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|NI FEATURE: FACING ADVERSITY…TOMORROW IS ANOTHER DAY! - LETTERS TO EDITOR
|Year : 2019 | Volume
| Issue : 3 | Page : 858-861
Acute confusional state induced by diclofenac: Report and review of literature
Dhananjay Gupta, Mahendra Javali, Rangaiah Pradeep, Anish Mehta, Purushottam T Acharya, Rangasetty Srinivasa
Department of Neurology, Ramaiah Medical College, Bengaluru, Karnataka, India
|Date of Web Publication||23-Jul-2019|
Dr. Mahendra Javali
Department of Neurology, Ramaiah Medical College and Hospitals, Bengaluru - 560 054, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta D, Javali M, Pradeep R, Mehta A, Acharya PT, Srinivasa R. Acute confusional state induced by diclofenac: Report and review of literature. Neurol India 2019;67:858-61
|How to cite this URL:|
Gupta D, Javali M, Pradeep R, Mehta A, Acharya PT, Srinivasa R. Acute confusional state induced by diclofenac: Report and review of literature. Neurol India [serial online] 2019 [cited 2019 Aug 21];67:858-61. Available from: http://www.neurologyindia.com/text.asp?2019/67/3/858/263243
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used over-the-counter and prescription drugs for the management of pain and inflammation. They account for 5–10% of all drug prescriptions. Diclofenac is a potent NSAID, available in topical, oral, rectal, and intramuscular formulations, making it one of the preferable choices in inflammatory rheumatic and nonrheumatic diseases. The efficacy of diclofenac is relatively well known. The safety and adverse risk profiles have been reviewed recently by both European as well as Australian Pharmacovigilance Committees  The most common adverse effects include gastrointestinal, renal, and cardiac events. Recent reports have mentioned some rare but clinically relevant events such as psychiatric disturbances, tissue necrosis  and rhabdomyolysis  associated with this drug. We report two patients who developed an acute-onset, self-resolving confusional state after the use of diclofenac.
The first patient was a 64-year old lady, without any previous comorbidities, who underwent laparoscopic umbilical mesh hernioplasty for paraumbilical hernia. Postoperatively, on day 2, she was given diclofenac transdermal patch for pain. On postoperative day 3, she developed agitation and altered sensorium with a drop in Glasgow Coma Scale (GCS) score, for which she had to be intubated and maintained on ventilator. She was afebrile. The metabolic workup with total counts, electrolytes, kidney and liver function, blood and urine cultures, chest radiograph, and brain imaging were all normal. A lumbar puncture showed normal cerebrospinal fluid (CSF) analysis. Electroencephalogram (EEG) showed slowing of background rhythm [Figure 1]. The diclofenac patch was removed and the patient showed symptomatic improvement within 8–10 h. She was extubated and did not have any residual deficits. A repeat EEG was normal. Consequently, her symptoms were attributed to the diclofenac patch.
The second patient was a 52-year old lady, without previous comorbidities, who experienced knee pain after her daily morning walk. She took two tablets of diclofenac 50 mg. Around 2 h after taking diclofenac, the relatives noticed that she became agitated, confused, and was not following commands. On presentation to the hospital, she was in delirium. She was afebrile; there was no neck rigidity. Neurological examination did not reveal any lateralizing deficits. Blood investigations, total counts, electrolytes, renal and liver function tests, brain imaging, and CSF analysis were normal. EEG at presentation could not be done as the patient was agitated. She was managed with intravenous hydration and symptomatic therapy, after which she recovered within 10–12 h, without any residual deficits. EEG done on the day after admission was normal.
Diclofenac is a nonselective cyclooxygenase (COX) inhibitor with analgesic, anti-inflammatory, and antipyretic properties. In addition, novel mechanisms including stimulation of nitric oxide-cyclic guanosine monophosphate (NO–cGMP) pathway, N-methyl-D-aspartate (NMDA)-receptor inhibition, inhibition of peroxisome proliferator-activated receptor gamma (PPAR)-γ and effects on various cytokines and thromboxane A2 receptors have been proposed. Psychiatric side effects are emerging with the use of NSAIDs, more with the newer selective COX-2 than the older nonselective ones. The most common psychiatric symptoms reported are disorientation, restlessness, agitation, psychosis, personality changes, anxiety, and depression [Table 1].,, In the last 20 years, of all the diclofenac-related side effects reported to the United States Food and Drug administration, less than 0.5% patients reported psychiatric manifestations. Delirium was more common in females above 60 years of age, who had been taking diclofenac for less than 1 month or were taking furosemide along with diclofenac. The underlying mechanisms are still debatable and various theories have been proposed [Table 2].,,,,,, Prostanoids and prostaglandin modulation of PPAR-γ receptors have been suggested to play a role in the pathogenesis of neuropsychiatric syndromes such as depression, schizophrenia, and probably delirium., New research on the mechanism of diclofenac points to a more selective COX-2 inhibition, similar to celecoxib, which may modulate the central nervous system (CNS) side effects. COX-2 is the most abundant CNS isoform and is involved in synaptic transmission. Sparse case reports regarding psychiatric side-effects of NSAIDs make it difficult to define the risk factors, diagnostic criteria, and their management, and we believe our report would add to the growing body of literature on the subject.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]