffone et al (2026)⁹ reported significant reductions in suicidal ideation, suicidal behavior, and deliberate self-harm over the 6-month period in the overall study population. In patients with BPD, the frequency of deliberate self-harm episodes decreased from baseline (mean, 30.8) to 6 months (mean, 2.4). At baseline, impulsivity was correlated with self-harm and suicidality measures; however, these correlations were attenuated at 6 months.
• Across both analyses,^8,9 no serious adverse events (AEs) or treatment discontinuations were reported during follow-up. Overall, the most common AE was nausea (7.8%).
• Limitations included observational design without a control group, limited measures of personality disorder severity, and potential residual confounding from clinical factors and concurrent treatments. Selection bias, limited generalizability, and reduced power to detect small between-group differences, such as remission, may also have affected the findings.^8,9

Retrospective Real-World Studies

Elmaadawi et al (2025)¹⁰ conducted a retrospective chart review of 200 adult patients with TRD treated with intravenous (IV) ketamine or SPRAVATO. Depression severity was assessed using MADRS and Patient Health Questionnaire-9 (PHQ-9). The study evaluated the impact of treatment modality, psychiatric comorbidities, number of prior antidepressant failures, age, and sex on treatment outcomes. Twenty-two patients had comorbid BPD.

Results

• Both IV ketamine and SPRAVATO were associated with significant improvements in depressive symptoms. In the IV ketamine group (n=98), mean MADRS decreased from 34.9 to 24.1 and mean PHQ-9 score decreased from 18.5 to 13.5 after 4 weeks (both, P<0.001). In the SPRAVATO group (n=102), mean MADRS decreased from 35.4 to 29.2, while PHQ-9 decreased from 19.0 to 16.2 (both, P<0.001).
• Patients without psychiatric comorbidities experienced the greatest improvement in depressive symptoms, whereas patients with comorbid BPD demonstrated minimal improvement. In patients with BPD, the least-squares (LS) mean change in MADRS was -3.67 while the LS mean change in PHQ-9 was -1.84.
• Limitations included the small sample of BPD patients, selection bias due to retrospective design, and the potential for unmeasured confounders, such as concomitant psychotherapy or other medications.

Dvorak et al (2024)¹¹ conducted a single-center, real-world, retrospective study in Israel from January 2021 to 2023 to evaluate the effectiveness of SPRAVATO in 62 adult patients with TRD, including 25 patients with comorbid personality disorders. Assessments were made using the Quick Inventory of Depressive Symptomatology (QIDS) score at baseline, acute (8 weeks), and maintenance phase (4-6 months).

Results

• In the overall population, patients had a mean age of 43.6 years, and 54.8% were female. QIDS scores significantly decreased from baseline (mean, 22.73) to the acute phase (mean, 16.55) and then to the maintenance phase (mean, 12.15) (P<0.001).
• The study found no influence of comorbid personality disorders on the QIDS scores during the acute phase, but a significant difference in mean QIDS scores was reported between patients with comorbid personality disorders and those without during the maintenance phase.
• Although the mean QIDS score in the cohort with a personality disorder did not further improve from the acute phase to the maintenance phase, a significant improvement was seen in the cohort without a personality disorder during this time.
• The authors noted limitations that may have affected outcomes and acknowledged that further research is needed to assess the effectiveness of SPRAVATO in this comorbid patient population.

Case Reports

Gao et al (2025)¹⁴ described a case-report of an 18-year-old female patient with TRD and comorbid eating disorder, in addition to generalized anxiety disorder, post-traumatic stress disorder and BPD who was treated with SPRAVATO.

• In addition to psychotherapy, the patient was previously treated with antidepressants, adjunctive antipsychotics, lithium, lamotrigine, several series of electroconvulsive therapy (ECT), and ketamine as an infusion and compounded intranasal spray.
• She initially received SPRAVATO twice weekly for 4 weeks followed by weekly administration, in addition to weekly ECT. She had transient benefit with SPRAVATO but relapsed with a serious suicide attempt after stopping treatment.
• SPRAVATO was restarted following a residential treatment for her eating disorder (56 mg for the first session increasing to 84 mg for subsequent sessions, twice weekly for four weeks). The patient missed her second weekly SPRAVATO session and experienced a relapse, resulting in hospitalization.
• During the hospitalization, SPRAVATO was resumed twice a week for two weeks and then once weekly. The patient’s mood has remained relatively stable with ongoing weekly SPRAVATO treatments for more than 2 years.

De Filippis et al (2023)¹³ presented a case report of a 39-year-old female patient diagnosed with BD-I and BPD who presented to the hospital after a drug ingestion-related suicide attempt.

• The patient had a long history of alcohol and drug abuse, with prior reports of manic episodes, voluntary and compulsory hospitalizations, drug ingestion-related suicide attempts, and depression.
• A month after her recent drug ingestion-related suicide attempt, the patient was initiated on SPRAVATO as an adjuvant to the current treatment regimen, including fluoxetine, lithium, lurasidone, and quetiapine. She received a twice-weekly 56 mg SPRAVATO dose for 4 weeks followed by 56 mg once weekly.
• After 3 months, a clinical response (50% reduction in the MADRS score) was reported, and at the 12-month follow-up, a clinical remission (MADRS<10) with improvements in global functioning, sleep cycle, suicidality risk, binge eating, and anxiety symptoms were reported.
• In the continuation phase, the patient had no clinical relapses or hospitalizations, held a part-time job, and started caring for herself and her daughters.

Nandan et al (2022)¹² presented a case report of a 27-year-old female patient with TRD and BPD who initially presented to the hospital after a suicide attempt.

• The patient was diagnosed with major depressive disorder (MDD) at age 7 and BPD by age 8-9. She had a history of drug and alcohol abuse with multiple impulsive suicidal and non-suicidal self-harm episodes.
• After discharge from the current hospitalization, the patient was initiated on SPRAVATO with daily citalopram 20 mg and buspirone for anxiety. SPRAVATO 56 mg was administered twice weekly for 4 weeks, followed by 56 mg once weekly, which was titrated to 84 mg once weekly. Within 4-5 weeks, assessment using the Hamilton Depression Rating Scale (HAM-D) showed a response in terms of suicidal ideation and depression, with a significant improvement in core BPD symptoms.
• Nearly 2 years into treatment, the patient’s affective instability and impulsivity significantly improved, and the HAM-D score decreased. The patient and her mother reported a 70% improvement in depression and anxiety and an 80% improvement in behavioral symptoms. Attempts to self-harm decreased from once a week to once every 3 months, and she also maintained a steady job.
• The patient’s interpersonal relationships improved, and the frequency of anxiety and anger outbursts and emergency department visits decreased over time.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 03 July 2026.