Vinayak Koparde, Adarsh Bellad, Sandeep Patil
Jawaharlal Nehru Medical College, Karnataka Lingayat Education Society Dr. Prabhakar Kore Hospital, Belgaum, Karnataka, India
Introduction: Neuroleptic malignant syndrome (NMS) is an uncommon but life threatening idiosyncratic drug reaction that occurs following neuroleptic drug exposure. The estimated incidence of NMS is about 0.2% and mortality rates range between 4-30% (Andreassen). The characteristic clinical features of NMS include extrapyramidal signs like rigidity, autonomic signs like hyperthermia, fluctuating blood pressure, tachycardia, tachypnea and mental status changes like confusion. Other features include raised Creatine phosphokinase (CPK) levels, leucocytosis, myoglobinuria, hypernatremia, hyperkalemia, metabolic acidosis. Death in NMS may occur due to complications involving renal, cardiovascular systems and respiratory insufficiency. NMS is also reported with agents other than classic neuroleptic drugs leading to changing concepts of NMS. NMS has been reported to occur in patients exposed to Selective Serotonin Reuptake Inhibitors (SSRI). NMS has been reported in a patient treated with Fluoxetine (Halman), Citalopram (Aydin). NMS is also reported when SSRI like Fluvoxamine is combined with a second generation antipsychotic i.e Quetiapine (Matsumoto). Combination treatment with Risperidone and Fluvoxamine is reported to cause neurotoxic syndrome in one patient (Reeves). Here we report a case of NMS with Fluvoxamine treatment alone.
Case Report: A 64 year old woman with Obsessive compulsive disorder for past 15 years, with no history of Diabetes mellitus and Hypertension was treated in past with Fluoxetine 60 mg/day and Clomipramine 25mg/day and improved. She was recently started on Fluvoxamine controlled release 50mg/ day tablet for worsening of her symptoms of OCD. Patient within 2 days of starting Fluvoxamine started complaining of severe generalized weakness, fever, excessive drowsiness. Patient when presented to us on 3rd day had fever, extremity muscle rigidity, hypertension, tachycardia, diaphoresis, decreased urine output. There was no history of taking any other medication, myoclonus, seizure, any focus of infection. Subsequently patient was admitted in ICU care. On clinical examination patient continued to have rigidity of extremities, perspiration, tachycardia, decreased urine output, fluctuating blood pressure suggestive of autonomic instability. Patient on 3rd day of admission developed disorientation to time and visual hallucinations. When investigated further patient had developed metabolic acidosis. The laboratory parameters of the patient from day of admission are given in Table 1.
Table 1.
Patient's investigations on admission showed raised levels of CPK, Total leucocyte count, Urea and Creatine. Myoglobinuria was present. A diagnosis of Neuroleptic Malignant Syndrome with OCD was made and patient was admitted in Intensive Care Unit. Fluvoxamine was discontinued and she was treated with Paracetamol for fever, Intravenous fluids to maintain hydration and electrolyte balance, intravenous Sodium Bicarbonate to treat acidosis and Clonazepam 0.25 mg for complains of anxiety and insomnia. By day 7 of admission patient started showing improvement, i.e. rigidity decreased, sleep and urine output improved, there was no fever but weakness persisted. Laboratory investigations done at the time of discharge from hospital were within normal limits.
Discussion: Neuroleptic malignant syndrome and Serotonin syndrome (SS) are both serious adverse drug reactions related to exposure to psychotropics and diagnostic difficulty may arise in patients because of overlapping clinical features of these two syndromes. There are some features which distinguish NMS from SS like elevated creatine kinase, lactate dehydrogenase, aspartate transaminase, and white blood cell count. NMS is classically reported with typical antipsychotics but in recent years this concept is changing because of its association with atypical antipsychotics, SSRIs and other psychotropic medications. The majority of SSRI-related reactions appear to occur within the first month of treatment (Caley). SSRIs may cause NMS by their facilitative action on neurotransmitter serotonin along with central dopaminergic blockade (Halman). Addition of SSRI to Second Generation Antipsychotic is also reported to increase the risk of NMS by inhibiting Dopamine release by SSRIs (Stevens). Treatment of NMS whether induced by an antipsychotic or SSRI consists primarily of early recognition, discontinuation of triggering drugs, management of fluid balance, temperature reduction, and monitoring for complications. Dantrolene is indicated in more severe, prolonged, or refractory cases. Electroconvulsive therapy has been used successfully in some cases. Health care workers should be aware of SSRI induced NMS for early recognition and treatment of these patients and also to differentiate it from Serotonin Syndrome because of overlapping clinical features.
