Recurrent Catatonia in Parkinson Disease

Letters to the Editors Journal of Clinical Psychopharmacology • Volume 36, Number 1, February 2016

6. Keating GM. Nalmefene: a review of its use She had a medical history significant symptoms and a deferred ECT due to clin- in the treatment of alcohol dependence. for hypertension, coronary artery disease, ical instability, memantine at 5 mg daily CNS Drugs. 2013;27:761–772. asthma, and hypothyroidism. Further in- dose was initiated by enteral route. At the 7. Spanagel R. Alcoholism: a systems formation revealed a history of hospitaliza- 16th to 18th days, her negativism and im- approach from molecular physiology to tion at another center 1 and a half years mobility resolved markedly, and she be- addictive behavior. Physiol Rev. 2009;89: ago, because of a similar episode of immo- gan oral intake of food and fluids. At this 649–705. bility and mutism preceded by a short pe- stage, her mental examination revealed a 8. Nealey KA, Smith AW, Davis SM, et al. riod of agitation and visual hallucinations. general mental confusion and incoherence, κ-opioid receptors are implicated in the She had been continuously treated with ser- but no active psychotic symptoms. At the increased potency of intra-accumbens traline 50 mg and quetiapine 50 mg once 21st day, with near complete resolution of nalmefene in ethanol-dependent rats. daily afterward. the initial symptoms, she was discharged. Neuropharmacology.2011;61:35–42. At our initial examination, patient's On an outpatient visit a month later, she 9. Katsuura Y, Heckmann JA, Taha SA. eyes and mouth were firmly closed and was better off with memantine 10 mg mu-Opioid receptor stimulation in the she had gegenhalten rigidity at her neck BID. Her mental examination revealed mod- nucleus accumbens elevates fatty tastant and extremities. She had no focal neurolog- erate dementia with a mini–mental state ex- intake by increasing palatability and ical signs or meningeal irritation and was amination score of 18/30. suppressing satiety signals. Am J Physiol afebrile with normal vital signs. A physical Five months later, the family reported Regul Integr Comp Physiol. 2011;301: examination revealed findings of dehydra- that the patient had suspiciousness and in- 244–254. tion. An initial complete blood count and somnia and also exhibited a waxing and 10. Gosnell BA, Levine AS. Reward systems blood chemistry including a serum creati- waning overactivity, which involved some and food intake: role of opioids. Int J Obes nine phosphokinase level were in the normal home activities such as cleaning and tidy- (Lond). 2009;33:S54–S58. range, except for moderate hypernatremia ing. The patient was then on a stable antiparkinson regimen arranged at another 11. Soyka M. Nalmefene a treatment of (150 mEq/L) and hypoglycemia (45 mg/dL). alcohol dependence: a current update. Further laboratory analyses revealed a nor- center 3 months earlier, and it consisted of Int J Neuropsychopharmacol. mal thyroid profile, serum vitamin B12/ levodopa/benserazide 50/12.5 mg BID, sus- 2013;18:1–10. folic acid levels, and negative serum tained release levodopa/benserazide 100/ VDRL/rapid plasma reagin tests. A cranial 25 mg BID, levodopa/carbidopa/entacapone magnetic resonance imaging showed a 100/25/200 mg and 150/37.5/200 mg BID, moderately severe global cortical atrophy and pramipexol 2 mg BID. She also received Recurrent Catatonia in and several small periventricular T2 hy- memantine 10 mg BID. Soon afterward, perintensities. After admission, patient's she had a loss of interest in daily activities Parkinson Disease dehydration and hypoglycemia were man- for a period of 3 weeks and became preoc- aged with intravenous fluids. Afterward, a cupied with vague abdominal complaints To the Editors: therapeutic trial of diazepam 5 mg intra- and constipation. According to the family, atatonia is a motor dysregulation syn- muscularly followed by lorazepam 1 mg she was irritable and paranoid and was re- C drome that occurs in various medical orally was given. This brought about a luctant to take her medications. At the in- 1 conditions. However, few reports have de- marked response within2to3hours;thepa- terview, she was unwilling to respond to scribed catatonia in patients with Parkinson 2,3 tient could walk, albeit slowly, sat on a chair, questions and had little eye contact. She also disease (PD). We present an elderly pa- and asked whether the police were after her. demonstrated psychomotor retardation with tient with PD, who developed recurrent ep- However, the response did not persist, and frequent thought blocking. Her mental ex- isodes of catatonia for a period of 3 years, consequently, the dose of lorazepam was amination revealed some depressed mood and discuss the challenges of managing gradually increased up to 5 mg/d by the and anhedonia; thus, duloxetine 30 mg/d catatonia in this clinical setting. third day. In the following days, she was and lamotrigine 25 mg/d were prescribed. persistently