Borderline personality disorder (BPD) is clinically distinguished by affective dysregulation and impulsive behaviors, frequently manifesting as suicidal tendencies and self-injurious attempts. Although psychopharmacological strategies are conventionally regarded as adjuncts to psychotherapy, the phenomenological overlap between BPD and mood disorders may provide a robust theoretical framework for the use of mood stabilizers (Abraham and Calabrese 2008). However, while numerous pharmacological agents have been proposed for the treatment of BPD, systematic reviews have consistently revealed their substantial inefficacy (Stoffers-Winterling et al. 2022). Lithium may exhibit anti-suicidal effects, demonstrating unique efficacy in mitigating impulsivity and self-injurious acts across diverse clinical populations (Müller-Oerlinghausen and Lewitzka 2010). Despite these therapeutic properties, studies explicitly investigating the efficacy of lithium in BPD remain scarce, rendering its clinical utility in the management of self-injurious thoughts and behaviors a subject of significant scientific interest (Almeida and Sanches 2024). We present the case of a 21-year-old male patient who presented to our outpatient clinic in 2024 with a clinical picture characterized by depressed mood, frequent diurnal mood fluctuations, spontaneous crying spells, outbursts of anger, and recurrent self-injurious behaviors (superficial cuts on his arms). The patient reported infrequent alcohol consumption (one to two standard drinks biweekly) and denied any illicit substance use. His family history was notable for substance use disorder and a suicide attempt by hanging in his older brother. Regarding his past psychiatric history, the patient reported a lack of response to fluoxetine, quetiapine, and sertraline, despite utilization at adequate doses and durations. There was no history of psychiatric hospitalization. At the time of presentation, he had been regularly taking venlafaxine 150 mg/day and aripiprazole 5 mg/day for the past 6 months, without any perceived clinical benefit. During a 1.5-year follow-up period in our clinic, the patient was diagnosed with BPD. Given that BPD is a heterogeneous diagnosis that can overlap with numerous other conditions, particularly bipolar disorder and bipolar spectrum disorders (Almeida and Sanches 2024), this diagnosis was established not merely through cross-sectional DSM-5 criteria; rather, it was ascertained via a comprehensive longitudinal clinical assessment over the 1.5-year period, which delineated pervasive and enduring patterns of instability in interpersonal relationships, self-image, and affects, alongside marked impulsivity. Furthermore, significant elevations in both neurotic and psychotic subscales on the Minnesota Multiphasic Personality Inventory (MMPI), administered as a psychometric test, were interpreted in favor of BPD when evaluated in conjunction with the longitudinal clinical interviews. Subsequent sequential pharmacotherapy trials included bupropion (300 mg/day), an olanzapine/fluoxetine combination (prescribed at another center, 3/25 mg/day), trazodone (50 mg/day), and quetiapine (200 mg/day). None of these pharmacological interventions were successful in achieving remission of the patient's affective lability or impulsive self-injurious behaviors. Consequently, the patient's pharmacotherapy was modified to low-dose lithium monotherapy (a single daily dose of 300 mg/day). Serum lithium levels were maintained between 0.2 and 0.3 mEq/L during the follow-ups. A dramatic clinical response was observed within the first 4 weeks of treatment. During regular follow-ups over the subsequent 5-month maintenance phase under this specific regimen, the patient reported a complete resolution of affective fluctuations and a total cessation of impulsive self-injurious thoughts and behaviors. Subjectively, the patient reported that lithium provided the most pronounced therapeutic benefit among all previously prescribed psychotropic agents. The resolution of impulsive self-injurious attempts in this treatment-resistant case is consistent with the established efficacy of lithium on impulsive self-injurious behaviors (Müller-Oerlinghausen and Lewitzka 2010; Almeida and Sanches 2024). Crucially, this clinical remission was achieved utilizing a low-dose regimen. Recent epidemiological analyses corroborate that even trace amounts or microdoses of lithium can significantly reduce suicide attempts and impulsive acts, independent of its classical mood-stabilizing mechanisms (Barjasteh-Askari et al. 2020). At the molecular level, subtherapeutic lithium concentrations (≤ 0.5 mM) confer substantial neuroprotection, primarily via the inhibition of Glycogen Synthase Kinase-3. This pathway is known to enhance cellular resilience and modulate neuroinflammation, notably circumventing the systemic toxicity associated with standard bipolar dosing parameters (Hamstra et al. 2023). Clinically, the administration of low-dose lithium may offer an optimal balance between therapeutic efficacy and tolerability. Empirical evidence indicates that maintaining lower serum lithium concentrations significantly reduces burdensome side effects such as tremor, weight gain, and renal/thyroid dysfunction while preserving prophylactic efficacy (Abou-Saleh and Coppen 1989). In interpreting these findings, diagnostic complexities must be carefully considered. First, affective dysregulation is a well-recognized symptom in bipolar disorder and is highly correlated with mood symptoms (Oliva et al. 2023). Given this prominent phenomenological overlap, we must also account for the possibility that our patient's presentation may represent a form of bipolar spectrum disorder, which would also align with the robust therapeutic response to lithium. Furthermore, as current research regarding personality disorders shifts toward dimensional models of personality pathology (Tyrer et al. 2025), focusing on specific, severe symptom domains such as affective instability and impulsivity may be of paramount clinical importance. In summary, considering the clinical manifestation of these overlapping symptom domains and the inherent limitations of current psychopharmacological algorithms, low-dose lithium may emerge as a highly tolerable and effective intervention for affective instability and impulsive self-injurious thoughts and behaviors. We contend that future randomized controlled trials are required to rigorously determine the precise efficacy and optimal dosing parameters of lithium, specifically in patients diagnosed with BPD. The authors have nothing to report. Written informed consent was obtained from the patient for the publication of this case report and any accompanying details. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
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