Memantine as an Adjunct in the Treatment of Inappropriate Sexual Behavior

Memantine is a noncompetitive N-methyl-D-aspartate receptor antagonist approved for the treatment of moderate-to-severe Alzheimer disease. Given its involvement in glutamate pathways, memantine has demonstrated efficacy in several psychiatric conditions, both as monotherapy and as an adjunct.¹ Inappropriate sexual behavior (ISB) includes sexual talk, implied sexual behaviors, and overt sexual acts.² Evidence supporting memantine for ISB remains limited, though its proposed mechanism is biologically plausible.

We present 2 patients with intellectual disability (ID) and major neurocognitive disorder (NCD), respectively, who exhibited ISB that significantly decreased after memantine was added as adjunctive therapy.

Case 1

A 67-year-old single, white man with ID and multiple medical comorbidities developed new-onset ISB over approximately 1.5 years, including public genital touching with pants down, propositioning another person at a pool, and intrusive proximity to a man during class. His Montreal Cognitive Assessment (MoCA)³ score was 16/30, with unremarkable neuroimaging and laboratory tests except for low-normal thiamine (75 nmol/L) and borderline vitamin B₁₂ (291 pg/mL); supplementation was initiated. Initial treatment with gabapentin (up to 600 mg 3 times daily), risperidone (0.5 mg twice daily), and citalopram (40 mg daily) reduced ISB but resulted in falls, slurred speech, and cognitive worsening, necessitating a reduction of gabapentin to 300 mg daily. Memantine was initiated at 5 mg daily and titrated to 10 mg twice daily, leading to improved cognition and resolution of ISB, alongside behavioral therapy.

Two years later, ISB recurred with obsessive, unwanted sexual pursuit of a man, which remitted following an increase in memantine to 25 mg daily, with stable renal function. A subsequent brief recurrence resolved with counseling and behavioral strategies. Serial MoCA scores remained stable (16–18/30) over 3 years, and the absence of functional decline did not support a diagnosis of progressive NCD.

Case 2

A 73-year-old single, white man with recurrent depression, left hemiparesis, and major vascular NCD developed severe ISB while residing in a skilled nursing facility after a hip fracture. ISB manifested as compulsive masturbation and preoccupation with pornography, accompanied by verbal and physical aggression; he sustained genital injury from excessive masturbation, reportedly using 4 bottles of lubricant overnight. Trials of divalproex sodium provided partial benefit but were limited by medication refusal. Risperidone (up to 0.75 mg twice daily, reduced to 0.25 mg twice daily due to bradycardia) reduced aggression but did not adequately control ISB. Memantine, added to risperidone and titrated from 5 mg daily to 10 mg twice daily, led to complete resolution of aggression and a marked reduction in compulsive sexual behavior.

Discussion

Approximately 90% of patients with major NCD manifest behavioral and psychiatric symptoms.⁴ Neurobiological systems implicated in the etiology of ISB include the frontal lobes, temporolimbic network, hypothalamus, and corticostriatal circuits.² ISB has been reported in geriatric patients following right frontal stroke,⁵ temporolimbic strokes or tumors, temporal lobe epilepsy,² and frontal lobe hypometabolism in frontotemporal dementia.⁶

Hypersexuality has been conceptualized as sharing features of obsessive-compulsive disorder (OCD).² Given its modulation of glutamate pathways, memantine has demonstrated therapeutic benefit in attention-deficit/hyperactivity disorder, autism spectrum disorder, OCD, bipolar mania, binge-eating disorder, posttraumatic stress disorder, generalized anxiety disorder, negative symptoms of schizophrenia, catatonia, pathological gambling, trichotillomania and excoriation disorder.^1,7,8,9 Nonpharmacologic measures can be effective in reducing ISD; however, pharmacologic agents are also frequently required.¹⁰ Memantine has been shown to improve OCD when added to fluvoxamine,¹¹ as well as when combined with selective serotonin reuptake inhibitors or used as monotherapy.¹ Various pharmacologic agents—including antidepressants, anxiolytics, antipsychotics, anticonvulsants, cholinesterase inhibitors, hormonal agents, and beta-blockers—have been reported to reduce ISB.² Hormonal therapies, such as medroxyprogesterone and antiandrogens, may be considered when ISB is refractory to pharmacologic and psychosocial interventions.^5,6 Gabapentin may decrease ISB through reduced libido, anorgasmia, and erectile dysfunction²; however, therapeutic dosing was poorly tolerated in case 1.

There is limited literature addressing ISB in patients with ID, and diagnosis of NCD in this population is challenging due to the lack of standardized diagnostic criteria.¹² NCD is typically suspected in the context of new-onset cognitive impairment, behavioral disturbance, and functional decline. Memantine was therefore initiated in case 1; however, longitudinal follow-up with stable serial MoCA scores over 3 years did not support a diagnosis of NCD. In contrast, ISB in case 2 was likely secondary to cognitive decline following stroke.

Conclusion

These cases suggest that memantine may be an effective adjunctive treatment for ISB in patients with ID or major NCD, particularly when symptoms are refractory to standard pharmacologic and behavioral approaches or limited by adverse effects. In both patients, memantine was associated with substantial and sustained reductions in ISB. Given the limited evidence guiding ISB management, especially in individuals with ID, further systematic studies are warranted to clarify memantine’s role in this population.

Article Information

Published Online: May 14, 2026. https://doi.org/10.4088/PCC.26cr04190
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(3):26cr04190
Submitted: January 17, 2026; accepted March 26, 2026.
To Cite: Hafeez ZH, Jahed I. Memantine as an adjunct in the treatment of inappropriate sexual behavior. Prim Care Companion CNS Disord 2026;28(3):26cr04190.
Author Affiliations: Kaiser Permanente, Santa Rosa, California (Hafeez, Jahed); Touro College of Osteopathic Medicine, Vallejo, California (Hafeez).
Corresponding Author: Zeba Hasan Hafeez, MD, FAPA, MCPS (Dermatology) Kaiser Permanente, Santa Rosa, California ([email protected]).
Patient Consent: Written permission for publication was obtained from both patients’ guardians, and information has been de-identified to protect patient anonymity.