Haloperidol as a Novel Augmentation Strategy in Treatment-Resistant Depression: A Clinical Practice Perspective with Case Series

Abstract

Treatment-resistant depression (TRD) remains a major clinical challenge when adequate antidepressant trials fail to achieve remission. This clinical practice perspective examines low-dose haloperidol as a potential augmentation strategy in carefully selected, treatment-refractory affective presentations. The manuscript combines an integrative theoretical review of dopaminergic dysregulation with an observational case series of three inpatients with severe treatment-refractory depression, including bipolar and unipolar presentations. Clinical outcomes were evaluated through psychiatric assessment and symptom-severity measures, with attention to depressive symptoms, suicidal ideation, anxiety, psychomotor activity, sleep, and neurological adverse effects. Following the introduction of low-dose haloperidol alongside existing treatment, all three patients showed clinically meaningful short-term improvement, including resolution or reduction of suicidal ideation, mood stabilisation, reduced anxiety, improved sleep, and greater psychomotor or social engagement. At three-month follow-up, two patients remained clinically stable on the augmented regimen, while one patient required haloperidol dose reduction because of mild parkinsonian symptoms, which subsequently resolved. Interpretation is limited by the small uncontrolled sample, concomitant medications, inpatient therapeutic milieu, selection bias, and brief follow-up. The findings therefore do not establish efficacy or causality. Rather, they support a preliminary clinical-neurobiological hypothesis that warrants systematic evaluation in controlled studies with rigorous neurological monitoring and longer-term safety assessment in future research.