clozapine and Muscle-Rigidity

Topics: Antipsychotic Agents; Clozapine; Consciousness; Diagnosis, Differential; Fever; Humans; Male; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid; Substance Withdrawal Syndrome

A 54-year-old woman with schizophrenia presented to hospital with unconsciousness, fever and marked muscle rigidity. She had been given fluphenazine decanoete 20 mg intramuscularly 15 days before the admission and she had continued taking haloperidol 20 mg daily and oral biperiden 2-4 mg. She was extremely rigid and unresponsive. On laboratory investigations revealed: serum sodium 120 mEq/l, creatinine phosphokinase 12,980 IU/l (normal up to 170), lactate dehydrogenase 1544 IU/l (150-500), free trioidothyronine < 1.00 pg/ml (1.5-4.5), free throxyine 0.76 ng/dl (0.8-1.9), thyroid stimulating hormone 1.14 microU/ml (0.4-4), cortisol (at 8.00 a.m.) 9 microg/dl (5-25). Antipsychotic drugs were withdrawn after admission. A diagnosis of secondary adrenal insufficiency and secondary hypothyroidism was made. Hormonal substitution with hydrocortisone and levothyroxine and correction of hyponatremia with intravenous hypertonic saline solution resulted in rapid improvement of symptoms and signs. It seems that the symptoms and signs of hypothyroidism and hyponatremia were attributed to acute psychosis in this patient. As a conclusion failure to recognize the endocrinopathy may not only produce recovery difficulties but also psychiatric and endocrine repercussions if psychotropic medications are given in such masked cases.

Topics: Adrenal Insufficiency; Antipsychotic Agents; Body Temperature; Clozapine; Female; Haloperidol; Humans; Hyponatremia; Hypothyroidism; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia

The aim of the present study was to investigate the relationship between effects on muscle tone and D2 receptor occupancy of two typical antipsychotic drugs, raclopride and chlorpromazine, and the atypical drug, clozapine. Increased muscle tone (i.e., muscle rigidity), was measured as increases in tonic electromyographic (EMG) activity of the antagonistic muscles of the rat hind limb. D2 dopamine receptor occupancy was assessed in the striatum and substantia nigra, areas involved in the regulation of muscle tone. Raclopride and chlorpromazine produced dose-dependent increases in EMG activity associated with D2 occupancy of 68%-80% in the striatum and 67%-76% in the nigra. No significant increases in EMG were observed with clozapine which showed low D2 occupancy. The results are consistent with those from human studies showing extrapyramidal side effects were associated with striatal D2 occupancy of > 70%.

Topics: Animals; Antipsychotic Agents; Autoradiography; Brain Chemistry; Chlorpromazine; Clozapine; Dose-Response Relationship, Drug; Electromyography; Hindlimb; Male; Muscle Rigidity; Muscle Tonus; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Salicylamides

Clozapine is an atypical neuroleptic drug that was initially thought not to cause neuroleptic malignant syndrome (NMS). We report a case of NMS associated with clozapine as a single agent that developed in a patient with no prior history of NMS. In contrast to other reported cases of NMS with clozapine monotherapy in which rigidity was reported to be absent, our patient had classic NMS with lead-pipe rigidity. NMS should be included in the differential diagnosis of a febrile patient with a history of any neuroleptic treatment, including clozapine.

Topics: Adult; Antipsychotic Agents; Bromocriptine; Clozapine; Dantrolene; Diagnosis, Differential; Fever; Humans; Male; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia