In a groundbreaking case report published in BMC Psychiatry, researchers have unveiled a rare and complex phenomenon termed “psychotropic-associated delusional pseudo-gender dysphoria.” This novel classification emerges from an unprecedented clinical account involving a 30-year-old female patient with bipolar disorder, whose experience challenges existing paradigms in psychiatric symptomology and psychopharmacology. The report provides an intricate analysis of how psychotropic medications may play a vital role in the manifestation and transformation of gender dysphoric delusions, expanding the discourse far beyond previous understandings.
Gender dysphoric delusions have been documented in approximately 20 to 25 percent of individuals diagnosed with schizophrenia, traditionally viewed as fixed or arising solely from intrinsic psychopathology. However, this case introduces a revolutionary concept: that psychotropic agents themselves, through their side effect profiles and neurochemical influences, can induce or modulate aberrant experiences of gender identity at the delusional level. This insight introduces a new dimension into the psychiatric understanding of gender identity disturbances, implicating neurochemical and pharmacodynamic mechanisms in shaping phenomenological realities experienced by patients.
The patient in this report had been prescribed sodium valproate and monthly paliperidone, an antipsychotic, both staple treatments for bipolar disorder and psychotic symptoms. Over time, the patient exhibited notable adverse effects, including pronounced hirsutism—unwanted facial hair growth—and persistent amenorrhea, or absence of menstruation. These physiological changes appeared to coincide temporally with the emergence of unusual gender-related delusions, suggesting a biopsychosocial interplay between drug-induced somatic alterations and the patient’s evolving psychiatric narrative.
Following the cessation of sodium valproate and paliperidone, the patient reported unprecedented subjective experiences where her body was perceived as dichotomously gendered—her lower half as female and her upper half as male. This mixed gender delusion manifested uniquely and was followed by a more traditional gender dysphoric delusion characterized by a firm conviction of being a man trapped in a woman’s body. The evolution of these delusions within one individual, shifting from a hybrid gender experience to an exclusive transgender identity, has not been previously documented in psychiatric literature.
Treatment with clozapine, a highly specialized antipsychotic known for its efficacy in refractory psychosis, elicited a remarkable clinical response. The patient’s delusional belief in a dual-gender identity dissociated, culminating in an affirmation of a 100 percent female identity—returning to a pre-delusional baseline of gender perception. This therapeutic outcome underscores the potential for targeted pharmacological strategies to recalibrate disturbed neurochemical pathways underlying complex delusional constructs.
From a neurobiological perspective, psychotropics such as paliperidone and sodium valproate modulate neurotransmitter systems including dopamine, serotonin, and gamma-aminobutyric acid (GABA). Alterations in these systems may influence not only mood and psychosis but also viscerosensory feedback and body image perception. The reported hirsutism and amenorrhea introduce additional layers, as endocrine disruptions caused by these medications can profoundly affect the hypothalamic-pituitary-gonadal axis, potentially contributing to gender-related perceptual changes at a neuropsychological level.
This case spotlights the intricate biopsychosocial matrix in mental health where pharmacodynamics, hormonal physiology, and subjective identity symptoms converge. It challenges clinicians to reconsider the boundaries between medication side effects and psychotic symptom development, particularly in disorders where identity is central. Moreover, it stresses the importance of continuous, nuanced assessment of psychotropic side effects beyond traditional psychiatric symptom checklists.
The implications of this report are manifold, inviting researchers and clinicians to explore the neuropsychiatric substrates of gender dysphoria within psychosis through the lens of pharmacological influence. It also calls for heightened vigilance in prescribing practices and symptom monitoring, especially when managing bipolar disorder and schizophrenia with potent mood stabilizers and antipsychotics.
Furthermore, this case elucidates the potential for psychotropics to induce transient, state-dependent alterations in gender identity, revealing a previously unrecognized form of delusional pseudo-gender dysphoria. It prompts significant ethical, diagnostic, and therapeutic discussions around understanding identity perceptions through neurochemical frameworks and tailoring interventions that mitigate iatrogenic psychiatric phenomena.
While the broader epidemiological significance remains to be determined, this clinical vignette lays foundational groundwork for future systematic investigations into the psychotropic-linked onset of gender dysphoric delusions. It also highlights the critical interplay between hormonal side effects and psychiatric symptomatology in shaping patient experiences of self and body.
Importantly, this discovery reinforces the dynamic, fluid nature of delusional content and the influence of external factors such as medication on the psychotic landscape. It expands the conceptual boundaries of gender dysphoria in psychiatric contexts, facilitating more informed, compassionate, and scientifically grounded approaches to patient care.
In conclusion, this pioneering case offers a remarkable window into the complexity of mind-body interactions governed by psychotropic medications. It forces the mental health community to rethink traditional categorizations of gender dysphoria, psychosis, and medication side effects, ultimately contributing to a more holistic and nuanced understanding of human psychiatric experience.
Subject of Research: Psychotropic-induced gender dysphoric delusions in a bipolar disorder patient, exploring neuropsychiatric effects of psychotropic medications on identity
Article Title: Psychotropic-associated delusional pseudo-gender dysphoria: a case report
Article References:
Abdel Aziz, K., Al Ammari, A.S., Alzaabi, M.S. et al. Psychotropic-associated delusional pseudo-gender dysphoria: a case report. BMC Psychiatry 25, 969 (2025). https://doi.org/10.1186/s12888-025-07450-7
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