Topiramate Effect in Catatonia: A Case Series

A 19-year-old Caucasian woman with a 3-year history of chronic psychotic illness with auditory hallucinations and paranoid and referential delusions had been stable with risperidone therapy at a dose of 4 mg daily. The patient was compliant by all accounts. However, she later became agitated, and this agitation was, most likely, the result of Cannabis abuse, which was confirmed by laboratory testing. She was committed to a local hospital where she was treated with risperidone, which had until then given her very good symptom relief. During this episode, the patient deteriorated further and began to demonstrate catatonic mutism, negativism, and occasional posturing. Lorazepam was added in low dose (about 3 mg daily in divided doses). At the family’s request, the patient was transferred to our facility, in part to explore other treatment options, including ECT. After arrival at our facility, the patient and her family decided against a trial of ECT, and a trial of high-dose lorazepam, up to 9 mg daily, was offered. This was well tolerated, but signs of catatonic agitation, including posturing and catalepsy, only worsened. Marked sedation made further dose increases an impractical option. A trial of divalproex was unhelpful and was poorly tolerated due to gastrointestinal side effects. On the basis of an argument that glutamate antagonism might offer further relief of catatonic agitation without excess sedation and because of a recent report on the success of topiramate in treatment of schizophrenia, a trial of topiramate was offered. Topiramate dose was gradually titrated from 25 mg b.i.d. to 100 mg b.i.d. The patient’s catalepsy, posturing, and episodic immobility remitted as the daily dose reached 200 mg per day, and lorazepam was gradually withdrawn. Risperidone therapy was continued with topiramate as the patient was discharged home in the care of her family. At the 3-month follow-up, the patient had experienced no recurrence of catatonic agitation, and at the 1-year follow-up, she had improved enough to return to college.

A 19-year-old Caucasian woman with only a 1-year history of psychotic and depressive illness with bizarre delusions had nine prior hospitalizations at area hospitals, during the span of her 1-year history. In addition, the patient had a history of violent suicide attempts, most recently by trying to sever one hand with her father’s circular saw. When the patient was transferred to our unit after surgical reattachment of her injured hand, she was cooperative with postoperative care, but she was mute and immobile for a period and was observed to demonstrate posturing and waxy flexibility by the third morning of her stay at our facility. She was already receiving high dose benzodiazepine therapy with the olanzapine that she had been taking as an outpatient before the crisis that culminated in the severing of her hand. The patient already had failed to improve during adequate trials of risperidone, quetiapine, ziprasidone, most of them in combination with lithium or divalproex. At the time of admission, the patient was compliant with divalproex 1,000 mg daily and olanzapine 15 mg daily, according to both the patient and to her parents, with whom she lived. The working diagnosis to date had been bipolar disorder, mixed with psychotic features, although her flat affect and the bizarre character of her delusions forced us to consider schizophrenia in the differential diagnosis. A trial of clozapine was offered and accepted, and the patient stated it seemed to help her more than the other agents she had taken. Episodic muteness and immobility continued despite this improvement and continued lorazepam therapy. Our experience with the patient prompted another recommendation for a trial of topiramate, in lieu of divalproex. Signs of catatonia disappeared as the daily dose passed 150 mg, and the dose was again titrated to 200 mg daily. The patient continued to improve and was discharged home on topiramate at the same dose and clozapine 300 mg daily. She did well for approximately 3 weeks before being hospitalized for suicidal behavior again.

A 61-year-old woman with a history of bipolar disorder (type I) since age 20 had been fairly stable until suffering a myocardial infarction and undergoing coronary artery bypass graft surgery. She then suffered a recurrence of mania with paranoid delusions that developed despite compliance with lithium carbonate and quetiapine therapy, with proven therapeutic levels of lithium of 1meq/liter. She appeared to stabilize with the addition of divalproex sodium but again became psychotic and agitated when her sternotomy wound from bypass surgery was complicated by sternal osteomyelitis. While still receiving intravenous antibiotics, she was transferred to the psychiatry service due to disorganized, agitated behavior, with extreme negativism—so great that she refused to rise from bed or even to feed herself. The development of catalepsy convinced us that her condition was a catatonic agitation. High-dose lorazepam led only to sedation, even when quetiapine was discontinued. A trial of topiramate was well tolerated, and led to gradual resolution of signs of catatonia after the daily dose reached 200 mg. The patient developed stupor with fever after antibiotic therapy was discontinued, and all psychotropic medications were stopped. Medical evaluation revealed a urinary tract infection that was subsequently treated. As the stupor and delirium cleared, the patient again demonstrated agitation, extreme negativism, and catalepsy. Topiramate therapy was resumed and again titrated to 200 mg daily. Signs of catatonic agitation remitted, and the patient was able to return home to care for herself.

A 65-year-old woman with chronic schizophrenia and a history of repeated hospitalizations for catatonic states with catalepsy and muteness was admitted to the medical service of the hospital. She was dehydrated and had early sepsis from sacral decubitus ulcers that developed during immobility caused by a new recurrence of catatonia. When medically stable, she was transferred to the psychiatry service. High dose lorazepam therapy, up to 12 mg daily, made no difference in her mute immobility, nor did the addition of divalproex up to 1,500 mg daily (valproate level was 95 mcg/ml). A trial of topiramate was made, and the patient began to speak, feed herself, and ambulate as the dose reached 200 mg daily. The patient continued to receive topiramate therapy and was well for about 1 year, during which time lorazepam was gradually withdrawn. She suffered a recurrence of catatonic agitation with mute immobility, posturing, catalepsy, and gegenhalten. Symptoms improved gradually during the second hospitalization with continuation of topiramate 400 mg daily and a daily dose of lorazepam totaling 12 mg daily.

During the same period of time, two patients were seen with catatonia who responded to lorazepam therapy, and two who were treated with ECT. There were no patients with catatonia who were treated with topiramate first, and no patients who were treated with topiramate who did not experience remission.