Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam

Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1176-8. doi: 10.1016/j.pnpbp.2006.04.006. Epub 2006 May 23.


A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Alprazolam / adverse effects*
  • Alprazolam / therapeutic use
  • Antidepressive Agents, Second-Generation / adverse effects*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Depressive Disorder / drug therapy
  • Depressive Disorder / psychology
  • Drug Therapy, Combination
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Neuroleptic Malignant Syndrome / etiology*
  • Paroxetine / adverse effects*
  • Paroxetine / therapeutic use
  • Psychiatric Status Rating Scales


  • Antidepressive Agents, Second-Generation
  • Hypnotics and Sedatives
  • Paroxetine
  • Alprazolam