Beyond Extrapyramidal Symptoms: A Case Report of Trihexyphenidyl Dependence in Patient with Major Depression and Cognitive Vulnerability

Abstract

Background: Major depressive disorder with psychotic features is a severe mental disorder associated with significant functional impairment and elevated suicide risk. Clinical management becomes more complex in the presence of comorbid substance dependence and cognitive vulnerability. Trihexyphenidyl, an anticholinergic medication primarily indicated for extrapyramidal symptoms, has been increasingly misused for its euphoric effects. Dependence on trihexyphenidyl may contribute to affective instability, psychotic symptoms, and maladaptive coping, particularly when used to alleviate depressed mood. Individuals with intellectual functioning below their chronological age may have limited adaptive skills and reduced capacity for emotional regulation, further increasing vulnerability to both mood disorders and substance dependence. Case: We report a 24-year-old male presenting with a major depressive episode with psychotic features, recurrent suicide attempts, and long-standing trihexyphenidyl dependence. The patient had used trihexyphenidyl daily since adolescence with progressive dose escalation, withdrawal symptoms, and impaired control, primarily to obtain euphoric and anxiolytic effects. Presented clinical cognitive assessment revealed intellectual functioning below his chronological age, with impairments in abstraction, attention, language, visuospatial ability, and executive functioning. Additional diagnoses included nicotine dependence, harmful use of benzodiazepines, and recreational use of methamphetamine and alcohol. The patient received inpatient psychiatric treatment with pharmacotherapy, complemented by behavioral therapy and psychoeducation. Discussion: Trihexyphenidyl dependence in this patient appeared to function as a maladaptive self-regulation strategy for depressive affect and emotional distress, while cognitive limitations likely reduced adaptive coping and increased reliance on substance use. Behavioral therapy was particularly appropriate in addressing observable behaviors, reinforcing abstinence, and improving daily functioning. Conclusion: Assessment of nontraditional substance dependence, cognitive functioning, and tailored behavioral interventions is essential in patients with major depression with psychotic features to optimize clinical outcomes and reduce suicide risk.