Case Study: When Psychiatric Symptoms Blur the Lines in Multiple Sclerosis Care

A 68-year-old woman with relapsing-remitting multiple sclerosis (MS) presented for a psychiatric evaluation with eight months of anxiety, irritable mood and increased energy despite sleeping only one to two hours per night, and sometimes not at all. In addition to MS – diagnosed in 1988 – she had a history of chronic back pain and unspecified anxiety disorder. She was not currently receiving disease-modifying therapy, and her health was otherwise clinically stable.

Although the patient described a markedly decreased need for sleep and worsened anxiety over the preceding months, she denied other hallmark signs of classic mania, including racing thoughts, pressured speech, grandiosity, increased goal-directed behaviors and new high-risk behaviors. She had no family history of bipolar-spectrum illness.

The treating physician noted that the patient’s worsened irritability met the mood-change criterion which, coupled with the decreased need for sleep, appeared to meet the diagnostic criteria for bipolar and related disorders due to another medical condition (MS), with manic features.

Brain MRI showed no evidence of an active MS flare but was notable for stable periventricular white-matter lesions and moderate volume loss in the bilateral temporal and medial-frontal lobes.

Overlapping issues

Mood and behavioral changes are well-documented but often underrecognized complications of MS, particularly when psychiatric symptoms blur the line between neurological disease progression and primary mental illness. This case study illustrates just how challenging that distinction can be — and why collaborative care across specialties is essential, says Cleveland Clinic neuropsychiatrist Drew Cumming, MD.

“Psychiatric disorders in patients with MS can arise from a variety of overlapping causes, including active inflammatory disease, neurodegeneration, medication effects or an underlying primary psychiatric illness,” he explains. “In such cases, it can be quite difficult to differentiate between active disease relapse, neurodegeneration and primary psychiatric complaints – a challenge that can create interesting therapeutic dilemmas.”

Dr. Cumming says psychiatric manifestations of MS are increasingly recognized in the literature, with secondary bipolar disorders most often associated with lesions affecting the right posterior frontoparietal and left cingulate regions of the brain. He notes that mood issues in MS have historically been linked to active inflammation, lesion burden and treatments like high-dose corticosteroids, which are commonly used to manage relapses.

Dr. Cumming and Cleveland Clinic psychiatry resident Gabriel Hastreiter, MD, presented the case at the 2026 annual meeting of the American Neuropsychiatric Association.

Clinical strategy and outcome

The patient was started on trazodone (maximum 100 mg) but saw no improvement. She was transitioned to olanzapine (maximum 10 mg), which also failed to alleviate her symptoms. The psychiatrist ultimately prescribed a nightly dose of valproic acid (750 mg, delayed release). Although the patient’s sleep pattern improved, she continued to complain of heightened anxiety and irritability, so sertraline was added to her treatment regimen.

Approximately three months after her first assessment and one month after starting sertraline, the patient returned with worsened sleep, including two days of complete sleeplessness without fatigue or sleepiness, after running out of valproic acid. The psychiatrist discontinued sertraline and slowly increased the valproic acid to 2,250 mg, at which point the patient’s symptoms resolved.

The fact that the patient’s symptoms worsened significantly after the initiation of sertraline, a widely prescribed selective serotonin reuptake inhibitor, raised further suspicion for an underlying bipolar-spectrum illness. Dr. Cumming notes that bipolar disorder occurs at greater than twice the rate in patients with MS compared with the general population.

Key takeaways

Dr. Cumming emphasizes a growing recognition that MS-related neuropsychiatric complaints require a nuanced evaluation that extends beyond traditional diagnostic boundaries. Because presentations like insomnia, irritability, mood elevation and anxiety may stem from multiple interacting mechanisms, treatment decisions frequently require input from specialists across disciplines.

He concludes that comprehensive neurologic examination, psychiatric assessment and neuroimaging can all play important roles in guiding care.

“This case underscores how risky it can be to confidently attribute psychiatric symptoms to mental illness alone,” Dr. Cumming says. “I can’t overemphasize the value of integrated care teams capable of evaluating the whole clinical picture and offering a carefully considered treatment path.”