|Year : 2022 | Volume
| Issue : 1 | Page : 165-167
Benzodiazepine withdrawal catatonia: Two cases from a tertiary care center in Eastern India
Uttam Majumder, Avik K Layek
Department of Psychiatry, North Bengal Medical College, Sushrutanagar, Darjeeling, West Bengal, India
|Date of Submission||23-Dec-2021|
|Date of Acceptance||05-Mar-2022|
|Date of Web Publication||20-May-2022|
Dr. Avik K Layek
Department of Psychiatry, North Bengal Medical College, Sushrutanagar, Darjeeling - 734 012, West Bengal
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Catatonia is a diagnostic entity of a neuropsychiatric cluster of symptoms that can occur in a number of different psychiatric, neurologic, and metabolic disorders. Benzodiazepines remain the mainstay of the treatment of catatonia through their possible effect on the gamma-aminobutyric acid (GABA) receptor modulation in the central nervous system (CNS). Rarely, patients have been seen to manifest catatonic symptoms when they face sudden withdrawal from long-term benzodiazepine treatment. Here, we have presented two such cases of different clinical profiles where following benzodiazepine withdrawal, sudden catatonic symptoms emerged that responded quickly on re-administration of benzodiazepines.
Keywords: Benzodiazepine, catatonia, treatment, withdrawal
|How to cite this article:|
Majumder U, Layek AK. Benzodiazepine withdrawal catatonia: Two cases from a tertiary care center in Eastern India. Ind Psychiatry J 2022;31:165-7
| Introduction|| |
Catatonia, as coined by Kahlbaum, is comprised of a wide array of cognitive, behavioral, and motor symptoms associated with different types of psychiatric, neurological, metabolic, medical, and drug-related ailments. Catatonia can present with around 40 clinical signs and symptoms, usually from an abnormality in social engagement as well as stuporous or excitatory behavior. Catatonia has been awarded separate diagnostic status as per the Diagnostic and Statistical Manual (5th edition).
Different neurobiological mechanisms have been proposed regarding the etiopathogenesis of catatonia. One important mechanism is the overactivity of the glutamatergic system over the Gamma-Aminobutyric acid mimetic system in the dorsolateral prefrontal and orbitofrontal cortex. That catatonia treatment is mostly achieved by prominent gamma-aminobutyric acid (GABA) enhancing drug benzodiazepines ratifies this hypothesis to a large extent. Being positive allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors, benzodiazepines enhance the activity of GABA on the receptors and strengthen the inhibitory effect.,
One interesting hypothesis for catatonia comes from the standpoint of evolutionary psychology that states that it can be a primitive response to fear provoked by some extreme level of stress as shown in certain animal defense models of tonic immobility or freezing. That benzodiazepines have accepted anxiolytic characteristics also supports this hypothesis.
Apart from catatonia, benzodiazepines are used in the treatment of many disorders and clinical conditions commonly come across in psychiatry including anxiety and affective disorders, substance use, primary insomnia, acute agitation, and many more. Like few other medications, they are sometimes prone to certain withdrawal symptoms that come with medicine discontinuation. The appearance of catatonic symptoms upon benzodiazepine discontinuation is pretty rare, though case reports are there that described such incidence with or without various psychiatric disorders as background diagnoses.,,,,, Here, we narrate two such cases that we have come across in our in-patient department over last year (September 2020 to August 2021). Such withdrawal cases with decreased drug adherence were more prevalent during the coronavirus disease 2019 (COVID-19) pandemic with regard to various chronic non-communicable diseases including psychiatric illnesses as seen in different parts of the world., All of them were successfully treated in the in-patient department. Informed consent was obtained from each of the patients or the respective caregiver for the publication of the scenario.
| Case Reports|| |
The first case was a 70-year-old Hindu urban widow lady weighing 75 kg from an upper-middle socio-economic extended family without any prior history of psychotic or affective disorder. She used to take 0.5 mg clonazepam daily for the last 15 years that was initially prescribed by the general physician for possible primary insomnia and later on continued by herself. She was overweight but without any known metabolic abnormality. She stopped the drug thinking that it might harm her in the long run. Two days after the cessation, she developed rebound insomnia with echolalia and rigidity of the limbs for which she was advised to attend the psychiatry outpatient department (OPD) by her treating physician. On examination at psychiatry OPD, she was found to have rigidity, waxy flexibility, echolalia, echopraxia, and ambivalence. On examination, there was no definite neurodeficit. The initial Bush–Francis Catatonia Rating Scale (BFCRS) score was 14. She underwent a detailed biochemistry examination and brain imaging after examination, which failed to have any definite clue.