stuporous, negativistic, and Two weeks later, however, she had to be CASE REPORT uncooperative and had no oral intake. hospitalized for recurrence of catatonic stu- An 80-year-old woman, who had been di- Electroconvulsive therapy (ECT) was then por with fairly similar symptoms at previ- agnosed with idiopathic PD 12 years ago, considered; however, it was deferred be- ous hospitalizations. presented to our emergency department cause of an acute exacerbation of patient's On admission, her physical neurologi- with stupor, mutism, and immobility with asthma and concurrent clinical findings of cal examination was unremarkable except minimal response to painful stimuli. Ac- aspiration pneumonia with a moderate de- for a generalized rigidity, and an extensive cording to her family, during the previous gree of hypoxia, which required treatment biochemical workup of plasma and urine week, she had been severely agitated and with a parenteral antibiotic, inhaled bron- revealed normal results. A standard para- had visual hallucinations. She also became chodilators, and nasal oxygen. At the tenth neoplastic panel and a test for anti-N-methyl- suspicious of her children and believed day, while the patient was still stuporous, D-aspartate receptor antibodies were also that her food was poisoned. Therefore, they an electroencephalogram revealed gener- negative. Because of the anticipated medi- sought help in an emergency unit of a alized low-amplitude theta activity, vertex cal risks related to immobility and lack of psychiatric hospital. However, she became waves, and positive occipital sharp tran- oral intake, modified ECT treatment was increasingly unresponsive afterward and sients of sleep. Hence, an iatrogenic toxic started promptly with family's consent on refused food and fluids for the last few encephalopathy secondary to lorazepam hospital day 3. Electroconvulsive therapy days. The patient had been on stable doses was suspected, and this agent was dis- was repeated on the 2 consecutive days of levodopa/benserazide 200/50 mg 4 times continued. In the following days, the pa- and continued biweekly thereafter. Mean- daily and pramipexol 2 mg twice daily tient was slightly more responsive; she while, levodopa/benserazide 100/25 mg (BID) in the preceding year, with fairly well could open her eyes shortly and occasion- 6 times a day, pramipexol 1 mg BID, and controlled motor symptoms. Her daughter ally follow simple commands. At the 15th memantine 10 mg BID were administered also had PD with age of onset at 40 years. day, on the grounds of resistant catatonic by nasogastric tubing. A mild to moderate

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Journal of Clinical Psychopharmacology • Volume 36, Number 1, February 2016 Letters to the Editors response to ECT appeared after the fourth was treated with parenteral followed by oral lorazepam-resistant catatonic symptoms, session (on day 10) as demonstrated by olanzapine several days before the second ECT unresponsive catatonia, and apathy – spontaneous opening of eyes, after some episode, and an unknown parenteral seda- associated with neurological insults.8,10 12 simple commands and the rare “yes/no” an- tive agent was administered before the Our final observation was that loraz- swers. During this period, on several occa- first. On these 2 occasions, a neuroleptic epam should be administered cautiously sions, she had horrifying complex visual malignant-like syndrome or acute akinesia for catatonia in the elderly patients with and auditory hallucinations, which were in Parkinson disease was an important diag- neurodegenerative diseases such as PD, accompanied by persecutory delusions nostic alternative. However, this could be because higher doses might result in a se- (“thieves coming up” and “bombs ex- effectively ruled out by the absence of hyper- vere encephalopathy or deep sedation, ploding outside”). Therefore, quetiapine termia, severe rigidity, autonomic symp- and it might be particularly challenging 25 mg at bedtime was started, whereas pra- toms, and serum creatinine phosphokinase to distinguish this complication in pres- mipexol was gradually discontinued and elevation. In the last catatonic episode, ence of catatonic stupor. It should be total daily dose of L-dopa was increased where the patient was for a long time under recognized that a general recommenda- up to 900 mg in 5 days. A significantly our follow-up; symptoms emerged gradu- tion of benzodiazepines for the treatment greater improvement of patient's negativ- ally for weeks without an intervening dopa- of catatonia was reached after reports ism was observed after the sixth and the fi- mine antagonist; hence, we had an initial largely from young patients with primary nal ECT session (15th day). Nevertheless, impression that these were associated with psychiatric disorders. at this point, the patient appeared severely an underlying major depressive disorder. apathetic and exhibited prolonged immo- However, further observation of the patient's bility when left unattended. She did not mental state over the treatment course AUTHOR DISCLOSURE initiate any motor acts by herself, ask for yielded no appreciable depressive symp- INFORMATION food or fluids, or change position in bed, toms, and visual hallucinations and perse- The authors declare no conflicts yet she tended to follow most commands cutory delusions were predominant after of interest. without any hesitation (symptoms of severe resolution of the initially severe negativ- Written informed consent was obtained passivity). Furthermore, her speech was ism. These together with the prodromal from patient's next-of-kin (her daughter) for nonspontaneous, perseverative, and inco- period of overactivity and punding-like publication of this case report. herent with occasional echolalia. Conse- phenomena indicate that the patient's cata- quently on day 22, a therapeutic trial with tonia might be a severe motor manifesta- Burç Çağrı Poyraz, MD oral amantadine (started at 50 mg and ti- tion of psychosis and a late complication Department of Psychiatry trated in 50 mg daily increments) was initi- of PD, which were accentuated by the mod- Cerrahpaşa Faculty of Medicine ated. A mild resolution of the residual erate cognitive impairment and excessive University of Istanbul Istanbul, Turkey catatonic symptoms was noted by the 24th dopaminergic dosing. Nevertheless, it is possible that in the initial and the second day with this treatment, and a major im- Cana Aksoy Poyraz, MD provement followed on day 27 at a daily episodes of catatonia, emergency adminis- Department of Psychiatry dose of 200-mg amantadine. At that time, tration of dopamine receptor antagonists Cerrahpaşa Faculty of Medicine her mini–mental state examination score might have also contributed. University of Istanbul was 22/30. She was discharged on day 30. Catatonia is hypothesized to reflect a Istanbul, Turkey “top-down” (frontal) dysregulation of basal [email protected] DISCUSSION ganglia in severe psychiatric states and a GABAergic deficiency and/or an increased Ahmet Yassa, MD Catatonic stupor is a life-threatening medical glutamergic activity have been suggested as Mehmet Kemal Arıkan, MD, PhD emergency, which should be differentiated 6–8 Department of Psychiatry underlying neurochemical dysfunction. ş from other causes of general unresponsive- Similarly, a severe blockade of dopamine Cerrahpa a Faculty of Medicine ness and treated urgently to prevent associ- University of Istanbul 4 at these brain regions has also been pro- Istanbul, Turkey ated complications. Nonetheless, catatonia posed.6,7 In our case, both top-down and remains to be a widely underrecognized “bottom-up” mechanisms of dysregulation ş phenomenon.5 Its diagnosis might be even Ay egül Gündüz, MD of the frontal-basal ganglionic system Güneş Kızıltan, MD more problematic in the elderly patients and might have played a role, as suggested by Department of Neurology in presence of neurodegenerative diseases, active psychotic symptoms and the pres- Cerrahpaşa Faculty of Medicine where catatonia-related symptoms can be ence of PD, which is primarily a disease University of Istanbul easily ascribed to the primary neurological of basal ganglia. N-methyl-D-aspartate re- Istanbul, Turkey syndrome or some unrelated/secondary ceptor antagonists memantine and amanta- medical conditions. To our knowledge, only dine were found effective in alleviation of REFERENCES 2 case reports described catatonia in pa- our patient's catatonic symptoms on the sep- tients with PD. In 1 reported case, cata- arate episodes. However, it is interesting 1. Taylor MA, Fink M. Catatonia in tonic symptoms developed after a switch that the third catatonic episode emerged de- psychiatric classification: a home of in the ongoing dopaminergic treatment (af- spite the ongoing treatment with memantine. its own. Am J Psychiatry. 2003;160: – ter withdrawal of pramipexol and talipexol On this occasion, an ECT course was effec- 1233 1241. 2 due to hallucinations and delusions), and tive in reducing negativism and unrespon- 2. Kamigaichi R, Kubo S, Ishikawa K, et al. in the other, these followed a state, which siveness, although amantadine was required Effective control of catatonia in Parkinson's resembled neuroleptic malignant syndrome.3 eventually for recovery from the particularly disease by electroconvulsive therapy: a case In our case, catatonia was recurrent and severe amotivational state. Amantadine has report. Eur J Neurol. 2009;16:e6. 9 these episodes followed an acutely psy- a moderate dopaminergic affinity, and this 3. Suzuki K, Awata S. Catatonic stupor during chotic and agitated period. According to might have brought about the additional the course of Parkinson's disease resolved with further information gathered from medical clinical benefit. Both of these agents have electroconvulsive therapy. Mov Disord.2006; records and the family, patient's agitation been successfully used in treatment of 21:123–124.

4. Swartz C, Galang RL. Adverse outcome chest which were considered psychological received a short-term antihistaminic and ste- with delay in identification of catatonia in in origin by a dermatologist and pediatri- roid treatment. His skin rash resolved within elderly patients. Am J Geriatr Psychiatry. cian. He had no known drug allergy but 10 days of discontinuation. He denied using 2001;9:78–80. had a few episodes of skin eruptions possi- any other medication or unusual food. We 5. Van der Heijden FM, Tuinier S, Arts NJ, et al. bly related to food. obtained verbal consent from both the pa- Catatonia: disappeared or under-diagnosed? He was first started on sertraline 25 mg. tient and his family to publish this report Psychopathology.2005;38:3–8. He used this dosage for 3 months without and to include his photograph. 6. Taylor MA. Catatonia: a review of the any significant side effects. Then sertraline behavioral neurologic syndrome. was increased to 50 mg/d. He generally tol- erated it well except he developed itching Neuropsychiatry Neuropsychol Behav DISCUSSION Neurol. 1990;3:48–72. and mild skin eruptions on his arms and 7. Fink M, Taylor MA. Catatonia: A Clinician's upper chest. Sertraline was discontinued Methylphenidate has been the first-line Guide to Diagnosis and Treatment.Cambridge by the family for 1 month, during which psychopharmacological treatment in chil- UK: Cambridge University Press; 2003. time, there were no skin eruptions and dren and adolescents with attention-deficit 8. Carroll BT, Thomas C, Jayanti K, et al. Treating itching. On the next visit, it was revealed hyperactivity disorder and results in sig- he had some problems in his school due nificant improvement in 70% to 80% of persistent catatonia when benzodiazepines fail. 7 Curr Psychiatry. 2005;4:56–64. mainly due to attention problems. His re- affected children. Nausea, decreased ap- cent episode of itching and mild and local petite, weight loss, and sleep disturbances 9. Northoff G, Eckert J, Fritze J. Glutamatergic skin eruptions were considered as stress are among the most frequently reported dysfunction in catatonia? Successful related, and we decided to restart sertra- adverse effects during MPH treatment.7 treatment of three acute akinetic catatonic patients with the NMDA antagonist line 50 mg and add MPH 27 mg/d. His Besides these common adverse effects, amantadine. J Neurol Neurosurg Psychiatry. anxiety and attention problems showed MPH has also been reported to cause 1997;62:404–406. moderate to much improvement during some unusual adverse effects, such as hallu- 4 months of treatment. There were no sig- cinations,8,9 hypersexuality or inappropri- 10. Utumi Y, Iseki E, Arai H. Three patients nificant side effects except some level of ate sexual behaviors,10,11 skin eruptions,1–6 with mood disorders showing catatonia decreased appetite during the day and re- obsessive-compulsive symptoms,12,13 gy- and frontotemporal lobes atrophy. bound increased appetite at nights with- necomastia,14 and painful muscle cramps.15 Psychogeriatrics. 2013;13:254–259. out any significant weight change. His A review of the literature regarding 11. Obregon DF, Velasco RM, Wuerz TP, et al. weight was 58 kg, and we decided to MPH-related skin eruptions revealed that Memantine and catatonia: a case report increase MPH to 54 mg/d. After 1 week skin eruptions were usually local or in- and literature review. J Psychiatr Pract. of treatment, he developed nonpruritic cluded several parts (such as face, neck, 2011;17:292–299. maculopapular skin rash first on his face arms, scrotum, chest, or trunk) of the 1–5 12. Links KA, Black SE, Graff-Guerrero A, et al. and chest and then the rash spread all body in these reports. Skin eruptions over the body within 1 day (Fig. 1). We in these reports included pruritic maculo- A case of apathy due to frontotemporal 1,4 dementia responsive to memantine. discontinued sertraline and MPH. He papular, pruritic raised edematous circular Neurocase. 2013;19:256–261.

Diffuse Maculopapular Rash With Increasing Dosage of Methylphenidate To the Editors: here have been several reports of meth- T ylphenidate hydrochloride (MPH)-related skin reactions in children and adolescents with attention-deficit hyperactivity disorder treated with this medication.1–6 Here we present an 11-year-old boy who developed diffuse nonpruritic maculopapular skin rash with increasing dosage of MPH.

CASE E is an 11-year-old boy who has been followed up with diagnosis of social and generalized anxiety and attention deficit disorders for the last 2 years. His devel- opmental history and intellectual capacity were within normal limits. He had no significant medical or neurological history but had several episodes of itching and mild and local skin eruptions on his arms and FIGURE 1. Diffuse maculopapuler rash after increasing dosage of OROS-methylphenidate.