Catatonia and CPK Elevation in Neurosyphilis: Role of Plural Pharmacodynamic Mechanisms

Objectives: To report catatonia in neurosyphilis with elevated creatine phosphokinase (CPK) and to understand the pharmacodynamics of catatonia. Experimental design: Case report. Principal Observations: We encountered catatonia in a man with neurosyphilis after increasing aripiprazole and valproate (drugs reported to improve catatonia) and reducing doxycycline and temazepam dosages, consistent with identified dopamine D2, serotonin 5HT2, and 5HT1a (aripiprazole), GABA-B (valproate), glutamatergic NMDA (aripiprazole, valproate, doxycycline), and GABA-A (aripiprazole, temazepam) mechanisms of catatonia. CPK was markedly elevated despite the absence of neuroleptic malignant syndrome (NMS) and responded to lorazepam, as did the catatonia. Conclusions: This appears to be the first case report of catatonia without NMS associated with each of the following: neurosyphilis, aripiprazole, and temazepam withdrawal. This case further adds to the emerging literature of catatonia arising with valproate and atypical antipsychotic co-administration, and of non-NMS catatonia associated with CPK elevations. Plural simultaneously–operant pharmacodynamic mechanisms may explain catatonia of unclear etiology and reconcile a seemingly contradictory literature (e.g., the capacity of certain drugs (e.g., aripiprazole, valproate) to either relieve or precipitate catatonia depending on their pharmacological contexts). Besides reduced D2, 5HT2, and GABA-A and increased 5HT1a, GABA-B, and NMDA receptor stimulation appreciated in the clinical literature, stimulation of adenosine, muscarinic, and H1 histamine receptors may also have promoted catatonia in this case and others, whereas the alpha-2 agonist clonidine has alleviated it. Multiple drugs in this regimen and our current reliance on mechanisms determined primarily in preclinical studies now indicate the need for clinical studies to determine the relative importance of each mechanism in human patients. Psychopharmacology Bulletin. 2009;42(4):53–63.