She was provisionally diagnosed with catatonia in the in-patient department and treatment was started using clonazepam 0.5 mg twice daily. Rigidity and echolalia started to wean within the first hour of treatment initiation. On the second day, she was fully recovered from the previous symptoms. BFCRS score on the second morning was 3. Mental state examination revealed no active psychiatric illness. The cognitive ability assessed by mini-mental state examination (MMSE) was found to be adequate (MMSE = 28). Clonazepam was gradually tapered down to 0.5 mg by the fourth day without any exacerbation of symptoms. She was counseled for proper sleep hygiene practice. She was discharged with plans to a gradual substitution of clonazepam with non-benzodiazepine sedatives garnered with sleep hygiene and lifestyle modification.
The second case was a 25-year-old unmarried Hindu male weighing 70 kg from an urban middle socio-economic nuclear family who was on sodium valproate 750 mg twice daily with lorazepam 2 mg for the last 2 years as maintenance treatment of a bipolar affective disorder. He was reluctant to attend his treating psychiatrist for follow-up as he thought he was well controlled with regard to his illness. Upon difficulties procuring lorazepam over the counter, he stopped taking the drug 7 days back. He initially complained of having rebound insomnia and a few anxiety symptoms. After 7 days, there was a slowness of movement, less speaking, keeping food in the mouth for a long time before swallowing. This prompted the family members to take him to the psychiatry OPD. On examination, he was found to have rigidity, mutism, negativism, mundane posturing, and staring. BFCRS scale was applied and the score was 21.
After admission, serum tests for creatine phosphokinase (CPK), electrolytes, metabolic, and biochemistry profile, and imaging of the brain with electroencephalogram (EEG) were advised. He was administered injectable lorazepam and Ryle's tube feeding. A neurological consultation referral was done and that revealed no central nervous system (CNS) abnormality. The dose of lorazepam was supervised to be under the sedative threshold. He started responding in the evening after intake of 8 mg lorazepam. It was continued and by the third day, the BFCRS score came down to 10 and he started to move, sit on the edge of the bed, and take food orally. Meanwhile, the serum and imaging reports were collected and found to be unremarkable except the serum sodium level was 130 mmol/L for which appropriate addition of salt was recommended. On the sixth day, the BFCRS score came down to zero and the serum sodium level was 139. A detailed history was taken that revealed two manic episodes without psychotic symptoms over the last two-and-a-half years with no history of substance use. His mental status examination found worriedness and inability to concentrate for a long time. Sodium valproate was re-instituted at a dose of 750 mg/day. Lorazepam was gradually tapered down to 2 mg/day over the next 4 days and he was discharged with sodium valproate 1.5 g/day and lorazepam 2 mg/day with suggestions of regular follow-up and sleep hygiene maintenance.
| Discussion and Conclusion|| |
If we consider the common features of the cases discussed above, catatonic features started appearing soon after the discontinuation of benzodiazepines, mostly within a week. And each case was associated with long-term intake of prior benzodiazepines on a daily basis. Despite the difference in clinical profile and background psychiatric diagnoses, all of them responded pretty early with re-institution of benzodiazepines of varying doses. Interestingly, the initial response began to be recorded with 2–6 h at maximum.
As per the existing literature, drug discontinuation symptoms are thought to appear owing to the pharmacokinetics of the drug, its cellular mechanisms, and the homeostatic modification of the body to its targets following its administration on a long-term basis. In the case of benzodiazepine withdrawal, it is hypothesized to involve the GABA system in the CNS. Though the exact mechanism may not be that simplified, benzodiazepines being an allosteric modulator of GABAA receptors can potentiate its activity with chronic use resulting in GABAA receptor function down-regulation.,, Upon sudden withdrawal, a sudden GABA deficient state at the orbitofrontal and dorsolateral prefrontal cortex may lead to the manifestation of catatonic symptoms., With all the cases having a history of chronic benzodiazepine use, our cases also support the clinical correlation of this hypothesis.
Prior studies have shown that the clinic-pathological manifestation of catatonia can simulate each other to a large extent even if they come with a wide array of background psychiatric diagnoses., Also the treatment protocol remains in the same line irrespective of the diagnostic difference., The second case had bipolar disorder and the first one did not meet any psychiatric diagnosis at discharge, though their commonalities in terms of presentation and treatment point to the importance of catatonia as a separate diagnostic construct.
We can conclude that patients and clinicians should be aware of the fact that sudden withdrawal of benzodiazepine can precipitate catatonia irrespective of the existing physical or psychiatric illness. Proper protocol regarding benzodiazepine withdrawal is best to be followed where it can be substituted by another GABA-mimetic drug for a short duration before active withdrawal so that the sudden GABA deficient state can be avoided., And slow tapering over relatively moderate duration should be considered to prevent such untoward circumstances that can arise out of the abrupt cessation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Narayanaswamy JC, Tibrewal P, Zutshi A, Srinivasaraju R, Math SB. Clinical predictors of response to treatment in catatonia. Gen Hosp Psychiatry 2012;34:312-6.
Vahia VN. Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J Psychiatry 2013;55:220-3.
] [Full text]
Parenti A, Jardri R, Geoffroy PA. How anti-NMDAR encephalitis sheds light on the mechanisms underlying catatonia: The neural excitatory/inhibitory imbalance model. Psychosomatics 2016;57:336-8.
Sienaert P, Dhossche DM, Vancampfort D, De Hert M, Gazdag G. A clinical review of the treatment of catatonia. Front Psychiatry 2014;5:181.
Daniels J. Catatonia: Clinical aspects and neurobiological correlates. J Neuropsychiatry Clin Neurosci 2009;21:371-80.
Perkins RJ. Catatonia: The ultimate response to fear? Aust N Z J Psychiatry 1982;16:282-7.
Griffin CE 3rd
, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 2013;13:214-23.
Mader EC Jr, Rathore SH, England JD, Branch LA, Copeland BJ. Benzodiazepine withdrawal catatonia, delirium, and seizures in a patient with schizoaffective disorder. J Investig Med High Impact Case Rep 2020;8:2324709620969498.
Pétursson H. The benzodiazepine withdrawal syndrome. Addiction 1994;89:1455-9.
Hauser P, Devinsky O, De Bellis M, Theodore WH, Post RM. Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders. Arch Neurol 1989;46:696-9.
Rosebush PI, Mazurek MF. Catatonia after benzodiazepine withdrawal. J Clin Psychopharmacol 1996;16:315-9.
Brown M, Freeman S. Clonazepam withdrawal-induced catatonia. Psychosomatics 2009;50:289-92.
Parameswaran R, Moore K, Hannan T, Austin M. Catatonia associated with temazepam withdrawal. Aust N Z J Psychiatry 2011;45:1006-7.
Shimels T, Asrat Kassu R, Bogale G, Bekele M, Getnet M, Getachew A, et al
. Magnitude and associated factors of poor medication adherence among diabetic and hypertensive patients visiting public health facilities in Ethiopia during the COVID-19 pandemic. PLoS One 2021;16:e0249222.
Gasteiger N, Vedhara K, Massey A, Jia R, Ayling K, Chalder T, et al
. Depression, anxiety and stress during the COVID-19 pandemic: Results from a New Zealand cohort study on mental well-being. BMJ Open 2021;11:e045325.
Sivakumar T, Yadav A, Sood M, Khandelwal SK. Lorazepam withdrawal catatonia: A case report. Asian J Psychiatr 2013;6:620-1.
Swain SP, Behura SS, Dash MK. The phenomenology and treatment response in catatonia: A hospital based descriptive study. Indian J Psychol Med 2017;39:323-9.
] [Full text]
Brett J, Murnion B. Management of benzodiazepine misuse and dependence. Aust Prescr 2015;38:152-5.