|Year : 2011 | Volume
| Issue : 1 | Page : 78-80
A case of neuroleptic malignant syndrome induced by desvenlafaxine in a patient on clozapine
Suddhendu Chakraborty1, Debasish Sanyal2, Bhaskar Mukherjee3, Sumit Roy4
1 Department of Psychiatry, KPC Medical College and Hospital, Kolkata, India
2 Department of Psychiatry , Calcutta National Medical College and Hospital, Kolkata, India
3 Department of Psychiatry , NRS Medical College and Hospital, Kolkata, Kolkata, India
4 Department of Cardiology, Calcutta National Medical College and Hospital, Kolkata, India, India
|Date of Submission||20-Oct-2010|
|Date of Acceptance||01-Nov-2010|
|Date of Web Publication||11-Mar-2011|
Department of Psychiatry, KPC Medical College and Hospital, Kolkata
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Neuroleptic malignant syndrome is a rare and potentially serious syndrome associated with the use of many antipsychotic, antiparkinsonian, antidepressants, etc. Moreover, of the agents known to cause this entity, clozapine has been mentioned a fewer times, but desvenlafaxine has never been known to precipitate it. However in this study, we present a case of established Neuroleptic syndrome that precipitated after administration of desvenlafaxine in a patient of resistant schizophrenia who was on clozapine. The presenting case explores the possibility of the potential of desvenlafaxine in causing this rare clinical entity and also a possible idiosyncratic interaction between desvenlafaxine and clozapine, whose mechanism is yet to be known.
Keywords: Clozapine, desvenlafaxine, neuroleptic malignant syndrome
|How to cite this article:|
Chakraborty S, Sanyal D, Mukherjee B, Roy S. A case of neuroleptic malignant syndrome induced by desvenlafaxine in a patient on clozapine. Int J Nutr Pharmacol Neurol Dis 2011;1:78-80
|How to cite this URL:|
Chakraborty S, Sanyal D, Mukherjee B, Roy S. A case of neuroleptic malignant syndrome induced by desvenlafaxine in a patient on clozapine. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2020 Jan 18];1:78-80. Available from: http://www.ijnpnd.com/text.asp?2011/1/1/78/77537
| Introduction|| |
Neuroleptic malignant syndrome (NMS) is a rare, life-threatening idiosyncratic phenomenon that has been reported due to use of antipsychotic and a few other psychotropic drugs. The syndrome is characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction. Typical and atypical antipsychotics (e.g., chlorpromazine, flupenthixole, fluphenazine,  haloperidol, loxapine,  olanzapine,  quetiapine,  aripiprazole  ), antiparkinsonians ,, [e.g., amantadine, levodopa withdrawal], antidepressants [amoxapine, clomipramine, desipramine, venlafaxine], and a few others (e.g., metoclopramide, carbamazepine, oral contraceptives) have been reported to cause NMS.  However, desvenlafaxine and clozapine were not known to cause this disease very frequently. In the present study, we are going to present a case who presented with features suggestive of NMS supposedly precipitated by desvenlafaxine and clozapine overdose.
| Case Report|| |
A 25-year-old, unmarried, male college student was admitted in the intensive care unit of the hospital with altered level of consciousness, confusion, restlessness, high fever (up to 104 degrees Fahrenheit), palpitation, and hypotension since the last 3 days. History as obtained from the informants (his parents) revealed that the patient was under psychiatric treatment for the last 10 years for recurrent episodes of abnormalities of behavior, suspiciousness, fearfulness, self muttering, auditory hallucination, occasional violent unprovoked anger outbursts, and at least one episode of deliberate self harm 6 years back. Immediately before the present episode, patient had a triggering event in his personal and professional life. The patient became drowsy and gradually became unconscious within 7 days of initiating desvenlafaxine. The onset was slow to progress and his sensorium deteriorated gradually. There was no history of any substance abuse previously. The family history of the patient did not reveal any psychiatric illness. The patient was not known to be suffering from any chronic medical illness before the event. History of previous medication suggested that the patient was earlier tried on risperidone and haloperidol in adequate dose and duration but he failed to respond satisfactorily. He was further put on clozapine; dose escalated up to 100 mg for the past 5 years and it was well tolerated. He was recently put on desvenlafaxine 50 mg for the past 1 week as he was complaining of low mood, loss of energy, and central type headache. He was monitored monthly for routine blood count that did not show any alteration before the present episode.
On examination, the patient had fever (103.5 degree Fahrenheit), altered sensorium, tachycardia, tachypnea, hypotension, sialorrhea, tremor, bladder and bowel incontinence, and significant lead pipe muscle rigidity in all the four limbs. There was no neck rigidity, Kernig's sign was negative, and pupil was bilaterally symmetrical and reacting. There were no echo phenomenon, ambitendency, and posturing. Detailed mental status examination was not possible initially as the patient failed to cooperate. Laboratory investigations revealed a significantly high serum creatinine phosphokinase level, leukocytosis, and marginally elevated serum urea level. The urine showed positive results for myoglobin detection and evidences of red blood cells. Computed tomography scan of brain was inconclusive. Exact laboratory investigation parameters on the date of admission are summarized in [Table 1].
CPK-Creatinine Phosphokinase, CPKMB-Creatinine Phosphokinase Cardiac Isoenzyme, SGPT-serum glutamate pyruvate transaminase, SGOT- serum glutamic-oxaloacetic transaminase, VDRL-Veneral Disease Research Laboratory, CSF-Cerebro Spinal Fluid, CT-Computerized Tomography
The patient was managed in intensive care unit. All psychotropic medications were withheld temporarily. He was managed with intravenous lorazepam, supportive measures (which consisted of moist oxygen inhalation, intravenous fluids, antipyretics, cooling blankets), and bromocriptine (initially starting at 7.5 mg/day and escalating dosage to 15 mg/day in three divided doses).  The patient improved within 6 days  and detailed mental status examination showed his psychiatric diagnosis to be resistant schizophrenia (paranoid type). The patient was rechallenged with clozapine under careful precaution; dose gradually titrated over 6 weeks. The patient responded well to the medication and did not develop any signs of the presenting episode over a period of 6-month follow-up period. He returned back mostly to his normal social and professional work after 6 months on continuing the psychopharmacological treatment and psychosocial interventions.
| Discussion|| |
The history of onset of the present episode, clinical findings, and laboratory parameter findings excluded the possibility of other important differential diagnoses in this case, namely encephalitis or meningitis, Parkinsonism More Details or acute dystonia, malignant hyperthermia, ,, substance-induced toxicity (e.g., amphetamine, cocaine), delirium tremens, rhabdomyolysis, septic shock, hemorrhagic stroke, pheochromocytoma, strychnine poisoning, etc. As desvenlafaxine is an SNRI, there is always a possibility that it might have precipitated an episode of serotonin syndrome in this presenting patient and speaking pharmacogenetically, there are always poor metabolizers to drugs and these poor metabolizers are at high risk of drug toxicity. Serotonin syndrome can also produce all the biochemical abnormalities of NMS (although rarely) and many of the clinical symptoms, especially if the patient is unconscious or unable to allow a full neurological examination. However, the thing to consider in this case is desvenlafaxine is a metabolite itself and thus is not known to be metabolized much in body. And further mimicking every symptom of NMS is rarer still. Therefore, by all possibilities, this patient is a case of NMS.
The presenting case is unique due to the fact that although a few cases of NMS have been reported to be precipitated by the use of clozapine, none has been found to be associated with use of desvenlafaxine.  There is no adequate evidence as of now regarding any idiosyncratic interaction between clozapine and desvenlafaxine which may have precipitated the present NMS episode. Moreover, as the patient had been on clozapine for a comparatively longer period of 5 years and desvenlafaxine was introduced much later, and the fact that the patient did not show any evidence of such an episode when he was rechallenged with clozapine alone under supervision for a considerable period of time, desvenlafaxine can be suspected to have played an important role in precipitating the reported event.
| Conclusion|| |
Considering the fact that desvenlafaxine is a new congener in the family of dual-acting antidepressants, detailed pharmacological studies exploring its potential side effects are still awaited. The present case of NMS was found to be associated with the use of clozapine and desvenlafaxine, both not very well known of causing this clinical entity. This warrants further studies on clinicopharmacological profile and interaction between these two drugs in future.
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